Profile and outcomes of children presenting with infection-related glomerulonephritis

Poststreptococcal acute glomerulonephritis (PSGN) was reported as the most common cause of GN in children. There has been, however, a marked shift in epidemiology in recent years with the decline in poststreptococcal cases. Various other bacteria and rarely viral and fungal infections are associated with GN. More cases are now being reported with ongoing infection at the time GN is diagnosed. Therefore, the term infection-related GN (IRGN) is now being used increasingly. We describe the clinical profile and outcomes of children presenting with IRGN at a tertiary care center in the past 1 year. 5 children presented with features of GN. Only 1 of the 5 had the course typically described in PSGN. Two patients also had a post-infectious course but with some unusual features. Another patient had an ongoing systemic infection in the form of pneumonia at the time of onset of features GN, while our fifth patient developed an infection-related GN with dengue illness

Pediatric surgery experiences of a tertiary referral hospital: International Classification of Diseases spectrum for teaching, planning, and scaling up services

Introduction: Pediatric surgery provides the opportunity to intervene positively in a wide array of diseases with potential lifelong impact. Objective: The objective of this study was to evaluate the significance of pediatric surgery under vast circumstances. Materials and Methods: All children in the age group of 0–10 years operated in a tertiary care hospital were analyzed. Grouping of cases was done using the International Statistical Classification of Diseases and Related Health Problems 10th Revision (International Classification of Diseases [ICD]-10)-WHO Version (2016) and incorporating terminology from the ICD-11 Beta Draft. Results: “Developmental anomalies” accounted for 79.1% of cases, while 20.9% were “acquired conditions requiring surgical intervention.” The common congenital malformations were those of the genital organs (17%), followed by those of the digestive (13%) and nervous system (13%), urinary system (12%), circulatory system (8%), and cleft lip and palate (7%). The essential surgery package for congenital anomalies should include expertise in repair of cleft lip and palate, anomalies of genital, digestive, nervous, urinary, and musculoskeletal system. Referral to superspecialty center is required only for “congenital malformations of the circulatory system.” Conclusion: Majority of the workload (79.1%) due to “developmental anomalies” points toward need for skills in correcting these, restoring anatomy for the proper growth, and physiological functioning. Inclusion of indirect inguinal hernia in the Chapter 20 ‘Developmental anomalies’ (ICD-11) will contribute to correct international comparisons and guide planning

Numerical Modeling of Fluid Flow in Solid Tumors

A mathematical model of interstitial fluid flow is developed, based on the application of the governing equations for fluid flow, i.e., the conservation laws for mass and momentum, to physiological systems containing solid tumors. The discretized form of the governing equations, with appropriate boundary conditions, is developed for a predefined tumor geometry. The interstitial fluid pressure and velocity are calculated using a numerical method, element based finite volume. Simulations of interstitial fluid transport in a homogeneous solid tumor demonstrate that, in a uniformly perfused tumor, i.e., one with no necrotic region, because of the interstitial pressure distribution, the distribution of drug particles is non-uniform. Pressure distribution for different values of necrotic radii is examined and two new parameters, the critical tumor radius and critical necrotic radius, are defined. Simulation results show that: 1) tumor radii have a critical size. Below this size, the maximum interstitial fluid pressure is less than what is generally considered to be effective pressure (a parameter determined by vascular pressure, plasma osmotic pressure, and interstitial osmotic pressure). Above this size, the maximum interstitial fluid pressure is equal to effective pressure. As a consequence, drugs transport to the center of smaller tumors is much easier than transport to the center of a tumor whose radius is greater than the critical tumor radius; 2) there is a critical necrotic radius, below which the interstitial fluid pressure at the tumor center is at its maximum value. If the tumor radius is greater than the critical tumor radius, this maximum pressure is equal to effective pressure. Above this critical necrotic radius, the interstitial fluid pressure at the tumor center is below effective pressure. In specific ranges of these critical sizes, drug amount and therefore therapeutic effects are higher because the opposing force, interstitial fluid pressure, is low in these ranges

Anthracycline-Induced Cardiotoxicity: Cardiac Monitoring by Continuous Wave-Doppler Ultrasound Cardiac Output Monitoring and Correlation to Echocardiography

Background: Anthracyclines are agents with a well-known cardiotoxicity. The study sought to evaluate the hemodynamic response to an anthracycline using real-time continuous-wave (CW)-Doppler ultrasound cardiac output monitoring (USCOM) and echocardiography in combination with serum biomarkers. Methods: 50 patients (26 male, 24 female, median age 59 years) suffering from various types of cancer received an anthracycline-based regimen. Patients' responses were measured at different time points (T0 prior to infusion, T1 6 h post infusion, T2 after 1 day, T3 after 7 days, and T4 after 3 months) with CW-Doppler ultrasound (T0-T4) and echocardiography (T1, T4) for hemodynamic parameters such as stroke volume (SV; SVUSCOM ml) and ejection fraction (EF; EFechocardiography%) and with NT-pro-BNP and hs-Troponin T (T0-T4). Results: During the 3-month observation period, the relative decrease in the EF determined by echocardiography was -2.1% (Delta T0-T4, T0 71 +/- 7.8%, T4 69.5 +/- 7%, p = 0.04), whereas the decrease in SV observed using CW-Doppler was -6.5% (Delta T0-T4, T0 54 +/- 19.2 ml, T4 50.5 +/- 20.6 ml, p = 0.14). The kinetics for serum biomarkers were inversely correlated. Conclusions: Combining real-time CW-Doppler USCOM and serum biomarkers is feasible for monitoring the immediate and chronic hemodynamic changes during an anthracycline-based regimen; the results obtained were comparable to those from echocardiography

Unique contributions to the scalar bispectrum in `just enough inflation'

A scalar field rolling down a potential with a large initial velocity results in inflation of a finite duration. Such a scenario suppresses the scalar power on large scales improving the fit to the cosmological data. We find that the scenario leads to a hitherto unexplored situation wherein the boundary terms dominate the contributions to the scalar bispectrum over the bulk terms. We show that the consistency relation governing the non-Gaussianity parameter $f_{_{\rm NL}}$ is violated on large scales and that the contributions at the initial time can substantially enhance the value of $f_{_{\rm NL}}$.Comment: v1: 5 pages, 4 figure

A tumor cord model for Doxorubicin delivery and dose optimization in solid tumors

<p>Abstract</p> <p>Background</p> <p>Doxorubicin is a common anticancer agent used in the treatment of a number of neoplasms, with the lifetime dose limited due to the potential for cardiotoxocity. This has motivated efforts to develop optimal dosage regimes that maximize anti-tumor activity while minimizing cardiac toxicity, which is correlated with peak plasma concentration. Doxorubicin is characterized by poor penetration from tumoral vessels into the tumor mass, due to the highly irregular tumor vasculature. I model the delivery of a soluble drug from the vasculature to a solid tumor using a tumor cord model and examine the penetration of doxorubicin under different dosage regimes and tumor microenvironments.</p> <p>Methods</p> <p>A coupled ODE-PDE model is employed where drug is transported from the vasculature into a tumor cord domain according to the principle of solute transport. Within the tumor cord, extracellular drug diffuses and saturable pharmacokinetics govern uptake and efflux by cancer cells. Cancer cell death is also determined as a function of peak intracellular drug concentration.</p> <p>Results</p> <p>The model predicts that transport to the tumor cord from the vasculature is dominated by diffusive transport of free drug during the initial plasma drug distribution phase. I characterize the effect of all parameters describing the tumor microenvironment on drug delivery, and large intercapillary distance is predicted to be a major barrier to drug delivery. Comparing continuous drug infusion with bolus injection shows that the optimum infusion time depends upon the drug dose, with bolus injection best for low-dose therapy but short infusions better for high doses. Simulations of multiple treatments suggest that additional treatments have similar efficacy in terms of cell mortality, but drug penetration is limited. Moreover, fractionating a single large dose into several smaller doses slightly improves anti-tumor efficacy.</p> <p>Conclusion</p> <p>Drug infusion time has a significant effect on the spatial profile of cell mortality within tumor cord systems. Therefore, extending infusion times (up to 2 hours) and fractionating large doses are two strategies that may preserve or increase anti-tumor activity and reduce cardiotoxicity by decreasing peak plasma concentration. However, even under optimal conditions, doxorubicin may have limited delivery into advanced solid tumors.</p

Could it be advantageous to tune the temperature controller during radiofrequency ablation? A feasibility study using theoretical models

Purpose: To assess whether tailoring the Kp and Ki values of a proportional-integral (PI) controller during radiofrequency (RF) cardiac ablation could be advantageous from the point of view of the dynamic behaviour of the controller, in particular, whether control action could be speeded up and larger lesions obtained. Methods: Theoretical models were built and solved by the finite element method. RF cardiac ablations were simulated with temperature controlled at 55 degrees C. Specific PI controllers were implemented with Kp and Ki parameters adapted to cases with different tissue values (specific heat, thermal conductivity and electrical conductivity) electrode-tissue contact characteristics (insertion depth, cooling effect of circulating blood) and electrode characteristics (size, location and arrangement of the temperature sensor in the electrode). Results: The lesion dimensions and T(max) remained almost unchanged when the specific PI controller was used instead of one tuned for the standard case: T(max) varied less than 1.9 degrees C, lesion width less than 0.2 mm, and lesion depth less than 0.3 mm. As expected, we did observe a direct logical relationship between the response time of each controller and the transient value of electrode temperature. Conclusion: The results suggest that a PI controller designed for a standard case (such as that described in this study), could offer benefits under different tissue conditions, electrode-tissue contact, and electrode characteristics.This work received financial support from the Spanish 'Plan Nacional de I+D+I del Ministerio de Ciencia e Innovacion' Grant no. TEC2008-01369/TEC and FEDER Project MTM2010-14909. The translation of this paper was funded by the Universitat Politecnica de Valencia, Spain. The authors alone are responsible for the content and writing of the paperAlba Martínez, J.; Trujillo Guillen, M.; Blasco Giménez, RM.; Berjano Zanón, E. (2011). Could it be advantageous to tune the temperature controller during radiofrequency ablation? A feasibility study using theoretical models. International Journal of Hyperthermia. 27(6):539-548. https://doi.org/10.3109/02656736.2011.586665S539548276Gaita, F., Caponi, D., Pianelli, M., Scaglione, M., Toso, E., Cesarani, F., … Leclercq, J. F. (2010). Radiofrequency Catheter Ablation of Atrial Fibrillation: A Cause of Silent Thromboembolism? Circulation, 122(17), 1667-1673. doi:10.1161/circulationaha.110.937953Anfinsen, O.-G., Aass, H., Kongsgaard, E., Foerster, A., Scott, H., & Amlie, J. P. (1999). Journal of Interventional Cardiac Electrophysiology, 3(4), 343-351. doi:10.1023/a:1009840004782PETERSEN, H. H., CHEN, X., PIETERSEN, A., SVENDSEN, J. H., & HAUNSO, S. (2000). Tissue Temperatures and Lesion Size During Irrigated Tip Catheter Radiofrequency Ablation: An In Vitro Comparison of Temperature-Controlled Irrigated Tip Ablation, Power-Controlled Irrigated Tip Ablation, and Standard Temperature-Controlled Ablation. Pacing and Clinical Electrophysiology, 23(1), 8-17. doi:10.1111/j.1540-8159.2000.tb00644.xTungjitkusolmun, S., Woo, E. J., Cao, H., Tsai, J. Z., Vorperian, V. R., & Webster, J. G. (2000). Thermal—electrical finite element modelling for radio frequency cardiac ablation: Effects of changes in myocardial properties. Medical & Biological Engineering & Computing, 38(5), 562-568. doi:10.1007/bf02345754Lai, Y.-C., Choy, Y. B., Haemmerich, D., Vorperian, V. R., & Webster, J. G. (2004). Lesion Size Estimator of Cardiac Radiofrequency Ablation at Different Common Locations With Different Tip Temperatures. IEEE Transactions on Biomedical Engineering, 51(10), 1859-1864. doi:10.1109/tbme.2004.831529Jain, M. K., & Wolf, P. D. (1999). Temperature-controlled and constant-power radio-frequency ablation: what affects lesion growth? IEEE Transactions on Biomedical Engineering, 46(12), 1405-1412. doi:10.1109/10.804568Panescu, D., Whayne, J. G., Fleischman, S. D., Mirotznik, M. S., Swanson, D. K., & Webster, J. G. (1995). Three-dimensional finite element analysis of current density and temperature distributions during radio-frequency ablation. IEEE Transactions on Biomedical Engineering, 42(9), 879-890. doi:10.1109/10.412649Hong Cao, Vorperian, V. R., Tungjitkusolmun, S., Jan-Zern Tsai, Haemmerich, D., Young Bin Choy, & Webster, J. G. (2001). Flow effect on lesion formation in RF cardiac catheter ablation. IEEE Transactions on Biomedical Engineering, 48(4), 425-433. doi:10.1109/10.915708Tungjitkusolmun, S., Vorperian, V. R., Bhavaraju, N., Cao, H., Tsai, J.-Z., & Webster, J. G. (2001). Guidelines for predicting lesion size at common endocardial locations during radio-frequency ablation. IEEE Transactions on Biomedical Engineering, 48(2), 194-201. doi:10.1109/10.909640Schutt, D., Berjano, E. J., & Haemmerich, D. (2009). Effect of electrode thermal conductivity in cardiac radiofrequency catheter ablation: A computational modeling study. International Journal of Hyperthermia, 25(2), 99-107. doi:10.1080/02656730802563051Langberg, J. J., Calkins, H., el-Atassi, R., Borganelli, M., Leon, A., Kalbfleisch, S. J., & Morady, F. (1992). Temperature monitoring during radiofrequency catheter ablation of accessory pathways. Circulation, 86(5), 1469-1474. doi:10.1161/01.cir.86.5.1469Calkins, H., Prystowsky, E., Carlson, M., Klein, L. S., Saul, J. P., & Gillette, P. (1994). Temperature monitoring during radiofrequency catheter ablation procedures using closed loop control. Atakr Multicenter Investigators Group. Circulation, 90(3), 1279-1286. doi:10.1161/01.cir.90.3.1279Lennox CD, Temperature controlled RF coagulation. Patent number: 5.122.137 Hudson NHEdwards SD, Stern RA, Electrode and associated system using thermally insulated temperature sensing elements. Patent number: US Patent 5,456,682Panescu D, Fleischman SD, Whayne JG, Swanson DK, (EP Technology. Effects of temperature sensor placement on performance of temperature-controlled ablation. IEEE 17th Annual Conference, Engineering in Medicine and Biology Society, Montreal, Canada (1995)BLOUIN, L. T., MARCUS, F. I., & LAMPE, L. (1991). Assessment of Effects of a Radiofrequency Energy Field and Thermistor Location in an Electrode Catheter on the Accuracy of Temperature Measurement. Pacing and Clinical Electrophysiology, 14(5), 807-813. doi:10.1111/j.1540-8159.1991.tb04111.xBerjano, E. J. (2006). BioMedical Engineering OnLine, 5(1), 24. doi:10.1186/1475-925x-5-24Bhavaraju, N. C., Cao, H., Yuan, D. Y., Valvano, J. W., & Webster, J. G. (2001). Measurement of directional thermal properties of biomaterials. IEEE Transactions on Biomedical Engineering, 48(2), 261-267. doi:10.1109/10.909647Hong Cao, Tungjitkusolmun, S., Young Bin Choy, Jang-Zern Tsai, Vorperian, V. R., & Webster, J. G. (2002). Using electrical impedance to predict catheter-endocardial contact during RF cardiac ablation. IEEE Transactions on Biomedical Engineering, 49(3), 247-253. doi:10.1109/10.983459PETERSEN, H. H., & SVENDSEN, J. H. (2003). Can Lesion Size During Radiofrequency Ablation Be Predicted By the Temperature Rise to a Low Power Test Pulse in Vitro? Pacing and Clinical Electrophysiology, 26(8), 1653-1659. doi:10.1046/j.1460-9592.2003.t01-1-00248.xLANGBERG, J. J., LEE, M. A., CHIN, M. C., & ROSENQVIST, M. (1990). Radiofrequency Catheter Ablation: The Effect of Electrode Size on Lesion Volume In Vivo. Pacing and Clinical Electrophysiology, 13(10), 1242-1248. doi:10.1111/j.1540-8159.1990.tb02022.

Silicon particles as trojan horses for potential cancer therapy

[EN] Background: Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells. Results: We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents. Conclusions: In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular.The authors acknowledge financial support from the following projects FIS2009-07812, MAT2012-35040, PROMETEO/2010/043, CTQ2011-23167, CrossSERS, FP7 MC-IEF 329131, and HSFP (project RGP0052/2012) and Medcom Tech SA. Xiang Yu acknowledges support by the Chinese government (CSC, Nr. 2010691036).Fenollosa Esteve, R.; Garcia-Rico, E.; Alvarez, S.; Alvarez, R.; Yu, X.; Rodriguez, I.; Carregal-Romero, S.... (2014). Silicon particles as trojan horses for potential cancer therapy. Journal of Nanobiotechnology. 12:1-10. https://doi.org/10.1186/s12951-014-0035-7S11012Prasad PN: Introduction to Nanomedicine and Nanobioengineering. Wiley, New York, 2012.Randall CL, Leong TG, Bassik N, Gracias DH: 3D lithographically fabricated nanoliter containers for drug delivery. Adv Drug Del Rev. 2007, 59: 1547-1561. 10.1016/j.addr.2007.08.024.Reibetanz U, Chen MHA, Mutukumaraswamy S, Liaw ZY, Oh BHL, Venkatraman S, Donath E, Neu BR: Colloidal DNA carriers for direct localization in cell compartments by pH sensoring. Biogeosciences. 2010, 11: 1779-1784.Tasciotti E, Liu X, Bhavane R, Plant K, Leonard AD, Price BK, Cheng MM-C, Decuzzi P, Tour JM, Robertson F, Ferrari M: Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nat Nano. 2008, 3: 151-157. 10.1038/nnano.2008.34.Park J-H, Gu L, von Maltzahn G, Ruoslahti E, Bhatia SN, Sailor MJ: Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nat Mater. 2009, 8: 331-336. 10.1038/nmat2398.Hong C, Lee J, Son M, Hong SS, Lee C: In-vivo cancer cell destruction using porous silicon nanoparticles. Anti-Cancer Drugs. 2011, 22: 971-977. 910.1097/CAD.1090b1013e32834b32859cCanham LT: Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7. Book Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7 (Editor ed.^eds.). 2003, UK Patent Nr. 0302283.7, CityXiao L, Gu L, Howell SB, Sailor MJ: Porous silicon nanoparticle photosensitizers for singlet oxygen and their phototoxicity against cancer cells. ACS Nano. 2011, 5: 3651-3659. 10.1021/nn1035262.Gil PR, Parak WJ: Composite nanoparticles take Aim at cancer. ACS Nano. 2008, 2: 2200-2205. 10.1021/nn800716j.Gomella LG: Is interstitial hyperthermia a safe and efficacious adjunct to radiotherapy for localized prostate cancer?. Nat Clin Pract Urol. 2004, 1: 72-73. 10.1038/ncpuro0041.Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, Orawa H, Budach V, Jordan A: Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neuro-Oncol. 2011, 103: 317-324. 10.1007/s11060-010-0389-0.Lal S, Clare SE, Halas NJ: Nanoshell-enabled photothermal cancer therapy: Impending clinical impact. Acc Chem Res. 2008, 41: 1842-1851. 10.1021/ar800150g.Lee C, Kim H, Hong C, Kim M, Hong SS, Lee DH, Lee WI: Porous silicon as an agent for cancer thermotherapy based on near-infrared light irradiation. J Mater Chem. 2008, 18: 4790-4795. 10.1039/b808500e.Osminkina LA, Gongalsky MB, Motuzuk AV, Timoshenko VY, Kudryavtsev AA: Silicon nanocrystals as photo- and sono-sensitizers for biomedical applications. Appl Phys B. 2011, 105: 665-668. 10.1007/s00340-011-4562-8.Jain PK, Huang X, El-Sayed IH, El-Sayed MA: Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc Chem Res. 2008, 41: 1578-1586. 10.1021/ar7002804.Serda RE, Godin B, Blanco E, Chiappini C, Ferrari M: Multi-stage delivery nano-particle systems for therapeutic applications. Biochim Biophys Acta. 1810, 2011: 317-329.Xu R, Huang Y, Mai J, Zhang G, Guo X, Xia X, Koay EJ, Qin G, Erm DR, Li Q, Liu X, Ferrari M, Shen H: Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy. Small. 2013, 9: 1799-1808. 10.1002/smll.201201510.Park JS, Kinsella JM, Jandial DD, Howell SB, Sailor MJ: Cisplatin-loaded porous Si microparticles capped by electroless deposition of platinum. Small. 2011, 7: 2061-2069. 10.1002/smll.201100438.Xue M, Zhong X, Shaposhnik Z, Qu Y, Tamanoi F, Duan X, Zink JI: pH-operated mechanized porous silicon nanoparticles. J Am Chem Soc. 2011, 133: 8798-8801. 10.1021/ja201252e.Canham LT: Bioactive silicon structure fabrication through nanoetching techniques. Adv Mater. 1995, 7: 1033-1037. 10.1002/adma.19950071215.Popplewell JF, King SJ, Day JP, Ackrill P, Fifield LK, Cresswell RG, Di Tada ML, Liu K: Kinetics of uptake and elimination of silicic acid by a human subject: a novel application of 32Si and accelerator mass spectrometry. J Inorganic Biochem. 1998, 69: 177-180. 10.1016/S0162-0134(97)10016-2.Shabir Q, Pokale A, Loni A, Johnson DR, Canham LT, Fenollosa R, Tymczenko M, Rodr guez I, Meseguer F, Cros A, Cantarero A: Medically biodegradable hydrogenated amorphous silicon microspheres. Silicon. 2011, 3: 173-176. 10.1007/s12633-011-9097-4.Chen Y, Wan Y, Wang Y, Zhang H, Jiao Z: Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles. Int J Nanomed. 2011, 6: 2321-2326.Mackowiak SA, Schmidt A, Weiss V, Argyo C, von Schirnding C, Bein T, Bräuchle C: Targeted drug delivery in cancer cells with Red-light photoactivated mesoporous silica nanoparticles. Nano Lett. 2013, 13: 2576-2583. 10.1021/nl400681f.Li Z, Barnes JC, Bosoy A, Stoddart JF, Zink JI: Mesoporous silica nanoparticles in biomedical applications. Chem Soc Rev. 2012, 41: 2590-2605. 10.1039/c1cs15246g.O Mara WC, Herring B, Hunt P: Handbook of Semiconductor Silicon Technology. Noyes Publication, New Jersey, 1990.Mikulec FV, Kirtland JD, Sailor MJ: Explosive nanocrystalline porous silicon and its Use in atomic emission spectroscopy. Adv Mater. 2002, 14: 38-41. 10.1002/1521-4095(20020104)14:13.0.CO;2-Z.Clement D, Diener J, Gross E, Kunzner N, Timoshenko VY, Kovalev D: Highly explosive nanosilicon-based composite materials. Phys Stat Sol A. 2005, 202: 1357-1359. 10.1002/pssa.200461102.Canham LT: Silicon quantum wire array fabrication by electrochemical and chemical dissolution of wafers. Appl Phys Lett. 1990, 57: 1046-1049. 10.1063/1.103561.Canham LT: Properties of Porous Silicon. INSPEC, United Kindom, 1997.Heinrich JL, Curtis CL, Credo GM, Sailor MJ, Kavanagh KL: Luminescent colloidal silicon suspensions from porous silicon. Science. 1992, 255: 66-68. 10.1126/science.255.5040.66.Littau KA, Szajowski PJ, Muller AJ, Kortan AR, Brus LE: A luminescent silicon nanocrystal colloid via a high-temperature aerosol reaction. J Phys Chem. 1993, 97: 1224-1230. 10.1021/j100108a019.Menz WJ, Shekar S, Brownbridge GPE, Mosbach S, Kōrmer R, Peukert W, Kraft M: Synthesis of silicon nanoparticles with a narrow size distribution: a theoretical study. J Aerosol Sci. 2012, 44: 46-61. 10.1016/j.jaerosci.2011.10.005.Swihart MT, Girshick SL: Thermochemistry and kinetics of silicon hydride cluster formation during thermal decomposition of silane. J Phys Chem B. 1998, 103: 64-76. 10.1021/jp983358e.Fenollosa R, Ramiro-Manzano F, Tymczenko M, Meseguer F: Porous silicon microspheres: synthesis, characterization and application to photonic microcavities. J Mater Chem. 2010, 20: 5210-5214. 10.1039/c0jm00079e.Ramiro-Manzano F, Fenollosa R, Xifré-Pérez E, Garín M, Meseguer F: Porous silicon microcavities based photonic barcodes. Adv Mater. 2011, 23: 3022-3025. 10.1002/adma.201100986.Kastl L, Sasse D, Wulf V, Hartmann R, Mircheski J, Ranke C, Carregal-Romero S, Martínez-López JA, Fernández-Chacón R, Parak WJ, Elsasser HP, Rivera-Gil P: Multiple internalization pathways of polyelectrolyte multilayer capsules into mammalian cells. ACS Nano. 2013, 7: 6605-6618. 10.1021/nn306032k.Schweiger C, Hartmann R, Zhang F, Parak W, Kissel T, Rivera_Gil P: Quantification of the internalization patterns of superparamagnetic iron oxide nanoparticles with opposite charge. J Nanobiotech. 2012, 10: 28-10.1186/1477-3155-10-28.Sanles-Sobrido M, Exner W, Rodr guez-Lorenzo L, Rodríguez-Gonzílez B, Correa-Duarte MA, Álvarez-Puebla RA, Liz-Marzán LM: Design of SERS-encoded, submicron, hollow particles through confined growth of encapsulated metal nanoparticles. J Am Chem Soc. 2009, 131: 2699-2705. 10.1021/ja8088444.Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J: Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011, 365: 1273-1283. 10.1056/NEJMoa0910383.Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G, Kelsey SM, Fyfe G: Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol. 2005, 23: 2534-2543. 10.1200/JCO.2005.03.184.Colombo M, Mazzucchelli S, Montenegro JM, Galbiati E, Corsi F, Parak WJ, Prosperi D: Protein oriented ligation on nanoparticles exploiting O6-alkylguanine-DNA transferase (SNAP) genetically encoded fusion. Small. 2012, 8: 1492-1497. 10.1002/smll.201102284.Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004, 5: 317-328. 10.1016/S1535-6108(04)00083-2.Paris L, Cecchetti S, Spadaro F, Abalsamo L, Lugini L, Pisanu ME, Lorio E, Natali PG, Ramoni C, Podo F: Inhibition of phosphatidylcholine-specific phospholipase C downregulates HER2 overexpression on plasma membrane of breast cancer cells. Breast Cancer Res. 2010, 12: R27-10.1186/bcr2575.Fenollosa R, Meseguer F, Tymczenko M: Silicon colloids: from microcavities to photonic sponges. Adv Mater. 2008, 20: 95-98. 10.1002/adma.200701589.Jasinski JM, Gates SM: Silicon chemical vapor deposition one step at a time: fundamental studies of silicon hydride chemistry. Acc Chem Res. 1991, 24: 9-15. 10.1021/ar00001a002.Xiao Q, Liu Y, Qiu Y, Zhou G, Mao C, Li Z, Yao Z-J, Jiang S: Potent antitumor mimetics of annonaceous acetogenins embedded with an aromatic moiety in the left hydrocarbon chain part. J Med Chem. 2010, 54: 525-533. 10.1021/jm101053k.Allman SA, Jensen HH, Vijayakrishnan B, Garnett JA, Leon E, Liu Y, Anthony DC, Sibson NR, Feizi T, Matthews S, Davis BG: Potent fluoro-oligosaccharide probes of adhesion in toxoplasmosis. ChemBioChem. 2009, 10: 2522-2529. 10.1002/cbic.200900425.Chambers DJ, Evans GR, Fairbanks AJ: Elimination reactions of glycosyl selenoxides. Tetrahedron. 2004, 60: 8411-8419. 10.1016/j.tet.2004.07.005.Tomabechi Y, Suzuki R, Haneda K, Inazu T: Chemo-enzymatic synthesis of glycosylated insulin using a GlcNAc tag. Bioorg Med Chem. 2010, 18: 1259-1264. 10.1016/j.bmc.2009.12.031.Pastoriza-Santos I, Gomez D, Perez-Juste J, Liz-Marzan LM, Mulvaney P: Optical properties of metal nanoparticle coated silica spheres: a simple effective medium approach. Phys Chem Chem Phys. 2004, 6: 5056-5060. 10.1039/b405157b

High Interstitial Fluid Pressure Is Associated with Tumor-Line Specific Vascular Abnormalities in Human Melanoma Xenografts

PURPOSE: Interstitial fluid pressure (IFP) is highly elevated in many solid tumors. High IFP has been associated with low radiocurability and high metastatic frequency in human melanoma xenografts and with poor survival after radiation therapy in cervical cancer patients. Abnormalities in tumor vascular networks have been identified as an important cause of elevated tumor IFP. The aim of this study was to investigate the relationship between tumor IFP and the functional and morphological properties of tumor vascular networks. MATERIALS AND METHODS: A-07-GFP and R-18-GFP human melanomas growing in dorsal window chambers in BALB/c nu/nu mice were used as preclinical tumor models. Functional and morphological parameters of the vascular network were assessed from first-pass imaging movies and vascular maps recorded after intravenous bolus injection of 155-kDa tetramethylrhodamine isothiocyanate-labeled dextran. IFP was measured in the center of the tumors using a Millar catheter. Angiogenic profiles of A-07-GFP and R-18-GFP cells were obtained with a quantitative PCR array. RESULTS: High IFP was associated with low growth rate and low vascular density in A-07-GFP tumors, and with high growth rate and high vascular density in R-18-GFP tumors. A-07-GFP tumors showed chaotic and highly disorganized vascular networks, while R-18-GFP tumors showed more organized vascular networks with supplying arterioles in the tumor center and draining venules in the tumor periphery. Furthermore, A-07-GFP and R-18-GFP cells differed substantially in angiogenic profiles. A-07-GFP tumors with high IFP showed high geometric resistance to blood flow due to high vessel tortuosity. R-18-GFP tumors with high IFP showed high geometric resistance to blood flow due to a large number of narrow tumor capillaries. CONCLUSIONS: High IFP in A-07-GFP and R-18-GFP human melanoma xenografts was primarily a consequence of high blood flow resistance caused by tumor-line specific vascular abnormalities