Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions

<p>Abstract</p> <p>Background</p> <p>Persistent high risk HPV infection can lead to cervical cancer, the second most common malignant tumor in women worldwide. NK cells play a crucial role against tumors and virus-infected cells through a fine balance between activating and inhibitory receptors. Expression of triggering receptors NKp30, NKp44, NKp46 and NKG2D on NK cells correlates with cytolytic activity against tumor cells, but these receptors have not been studied in cervical cancer and precursor lesions. The aim of the present work was to study NKp30, NKp46, NKG2D, NKp80 and 2B4 expression in NK cells from patients with cervical cancer and precursor lesions, in the context of HPV infection.</p> <p>Methods</p> <p>NKp30, NKp46, NKG2D, NKp80 and 2B4 expression was analyzed by flow cytometry on NK cells from 59 patients with cervical cancer and squamous intraepithelial lesions. NK cell cytotoxicity was evaluated in a 4 hour CFSE/7-AAD flow cytometry assay. HPV types were identified by PCR assays.</p> <p>Results</p> <p>We report here for the first time that NK cell-activating receptors NKp30 and NKp46 are significantly down-regulated in cervical cancer and high grade squamous intraepithelial lesion (HGSIL) patients. NCRs down-regulation correlated with low cytolytic activity, HPV-16 infection and clinical stage. NKG2D was also down-regulated in cervical cancer patients.</p> <p>Conclusion</p> <p>Our results suggest that NKp30, NKp46 and NKG2D down-regulation represent an evasion mechanism associated to low NK cell activity, HPV-16 infection and cervical cancer progression.</p

Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is the second most common cancer in women worldwide. NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Increased serum levels of MICA have been found in patients with epithelial tumors. The aim of this study was to compare the levels of soluble MICA (sMICA) and NKG2D-expressing NK and T cells in blood samples from patients with cervical cancer or precursor lesions with those from healthy donors.</p> <p>Methods</p> <p>Peripheral blood with or without heparin was collected to obtain mononuclear cells or sera, respectively. Serum sMICA levels were measured by ELISA and NKG2D-expressing immune cells were analyzed by flow cytometry. Also, a correlation analysis was performed to associate sMICA levels with either NKG2D expression or with the stage of the lesion.</p> <p>Results</p> <p>Significant amounts of sMICA were detected in sera from nearly all patients. We found a decrease in the number of NKG2D-expressing NK and T cells in both cervical cancer and lesion groups when compared to healthy donors. Pearson analysis showed a negative correlation between sMICA and NKG2D-expressing T cells; however, we did not find a significant correlation when the analysis was applied to sMICA and NKG2D expression on NK cells.</p> <p>Conclusion</p> <p>Our results show for the first time that high sMICA levels are found in sera from patients with both cervical cancer and precursor lesions when compared with healthy donors. We also observed a diminution in the number of NKG2D-expressing NK and T cells in the patient samples; however, a significant negative correlation between sMICA and NKG2D expression was only seen in T cells.</p

The debris-flow of Minatitlan (Colima, Mexico)

Presentazione oral

The large-scale debris avalanche from the Tancitaro Volcano (Mexico): characterization and modeling

The Tancitaro is an andesitic-dacitic stratovolcano located in the Michoacán Guanajuato volcanic field within the west-central portion of the trans-Mexican Volcanic Belt. The volcanism in this area is characterized by two composite volcanoes, the highest of which is the Tancitaro volcanic edifice (3840 m), some low angle lava cones and more than 1,000 monogenetic cinder cones. The distribution of the cinder cones is controlled by NE-SW active faults, although there are also additional faults with NNW-SSE trends along which some cones are aligned. The Tancitaro stratovolcano is located at the intersection of the tectonical structures that originate these alignments. All this geological activity has contributed to the gravitational instability of the volcano, leading to a huge sector collapse which produced the investigated debris avalanche. The collapse structure is an east-facing horseshoe-shaped crater (4 km wide and 5.3 km long), related with a large fan that was deposited within the Tepalcatepec depression. The deposit starts only 7 km downslope from the failure scar, it is 66 km long and covers an area of approximately 1155 km2. The landslide magnitude is about 20 km3 and it was firstly determined by the reconstruction of the paleo-edifice using a GIS software and then validated by the observation of significant outcrops. The fan was primarily formed by the deposit of this huge debris avalanche and subsequently by debris flow and fluvial deposits. Field investigations on the fan area highlighted the presence of two texturally distinct parts, which are referred to the 'block facies' and the 'matrix facies'. The first sedimentary structure is responsible for the typical hummock morphologies in the proximal area, as seen in many other debris avalanche deposits. Instead in the distal zones, the deposit is made up by the 'mixed block and matrix facies'. Blocks and megablocks, some of which are characterized by a jigsaw puzzle texture, gradually decrease in size until they disappear entirely in the most distal reaches. The granulometric analysis and the comparison between the debris avalanche of the Tancitaro and other collapses with similar morphometric features (vertical relief during runout, travel distance, volume and area of the deposit) indicate that the collapse was most likely not primed by any type of eruption, but rather triggered by a strong seismic shock that could have induced the failure of a portion of the edifice, already deeply altered by intense hydrothermal fluid circulation. It is also possible to hypothesize that mechanical fluidization may have been the mechanism controlling the long runout of the avalanche, as has been determined for other well-known events. The behavior of the Tancitaro debris avalanche was numerically modeled using the DAN-W code. By opportunely modifying the rheological parameters of the different models selectable within DAN, it was determined that the two-parameter 'Voellmy model' provides the best approximation of the avalanche movement. The Voellmy model produces the most realistic results in terms of runout distance, velocity and spatial distribution of the failed mass. Since the Tancitaro event was not witnessed directly, it is possible to infer approximate velocities only from comparisons with similar and documented events, namely the Mt. St. Helens debris avalanche occurred on May 18, 1980

Field investigation and modeling of a huge debris avalanche from Tancitaro Volcano (Mexico)

The Tancitaro (3840 m) is one of the highest volcanoes of the central portion of the Mexican Volcanic Belt. It is located in the SW sector of the Tarascan corridor, where two important types of volcanoes of quaternary age are observed: a single collapsed composite volcano (Tancitaro) surrounded by a field of monogenetic cinder cones. The distribution of the cinder cones is controlled by NE-SW faults, although there are also additional faults with NNW-SSE trends along which some cones are aligned. The Tancitaro stratovolcano is located at the intersection of the NW-SE and NE-SW structures. The Tancitaro is composed of andesitic to dacitic layers. From a morphological standpoint the volcano is characterized by U-shaped, glacially incised valleys, cut by an east-facing horseshoe-shaped crater. This collapse structure (4 km wide and 5.3 km long) is related with a large fan that was deposited within the Tepalcatepec depression starting only 7 km downslope from the failure scar. The fan was primarily formed by the deposit of this huge debris avalanche (˜18 km3) and subsequently by fluvial and debris flow deposits. It is 66 km long and covers an area of approximately 1155 km2. Field investigations on the fan area highlighted the presence of typical debris avalanche hummock morphologies in the proximal area. The hummocks are composed of structures ascribable to the so-called “block facies” seen in many other debris avalanche deposits (e.g. Capra et al., 2001). In the distal zones, blocks and megablocks, some of which are characterized by a jigsaw puzzle texture, gradually decrease in size until they disappear entirely in the most distal reaches; this portion of the deposit corresponds to the “mixed block and matrix facies” described by Glicken (1996) It was also possible to delimit a time frame for the occurrence of the Tancitaro debris avalanche by using an expeditious method of relative dating for the monogenic cinder cones of the area (Peña 1992). By combining this information with absolute dates from nearby deposits from previous studies (e.g. Scattolin, 1996) an upper temporal limit of approximately 4000 years was established. A lower limit was ascertained from geomorphologic and climatologic information. In fact, the debris avalanche cuts glacially incised valleys that date back to the most recent glaciological period, which occurred approximately 6000 - 10000 years BP. The age of the collapse can therefore be constrained to between 4000 and 10000 years BP. The comparison between the debris avalanche of the Tancitaro and other great collapses with similar morphometric features (vertical relief during runout, travel distance, volume and area of the deposit) indicate that the collapse was most likely not primed by any type of eruption, but rather triggered by a strong seismic shock that could have induced the failure of a portion of the edifice, already deeply altered by intense hydrothermal fluid circulation. It is also possible to hypothesize that mechanical fluidization (Hungr, 1990) may have been the mechanism controlling the long runout of the avalanche, as has been documented for other well-known events. The behavior of the Tancitaro debris avalanche was numerically modeled using the DAN code (Hungr, 1995). By opportunely modifying the rheological parameters of the different models selectable within DAN, it was determined that the two-parameter “Voellmy model” provides the best approximation of the avalanche movement. The Voellmy model produces the most realistic results in terms of runout distance, velocity and spatial distribution of the failed mass. It should be noted that although the Tancitaro event was not witnessed directly, it is possible to infer approximate velocities and overall dynamic behavior from comparisons with similar events, namely the Mt. St. Helens debris avalanche of 18 May 1980

Estudio preliminar de las caracteristicas morfologicas y geotecnicas de los flujos de avalancha del volcan el Tancitaro, en Michoacan, Mexico

Estudio preliminar de las caracteristicas morfologicas y geotecnicas de los flujos de avalancha del volcan el Tancitaro, en Michoacan, Mexic

The debris avalanche and debris flow from the Tancitaro volcano

In the SW sector of the Tarascan corridor we can observe two important volcanic activities, a composite collapsed volcano (Tancitaro) and a big concentration of monogenetical volcanoes. Both edified over granitic an andesitic bedrock. The NE-SW faults are the principal structures that control the distribution of the monogenetical volcanoes, but there is also NNW-SSE faulting with volcanic alineation. The Tancitaro volcano is located in the intersection of the NW-SE and NE-SW structures. The Tancitaro Volcano is one of the highest volcanoes in the central part of the Mexican Volcanic Belt (3840 msnm), is an andesitic to dacitic composite cone., its morphology is characterized also by U-shaped, glacially incised valleys, which are cut by an east-facing horseshoe-shaped crater. A big fan was deposited on the Tepalcatepec depression. The fan from the Tancitaro collapse is formed by fluvial, debris avalanche and debris flow deposit. It is 60 km large and has an area of approximately 176 km2. If we consider that the last glacial period was 10000 and 6000 years ago and that the Tancitaro collapse structures cut the glacial valleys the debris avalanche belongs to an Holocene deposit. A Morphological and mapped study was performed in the fan deposit and show two important flows, the first is formed by a debris avalanche and the second corresponds to a debris flow

Analysis and modeling of the Tancitaro debris avalanche (Mexico)

The Tancitaro (3840 m asl) is one of the highest volcanoes of the central portion of the Mexican Volcanic Belt. It is located in the SW sector of the Tarascan corridor, where two important types of volcanoes of quaternary age are observed: a single composite stratovolcano (Tancitaro) surrounded by a field of monogenetic cinder cones the distribution of which is mainly controlled by NE-SW trending faults. The Tancitaro is located at the intersection of the above-mentioned faults with the NW-SE trending structures of the Chapala-Oaxaca fault zone. Morphologically the volcano is characterized by a large east-facing horseshoe-shaped crater (4 km wide and 5.3 km long). This collapse structure can be related to a large deposit that occupies the Tepalcatepec tectonic depression starting from 7 km below the crater. The deposit, which also comprises a fan, appears to have been primarily formed by a huge debris avalanche (~18 km3) and by fluvial and debris flow deposits. From the head of the displaced material to the toe of the fan the deposit is 66 km long and covers an area of approximately 1155 km2. Field investigations on the fan area highlighted that the debris avalanche body is composed of unstratified and unsorted rubble with angular clasts ranging in size from millimetric to metric. It contains megablocks many tens of meters wide that create typical debris avalanche hummock morphologies in the proximal area. The hummocks are composed of structures ascribable to the so-called "block facies" seen in many other debris avalanche deposits (e.g. Capra et al., 2001). In the distal zones, blocks and mega-blocks, some of which are characterized by a "jigsaw" texture, gradually decrease in size until they disappear entirely in the most distal reaches; this portion of the deposit corresponds to the "mixed block and matrix facies" described by Glicken (1996). Recent studies (Ownby, et al., 2007) have used radiocarbon dating techniques that indicate that the landslide occurred between 261 and 238 ka BP. The comparison between the debris avalanche of the Tancitaro and other great collapses with similar morphometric characteristics (vertical relief during runout, travel distance, volume and area of the deposit) indicate that the collapse was most likely not primed by any type of eruption, but rather triggered by an intense seismic shock that could have induced the failure of a portion of the edifice, already deeply altered by intense hydrothermal fluid circulation. It is also possible to hypothesize that mechanical fluidization (Hungr, 1990) may have been the mechanism controlling the long runout of the avalanche. Numerical modeling was performed to study the behavior of the Tancitaro debris avalanche using DAN, a code developed by Hungr (1995). In this software it is possible to select the most appropriate rheological kernel for the event being studied. Trial-and-error analyses indicated that the two-parameter "Voellmy model" provides the best approximation of the Tancitaro avalanche movement. This model produces the most realistic results in terms of runout distance, velocity and spatial distribution of the failed mass. Approximate velocities and overall dynamic behavior of the debris avalanche were inferred from comparisons with similar events, mainly the Mt. St. Helens debris avalanche of 18 May 1980