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1.
Space Sci Rev ; 219(2): 18, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36874191

RESUMEN

A detailed overview of the knowledge gaps in our understanding of the heliospheric interaction with the largely unexplored Very Local Interstellar Medium (VLISM) are provided along with predictions of with the scientific discoveries that await. The new measurements required to make progress in this expanding frontier of space physics are discussed and include in-situ plasma and pick-up ion measurements throughout the heliosheath, direct sampling of the VLISM properties such as elemental and isotopic composition, densities, flows, and temperatures of neutral gas, dust and plasma, and remote energetic neutral atom (ENA) and Lyman-alpha (LYA) imaging from vantage points that can uniquely discern the heliospheric shape and bring new information on the interaction with interstellar hydrogen. The implementation of a pragmatic Interstellar Probe mission with a nominal design life to reach 375 Astronomical Units (au) with likely operation out to 550 au are reported as a result of a 4-year NASA funded mission study.

2.
J Geophys Res Space Phys ; 127(8): e2022JA030334, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36247326

RESUMEN

The Juno spacecraft's polar orbits have enabled direct sampling of Jupiter's low-altitude auroral field lines. While various data sets have identified unique features over Jupiter's main aurora, they are yet to be analyzed altogether to determine how they can be reconciled and fit into the bigger picture of Jupiter's auroral generation mechanisms. Jupiter's main aurora has been classified into distinct "zones", based on repeatable signatures found in energetic electron and proton spectra. We combine fields, particles, and plasma wave data sets to analyze Zone-I and Zone-II, which are suggested to carry upward and downward field-aligned currents, respectively. We find Zone-I to have well-defined boundaries across all data sets. H+ and/or H3 + cyclotron waves are commonly observed in Zone-I in the presence of energetic upward H+ beams and downward energetic electron beams. Zone-II, on the other hand, does not have a clear poleward boundary with the polar cap, and its signatures are more sporadic. Large-amplitude solitary waves, which are reminiscent of those ubiquitous in Earth's downward current region, are a key feature of Zone-II. Alfvénic fluctuations are most prominent in the diffuse aurora and are repeatedly found to diminish in Zone-I and Zone-II, likely due to dissipation, at higher altitudes, to energize auroral electrons. Finally, we identify significant electron density depletions, by up to 2 orders of magnitude, in Zone-I, and discuss their important implications for the development of parallel potentials, Alfvénic dissipation, and radio wave generation.

3.
Geophys Res Lett ; 49(9): e2022GL098741, 2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35859815

RESUMEN

Two distinct proton populations are observed over Jupiter's southern polar cap: a ∼1 keV core population and ∼1-300 keV dispersive conic population at 6-7 RJ planetocentric distance. We find the 1 keV core protons are likely the seed population for the higher-energy dispersive conics, which are accelerated from a distance of ∼3-5 RJ. Transient wave-particle heating in a "pressure-cooker" process is likely responsible for this proton acceleration. The plasma characteristics and composition during this period show Jupiter's polar-most field lines can be topologically closed, with conjugate magnetic footpoints connected to both hemispheres. Finally, these observations demonstrate energetic protons can be accelerated into Jupiter's magnetotail via wave-particle coupling.

4.
Geophys Res Lett ; 49(9): e2022GL098111, 2022 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-35864892

RESUMEN

Water-group gas continuously escapes from Jupiter's icy moons to form co-orbiting populations of particles or neutral toroidal clouds. These clouds provide insights into their source moons as they reveal loss processes and compositions of their parent bodies, alter local plasma composition, and act as sources and sinks for magnetospheric particles. We report the first observations of H2 + pickup ions in Jupiter's magnetosphere from 13 to 18 Jovian radii and find a density ratio of H2 +/H+ = 8 ± 4%, confirming the presence of a neutral H2 toroidal cloud. Pickup ion densities monotonically decrease radially beyond 13 R J consistent with an advecting Europa-genic toroidal cloud source. From these observations, we derive a total H2 neutral loss rate from Europa of 1.2 ± 0.7 kg s-1. This provides the most direct estimate of Europa's H2 neutral loss rate to date and underscores the importance of both ion composition and neutral toroidal clouds in understanding satellite-magnetosphere interactions.

5.
J Geophys Res Space Phys ; 126(7): e2021JA029278, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35865412

RESUMEN

Inside the magnetosheath, the IBEX-Hi energetic neutral atom (ENA) imager measures a distinct background count rate that is more than 10 times the typical heliospheric ENA emissions observed when IBEX is outside the magnetosheath. The source of this enhancement is magnetosheath ions of solar wind (SW) origin that deflect around the Earth's magnetopause (MP), scatter and neutralize from the anti-sunward part of the IBEX-Hi sunshade, and continue into the instrument as neutral atoms, behaving indistinguishably from ENAs emitted from distant plasma sources. While this background pollutes observations of outer heliospheric ENAs, it provides a clear signature of IBEX crossings over the magnetospheric boundaries. In this study, we investigate IBEX encounters with the magnetosheath boundaries using ∼8 yr of orbital data, and we determine the MP and bow shock (BS) locations derived from this background signal. We find 280 BS crossings from X GSE ∼ 11 Re to X GSE âˆ¼ -36 Re and 241 MP crossings from X GSE ∼ 6 Re to X GSE âˆ¼ -48 Re. We compare IBEX BS and MP crossing locations to those from IMP-8, Geotail, Cluster, Magion-4, ISEE, and Magnetospheric Multiscale Mission, and we find that IBEX crossing locations overlap with the BS and MP locations inferred from these other data sets. In this paper, we demonstrate how IBEX can be used to identify magnetosheath crossings, and extend boundary observations well past the terminator, thus further constraining future models of magnetosheath boundaries. Furthermore, we use the IBEX data set to show observational evidence of near-Earth magnetotail squeezing during periods of strong interplanetary magnetic field B y.

6.
Geophys Res Lett ; 47(19): e2020GL089362, 2020 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-33380756

RESUMEN

Energetic neutral atoms (ENAs) created by charge-exchange of ions with the Earth's hydrogen exosphere near the subsolar magnetopause yield information on the distribution of plasma in the outer magnetosphere and magnetosheath. ENA observations from the Interstellar Boundary Explorer (IBEX) are used to image magnetosheath plasma and, for the first time, low-energy magnetospheric plasma near the magnetopause. These images show that magnetosheath plasma is distributed fairly evenly near the subsolar magnetopause; however, low-energy magnetospheric plasma is not distributed evenly in the outer magnetosphere. Simultaneous images and in situ observations from the Magnetospheric Multiscale (MMS) spacecraft from November 2015 (during the solar cycle declining phase) are used to derive the exospheric density. The ~11-17 cm-3 density at 10 RE is similar to that obtained previously for solar minimum. Thus, these combined results indicate that the exospheric density 10 RE from the Earth may have a weak dependence on solar cycle.

7.
Geophys Res Lett ; 47(16): e2020GL088188, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-33132458

RESUMEN

The Interstellar Boundary Explorer (IBEX) mission provides global energetic neutral atom (ENA) observations from the heliosphere and the Earth's magnetosphere, including spatial, temporal, and energy information. IBEX views the magnetosphere from the sides and almost always perpendicular to noon-midnight plane. We report the first ENA images of the energization process in the Earth's ion foreshock and magnetosheath regions. We show ENA flux and spectral images of the dayside magnetosphere with significant energization of ENA plasma sources (above ~2.7 keV) in the region magnetically connected to the Earth's bow shock (BS) in its quasi-parallel configuration of the interplanetary magnetic field (IMF). We also show that the ion energization increases gradually with decreasing IMF-BS angle, suggesting more efficient suprathermal ion acceleration deeper in the quasi-parallel foreshock.

8.
Nature ; 576(7786): 223-227, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31802005

RESUMEN

NASA's Parker Solar Probe mission1 recently plunged through the inner heliosphere of the Sun to its perihelia, about 24 million kilometres from the Sun. Previous studies farther from the Sun (performed mostly at a distance of 1 astronomical unit) indicate that solar energetic particles are accelerated from a few kiloelectronvolts up to near-relativistic energies via at least two processes: 'impulsive' events, which are usually associated with magnetic reconnection in solar flares and are typically enriched in electrons, helium-3 and heavier ions2, and 'gradual' events3,4, which are typically associated with large coronal-mass-ejection-driven shocks and compressions moving through the corona and inner solar wind and are the dominant source of protons with energies between 1 and 10 megaelectronvolts. However, some events show aspects of both processes and the electron-proton ratio is not bimodally distributed, as would be expected if there were only two possible processes5. These processes have been very difficult to resolve from prior observations, owing to the various transport effects that affect the energetic particle population en route to more distant spacecraft6. Here we report observations of the near-Sun energetic particle radiation environment over the first two orbits of the probe. We find a variety of energetic particle events accelerated both locally and remotely including by corotating interaction regions, impulsive events driven by acceleration near the Sun, and an event related to a coronal mass ejection. We provide direct observations of the energetic particle radiation environment in the region just above the corona of the Sun and directly explore the physics of particle acceleration and transport.

9.
Geophys Res Lett ; 46(1): 19-27, 2019 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-30828110

RESUMEN

We compare electron and UV observations mapping to the same location in Jupiter's northern polar region, poleward of the main aurora, during Juno perijove 5. Simultaneous peaks in UV brightness and electron energy flux are identified when observations map to the same location at the same time. The downward energy flux during these simultaneous observations was not sufficient to generate the observed UV brightness; the upward energy flux was. We propose that the primary acceleration region is below Juno's altitude, from which the more intense upward electrons originate. For the complete interval, the UV brightness peaked at ~240 kilorayleigh (kR); the downward and upward energy fluxes peaked at 60 and 700 mW/m2, respectively. Increased downward energy fluxes are associated with increased contributions from tens of keV electrons. These observations provide evidence that bidirectional electron beams with broad energy distributions can produce tens to hundreds of kilorayleigh polar UV emissions.

10.
Meteorit Planet Sci ; 54(9): 2046-2066, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32256026

RESUMEN

Given the compositional diversity of asteroids, and their distribution in space, it is impossible to consider returning samples from each one to establish their origin. However, the velocity and molecular composition of primary minerals, hydrated silicates, and organic materials can be determined by in situ dust detector instruments. Such instruments could sample the cloud of micrometer-scale particles shed by asteroids to provide direct links to known meteorite groups without returning the samples to terrestrial laboratories. We extend models of the measured lunar dust cloud from LADEE to show that the abundance of detectable impact-generated microsamples around asteroids is a function of the parent body radius, heliocentric distance, flyby distance, and speed. We use Monte Carlo modeling to show that several tens to hundreds of particles, if randomly ejected and detected during a flyby, would be a sufficient number to classify the parent body as an ordinary chondrite, basaltic achondrite, or other class of meteorite. Encountering and measuring microsamples shed from near-Earth and Main Belt asteroids, coupled with complementary imaging and multispectral measurements, could accomplish a thorough characterization of small, airless bodies.

11.
Phys Rev Lett ; 121(7): 075102, 2018 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-30169088

RESUMEN

Nonthermal pickup ions (PUIs) are created in the solar wind (SW) by charge-exchange between SW ions (SWIs) and slow interstellar neutral atoms. It has long been theorized, but not directly observed that PUIs should be preferentially heated at quasiperpendicular shocks compared to thermal SWIs. We present in situ observations of interstellar hydrogen (H^{+}) PUIs at an interplanetary shock by the New Horizons' Solar Wind Around Pluto (SWAP) instrument at ∼34 au from the Sun. At this shock, H^{+} PUIs are only a few percent of the total proton density but contain most of the internal particle pressure. A gradual reduction in SW flow speed and simultaneous heating of H^{+} SWIs is observed ahead of the shock, suggesting an upstream energetic particle pressure gradient. H^{+} SWIs lose ∼85% of their energy flux across the shock and H^{+} PUIs are preferentially heated. Moreover, a PUI tail is observed downstream of the shock, such that the energy flux of all H^{+} PUIs is approximately six times that of H^{+} SWIs. We find that H^{+} PUIs, including their suprathermal tail, contain almost half of the total downstream energy flux in the shock frame.

12.
Science ; 356(6340): 821-825, 2017 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-28546206

RESUMEN

On 27 August 2016, the Juno spacecraft acquired science observations of Jupiter, passing less than 5000 kilometers above the equatorial cloud tops. Images of Jupiter's poles show a chaotic scene, unlike Saturn's poles. Microwave sounding reveals weather features at pressures deeper than 100 bars, dominated by an ammonia-rich, narrow low-latitude plume resembling a deeper, wider version of Earth's Hadley cell. Near-infrared mapping reveals the relative humidity within prominent downwelling regions. Juno's measured gravity field differs substantially from the last available estimate and is one order of magnitude more precise. This has implications for the distribution of heavy elements in the interior, including the existence and mass of Jupiter's core. The observed magnetic field exhibits smaller spatial variations than expected, indicative of a rich harmonic content.

13.
Science ; 351(6279): aad9045, 2016 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-26989259

RESUMEN

The New Horizons spacecraft carried three instruments that measured the space environment near Pluto as it flew by on 14 July 2015. The Solar Wind Around Pluto (SWAP) instrument revealed an interaction region confined sunward of Pluto to within about 6 Pluto radii. The region's surprisingly small size is consistent with a reduced atmospheric escape rate, as well as a particularly high solar wind flux. Observations from the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument suggest that ions are accelerated and/or deflected around Pluto. In the wake of the interaction region, PEPSSI observed suprathermal particle fluxes equal to about 1/10 of the flux in the interplanetary medium and increasing with distance downstream. The Venetia Burney Student Dust Counter, which measures grains with radii larger than 1.4 micrometers, detected one candidate impact in ±5 days around New Horizons' closest approach, indicating an upper limit of <4.6 kilometers(-3) for the dust density in the Pluto system.

14.
Nature ; 522(7556): 324-6, 2015 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-26085272

RESUMEN

Interplanetary dust particles hit the surfaces of airless bodies in the Solar System, generating charged and neutral gas clouds, as well as secondary ejecta dust particles. Gravitationally bound ejecta clouds that form dust exospheres were recognized by in situ dust instruments around the icy moons of Jupiter and Saturn, but have hitherto not been observed near bodies with refractory regolith surfaces. High-altitude Apollo 15 and 17 observations of a 'horizon glow' indicated a putative population of high-density small dust particles near the lunar terminators, although later orbital observations yielded upper limits on the abundance of such particles that were a factor of about 10(4) lower than that necessary to produce the Apollo results. Here we report observations of a permanent, asymmetric dust cloud around the Moon, caused by impacts of high-speed cometary dust particles on eccentric orbits, as opposed to particles of asteroidal origin following near-circular paths striking the Moon at lower speeds. The density of the lunar ejecta cloud increases during the annual meteor showers, especially the Geminids, because the lunar surface is exposed to the same stream of interplanetary dust particles. We expect all airless planetary objects to be immersed in similar tenuous clouds of dust.

15.
J Hum Hypertens ; 20(10): 780-6, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16761027

RESUMEN

Our aim was to investigate the association between serum heat-shock protein (Hsp) 70 concentration and hypertensive disorders of pregnancy. One hundred and forty-two pregnant women with hypertensive disorders (93 with preeclampsia, 29 with transient hypertension of pregnancy and 20 with superimposed preeclampsia) and 127 normotensive, healthy pregnant women were included in the study. Serum Hsp70 concentration was measured using enzyme-linked immunosorbent assay. The serum Hsp70 concentration was significantly higher in patients with transient hypertension of pregnancy, in preeclamptic patients and in patients with superimposed preeclampsia than in the control group (median (25-75 percentile): 0.66 (0.52-0.84), 0.55 (0.42-0.80), 0.61 (0.42-0.91) ng/ml vs 0.31 (0.27-0.39) ng/ml, respectively; P<0.001). Multivariate logistic regression analysis showed independent association of elevated serum Hsp70 level with transient hypertension of pregnancy, preeclampsia and superimposed preeclampsia. The difference in serum Hsp70 concentration between preeclamptic patients and the control group was statistically significant in each gestational age category. In the groups of preeclamptic and superimposed preeclamptic patients, there was no significant difference in serum Hsp70 concentration between mild and severe preeclamptic patients, between patients with late and early onset of the disease, as well as between preeclamptic patients without and with foetal growth restriction. In conclusion, serum Hsp70 concentration is elevated in transient hypertension of pregnancy, in preeclampsia and in superimposed preeclampsia. Circulating Hsp70 may not only be a marker for these conditions, but might also play a role in their pathogenesis. However, further studies are needed to explore its role in the pathogenesis of hypertensive disorders of pregnancy.


Asunto(s)
Eclampsia/sangre , Retardo del Crecimiento Fetal/sangre , Proteínas HSP70 de Choque Térmico/sangre , Preeclampsia/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Eclampsia/etiología , Femenino , Retardo del Crecimiento Fetal/etiología , Humanos , Preeclampsia/etiología , Valor Predictivo de las Pruebas , Embarazo/sangre
16.
J Histochem Cytochem ; 49(1): 49-66, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11118478

RESUMEN

Although PKC plays a major role in regulating the morphology and function of the cytoskeleton, little is known about in situ associations of specific isoforms with the cytoskeleton. We demonstrate that seven PKC isoforms are expressed in B16F10 melanoma cells and show different levels of induction by serum. Using cell cytoskeleton preparations (CSKs), confocal microscopy, and immunocytochemistry, all isoforms show specific patterns of localization to focal contact-like structures (alpha, delta), very small cytoplasmic granules/vesicles (all isoforms), dense ordered arrays of small granules in the perinuclear region (alpha, delta), granules/vesicles associated with a homogeneous framework in the cytoplasm adjacent to the nucleus (gamma), or irregular-shaped patches of granules at or near the nuclear perimeter (eta, theta). In addition, several isoforms are present as cytoplasmic granules/ vesicles in linear or curvilinear arrays (alpha, delta, epsilon, theta). When isoform localization is examined using 3.7% formaldehyde or methanol:acetone, the patterns of localization in CSKs are often difficult or impossible to detect, and many are described here for the first time. Double-labeling experiments with CSK demonstrate that PKC actin co-localizes with punctate alpha-rich particles above the nucleus, granules of epsilon throughout the cytoplasm, and with theta in irregular-shaped aggregates associated with the nucleus. Vimentin co-localizes with perinuclear granules of delta and beta(2), and alpha-tubulin co-localizes with theta in structures at or near the nuclear surface and in microtubules associated with the microtubule organizing center (MTOC). In summary, the present study demonstrates that seven PKC isoforms are endogenously expressed in B16F10 melanoma cells. These isoforms show various levels of induction by serum and specific patterns of association with various components of the detergent-resistant cell cytoskeleton.


Asunto(s)
Citoesqueleto/enzimología , Melanoma/enzimología , Proteína Quinasa C/metabolismo , Acetona , Animales , Western Blotting , Medios de Cultivo , Fluoresceína-5-Isotiocianato , Colorantes Fluorescentes , Formaldehído , Inmunohistoquímica , Indicadores y Reactivos , Isoenzimas/metabolismo , Melanoma/patología , Metanol , Ratones , Microscopía Confocal , Metástasis de la Neoplasia , Proteína Quinasa C beta , Proteína Quinasa C-alfa , Proteína Quinasa C-epsilon , Tubulina (Proteína)/metabolismo , Células Tumorales Cultivadas
17.
Reg Immunol ; 3(2): 97-102, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-1965137

RESUMEN

In earlier work, we demonstrated that in vivo derived B16F10 tumor cells metastasize aggressively from intracameral (ic) and subcutanous (sc) sites, colonizing the lungs and lymph nodes. Natural killer (NK) cells play an important role in metastasis from ocular tumors. Treatment of mice with MoAb PK136, a highly specific anti-NK antibody, altered the pattern of metastasis; metastases appeared in the lungs, adrenal glands, liver, and spleen. Treatment with cyclophosphamide (Cy) did not affect survival or metastasis, but combined treatment with the immunomodulator Linomide (LS2616) and Cy decreased metastasis and increased survival. In the present study, we examine the role played by NK cells in regulating metastasis of sc tumors. Treatment of mice with LS2616 enhanced NK cell activity and decreased metastasis. Treatment with MoAb PK136 decreased survival and increased metastasis, but did not affect the pattern of metastasis. Treatment with 25 mg/kg Cy alone resulted in a decrease in growth of the primary tumor, increased survival, and decreased metastasis. Combined treatment with LS2616 and Cy was very effective in decreasing metastasis, increasing survival, and affecting cures (30%). In summary, our experiments demonstrate the importance of NK cells in regulating metastasis from sc tumors of in vivo derived B16F10 melanoma and demonstrate the effectiveness of LS2616 and low doses of Cy on metastasis and survival. In combination with earlier work, the present experiments demonstrate: 1) that modulation of NK activity differentially affects metastasis from sc and ic compartments, and 2) that regional differences in the location of the primary tumor may determine the effectiveness of treatment with Cy.


Asunto(s)
Células Asesinas Naturales/inmunología , Melanoma Experimental/secundario , Metástasis de la Neoplasia/inmunología , Animales , Cámara Anterior , Anticuerpos Monoclonales/inmunología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carragenina/uso terapéutico , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Femenino , Rayos gamma , Hidroxiquinolinas/administración & dosificación , Hidroxiquinolinas/uso terapéutico , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/patología , Inyecciones Subcutáneas , Células Asesinas Naturales/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/secundario , Masculino , Melanoma Experimental/inmunología , Melanoma Experimental/terapia , Ratones , Ratones Endogámicos C57BL/inmunología , Ratones Mutantes/inmunología , Trasplante de Neoplasias/métodos , Dióxido de Silicio/uso terapéutico , Análisis de Supervivencia
18.
Zentralbl Gynakol ; 112(3): 151-9, 1990.
Artículo en Alemán | MEDLINE | ID: mdl-2336890

RESUMEN

Binding capacity (Bmax) and affinity (Kd) of cytoplasmatic estradiol and progesteron receptors were determined in trophoblastic tissue and in decidual endometrium by the authors. Results in normal and pathological endometrium and in mature placenta tissue were compared. Both estrogen and progesteron receptors were proved to exist in the decidual endometrium nearest to the molar tissue. Their binding parameters are similar to those in normal endometrium. No progesterone receptors were found in the molar tissue. Binding capacity of estrogens were found to be similar to that of the normal mature placenta. The lack of progesterone receptors might be an etiological factor in the pathogenesis of trophoblast diseases.


Asunto(s)
Mola Hidatiforme/patología , Neoplasias Hormono-Dependientes/patología , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Neoplasias Uterinas/patología , Aborto Espontáneo/patología , Adulto , Decidua/patología , Endometrio/patología , Femenino , Humanos , Recién Nacido , Embarazo
19.
Invest Ophthalmol Vis Sci ; 30(9): 1909-15, 1989 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-2777511

RESUMEN

In the current study we examine parameters affecting the metastasis of ocular tumors of in vivo derived B16F10 melanoma. In C57BL/6J beige (bg/bg) mice, with low NK activity, metastasis to the lungs was increased and survival time decreased. In C57BL/6J normal (+/+) mice treatment with PK136, a highly specific monoclonal anti-NK antibody (Ab), caused a depletion of NK cytotoxic activity, as demonstrated using a standard 51Cr release assay. In animals bearing ocular tumors, treatment with PK136 Ab resulted in significantly increased pulmonary metastasis and an altered pattern of metastasis. The effect of combined treatment protocols using LS2616 (linomide) and cyclophosphamide (Cy) was examined in enucleated and unenucleated animals. Treatment with LS2616 and Cy resulted in a significant decrease in mean pulmonary metastases (MPM), a decreased frequency of metastasis to the submandibular lymph nodes and an increase in mean survival time. In enucleated mice this combined treatment protocol resulted in apparent cures, the lowest MPM and the longest survival time observed. When tumor-bearing mice were treated with either silica, carrageenan or sublethal gamma irradiation, no effect on metastasis or survival was observed. This study demonstrates the importance of the NK cell as a primary effector cell for the control of metastasis from in vivo derived ocular B16F10 melanoma.


Asunto(s)
Neoplasias del Ojo/inmunología , Células Asesinas Naturales/fisiología , Neoplasias Pulmonares/inmunología , Melanoma/inmunología , Adyuvantes Inmunológicos/farmacología , Animales , Anticuerpos Monoclonales , Ciclofosfamida/farmacología , Enucleación del Ojo , Neoplasias del Ojo/mortalidad , Neoplasias del Ojo/cirugía , Femenino , Hidroxiquinolinas/farmacología , Células Asesinas Naturales/efectos de los fármacos , Neoplasias Pulmonares/secundario , Masculino , Melanoma/mortalidad , Melanoma/secundario , Melanoma/cirugía , Ratones , Ratones Endogámicos C57BL
20.
Invest Ophthalmol Vis Sci ; 29(10): 1505-10, 1988 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-3170123

RESUMEN

In experiments using cultured cells, LS2616 has been shown to decrease growth of primary tumors and pulmonary metastasis of murine melanoma. In the current study, we examine the efficacy of LS2616 for the prophylactic and therapeutic treatment of metastases from ocular and flank inoculations of the highly aggressive in vivo derived B16F10 melanoma in C57BL/6J mice. Experimental animals were treated with 160 mg/kg/day of this drug in drinking water, until they became moribund or died. When mice were pretreated for 7 days and inoculated subcutaneously (sc) or intracamerally (ic) with 10(5) in vivo derived B16F10 tumor cells, the mean number of pulmonary metastases was significantly reduced, and the incidence of pulmonary metastases decreased. In ocular experiments, when pretreatment with drug was combined with enucleation at day 7, the mean number of lung nodules was significantly reduced, the incidence of metastasis to the lung and lymph nodes decreased and survival increased. An apparent cure rate of 31% was observed. Treatment beginning on the day of enucleation (day 7) resulted in a reduction of pulmonary metastases, a decrease in metastasis to the lungs and lymph nodes and no change in survival. LS2616 did not alter tumorigenicity of either sc or ic inoculations. In an in vivo neutralization assay, spleen cells of mice treated for 7 days with LS2616 demonstrated an increase in cytostatic or cytotoxic activity when incubated with B16F10 melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Neoplasias del Ojo/tratamiento farmacológico , Hidroxiquinolinas/uso terapéutico , Melanoma/tratamiento farmacológico , Animales , Enucleación del Ojo , Neoplasias del Ojo/fisiopatología , Neoplasias del Ojo/cirugía , Femenino , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/secundario , Masculino , Melanoma/fisiopatología , Melanoma/secundario , Ratones , Neoplasias Cutáneas/tratamiento farmacológico , Bazo/citología , Bazo/fisiología , Células Tumorales Cultivadas/fisiología
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