Stable isotopes and Mg/Ca ratios on foraminifera and Ba/Ca ratios of sediment core SK168/GC-1

The past variability of the South Asian Monsoon is mostly known from records of wind strength over the Arabian Sea while high-resolution paleorecords from regions of strong monsoon precipitation are still lacking. Here, we present records of past monsoon variability obtained from sediment core SK 168/GC-1, which was collected at the Alcock Seamount complex in the Andaman Sea. We utilize the ecological habitats of different planktic foraminiferal species to reconstruct freshwater-induced stratification based on paired Mg/Ca and d18O analyses and to estimate seawater d18O (d18Osw). The difference between surface and thermocline temperatures (delta T) and d18Osw (delta d18Osw) is used to investigate changes in upper ocean stratification. Additionally, Ba/Ca in G. sacculifer tests is used as a direct proxy for riverine runoff and sea surface salinity (SSS) changes related to monsoon precipitation on land. Our delta d18Osw time series reveals that upper ocean salinity stratification did not change significantly throughout the last glacial suggesting little influence of NH insolation changes. The strongest increase in temperature gradients between the mixed layer and the thermocline is recorded for the mid-Holocene and indicate the presence of a significantly shallower thermocline. In line with previous work, the d18Osw and Ba/Ca records demonstrate that monsoon climate during the LGM was characterized by a significantly weaker southwest monsoon circulation and strongly reduced runoff. Based on our data the South Asian Summer Monsoon (SAM) over the Irrawaddyy strengthened gradually after the LGM beginning at ~18 ka. This is some 3 kyrs before an increase of the Ba/Ca record from the Arabian Sea and indicates that South Asian Monsoon climate dynamics are more complex than the simple N-S displacement of the ITCZ as generally described for other regions. Minimum d18Osw values recorded during the mid-Holocene are in phase with Ba/Ca marking a stronger monsoon precipitation, which is consistent with model simulations.

Isotope and Mg/Ca measurements from Cores ME0005A-43JC and 202-1242 of tropical Pacific

Multiproxy geologic records of d18O and Mg/Ca in fossil foraminifera from sediments under the Eastern Pacific Warm Pool (EPWP) region west of Central America document variations in upper ocean temperature, pycnocline strength, and salinity (i.e., net precipitation) over the past 30 kyr. Although evident in the paleotemperature record, there is no glacial-interglacial difference in paleosalinity, suggesting that tropical hydrologic changes do not respond passively to high-latitude ice sheets and oceans. Millennial variations in paleosalinity with amplitudes as high as 4 practical salinity units occur with a dominant period of 3-5 ky during the glacial/deglacial interval and 1.0-1.5 ky during the Holocene. The amplitude of the EPWP paleosalinity changes greatly exceeds that of published Caribbean and western tropical Pacific paleosalinity records. EPWP paleosalinity changes correspond to millennial-scale climate changes in the surface and deep Atlantic and the high northern latitudes, with generally higher (lower) paleosalinity during cold (warm) events. In addition to Intertropical Convergence Zone (ITCZ) dynamics, which play an important role in tropical hydrologic variability, changes in Atlantic-Pacific moisture transport, which is closely linked to ITCZ dynamics, may also contribute to hydrologic variations in the EPWP. Calculations of interbasin salinity average and interbasin salinity contrast between the EPWP and the Caribbean help differentiate long-term changes in mean ITCZ position and Atlantic-Pacific moisture transport, respectively.

Biogenic components, major, trace and rare earth elements of equatorial Pacific Ocean surface sediments (Table 1)

We have analyzed the major, trace, and rare earth element composition of surface sediments collected from a transect across the Equator at 135°W longitude in the Pacific Ocean. Comparing the behavior of this suite of elements to the CaCO3, opal, and Corg fluxes (which record sharp maxima at the Equator, previously documented at the same sampling stations) enables us to assess the relative significance of the various pathways by which trace elements are transported to the equatorial Pacific seafloor. The 1. (1) high biogenic source at the Equator, associated with equatorial divergence of surface water and upwelling of nutrient-rich water, and 2. (2) high aluminosilicate flux at 4°N, associated with increased terrigenous input from elevated rainfall at the Intertropical Convergence Zone (ITCZ) of the tradewinds, are the two most important fluxes with which elemental transport is affiliated. The biogenic flux at the Equator transports Ca and Sr structurally bound to carbonate tests and Mn primarily as an adsorbed component. Trace elements such as Cr, As, Pb, and the REEs are also influenced by the biogenic flux at the Equator, although this affiliation is not regionally dominant. Normative calculations suggest that extremely large fluxes of Ba and P at the Equator are carried by only small proportions of barite and apatite phases. The high terrigenous flux at the ITCZ has a profound effect on chemical transport to the seafloor, with elemental fluxes increasing tremendously and in parallel with Ti. Normative calculations, however, indicate that these fluxes are far in excess of what can be supplied by lattice-bound terrigenous phases. The accumulation of Ba is greater than is affiliated with biogenic transport at the Equator, while the P flux at the ITCZ is only 10% less than at the Equator. This challenges the common view that Ba and P are essentially exclusively associated with biogenic fluxes. Many other elements (including Mn, Pb, As, and REEs) also record greater accumulation beneath the ITCZ than at the Equator. Thus, adsorptive scavenging by terrigenous paniculate matter, or phases intimately associated with them, appears to be an extremely important process regulating elemental transport to the equatorial Pacific seafloor. These findings emphasize the role of vertical transport to the sediment, and provide additional constraints on the paleochemical use of trace elements to track biogenic and terrigenous fluxes.

(Table 1) AMS 14C dates from sediment cores RC12-10 and GYRE97-6PV-20

Proxy records from two piston cores in the Gulf of Mexico (GOM) provide a detailed (50-100 year resolution) record of climate variability over the last 14,000 years. Long-term (millennial-scale) trends and changes are related to the transition from glacial to interglacial conditions and movement of the average position of the Intertropical Convergence Zone (ITCZ) related to orbital forcing. The d18O of the surface-dwelling planktic foraminifer Globigerinoides ruber show negative excursions between 14 and 10.2 ka (radiocarbon years) that reflect influx of meltwater into the western GOM during melting of the Laurentide Ice Sheet. The relative abundance of the planktic foraminifer Globigerinoides sacculifer is related to transport of Caribbean water into the GOM. Maximum transport of Caribbean surface waters and moisture into the GOM associated with a northward migration of the average position of the ITCZ occurs between about 6.5 and 4.5 ka. In addition, abundance variations of G. sacculifer show century-scale variability throughout most of the Holocene. The GOM record is consistent with records from other areas, suggesting that century-scale variability is a pervasive feature of Holocene climate. The frequency of several cycles in the climate records is similar to cycles identified in proxy records of solar variability, indicating that at least some of the century-scale climate variability during the Holocene is due to external (solar) forcing.

Pollen and spore counts of sediment core GeoB12624

In tropical eastern Africa, vegetation distribution is largely controlled by regional hydrology, which has varied over the past 20 000 years. Therefore, accurate reconstructions of past vegetation and hydrological changes are crucial for a better understanding of climate variability in the tropical southeastern African region. We present high-resolution pollen records from a marine sediment core recovered offshore of the Rufiji River delta. Our data document significant shifts in pollen assemblages during the last deglaciation, identifying, through changes in both upland and lowland vegetation, specific responses of plant communities to atmospheric (precipitation) and coastal (coastal dynamics and sea-level changes) alterations. Specifically, arid conditions reflected by a maximum pollen representation of dry and open vegetation occurred during the Northern Hemisphere cold Heinrich event 1 (H1), suggesting that the expansion of drier upland vegetation was synchronous with cold Northern Hemisphere conditions. This arid period is followed by an interval in which forest and humid woodlands expanded, indicating a hydrologic shift towards more humid conditions. Droughts during H1 and the shift to humid conditions around 14.8 kyr BP in the uplands are consistent with latitudinal shifts of the intertropical convergence zone (ITCZ) driven by high-latitude Northern Hemisphere climatic fluctuations. Additionally, our results show that the lowland vegetation, consisting of well-developed salt marshes and mangroves in a successional pattern typical for vegetation occurring in intertidal habitats, has responded mainly to local coastal dynamics related to marine inundation frequencies and soil salinity in the Rufiji Delta as well as to the local moisture availability. Lowland vegetation shows a substantial expansion of mangrove trees after ~ 14.8 kyr BP, suggesting an increased moisture availability and river runoff in the coastal area. The results of this study highlight the decoupled climatic and environmental processes to which the vegetation in the uplands and the Rufiji Delta has responded during the last deglaciation.

Delta 44/40 Ca, Mg/Ca and Sr/Ca record of Globigerinoides sacculifer and calculated temperatures and salinity changes of ODP Hole 165-999A

The delta18O values of planktonic foraminifera increased in the Caribbean by about 0.5? relative to the equatorial East Pacific values between 4.6 and 4.2 Ma as a consequence of the closure of the Central American Gateway (CAG). This increase in delta18O can be interpreted either as an increase in Caribbean sea surface (mixed layer) salinity (SSS) or as a decrease in sea surface temperatures (SST). This problem represents an ideal situation to apply the recently developed paleotemperature proxy delta44/40Ca together with Mg/Ca and d18O on the planktic foraminifer Globigerinoides sacculifer from ODP Site 999. Although differences in absolute temperature calibration of delta44/40Ca and Mg/Ca exist, the general pattern is similar indicating a SST decrease of about 2-3 8C between 4.4 and 4.3 Ma followed by an increase in the same order of magnitude between 4.3 and 4.0 Ma. Correcting the delta18O record for this temperature change and assuming that changes in global ice volume are negligible, the salinity-induced planktonic delta18O signal decreased by about 0.4? between 4.4 and 4.3 Ma and increased by about 0.9? between 4.3 and 4.0 Ma in the Caribbean. The observed temperature and salinity trends are interpreted to reflect the restricted exchange of surface water between the Caribbean and the Pacific in response to the shoaling of the Panamanian Seaway, possibly accompanied by a southward shift of the Intertropical Convergence Zone (ITCZ) between 4.4 and 4.3 Ma. Differences in Mg/Ca- and delta44/40Ca-derived temperatures can be reconciled by corrections for secular variations of the marine Mg/Ca[sw] and delta44/40Ca, a salinity effect on the Mg/Ca ratio and a constant temperature offset of ~2.5 °C between both SST proxy calibrations.

(Table 1) Age control points and of sediment core MD01-2444

The marine isotopic stage 3 (MIS3) at Ocean Drilling Program (ODP) Site 1060 (Gulf Stream) shows both sharp onset and end of interstadials, the existence of very short lived warm events during stadials, and points to differences in detail between the sea surface temperature (SST) record from the western North Atlantic and the atmospheric temperature record inferred from d18O in Greenland ice. Investigating MIS3 and obtaining comparable data from other locations appears crucial. The eastern Atlantic provides well-documented records of climate changes. We have selected a core from off Portugal and use it to examine Dansgaard/Oeschger events (D/O) at centennial-scale resolution (139 years on average between two data points). We have obtained a faunal data set for core MD01-2444, 37°N, 10°W, 2600 m water depth and use a group of species (Globigerina bulloides + Globigerinita glutinata) as a proxy of upwelling intensity driven by trade winds intensity changes. We tentatively relate the variation of this group to a North Atlantic Oscillation-like phenomenon (NAO) off Portugal. We observe that it resembles the rainfall index in the Caribbean as recorded at ODP Site 1002 (Cariaco Basin) which traces the Intertropical Convergence Zone (ITCZ) location through changes of terrigenous inputs. The driest intervals (ITZC to the south) at Site 1002 correspond to intervals of increased upwelling in MD01-2444 as well as the driest periods identified during stadials on similar cores in the area. Because the ITZC to the south is consistent with an El Niño-Southern Oscillation (ENSO+) situation, our study suggests a positive correlation between ENSO-like conditions and NAO-like conditions at a millennial timescale. During interstadial intervals when increased wetness over Cariaco is recorded (ITCZ to the north) and the upwelling in MD01-2444 is decreased, we see from both SSTs and faunal tropical indicators that MD01-2444 site is warm. In addition, interstadials are equally warm through each so-called Bond cycle. This contrasts with the Greenland Ice Core Project (GRIP) record where interstadial peaks are successively cooler through each Bond cycle. This record confirms a link between tropical climate linked to ITCZ position and the climate of southern Europe at millennial timescales, in spite of showing a very good correlation with polar latitudes (GRIP) through d18O on Globigerina bulloides. In addition, because the warmest SSTs and the d18O on G. bulloides are so remarkably different, our work points to changes in seasonality as a strong control over the climatic pattern of the North Atlantic area and the marked influence of winter conditions.

Grain size distribution and bulk chemistry of eolian dust

Atmospheric dust samples collected along a transect off the West African coast have been investigated for their physical (grain-size distribution), mineralogical, and chemical (major elements) composition. On the basis of these data the samples were grouped into sets of samples that most likely originated from the same source area. In addition, shipboard-collected atmospheric meteorological data, modeled 4-day back trajectories for each sampling day and location, and Total Ozone Mapping Spectrometer aerosol index data for the time period of dust collection (February-March 1998) were combined and used to reconstruct the sources of the groups of dust samples. On the basis of these data we were able to determine the provenance of the various dust samples. It appears that the bulk of the wind-blown sediments that are deposited in the proximal equatorial Atlantic Ocean are transported in the lower level (>~900 hPa) NE trade wind layer, which is a very dominant feature north of the Intertropical Convergence Zone (ITCZ). However, south of the surface expression of the ITCZ, down to 5°S, where surface winds are southwesterly, we still collected sediments that originated from the north and east, carried there by the NE trade wind layer, as well as by easterly winds from higher altitudes. The fact that the size of the wind-blown dust depends not only on the wind strength of the transporting agent but also on the distance to the source hampers a direct comparison of the dust's size distributions and measured wind strengths. However, a comparison between eolian dust and terrigenous sediments collected in three submarine sediment traps off the west coast of NW Africa shows that knowledge of the composition of eolian dust is a prerequisite for the interpretation of paleorecords obtained from sediment cores in the equatorial Atlantic.

Dissolved Iron, Aluminium, and Dissolved Inorganic Phosphorus in the (Sub-)Tropical Atlantic Surface Ocean

Inorganic nitrogen depletion restricts productivity in much of the low-latitude oceans, generating a selective advantage for diazotrophic organisms capable of fixing atmospheric dinitrogen (N2). However, the abundance and activity of diazotrophs can in turn be controlled by the availability of other potentially limiting nutrients, including phosphorus (P) and iron (Fe). Here we present high-resolution data (~0.3°) for dissolved iron, aluminum, and inorganic phosphorus that confirm the existence of a sharp north-south biogeochemical boundary in the surface nutrient concentrations of the (sub)tropical Atlantic Ocean. Combining satellite-based precipitation data with results from a previous study, we here demonstrate that wet deposition in the region of the intertropical convergence zone acts as the major dissolved iron source to surface waters. Moreover, corresponding observations of N2 fixation and the distribution of diazotrophic Trichodesmium spp. indicate that movement in the region of elevated dissolved iron as a result of the seasonal migration of the intertropical convergence zone drives a shift in the latitudinal distribution of diazotrophy and corresponding dissolved inorganic phosphorus depletion. These conclusions are consistent with the results of an idealized numerical model of the system. The boundary between the distinct biogeochemical systems of the (sub)tropical Atlantic thus appears to be defined by the diazotrophic response to spatial-temporal variability in external Fe inputs. Consequently, in addition to demonstrating a unique seasonal cycle forced by atmospheric nutrient inputs, we suggest that the underlying biogeochemical mechanisms would likely characterize the response of oligotrophic systems to altered environmental forcing over longer timescales.

Sedimentology of sites 14-141, 41-366, 47-397 and 79-544B

Along the N-S-transect of DSDP-Sites 5446, 397, 141, and 366, oxygen and carbon isotopes, flux rates of calcium carbonate, terrigenous matter, and biogenic opal, clay minerals and the size distribution of terrigenous partictes were determined in order to assess the ties between atmospheric and oceanic surface and deep-water circulation off northwest Africa during the late Neogene. During the last 9 m.y., both the paleoceanography in the eastern Atlantic and west African paleodimates were intimately correlated with the evolution of the polar ice sheets as reflected in the benthos d18O curves of the 4 DSDP-Sites. These records make it possible to distinguish six major time intervals which were charaterized by long-term persistent regimes of climatic stability or climatic change. Short-term, "Milankovitch"-type cycles superimpose the long-term climatic evolution and may reflect the chronostratigraphic control fluctuations of the solar insolation persisting back to pre-Pleistocene times. Relatively stable, warm climates prevailed during the late Tortonian/early Messinean, 9 to 6 m.y., and the early Pliocene, 4.5 to 3.5 m.y. ago. Based on d18O curves, the amplitudes of short-term climatic variation were generally low, and the ice sheets were smaller than during peak Holocene time. Oceanic circulation and resulting paleoproductivity in upwelling zones were insignificant. The strength of dust supplying meridional trade winds was low (3 to 5 m/s), interglacial-style zonal winds near the ITCZ were dominant, as indicated by the high abundance of kaolinite. Phases of fluvial sediment supply were common. Humidity was characteristic of the climate in northwest Africa for the major part of this time. Major episodes of climatic deterioration in the subtropics occurred in the latest Miocene/early Pliocene, between some 5.6 and 5.2 and between 4.9 and 4.6 m.y. ago, in the late Pliocene, between 3.2 and 2.4 m.y. ago, and again in the Quaternary, near 1 m.y. ago. The episodes were correlated with marked increases of the global ice volume, as revealed by drastic increases of d18O values. They suggest sea-level falls of up to 70 m below the present sea level in the latest Miocene and earliest Pliocene and of 145 m in the latest Pliocene and Quaternary. The climatic changes resulted in strongly enhanced meridional trade winds as suggested by coarser terrigenous grain-sizes, increased mass accumulation rates of eolian dust, and changes in clay-mineral composition from dominantly kaolinite to illite and chlorite. The meridional trade winds reached speeds of 8 to 10 m/s with a maximum near 15 m/s. The enhanced winds probably led t o intensified coastal upwelling as shown by the contemporaneous local increase i n the deposition of biogenic silica and the local depletion of 13C at Site 397. The most drastic environmental changes near 2.4 and 1 m.y. ago coincide with hiatuses which may indicate phases of general erosion due to strongly enhanced deep-water circulation in the northeast At1antic along the northwest African continental margin. The occasional occurrence of quartz grains coarser than 250 µm may suggest ice-rafted debris in sediments off Morocco. During these time intervals the climate in NW-Africa was dominantly arid. Nevertheless, fluvial runoff (and humidity) continued to be important during intermittent warm phases of the short-term climatic cycles. During the end and the beginning of (inter-) glacial times, fluvial supply of nutrients seems to be the dominant factor, controling phases of enhanced paleoproductivity observed off northwest Africa, whereas during phases of glacial maximum strenger fertility of (increased) coastal upwelling becomes more important. A long-term evolution of paleoenvironments during the last 40 m.y. is depicted in the sediments of Site 366 and is clearly controlled by the plate tectonic route of this Site. During Oligocene times, Site 366 lay in the center of the equatorial upwelling, as shown by the high content of biogenic silica contributing up to 100 % of the carbonate-free sediment fraction >6 µm. The influence of equatorial upwelling abruptly terminated near 15 m.y. ago, a change in the record exaggerated by a hiatus of about 2 m.y. Prior to 25 m.y., the terrigenous input at the paleolatitude of Site 366 was restricted t o eolian sediment supply from South Africa by southeasterly trade winds, as shown by dominantly illite and chlorite in the clay fraction and extremely fine-grained terrigenous matter. Near the Oligocene/Miocene boundary, Site 366 drifted across the equator into the belt of the northeasterly trade winds, which is inferred from the increased content of kaolinite and coarser grain sizes of the terrigenous sediment fraction. The clay-mineral and grain-size compositions of Site 366 do not reflect a noteworthy northward shift of the ITCZ during late Miocene and early Pliocene times, i.e. no marked global circulation asymmetry due to the possible absence of a major Northern Hemisphere glaciation (Flohn 1981). This lack of a more northerly position of the ITCZ may result from a bipolar glaciation already existing during late Miocene times, such as also suggested by the evidence of tillites on Iceland and in southern Alaska during those intervals (e.g., Denton & Amstrong 1969, Mudie & Helgason 1983).

Global oceanic precipitation: A joint view by TOPEX and the TOPEX microwave radiometer

The TOPEX/POSEIDON mission offers the first opportunity to observe rain cells over the ocean by a dual-frequency radar altimeter (TOPEX) and simultaneously observe their natural radiative properties by a three-frequency radiometer (TOPEX microwave radiometer (TMR)). This work is a feasibility study aimed at understanding the capability and potential of the active/passive TOPEX/TMR system for oceanic rainfall detection. On the basis of past experiences in rain flagging, a joint TOPEX/TMR rain probability index is proposed. This index integrates several advantages of the two sensors and provides a more reliable rain estimate than the radiometer alone. One year's TOPEX/TMR TMR data are used to test the performance of the index. The resulting rain frequency statistics show quantitative agreement with those obtained from the Comprehensive Ocean-Atmosphere Data Set (COADS) in the Intertropical Convergence Zone (ITCZ), while qualitative agreement is found for other regions of the world ocean. A recent finding that the latitudinal frequency of precipitation over the Southern Ocean increases steadily toward the Antarctic continent is confirmed by our result. Annual and seasonal precipitation maps are derived from the index. Notable features revealed include an overall similarity in rainfall pattern from the Pacific, the Atlantic, and the Indian Oceans and a general phase reversal between the two hemispheres, as well as a number of regional anomalies in terms of rain intensity. Comparisons with simultaneous Global Precipitation Climatology Project (GPCP) multisatellite precipitation rate and COADS rain climatology suggest that systematic differences also exist. One example is that the maximum rainfall in the ITCZ of the Indian Ocean appears to be more intensive and concentrated in our result compared to that of the GPCP. Another example is that the annual precipitation produced by TOPEX/TMR is constantly higher than those from GPCP and COADS in the extratropical regions of the northern hemisphere, especially in the northwest Pacific Ocean. Analyses of the seasonal variations of prominent rainy and dry zones in the tropics and subtropics show various behaviors such as systematic migration, expansion and contraction, merging and breakup, and pure intensity variations, The seasonality of regional features is largely influenced by local atmospheric events such as monsoon, storm, or snow activities. The results of this study suggest that TOPEX and its follow-on may serve as a complementary sensor to the special sensor microwave/imager in observing global oceanic precipitation.

Pipkiiα Is Widely Expressed In Hematopoietic-derived Cells And May Play A Role In The Expression Of Alpha- And Gamma-globins In K562 Cells.

Characterized for the first time in erythrocytes, phosphatidylinositol phosphate kinases (PIP kinases) belong to a family of enzymes that generate various lipid messengers and participate in several cellular processes, including gene expression regulation. Recently, the PIPKIIα gene was found to be differentially expressed in reticulocytes from two siblings with hemoglobin H disease, suggesting a possible relationship between PIPKIIα and the production of globins. Here, we investigated PIPKIIα gene and protein expression and protein localization in hematopoietic-derived cells during their differentiation, and the effects of PIPKIIα silencing on K562 cells. PIPKIIα silencing resulted in an increase in α and γ globins and a decrease in the proliferation of K562 cells without affecting cell cycle progression and apoptosis. In conclusion, using a cell line model, we showed that PIPKIIα is widely expressed in hematopoietic-derived cells, is localized in their cytoplasm and nucleus, and is upregulated during erythroid differentiation. We also showed that PIPKIIα silencing can induce α and γ globin expression and decrease cell proliferation in K562 cells.

Obesity And Inflammation And The Effect On The Hematopoietic System.

Bone marrow is organized in specialized microenvironments known as 'marrow niches'. These are important for the maintenance of stem cells and their hematopoietic progenitors whose homeostasis also depends on other cell types present in the tissue. Extrinsic factors, such as infection and inflammatory states, may affect this system by causing cytokine dysregulation (imbalance in cytokine production) and changes in cell proliferation and self-renewal rates, and may also induce changes in the metabolism and cell cycle. Known to relate to chronic inflammation, obesity is responsible for systemic changes that are best studied in the cardiovascular system. Little is known regarding the changes in the hematopoietic system induced by the inflammatory state carried by obesity or the cell and molecular mechanisms involved. The understanding of the biological behavior of hematopoietic stem cells under obesity-induced chronic inflammation could help elucidate the pathophysiological mechanisms involved in other inflammatory processes, such as neoplastic diseases and bone marrow failure syndromes.

Antiangiogenic And Finasteride Therapies: Responses Of The Prostate Microenvironment In Elderly Mice.

The aim of this study was to evaluate the structural and molecular effects of antiangiogenic therapies and finasteride on the ventral prostate of senile mice. 90 male FVB mice were divided into: Young (18 weeks old) and senile (52 weeks old) groups; finasteride group: finasteride (20mg/kg); SU5416 group: SU5416 (6 mg/kg); TNP-470 group: TNP-470 (15 mg/kg,) and SU5416+TNP-470 group: similar to the SU5416 and TNP-470 groups. After 21 days, prostate ventral lobes were collected for morphological, immunohistochemical and Western blotting analyses. The results demonstrated atrophy, occasional proliferative lesions and inflammatory cells in the prostate during senescence, which were interrupted and/or blocked by treatment with antiangiogenic drugs and finasteride. Decreased AR and endostatin reactivities, and an increase for ER-α, ER-β and VEGF, were seen in the senile group. Decreased VEGF and ER-α reactivities and increased ER-β reactivity were verified in the finasteride, SU5416 groups and especially in SU5416+TNP-470 group. The TNP-470 group showed reduced AR and ER-β protein levels. The senescence favored the occurrence of structural and/or molecular alterations suggesting the onset of malignant lesions, due to the imbalance in the signaling between the epithelium and stroma. The SU5416+TNP-470 treatment was more effective in maintaining the structural, hormonal and angiogenic factor balance in the prostate during senescence, highlighting the signaling of antiproliferation via ER-β.

Egfr Activating Mutations And Their Association With Response To Platinum-doublet Chemotherapy In Brazilian Non-small Cell Lung Cancer Patients.

The aim of the study was to analyze the frequency of epidermal growth factor receptor (EGFR) mutations in Brazilian non-small cell lung cancer patients and to correlate these mutations with response to benefit of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Our cohort consisted of prospective patients with NSCLCs who received chemotherapy (platinum derivates plus paclitaxel) at the [UNICAMP], Brazil. EGFR exons 18-21 were analyzed in tumor-derived DNA. Fifty patients were included in the study (25 with adenocarcinoma). EGFR mutations were identified in 6/50 (12 %) NSCLCs and in 6/25 (24 %) adenocarcinomas; representing the frequency of EGFR mutations in a mostly self-reported White (82.0 %) southeastern Brazilian population of NSCLCs. Patients with NSCLCs harboring EGFR exon 19 deletions or the exon 21 L858R mutation were found to have a higher chance of response to platinum-paclitaxel (OR 9.67 [95 % CI 1.03-90.41], p = 0.047). We report the frequency of EGFR activating mutations in a typical southeastern Brazilian population with NSCLC, which are similar to that of other countries with Western European ethnicity. EGFR mutations seem to be predictive of a response to platinum-paclitaxel, and additional studies are needed to confirm or refute this relationship.