Clinical and epidemiological characteristics of breast cancer metastases

Introduction. Breast cancer is a highly variable disease, and long-term outcomes for individual patients are difficult to predict. We evaluated a retrospective cohort of early stage breast cancer (ESBC) patients based on a variety of clinical and epidemiological factors, specifically looking at the distribution of metastasis and associations with these clinical and epidemiological factors. ^ Methods. Patients were derived from the Early Stage Breast Cancer Repository (ESBCR) with a breast cancer diagnosed between 1985 and 2000. We conducted univariate and multivariate analysis of the data to evaluate associations between characteristics and occurrence of overall, visceral, and bone metastasis. Visceral metastasis was defined as lung, liver, peritoneal, lymph node (thoracic, abdominal, pelvis), and contralateral breast cancer. ^ Results. Overall, 394 (16%) patients developed a metastasis. Of these, 83% were visceral and 17% were bone. Multivariate analyses identified the following variables to be associated with metastasis: Any metastasis: age at diagnosis, stage, ER/PR status, hormone treatment, and type of surgery (1)Visceral metastasis: age at diagnosis, stage, hormone treatment, and type of surgery (2) Bone metastasis –Alcohol use, stage, and ER/PR status ^ Discussion/conclusion. ER-/PR- status has previously been found to be associated with bone metastasis, as we confirm in our cohort. We report an association between alcohol use and bone metastasis whereas previous studies find an association with recurrence. Distribution of metastases varies from previous studies. Typically, previous studies reported bone metastasis >30%, yet our study found 17%. Previous studies varied in design, and definition of visceral metastasis. Future research is needed to further elucidate prognostic factors associated with specific metastases A more thorough understanding of what might predict which ESBC patients will develop metastases can help direct future treatment. Future studies of this nature could include the Perou intrinsic subtypes, biomarkers like Ki-67, and genetic analyses such as Oncotype DX or MammaPrint.^

Design, Synthesis and Development of Transporter Targeting Agents for Image-guided Therapy and Drug Delivery

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with 99mTc and 68Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both 99mTc-N4amG and 99mTc-GP were stable up to 6 hours, whereas 68Ga-GP was stable up to 2 hours. Cell culture studies confirmed radiolabeled N4amG and GP could penetrate the cell membrane through nucleoside transporters and amino acid transporters, respectively. Up to 40% of intracellular 99mTc-N4amG and 99mTc-GP was found within cell nucleus following 2 hours of incubation. Flow cytometry analysis revealed 99mTc-N4amG was a cell cycle S phase-specific agent. There was a significant difference of the uptake of 99mTc-GP between pre- and post- paclitaxel-treated cells, which suggests that 99mTc-GP may be useful in chemotherapy treatment monitoring. Moreover, radiolabeled N4amG and GP were tested in vivo using tumor-bearing animal models. 99mTc-N4amG showed an increase in tumor-to-muscle count density ratios up to 5 at 4 hour imaging. Both 99mTc-labeled agents showed decreased tumor uptake after paclitaxel treatment. Immunohistochemistry analysis demonstrated that the uptake of 99mTc-N4amG was correlated with Ki-67 expression. Both 99mTc-N4amG and 99mTc-GP could differentiate between tumor and inflammation in animal studies. Furthermore, 68Ga-GP was compared to 18F-FDG in rabbit PET imaging studies. 68Ga-GP had lower tumor standardized uptake values (SUV), but similar uptake dynamics, and different biodistribution compared with 18F-FDG. Finally, to demonstrate that GP can be a potential drug carrier for cancer theranostics, several drugs, including doxorubicin, were selected to be conjugated to GP. Imaging studies demonstrated that tumor uptake of GP-drug conjugates was increased as a function of time. GP-doxorubicin (GP-DOX) showed a slow-release pattern in in vitro cytotoxicity assay and exhibited anti-cancer efficacy with reduced toxicity in in vivo tumor growth delay study. In conclusion, both N4amG and GP are transporter-based targeting agents. Radiolabeled N4amG can be used for tumor cell proliferation assessment. GP is a potential agent for image-guided therapy and drug delivery.

Thermal conductivity at DSDP Leg 60 Holes

A total of 1547 thermal conductivity values were determined by both the NP (needle probe method) and the QTM (quick thermal conductivity meter) on 1319 samples recovered during DSDP Leg 60. The NP method is primarily for the measurement of soft sedimentary samples, and the result is free from the effect of porewater evaporation. Measurement by the QTM method is faster and is applicable to all types of samples-namely, sediments (soft, semilithified, and lithified) and basement rocks. Data from the deep holes at Sites 453, 458, and 459 show that the thermal conductivity increases with depth, the rate of increase ranging from (0.18 mcal/cm s °C)/100 m at Site 459 to (0.72 mcal/cm s °C)/100 m at Site 456. A positive correlation between the sedimentary accumulation rate and the rate of thermal conductivity increase with depth indicates that both compaction and lithification are important factors. Drilled pillow basalts show nearly uniform thermal conductivity. At She 454 the thermal conductivity of one basaltic flow unit was higher near the center of the unit and lower toward the margin, reflecting variable vesicularity. Hydrothermally altered basalts at Site 456 showed higher thermal conductivity than fresh basalt because secondary calcite, quartz, and pyrite are generally more thermally conductive than fresh basalt. The average thermal conductivity in the top 50 meters of sediments correlates inversely with water depth because of dissolution of calcite, a mineral with high thermal conductivity, from the sediments as the water depth exceeds the lysocline and the carbonate compensation depth. Differences between the Mariana Trench data and the Mariana Basin and Trough data may reflect different abundances of terrigenous material in the sediment. There are remarkable correlations between thermal conductivity and other physical properties. The relationship between thermal conductivity and compressional wave velocity can be used to infer the ocean crustal thermal conductivity from the seismic velocity structure.

Description of two mass species of Pacific copepods in terms of two polymorphic loci

Population genetics of two species of mass copepods Undinula darwini and Calanus australis, with different range types, is investigated. Both species exhibit considerable genetic diversity, especially C. australis (observed heterozygoticity = 0.36), which inhabits a variable biotope in the zone of the Peru current. Samples of both species exhibited highly significant genetic heterogeneity as well as heterozygote deficiency compared with the situation expected from the Hardy-Weinberg law. Contribution of distance isolation to genetic differentiation of populations is estimated. Gene drift is discussed as a source of heterogeneity in populations of planktic copepods. Possible aspects of population genetic research on marine plank-tic crustaceans are discussed.

(Tables 1, 2) Permafrost borehole characteristics in the Nordic Area during the IPY 2007-2009

This paper provides a snapshot of the permafrost thermal state in the Nordic area obtained during the International Polar Year (IPY) 2007-2009. Several intensive research campaigns were undertaken within a variety of projects in the Nordic countries to obtain this snapshot. We demonstrate for Scandinavia that both lowland permafrost in palsas and peat plateaus, and large areas of permafrost in the mountains are at temperatures close to 0°C, which makes them sensitive to climatic changes. In Svalbard and northeast Greenland, and also in the highest parts of the mountains in the rest of the Nordic area, the permafrost is somewhat colder, but still only a few degrees below the freezing point. The observations presented from the network of boreholes, more than half of which were established during the IPY, provide an important baseline to assess how future predicted climatic changes may affect the permafrost thermal state in the Nordic area. Time series of active-layer thickness and permafrost temperature conditions in the Nordic area, which are generally only 10 years in length, show generally increasing active-layer depths and rising permafrost temperatures.

Accumulation rates and grain sizes of eolian dust in sediments of the Intertropical Convergence Zone in the northeast Pacific

A 328 cm-long piston core (KODOS 02-01-02) collected from the northeast equatorial Pacific at 16°12'N, 125°59'W was investigated for eolian mass fluxes and grain sizes to test these proxies as a tool for the paleo-position of the Intertropical Convergence Zone (ITCZ). The eolian mass fluxes of the lower interval below 250 cm (15.5-7.6 Ma) are very uniform at 5 +/- 1 mg/cm**2/kyr, while those of the upper interval above 250 cm (from 7.6 Ma) are over 2 times higher than the lower interval at 12 +/- 1 mg/cm**2/kyr. The median grain size of the eolian dusts in the lower interval increases from 8.4 Phi to 8.0 Phi downward, while that of the upper interval varies in a narrow range from 8.8 Phi to 8.6 Phi. The determined values compare well in magnitude to those of central Pacific sediments for the upper interval and equatorial and southeast Pacific sediments for the lower interval. This result suggests a possibility that the study site had been under the influence of southeast trade winds at its earlier depositional period due to the northerly position of the ITCZ, and subsequently of the northeast trade winds for a later period when the upper sediments were deposited. This interpretation is consistent with a mineralogical and geochemical study published elsewhere that assigned the provenance of the study core dust to Central/South America for the lower interval and to Asia for the upper interval. This study suggests that the distinct differences in eolian mass flux and grain size observed across the ITCZ can be used to trace the paleo-latitude of the ITCZ.