Spheroidal System Research Articles

Isolation and In Vitro Culture of Human Gut Progenitor Cells.

The gastrointestinal epithelium is a highly regenerative organ, where each cell is replaced in a cycle of 4-6days, depending on the mammalian species. This highly proliferative state is driven by gastrointestinal stem and progenitor cells, located at the base of crypts. These cells give rise to at least six types of differentiated epithelial cells, each with a distinct function in maintaining homeostasis between the intestinal interface and the luminal environment. The isolation and culture of these cells from mammalian gastrointestinal tissue is a novel technique, which allows for the generation and maintenance of an in vitro culture system for adult epithelial cells. There are two predominant methods for isolation and propagation of gastrointestinal epithelial cells, the first is the organoid system developed in 2009, and the second is a later version known as the L-WRN spheroid system. In this chapter, we describe the method to isolate and culture human gastrointestinal stem and progenitor cells and culture them as three-dimensional spheroids using L-WRN cell conditioned media.

On the Moving Trajectory of a Ball in a Viscous Liquid between Two Concentric Rigid Spheres

In the paper, the dynamic motion of a point ball with a mass of m , sliding in a viscous liquid between two concentric spheres under the influence of gravity and viscous and dry resistance, is investigated. In addition, it is considered that the ball starts its motion from some arbitrary point M 0 = M ( θ 0 , φ 0 ) . A system of nonlinear differential equations in a spheroidal coordinate system is obtained for the angular variables θ and φ to account for all the forces acting on the ball. The dependence of the reaction force on the angular variables is found, and the solution of the resulting system of equations is numerically analyzed. The projections of the trajectories on the plane x − y , y − z , x − z are found.

IPSC-Derived NK Cells and Anti-PD-1 Antibody Synergize to Enhance T Cell Cytokine and Cytolytic Responses Against Multiple Tumors

The development of immunotherapeutic monoclonal antibodies targeting checkpoint inhibitory receptors (CIR), such as programmed death 1 (PD-1), has transformed the oncology landscape. However, many tumor subtypes are resistant to CIR-targeted therapy, and relapse remains a significant concern. Therefore, combination of novel immunotherapies with CIR targeting remains a promising and widely investigated approach to bolster anti-tumor responses and to overcome tumor resistance to CIR therapy.Natural killer (NK) cells mediate direct tumor cell lysis and are key regulators of T cell responses through the production of inflammatory cytokines and chemokines. In many cancers, NK cell numbers are low and their functional responses are sub-optimal. The use of allogeneic NK cell immunotherapy has shown significant clinical promise for the treatment of acute myelogenous leukemia (AML). However, this approach has inherent limitations with respect to the number of NK cells that can be isolated and variability in the quantity and quality of NK cells between donors. To overcome these barriers, we have developed a system for large scale expansion of NK cells derived from induced pluripotent stem cells (iPSCs) to be combined with CIR antibodies for multiple tumor types (Figure 1A). iPSC derive NK (iNK) cells (defined as CD45+CD3-CD56+) differentiated with high efficiency in this culture system (Figure 1B), and overall expansion from the hematopoietic progenitor stage to end of the protocol was approximately 1 million-fold (Figure 1C).iNK cells displayed a cell surface phenotype typical of primary peripheral blood NK cells, with high expression of the cytotoxicity molecules granzyme B and perforin. Functionally, iNK cells degranulated and produced the pro-inflammatory cytokines tumor necrosis factor (TNF) and interferon (IFN)-γ at high frequencies in response to K562 cells (a myeloid leukemia cell line) (Figure 1D). These cells also effectively killed a broad range of solid tumor targets, including ovarian cancer (SKOV-3), lung cancer (A549) and pancreatic cancer (PANC-1) cell lines, in 2D tissue culture assays (Figure 1E). To interrogate the ability of iPSC-derived NK cells to synergize with CIR therapy, we used an in vitro 3D tumor spheroid system to model the combinatorial effects of T cells, iNK cells, and checkpoint blockade in the context of anti-tumor function. Using SKOV-3 spheroids as targets in a 160-hour killing assay, we found that iNK cells could mediate significant, but not complete destruction of tumor spheroids (46% tumor reduction). Addition of twice as many activated T cells by themselves induced tumor spheroid destruction (58% tumor reduction). The combination of iNK and activated T cells led to robust target cell destruction (71% tumor reduction). Importantly, the combination of activated T cells, iNK cells and anti-PD-1 antibody led to a near complete elimination of tumor spheroid targets, with greater than 99% tumor reduction (Figure 1F). In addition to synergistic lysis of tumor spheroids, analyses of cytokine secretion in iNK, activated T cell and CIR spheroid cultures revealed synergistic production of TNF and IFN-g (Figure 1G).The results from our 3D spheroid assays led us to hypothesize that iNK cells could recruit T cells to promote tumor lysis. To test this hypothesis, we performed transwell migration assays to test the relative abilities of iNK cells and K562 cells to promote T cell migration. We found that, relative to media controls, both iNK cells and K562 cells promoted T cell migration across transwells, and the highest amount of degree of migration was observed in the presence of both iNK and K562 cells (Figure 1H). Finally, we tested iNK-mediated T cell recruitment in an in vivo setting where iNK cells and IL-2 were injected with or without K562 cells into the peritoneal cavities of immune-deficient NSG mice, and activated T cells were injected retro-orbitally into the blood. Mice were sacrificed 4 days later, and total T cells in the peritoneal cavities were determined. Compared to the T cell only control group, iNK cells promoted significant T cell recruitment to the peritoneum, which was amplified upon iNK cell activation with the addition of K562 cells (Figure 1I). Together, our data demonstrate that iNK cells can serve as an off-the-shelf source of NK cells and have the potential to synergize with anti-PD-1 CIR therapy to enhance anti-tumor T cell responses. DisclosuresCichocki:Fate Therapeutics Inc.: Consultancy, Research Funding. Bjordahl:Fate Therapeutics Inc.: Employment. Gaidarova:Fate Therapeutics Inc: Employment. Mahmood:Fate Therapeutics Inc.: Employment. Rogers:Fate Therapeutics Inc: Employment. Ge:Fate Therapeutics Inc.: Employment. Kaufman:Fate Therapeutics: Consultancy, Research Funding. Valamehr:Fate Therapeutics Inc.: Employment.

Intrinsic method for the evaluation of beam shape coefficients in spheroidal coordinates for oblique illumination

When dealing with T-matrix scattering, e.g. in the framework of Generalized Lorenz-Mie Theory (GLMT) or of Extended Boundary Condition Method (EBCM), the incident electromagnetic fields are expanded over a set of vectorial wave functions, with expansion coefficients expressed in terms of beam shape coefficients (BSCs). In the case of structured beams, the evaluation of these BSCs may constitute a challenging issue, particularly in the case of spheroidal coordinates. BSCs in spheroidal coordinates have been originally evaluated using an extrinsic method, i.e. they have been expressed in terms of more conventional BSCs in spherical coordinates. Later on, it has been possible to provide expressions to evaluate spheroidal BSCs using an intrinsic approach, i.e. by working only inside the spheroidal coordinate system used to deal with the scattering problem. Fairly recently, the intrinsic method for the evaluation of BSCs in spheroidal coordinates for on-axis standard configuration has been released in the archival literature. The present paper extends the intrinsic method to the case of oblique illumination. It also serves as a review devoted to GLMTs in spheroidal coordinates.

Characterization System of Embryos, Embryoid Bodies and Multicellular Spheroids Based on an Electrochemical Method

Characterization System of Embryos, Embryoid Bodies and Multicellular Spheroids Based on an Electrochemical Method

Human hepatic 3D spheroids as a model for steatosis and insulin resistance

Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health concern as reflected in its widespread distribution in the general population. Yet, treatment options are scarce which is at least in part due to lack of reliable human in vitro disease models. Here, we report a human hepatic 3D spheroid system cultured under defined chemical conditions that has the potential to mimic steatotic conditions in a reversible manner, useful for identification of novel drug treatment conditions. Primary human hepatocytes (PHH) from different donors were cultured as spheroid microtissues in physiological in vivo -like culture conditions. Hepatic steatosis was induced over the course of three weeks in culture by supplementing the culture medium with pathophysiological concentrations of free fatty acids, carbohydrates and insulin. Effects of steatosis in the 3D system were evaluated on transcriptional, metabolomic and lipidomic levels. Free fatty acids on one hand as well as a combination of insulin and monosaccharides, promoted lipid accumulation in hepatocytes and increased expression of lipogenic genes, such as fatty acid synthase. This milieu also promoted development of insulin resistance within 2 weeks as manifested by an increase in gluconeogenic and insulin resistance markers, which are observed in type 2 diabetes mellitus and metabolic syndrome. Induced steatosis was reversible after withdrawal of lipogenic substrates and a further reduction in cellular fat content was observed following treatment with different antisteatotic compounds, such as metformin, glucagon, olaparib and antioxidants. Taken together, these results demonstrate that the 3D hepatic spheroids can serve as a valuable, HTS compatible model for the study of liver steatosis and facilitate translational discovery of novel drug targets.

Algebraic Analysis of the Poles in the Doppler Spectrum for Vehicle-to-Vehicle Channels

In vehicle-to-vehicle (V2V) wireless communications the time-variability of the propagation conditions is a challenge for channel estimation. The width of the Doppler spectrum depends on the propagation delay and the velocity vectors of the vehicles. So far, the time-variant width of the Doppler spectrum has been derived for single-bounce scattering close to the line-of-sight delay and for infinitely large delays. In this contribution, we generalize the time-variant, delay-dependent limiting frequencies for V2V channels for arbitrary delays and velocity vector configurations. The limiting frequencies are obtained by considering the geometric-stochastic channel representation in a prolate spheroidal coordinate system and determining the poles of the resulting Doppler spectrum. The poles in the spectrum are caused by the extrema of the Doppler frequency. Since the global maximum and minimum of the Doppler frequency define the limits of the spectrum, the time-variant delay-dependent width can be calculated in closed form.

On the estimation of parameters of a spheroid distribution from planar sections

We study two different methods for inferring the parameters of a spheroid distribution from planar sections of a stationary spatial system of spheroids: one method first unfolds non-parametrically the joint size–shape–direction distribution of the observable ellipses in the plane into the joint size–shape–direction distribution of the spheroids followed by a maximum likelihood estimation of the parameters; the second method directly estimates these parameters based on statistics of the observable ellipses using a quasi-likelihood approach. As an application we consider a metal-matrix composite with ceramic particles as reinforcing inclusions, model the inclusions as prolate spheroids and estimate the parameters of their distribution from planar sections.

Laplace’s equation for a point source near a sphere: improved internal solution using spheroidal harmonics

As shown recently [Phys. Rev. E 95, 033307 (2017)], spheroidal harmonics expansions are well suited for the external solution of Laplace's equation for a point source outside a spherical object. Their intrinsic singularity matches the line singularity of the analytic continuation of the solution and the series solution converges much faster than the standard spherical harmonic solution. Here we extend this approach to internal potentials using the Kelvin transformation, i.e. radial inversion, of the spheroidal coordinate system. This transform converts the standard series solution involving regular solid spherical harmonics into a series of irregular spherical harmonics. We then substitute the expansion of irregular spherical harmonics in terms of transformed irregular spheroidal harmonics into the potential. The spheroidal harmonic solution fits the image line singularity of the solution exactly and converges much faster. We also discuss why a solution in terms of regular solid spheroidal harmonics cannot work, even though these functions are finite everywhere in the sphere. We also present the analogous solution for an internal point source, and two new relationships between the solid spherical and spheroidal harmonics.

LBO‐03: Development of a 3D spheroid system of primary human hepatocytes that supports efficient HBV infection

Journal of Viral HepatitisVolume 25, Issue S2 p. 191-191 Abstract LBO-03: Development of a 3D spheroid system of primary human hepatocytes that supports efficient HBV infection First published: 12 June 2018 https://doi.org/10.1111/jvh.02_12935Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume25, IssueS2Special Issue: 16th International Symposium on Viral Hepatitis and Liver Diseases (ISVHLD) held from June 14th to 17th, 2018, in Toronto, CanadaJune 2018Pages 191-191 RelatedInformation

The Mixed Opioid Receptor Antagonist Naltrexone Mitigates Stimulant-Induced Euphoria: A Double-Blind, Placebo-Controlled Trial of Naltrexone.

Supratherapeutic doses of methylphenidate activate μ-opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed μ-opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with attention-deficit/hyperactivity disorder (ADHD). We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate (January 2013 to June 2015). Spheroidal Oral Drug Absorption System methylphenidate (SODAS-MPH) was administered twice daily, was titrated to ~1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with an oral test dose of 60 mg of immediate-release methylphenidate (IR-MPH). The primary outcome measure was Question 2 (Liking a Drug Effect) on the Drug Rating Questionnaire, Subject version, which was assessed after oral test doses of 60 mg of IR-MPH were administered after the third and sixth weeks of treatment with SODAS-MPH. Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS-MPH and randomized to naltrexone 50 mg/d or placebo. Thirty-one subjects completed through week 3, and 25 completed through week 6. Naltrexone significantly diminished the euphoric effect of IR-MPH during the heightened-risk titration phase (primary outcome; first 3 weeks) (χ² = 5.07, P = .02) but not the maintenance phase (weeks 4-6) (χ² = 0.22, P = .64) of SODAS-MPH treatment. Preclinical findings are extended to humans showing that naltrexone may mitigate stimulant-associated euphoria. Our findings provide support for further studies combining opioid receptor antagonists with stimulants to reduce abuse potential. ClinicalTrials.gov identifier: NCT01673594.

Sound Radiation From Point Acoustic Sources With Shield of Large Prolate Spheroidal Baffles

Sound radiation from stationary and rotating point acoustic sources with shield of rigid prolate spheroidal baffles is explored in the prolate spheroidal coordinate system. The formulae of far-field sound pressure and acoustic power are derived and acoustic power spectral density (PSD) in terms of circumferential and azimuthal wavenumber is manifested from the low frequency range to high frequency range. Acoustic wave propagation features in the spherical coordinate system as a particular case of the prolate spheroidal coordinate system are presented. Rotating sound sources cause the frequency veering phenomenon and change the patterns of PSD. Some spheroidal harmonic waves with lower and higher wavenumber for the large prolate spheroids cannot contribute to far-field sound radiation in the high frequency range when sound sources are close to the axes of the spheroids. Sound pressure directivity and acoustic power of stationary point sound sources are also analyzed with the variation of source location.

Light refocusing with up-scalable resonant waveguide gratings in confocal prolate spheroid arrangements

Resonant waveguide gratings (RWGs) are thin-film structures, where coupled modes interfere with the diffracted incoming wave and produce strong angular and spectral filtering. The combination of two finite-length and impedance matched RWGs allows the creation of a passive beam steering element, which is compatible with up-scalable fabrication processes. Here, we propose a design method to create large patterns of such elements able to filter, steer, and focus the light from one point source to another. The method is based on ellipsoidal mirrors to choose a system of confocal prolate spheroids where the two focal points are the source point and observation point, respectively. It allows finding the proper orientation and position of each RWG element of the pattern, such that the phase is constructively preserved at the observation point. The design techniques presented here could be implemented in a variety of systems, where large-scale patterns are needed, such as optical security, multifocal or monochromatic lenses, biosensors, and see-through optical combiners for near-eye displays.

РЕШЕНИЕ ЛИНЕАРИЗОВАННОЙ ПО СКОРОСТИ СИСТЕМЫ УРАВНЕНИЙ НАВЬЕ–СТОКСА С УЧЕТОМ СТЕПЕННОГО ВИДА ЗАВИСИМОСТИ ВЯЗКОСТИ, ТЕПЛОПРОВОДНОСТИ И ПЛОТНОСТИ ГАЗООБРАЗНОЙ СРЕДЫ ОТ ТЕМПЕРАТУРЫ

We received the solution of the system of Navier–Stokes equations linearized with respect to the velocity in the spheroidal coordinate system with regard of a power-law dependence of viscosity, thermal conductivity and the gaseous medium density on the temperature by means of generalized power series.

Shape matters: The case for Ellipsoids and Ellipsoidal Water11This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form

We describe the shape potentials used for the van der Waals interactions between soft-ellipsoids used to coarse-grain molecular moieties in Metropolis Monte-Carlo simulation software. The morphologies resulting from different expressions for these van der Waals interaction potentials are discussed for the case of a prolate spheroid system with a strong dipole at the center. We also show that the calculation of ellipsoids is, at worst, only about fivefold more expensive computationally when compared to a simple Lennard-Jones sphere. Finally, as an application of the ellipsoidal shape we parametrize water from the original SPC water model and observe – just through the difference in shape alone – a significant improvement of the O-O radial distribution function when compared to experimental data.

Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers.

Ethanol coadministered with immediate-release dl-methylphenidate (dl-MPH) or dexmethylphenidate (d-MPH) significantly increases the geomean maximum plasma concentration (Cmax) of d-MPH 22% and 15%, respectively, and elevates overall drug exposure and psychostimulant effects. We asked the question: Are these ethanol-MPH interactions based more fundamentally on (1) inhibition of postabsorption d-MPH metabolism or (2) acceleration of MPH formulation gastric dissolution by ethanol in the stomach? This was investigated using the pulsatile, distinctly biphasic, spheroidal oral drug absorption systems of dl-MPH and d-MPH. In a randomized, 4-way crossover study, 14 healthy subjects received pulsatile dl-MPH (40 mg) or d-MPH (20 mg), with or without ethanol (0.6 g/kg), dosed 4 hours later. These 4 hours allowed the delayed-release second MPH pulse to reach a more distal region of the gut to preclude gastric biopharmaceutical influences. Plasma was analyzed using a highly sensitive chiral method. Subjective/physiological effects were recorded. Ethanol increased the second pulse of d-MPH Cmax for dl-MPH by 35% (P < 0.01) and the partial area under the plasma concentration curve from 4 to 8 hours by 25% (P < 0.05). The respective values for enantiopure d-MPH were 27% (P = 0.001) and 20% (P < 0.01). The carboxylesterase 1-mediated transesterification metabolite ethylphenidate served as a biomarker for coexposure. Ethanol significantly potentiated stimulant responses to either formulation. These findings support drug dispositional interactions between ethanol and MPH as dominant over potential biopharmaceutical considerations. Understanding the pharmacology underlying the frequent coabuse of MPH-ethanol provides rational guidance in the selection of first-line pharmacotherapy for comorbid attention-deficit/hyperactivity disorder-alcohol use disorder.

Opiate Antagonists Do Not Interfere With the Clinical Benefits of Stimulants in ADHD

Methylphenidate activates μ-opioid receptors, which are linked to euphoria. μ-Opioid antagonists, such as naltrexone, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential. This study assessed whether the combination of naltrexone with methylphenidate is well-tolerated while preserving the clinical benefits of stimulants in subjects with attention-deficit/hyperactivity disorder (ADHD). We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate from January 2013 to July 2015. Spheroidal Oral Drug Absorption System (SODAS) methylphenidate was administered twice daily, was titrated to approximately 1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with a test dose of immediate-release methylphenidate. The primary outcome measure was the Adult ADHD Investigator Symptom Report Scale (AISRS). Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS methylphenidate and randomly assigned to naltrexone 50 mg or placebo. Thirty-one subjects completed the study through week 3, and 25 completed through week 6. Throughout 6 weeks of blinded naltrexone and open methylphenidate treatment, the coadministration of naltrexone with methylphenidate did not interfere with the clinical effectiveness of methylphenidate for ADHD symptoms. Additionally, the combination of naltrexone and methylphenidate did not produce an increase in adverse events compared with methylphenidate alone. Our findings provide support for the concept of combining opioid receptor antagonists with stimulants to provide an effective stimulant formulation with less abuse potential. ClinicalTrials.gov identifier: NCT01673594​.

Theoretical investigation on heat transfer to burning char of spheroidal particles

The combustion of biomass fuel provides efficient and inexpensive utilization of solid biomass. Biomass particles generally exhibit non-spherical shapes, which affect the heat and mass transfer and further the char surface reactions. The prolate and oblate spheroidal particles are considered presently. The energy balance is employed for the gas phase near the particle in spheroidal coordinate system. A theoretical study is conducted on the char combustion of the spheroidal particles under either static conditions or forced convection. The expressions for the Nusselt numbers of both prolate and oblate spheroids are obtained. The char combustion rates for the spheroidal particles are affected by the Nusselt number and the particle surface area.

An Automated Multiplexed Hepatotoxicity and CYP Induction Assay Using HepaRG Cells in 2D and 3D

Drug-induced liver injury (DILI) and drug–drug interactions (DDIs) are concerns when developing safe and efficacious compounds. We have developed an automated multiplex assay to detect hepatotoxicity (i.e., ATP depletion) and metabolism (i.e., cytochrome P450 1A [CYP1A] and cytochrome P450 3A4 [CYP3A4] enzyme activity) in two-dimensional (2D) and three-dimensional (3D) cell cultures. HepaRG cells were cultured in our proprietary micromold plates and produced spheroids. HepaRG cells, in 2D or 3D, expressed liver-specific proteins throughout the culture period, although 3D cultures consistently exhibited higher albumin secretion and CYP1A/CYP3A4 enzyme activity than 2D cultures. Once the spheroid hepatic quality was assessed, 2D and 3D HepaRGs were challenged to a panel of DILI- and CYP-inducing compounds for 7 days. The 3D HepaRG model had a 70% sensitivity to liver toxins at 7 days, while the 2D model had a 60% sensitivity. In both the 2D and 3D HepaRG models, 83% of compounds were predicted to be CYP inducers after 7 days of compound exposure. Combined, our results demonstrate that an automated multiplexed liver spheroid system is a promising cell-based method to evaluate DILI and DDI for early-stage drug discovery.

Transcriptional activation of HIF-1 by a ROS-ERK axis underlies the resistance to photodynamic therapy.

Photodynamic therapy (PDT), a promising treatment option for cancer, involves the activation of a photosensitizer (PS) by local irradiation with visible light. Excitation of the PS leads to a series of photochemical reactions and consequently the local generation of harmful reactive oxygen species (ROS) causing limited or none systemic defects. However, the development of resistance to this promising therapy has slowed down its translation into the clinical practice. Thus, there is an increase need in understanding of the molecular mechanism underlying resistance to PDT. Here, we aimed to examine whether a relationship exists between PDT outcome and ROS-involvement in the resistance mechanism in photosensitized cancer cells. In order to recapitulate tumor architecture of the respective original tumor, we developed a multicellular three-dimensional spheroid system comprising a normoxic periphery, surrounding a hypoxic core. Using Me-ALA, a prodrug of the PS PpIX, in human colorectal spheroids we demonstrate that HIF-1 transcriptional activity was strongly up-regulated and mediates PDT resistant phenotype. RNAi knockdown of HIF-1 impairs resistance to PDT. Oxidative stress-mediated activation of ERK1/2 followed PDT was involved on positive modulation of HIF-1 transcriptional activity after photodynamic treatment. ROS scavenging and MEK/ERK pathway inhibition abrogated the PDT-mediated HIF-1 upregulation. Together our data demonstrate that resistance to PDT is in part mediated by the activation of a ROS-ERK1/2-HIF-1 axis, thus, identifying novel therapeutic targets that could be used in combination with PDT.