Reversible Permeability Research Articles

The beneficial impact of ketogenic diets on chemically-induced colitis in mice depends on the diet's lipid composition

Previously, we showed that restrictive diets, including ketogenic diet (KD), have an anti-inflammatory impact on the healthy gastrointestinal tract of mice. Afterward, we found that energy-restricting diets mitigate inflammation in the dextran sodium sulfate (DSS) colitis mouse model. The current study aimed to verify the impact of KD on DSS colitis and assess if the diet's fat composition influences the outcomes of the intervention.Mice with mild chronic colitis were fed control chow, KD composed of long-chain triglycerides (KD LCT) or a KD containing a mix of LCT and medium-chain triglycerides (KD LCT/MCT).KDs did not reverse DSS-enhanced gut permeability and shortening of the colon. Both KDs had a similar impact on liver, cecum, and spleen weight, villi and colon length, the thickness of muscularis externa, and expression of ZO-1 and occludin. On the contrary, body weight, glutathione (GSH) and taurine-GSH levels, GSH-S transferase (GST), and myeloperoxidase (MPO) activity, as well as an abundance of several fecal bacteria, all were differentially affected by the two types of KDs. When compared to the DSS control diet, reduction in colon mucosa cytokines expression was stronger in KD LCT than in the KD LCT/MCT group.We conclude that the outcomes of the KD interventions in terms of potential therapeutical applications depend on lipid composition. KD LCT showed a strong positive impact on gut inflammation. A potential contribution of GSH to KD outcomes and a correlation between MPO activity and microbiota composition was identified.

Experimental and numerical analysis of injection-induced permeability changes in pre-existing fractures

This paper presents a combined laboratory and numerical investigation on the injection-induced permeability changes in pre-existing fractures. The analyses conducted were primarily based on the results of an innovative laboratory experiment designed to replicate the key mechanisms that occur during hydraulic stimulation of naturally fractured rocks and/or faulted zones. The experiment involved pressure-controlled fluid injection into a laboratory-scale pre-existing fracture within a granite block, which was subjected to true triaxial stress conditions. Rough and smooth fractures are investigated, and the results are discussed. Based on the experimental results, two contributing mechanisms were considered to describe the pressure-driven permeability changes in pre-existing fractures: (1) elastic opening/closure leading to a reversible permeability change, and (2) fracture sliding in shear mode, causing dilation and hence an irreversible permeability increase. With these assumptions, an aperture-dependent permeability function was adopted to couple the hydraulic flow with the mechanical deformations along the fracture. Subsequently, a 3D coupled hydro-mechanical model was developed to replicate fluid-injection tests conducted at various conditions, including different stress conditions and fracture surface roughness. The employed modeling framework effectively captured the experimental observations. Our results indicate that the maximum permeability increases twofold.

Solvent Activation for Building a Homogeneous Polyamide Layer to Enhance Reverse Osmosis Membrane Permeability

Solvent Activation for Building a Homogeneous Polyamide Layer to Enhance Reverse Osmosis Membrane Permeability

Restrictive diets have a beneficial impact on dextran sodium sulfate-induced colitis in male mice

BackgroundPreviously, we assessed the impact of restrictive diets, including caloric restriction (CR), intermittent fasting (IF), or fasting-mimicking diet (FMD), on a healthy gastrointestinal tract. We revealed that each of the diets shows anti-inflammatory outcomes. ObjectiveThe current study aimed to verify the diets' applicability in treating colitis. MethodsWe exposed a mouse model with mild chronic dextran sodium sulfate (DSS)-induced colitis to ad libitum control feeding, CR, IF, or FMD. The collected samples were analyzed for markers of inflammation. ResultsThe diets reduced DSS-triggered increases in spleen weight and myeloperoxidase (MPO) activity. Diet intervention also influenced occludin levels, small intestine morphology, as well as cytokine and inflammatory gene expression, mainly in the mucosa of the proximal colon. The diets did not reverse DSS-enhanced gut permeability and thickening of the colon muscularis externa. Concerning inflammatory gene expression, the impact of DSS and the dietary intervention was limited to the colon as we did not measure major changes in the jejunum mucosa, Peyer's patches, and mesenteric lymph nodes. Further, rather modest changes in the concentration of intestinal bile acids were observed in response to the diets, whereas taurine and its conjugates levels were strongly affected. ConclusionsDespite the differences in the dietary protocol, the tested diets showed very similar impacts and, therefore, may be interchangeable when aiming to reduce inflammation in the colon. However, FMD showed the most consistent beneficial impact.

Energy loss and hysteresis of reversible magnetization processes in iron-based soft magnetic composites

The paper focuses on investigation of the hysteresis originating from the reversible magnetization processes and the quantification of the corresponding energy dissipation, on soft magnetic composite materials differing in various parameters so exhibiting different proportions of magnetization processes types during quasi-static magnetizing reversal under different maximum inductions. It was confirmed that reversible magnetization processes show hysteresis too and generate energy losses. These losses come from frictional effects accompanying local rotations of spins at the microscopical view of all magnetization processes including the reversible ones. It was found that the area of a hysteresis loop obtained by the integration of reversible permeability reveals approximately the proportion of reversible magnetization vector rotations, which produce energy loss much more than reversible domain wall displacements.

Translocation and fate of nanospheres in pheochromocytoma cells following exposure to synchrotron-sourced terahertz radiation.

The routes by which foreign objects enter cells is well studied; however, their fate following uptake has not been explored extensively. Following exposure to synchrotron-sourced (SS) terahertz (THz) radiation, reversible membrane permeability has been demonstrated in eukaryotic cells by the uptake of nanospheres; nonetheless, cellular localization of the nanospheres remained unclear. This study utilized silica core-shell gold nanospheres (AuSi NS) of diameter 50 ± 5 nm to investigate the fate of nanospheres inside pheochromocytoma (PC 12) cells following SS THz exposure. Fluorescence microscopy was used to confirm nanosphere internalization following 10 min of SS THz exposure in the range 0.5-20 THz. Transmission electron microscopy followed by scanning transmission electron microscopy energy-dispersive spectroscopic (STEM-EDS) analysis was used to confirm the presence of AuSi NS in the cytoplasm or membrane, as single NS or in clusters (22% and 52%, respectively), with the remainder (26%) sequestered in vacuoles. Cellular uptake of NS in response to SS THz radiation could have suitable applications in a vast number of biomedical applications, regenerative medicine, vaccines, cancer therapy, gene and drug delivery.

Ultrasounds trigger reversible permeability of the cerebrovascular endothelium in a novel 3D-bioprinted model of the human blood-brain barrier

The blood-brain barrier (BBB) restricts the penetration of therapeutic agents to the brain. Focused ultrasound (FUS) insonation of microbubbles has enhanced drug delivery via a temporary opening of the tight junctions of the BBB. Rodents are often used for testing novel therapeutic strategies. However, biological discrepancies existing between rodents and humans impedes the translation of some results. We investigated the effect of FUS transient disruption of a human microphysiological model of the BBB consisting of human brain endothelial cells cultured within a 3D-bio printed scaffold designed to reconstitute the architecture of a perfused blood vessel. Cavitation activity was detected in the model when perfused with Lumason microbubbles and exposed to 500 kHz ultrasound at 0.4 MPa for 10 ms pulse duration and 2 Hz pulse repetition frequency. An increase in extravasation of a dye beyond the endothelial layer was detected within 2–3 h of ultrasound insonation. Our results support that this system could be used for targeted BBB opening with a human cell culture model. Moreover, this system holds a promise to further the translational study on US-mediated drug delivery and the development of personalized therapies for patients with brain cancer and other neurovascular disorders.

Magnetic properties of 09G2S steel, manufactured by selective laser melting and cyclically deformed by tension

Low-cycle fatigue tests in the elastic-plastic strain region of 09G2S steel specimens manufactured with a laser 3D printer by selective laser melting method (SLS steel) were carried out. The major hysteresis loops and field dependences of the reversible magnetic permeability were measured. It has been established that normalization at 980 °C (1 hour) reduces the ultimate strength of steel 09G2S in 2 times (502 MPa) and increases the relative elongation almost 6 times (34.6%), bringing this steel closer to cast steel 09G2S. The magnetic properties (Нс, Br, µmax) of cast and SLM normalized steel before and after cyclic tests are similar. The main changes in these properties of both cast and SLM steel are observed at the initial stage of low-cycle tests, a further increase in the number of cycles (up to the destruction of the tested samples) does not lead to their significant change. The nature of the change in the magnetoelastic field Hσ, determined from the experimental field dependences of the reversible magnetic permeability, during low-cycle tests for cast and SLM steels is radically different: for cast 09G2S steel the magnetoelastic field Hσ practically does not change with increasing number of cycles, whereas for SLM 09G2S steel a sharp increase of Hσ value by 30% is observed during the first test cycles, which is most likely associated with an increase in residual mechanical stresses.

The Co-Moving Velocity in Immiscible Two-Phase Flow in Porous Media

We present a continuum (i.e., an effective) description of immiscible two-phase flow in porous media characterized by two fields, the pressure and the saturation. Gradients in these two fields are the driving forces that move the immiscible fluids around. The fluids are characterized by two seepage velocity fields, one for each fluid. Following Hansen et al. (Transport in Porous Media, 125, 565 (2018)), we construct a two-way transformation between the velocity couple consisting of the seepage velocity of each fluid, to a velocity couple consisting of the average seepage velocity of both fluids and a new velocity parameter, the co-moving velocity. The co-moving velocity is related but not equal to velocity difference between the two immiscible fluids. The two-way mapping, the mass conservation equation and the constitutive equations for the average seepage velocity and the co-moving velocity form a closed set of equations that determine the flow. There is growing experimental, computational and theoretical evidence that constitutive equation for the average seepage velocity has the form of a power law in the pressure gradient over a wide range of capillary numbers. Through the transformation between the two velocity couples, this constitutive equation may be taken directly into account in the equations describing the flow of each fluid. This is, e.g., not possible using relative permeability theory. By reverse engineering relative permeability data from the literature, we construct the constitutive equation for the co-moving velocity. We also calculate the co-moving constitutive equation using a dynamic pore network model over a wide range of parameters, from where the flow is viscosity dominated to where the capillary and viscous forces compete. Both the relative permeability data from the literature and the dynamic pore network model give the same very simple functional form for the constitutive equation over the whole range of parameters.

Chronic magnesium deficiency causes reversible mitochondrial permeability transition pore opening and impairs hypoxia tolerance in the rat heart

Chronic magnesium (Mg) deficiency induces and exacerbates various cardiovascular diseases. We previously investigated the mechanisms underlying decline in cardiac function caused by chronic Mg deficiency and the effectiveness of Mg supplementation on this decline using the Langendorff-perfused isolated mouse heart model. Herein, we used the Langendorff-perfused isolated rat heart model to demonstrate the chronic Mg-deficient rats (Mg-deficient group) had lower the heart rate (HR) and left ventricular pressure (LVDP) than rats with normal Mg levels (normal group). Furthermore, decline in cardiac function due to hypoxia/reoxygenation injury was significantly greater in the Mg-deficient group than in the normal group. Experiments on mitochondrial permeability transition pore (mPTP) using isolated mitochondria revealed that mitochondrial membrane was fragile in the Mg-deficient group, implying that cardiac function decline through hypoxia/reoxygenation injury is associated with mitochondrial function. Mg supplementation for chronic Mg-deficient rats not only improved hypomagnesemia but also almost completely restored cardiac and mitochondrial functions. Therefore, proactive Mg supplementation in pathological conditions induced by Mg deficiency or for those at risk of developing hypomagnesemia may suppress the development and exacerbation of certain disease states.

The effect of direct current in a steel rod on the switching field dependence of magnetic permeability

It is theoretically shown that in cases where the process of irreversible magnetization reversal of ferromagnetic steels is determined by displacements of only 180° domain boundaries, the dependences of reversible permeability on the switching field in low-carbon steels when a direct current is passed along a rod sample should have two maxima instead of the usual one that occurs in the absence of this current. The distances between the maxima of these peaks linearly depend on the value of the constant component of the current and, consequently, on the constant circular magnetic field caused by it, perpendicular to the switching field. This phenomenon should occur both for undeformed steel samples in the state after annealing and for samples after plastic stretching. In the latter case, elastic tensile stresses of such magnitude should act to compensate for internal residual compressive stresses. The fields of both peaks of magnetic permeability in these two cases are close to each other.

Eco-friendly soft magnetic composites of iron coated by sintered ferrite via mechanofusion

The paper presents novel soft magnetic composite materials composed of iron coated by Ni-Zn/Cu-Zn soft ferrite powder using dry particle coating route, without any other non-magnetic insulation. High-pressure compaction was applied to achieve relatively low porosity and sufficiently high density of composites. Structure documentation indicated optimal insulation of iron particles by the ferrite, which was confirmed by magnetic, electrical and thermal properties evaluation. Relatively high frequency and DC bias stability of the permeability was found together with its relatively high values, as the ferrite was involved in magnetization process improving magnetic flux continuity. Sufficiently high specific electrical resistivity ensured also relatively low power losses at elevated frequencies. Proportions of reversible and irreversible magnetization processes were analysed by means of high and low induction loss separation and differential, reversible and irreversible permeability measurement. The investigation of thermal diffusivity revealed the heat transfer rate capability of composites and also confirmed good insulation of iron by ferrite powder. The properties were reached better compared to the ones of iron-based composites with non-magnetic matrix and competitive with those found in current literature, indicating the successful preparation of pure iron-ferrite composites by means of the use of progressive eco-friendly and cost-effective production techniques.

Origins of Lithium/Sodium Reverse Permeability Selectivity in 12-Crown-4-Functionalized Polymer Membranes.

Direct lithium extraction via membrane separations has been fundamentally limited by lack of monovalent ion selectivity exhibited by conventional polymeric membranes, particularly between sodium and lithium ions. Recently, a 12-Crown-4-functionalized polynorbornene membrane was shown to have the largest lithium/sodium permeability selectivity observed in a fully aqueous system to date. Using atomistic molecular dynamics simulations, we reveal that this selectivity is due to strong interactions between sodium ions and 12-Crown-4 moieties, which reduce sodium ion diffusivity while leaving lithium ion mobility relatively unaffected. Moreover, the ion diffusivities in the membrane, when scaled by their respective solution diffusivities and free ion fractions, can be collapsed to an almost universal relationship depending on solvent volume fraction.

Engineering Li/Na selectivity in 12-Crown-4–functionalized polymer membranes

Lithium is widely used in contemporary energy applications, but its isolation from natural reserves is plagued by time-consuming and costly processes. While polymer membranes could, in principle, circumvent these challenges by efficiently extracting lithium from aqueous solutions, they usually exhibit poor ion-specific selectivity. Toward this end, we have incorporated host-guest interactions into a tunable polynorbornene network by copolymerizing 1) 12-crown-4 ligands to impart ion selectivity, 2) poly(ethylene oxide) side chains to control water content, and 3) a crosslinker to form robust solids at room temperature. Single salt transport measurements indicate these materials exhibit unprecedented reverse permeability selectivity (∼2.3) for LiCl over NaCl-the highest documented to date for a dense, water-swollen polymer. As demonstrated by molecular dynamics simulations, this behavior originates from the ability of 12-crown-4 to bind Na+ ions more strongly than Li+ in an aqueous environment, which reduces Na+ mobility (relative to Li+) and offsets the increase in Na+ solubility due to binding with crown ethers. Under mixed salt conditions, 12-crown-4 functionalized membranes showed identical solubility selectivity relative to single salt conditions; however, the permeability and diffusivity selectivity of LiCl over NaCl decreased, presumably due to flux coupling. These results reveal insights for designing advanced membranes with solute-specific selectivity by utilizing host-guest interactions.

Iron Based Soft Magnetic Composite Material Prepared By Injection Molding

Abstract Soft magnetic composite materials consisting of FeSi powder and polypropylene were prepared by the injection molding method, with different polypropylene contents of 25, 30 and 35 vol. %. The magnetic and electrical properties as well as the structure of the composites were investigated. The samples exhibited very low porosity, high electrical resistivity, relatively low coercivity, sufficient saturation magnetic flux density and permeability, and high resonant frequency. FeSi particles were found to be well insulated from each other and homogeneously dispersed in the polymer matrix of the composite. The observed isotropic structure was confirmed by the fitting of the experimental dependence with the analytical expression of the reversible relative permeability vs. magnetic flux density.

Pulsed high magnetic field-induced reversible blood-brain barrier permeability to enhance brain-targeted drug delivery

ABSTRACT The present study aimed to select an effective Pulsed High Magnetic Field (PHMF) stimulation protocol that would induce the Blood-Brain Barrier’s (BBB) reversible permeability to enhance brain-targeted drug delivery. PHMF was applied to the skull over the right hemisphere of 60 Wistar rats. The sham group contained other 10 rats that did not receive PHMF stimulation. The investigated parameters were repetition frequencies (0.25, 1, and 4 Hz as well as the effective low frequency combined with 10 Hz) and numbers of pulses in each train. Evans Blue Dye (EBD) uptake within the brain parenchyma was measured to select an effective PHMF stimulation protocol. BBB reversibility was evaluated by measuring EBD uptake and Gadobutrol retention, through MRI signal intensity enhancement, within brain parenchyma after exposure to the effective PHMF stimulation protocol at different time points including 0.5, 1, and 24 hours. The obtained results showed that the PHMF stimulation increased the BBB’s reversible permeability; this increase was more significant for 28 pulses with 1 Hz frequency (P < .0001). Changes in EBD uptake and MRI signal intensity in the exposed side (right hemisphere) peaked within 0.5–1 hour and returned to normal levels 24 hours after exposure to the effective protocol of PHMF stimulation (28 pulses with 1 Hz frequency). The Contrast-Enhanced MRI (CE-MRI) signal intensity confirmed the changes in EBD concentration. PHMF stimulation can be used as an effective protocol for enhancing the permeability reversibly of BBB, hence considered a potential clinical approach to brain-targeted drug delivery.

Molecule‐Responsive Polymer Monolith as a Smart Gate Driven by Host–Guest Interaction with Morphology Restoration

AbstractMaterials that function in response to the molecules are attracting attention as smart materials. In particular, the autonomous change in permeability is an attractive function of the biomimetic materials in the fields of microfluidic devices, transport control, and sensing. In this study, a monolith that incorporates crosslinked points formed by an inclusion complex of β‐cyclodextrin and phenyl groups is prepared and applied for permeability control. Monoliths with continuous pores of several micrometers in size show a reversible permeability change in response to the specific molecules. During the supramolecular bond dissociation/reformation cycle, the monoliths restore their permeability along with their original porous structure.

EXTH-69. INCREASED CANCER CELL PERMEABILITY FOLLOWING TUMOR TREATING FIELDS (TTFIELDS) APPLICATION IN VITRO

Abstract INTRODUCTION Tumor Treating Fields (TTFields), encompassing alternating electric fields within the intermediate frequency range, is an anticancer treatment delivered to the tumor region through transducer arrays placed non-invasively on the skin. This novel loco-regional treatment has demonstrated efficacy and safety and is FDA-approved in patients with glioblastoma (GBM) and malignant pleural mesothelioma. TTFields are currently being investigated in other solid tumors in ongoing trials. Recently, TTFields were reported to alter the cellular membrane structure of GBM cells, rendering them more permeable. The objective of this study was to characterize TTFields-induced cellular permeability in cancerous cell lines. METHODS TTFields were applied to uterine sarcoma, glioblastoma, and breast adenocarcinoma cell lines across a range of frequencies (50–500 kHz). Cellular permeability was assessed by quantifying the percentages of cells with accumulated 7-aminoactinomycin D (7-AAD) using flow cytometry and cytotoxicity was assessed based on cell counts. Kinetics were determined using different 7-AAD exposure times relative to TTFields treatment end. Changes in intracellular accumulation of anthracycline chemotherapeutics were evaluated in chemotherapy-sensitive and chemotherapy-resistant cells. RESULTS TTFields induced cellular permeability to 7-AAD in all 4 cancer cell lines tested. The optimal frequency for TTFields-induced cellular permeability was different from the optimal cytotoxic frequency. Kinetics measurements demonstrated that TTFields-induced permeability is transient and is effective only during application of TTFields. In combination experiments, TTFields improved intracellular accumulation of chemotherapeutic agents. Furthermore, combining chemotherapy with TTFields treatment facilitated accumulation of chemotherapeutics in chemotherapy-resistant cells to levels comparable with accumulation in chemotherapy-sensitive cancer cells. CONCLUSIONS This study demonstrates that TTFields can transiently increase cancer cell permeability in vitro with an optimal frequency that is variable from the frequency that is used to induce cancer cell cytotoxicity. Moreover, this effect is reversible and cellular permeability is restored to a normal state upon TTFields treatment cessation.

Hydraulic-mechanical properties of microfaults in granitic rock using the Punch-Through Shear test

Fault zones are key features in crystalline geothermal reservoirs or in other subsurface environments due to the fact that they act as main fluid pathways. An adequate experimental description of the evolution of permeability of a realistic microscopic fault zone under in-situ reservoir and fracture parallel flow conditions is required. To address this topic, we demonstrate a novel experimental set up (Punch-Through Shear test) that is able to generate a realistic shear zone (microfault) under in-situ reservoir conditions while simultaneously measuring permeability and dilation. Three samples of intact granite from the Odenwald (Upper Rhine Graben) were placed into a MTS 815 tri-axial compression cell, where a self-designed piston assembly punched down the inner cylinder of the sample creating the desired microfault geometry with a given offset. Permeability was measured and fracture dilation was inferred from an LVDT extensometer chain, as well as the balance of fluid volume flowing in and out of the sample. After fracture generation, the shear displacement was increased to 1.2 mm and pore pressure changes of ± 5 or ± 10 MPa were applied cyclically to simulate injection and production scenarios. Formation of a microfault increased the permeability of the granite rock by 2 to almost 3 orders of magnitude. Further shear displacement led to a small increase in permeability by a factor of 1.1 to 4.0, but permeability was reduced by a factor of 2.5 to 4 within 16 h due to compaction and fault healing. Effective pressure cycling led to reversible permeability changes. CT images showed that the fracture network is rather complex, but depicts all features commonly observed in larger scale fault zones.

Abstract 5848: Tumor treating fields (TTFields) induce cancer cell permeability in vitro

Abstract Introduction Tumor Treating Fields (TTFields) are a clinically applied anti-neoplastic treatment modality delivered via noninvasive application of low-intensity, intermediate-frequency (100-500 kHz), alternating electric fields. TTFields had been shown to inhibit the growth of different cancerous cells, both in vitro and in vivo, by interrupting cancer cell mitosis. TTFields were recently reported to alter cellular membrane structure of glioblastoma cells, thus rendering them more permeable. In the current study, we characterized TTFields-induced cellular permeability in several cancerous cell lines including breast adenocarcinoma, uterine sarcoma and glioma. Methods Flow cytometry analysis of intracellular 7-aminoactinomycin D (7-AAD; fluorescent DNA marker of cell viability) accumulation was used to quantify the percentages of cells showing increased cellular permeability following TTFields application. The optimal TTFields frequency for membrane permeability was evaluated using a frequency scan of TTFields in the range of 100-500 kHz. Kinetics were determined using different 7-AAD exposure times. Changes in intracellular accumulation of anthracycline chemotherapeutics (doxorubicin and mitoxantron) were evaluated in chemotherapy-sensitive and chemotherapy-resistant cells. Results TTFields induced cellular permeability to 7-AAD, which is typically excluded by intact cells and was detected in all cancer cell lines tested with the highest permeability frequency of up to 80% of treated cells. The optimal frequency for TTFields induced cellular permeability was found to be different from the optimal cytotoxic frequency. Moreover, measurements of kinetics revealed that TTFields-induced permeability is transient and is effective only during application of TTFields. In combination experiments, TTFields improved intracellular accumulation of chemotherapeutic agents, which may explain the enhanced efficacy of combination treatment of TTFields with different chemotherapies. Furthermore, the combined treatment also facilitated the accumulation of chemotherapeutics in chemotherapy-resistant cells, and restored it to the level observed in the chemotherapy-sensitive cancer cells. Conclusions This study demonstrates that TTFields can transiently increase cancer cell permeability in vitro with an optimal frequency that is variable from the frequency that is used to induce cancer cell cytotoxicity. Moreover, this effect is reversible and cellular permeability is restored to normal state function upon TTFields treatment cessation. Future studies will include in vivo experiments to validate TTFields-induced permeability and to evaluate the efficacy of TTFields and chemotherapy combinations in tumor models that are both sensitive and resistant to chemotherapy. Citation Format: Tali Voloshin, Yaara Porat, Noa Kaynan, Anat Klein-Goldberg, Rom Paz, Alexandra Volodin, Moshe Giladi, Uri Weinberg, Yoram Palti. Tumor treating fields (TTFields) induce cancer cell permeability in vitro [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5848.