bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Targeted Nanomedicines: Enhanced Antitumor Efficacy In vivo of Doxorubicin-Loaded, Long-Circulating Liposomes Modified with Cancer-Specific Monoclonal Antibody
Authors: ElBayoumi Tamer A. , Torchilin Vladimir P. 
Published: March 2009

Abstract
Purpose: The efficacy of drug delivery systems can be enhanced by making them target specific via the attachment of various ligands. We attempted to enhance tumor accumulation and therapeutic effect of doxorubicin-loaded, long-circulating, polyethylene glycol–coated liposomes (Doxil, ALZA Corp.) by coupling to their surface the anticancer monoclonal antibody (mAb) 2C5 with nucleosome-restricted activity that can recognize the surface of various tumors but not normal cells and specifically targets pharmaceutical carriers to tumor cells in vitro and in vivo. Following earlier in vitro results with various cancer cell lines, the mAb 2C5 liposomes were studied in vivo versus plain and nonspecific-IgG liposomes.
Experimental Design: Antibody coupling to Doxil was done via the “postinsertion” technique. Using 111In-labeled liposomes, the tissue biodistribution and pharmacokinetic profile were studied, as well as their accumulation in tumors in mice, followed by the whole-body γ-scintigraphic imaging. Therapeutic efficacy of mAb 2C5–targeted Doxil versus nonspecific IgG–modified and original Doxil controls was followed by registering live tumor growth and determining tumor weights upon mice sacrifice.
Results: mAb 2C5–targeted liposomes showed enhanced accumulation in tumors, and the in vivo therapeutic activity of the mAb 2C5–Doxil treatment was found to be significantly superior, resulting in final tumor weights of only 25% to 40% compared with all Doxil control treatments, when tested against the s.c. primary murine tumors of 4T1 and C26 and human PC3 tumor in nude mice.
Conclusions: Our results showed the remarkable capability of 2C5-targeted Doxil to specifically deliver its cargo into various tumors, significantly increasing the efficacy of therapy.
Estrogen-related receptor-α antagonist inhibits both estrogen receptor–positive and estrogen receptor–negative breast tumor growth in mouse xenografts
Authors: Chisamore Michael J. , Wilkinson Hilary A. , Flores Osvaldo , Chen J. Don 
Published: March 2009

Abstract
Estrogen-related receptors (ERR) are orphan members of the nuclear receptor superfamily most closely related to estrogen receptors (ER). Although ERα is a successful target for treating breast cancer, there remains an unmet medical need especially for estrogen-independent breast cancer. Although estradiol is not an ERR ligand, ER and ERR share many commonalities and overlapping signaling pathways. An endogenous ERR ligand has not been identified; however, novel synthetic ERRα subtype–specific antagonists have started to emerge. In particular, we recently identified a novel compound, N-[(2Z)-3-(4,5-dihydro-1,3-thiazol-2-yl)-1,3-thiazolidin-2-yl idene]-5H dibenzo[a,d][7]annulen-5-amine (termed compound A) that acts specifically as an ERRα antagonist. Here, we show that compound A inhibited cell proliferation in ERα-positive (MCF-7 and T47D) and ERα-negative (BT-20 and MDA-MD-231) breast cancer cell lines. Furthermore, we report the differential expression of 83 genes involved in ERRα signaling in MCF-7 and BT-20 breast cancer cell lines. We show that compound A slowed tumor growth in MCF-7 and BT-20 mouse xenograft models, and displayed antagonistic effects on the uterus. Furthermore, a subset of genes involved in ERRα signaling in vitro were evaluated and confirmed in vivo by studying uterine gene expression profiles from xenograft mice. These results suggest for the first time that inhibition of ERRα signaling via a subtype-specific antagonist may be an effective therapeutic strategy for ER-positive and ER-negative breast cancers. [Mol Cancer Ther 2009;8(3):672–81]
Claudin-7 Regulates EpCAM-Mediated Functions in Tumor Progression
Authors: Nübel Tobias , Preobraschenski Julia , Tuncay Hüseyin , Weiss Tobias , Kuhn Sebastian , Ladwein Markus , Langbein Lutz , Zöller Margot 
Published: March 2009

Abstract
EpCAM has been described as a therapeutically relevant tumor marker. We noted an interaction between EpCAM and the tight junction protein claudin-7 and here explored the nature of this interaction and its effect on EpCAM-mediated functions. The interaction between EpCAM and claudin-7 was defined in HEK293 cells transfected with rat claudin-7 and EpCAM cDNA. Deletions of the epidermal growth factor–like and the thyroglobin repeat domains of EpCAM or the cytoplasmic domain of EpCAM or claudin-7 did not prevent the EpCAM-claudin-7 association. A chimeric EpCAM molecule with an exchange of the cytoplasmic and transmembrane domains and an EpCAM molecule with point mutations in an AxxxG motif in the transmembrane region do not associate with claudin-7. HEK cells and the rat pancreatic tumor line BSp73AS, transfected with (mutated) EpCAM and claudin-7 cDNA, revealed that the association of both molecules severely alters the functional activity of EpCAM. Claudin-7–associated EpCAM is recruited into tetraspanin-enriched membrane microdomains (TEM). The TEM-located claudin-7-EpCAM complex supports proliferation accompanied by sustained extracellular signal–regulated kinase-1/2 phosphorylation, up-regulation of antiapoptotic proteins, and drug resistance, but not EpCAM-mediated cell-cell adhesion. Enhanced motility may be supported by colocalization of claudin-7 with actin bundles, which is only seen in EpCAM-claudin-7–expressing cells. The EpCAM-claudin-7 complex strongly promotes tumorigenicity, accelerates tumor growth, and supports ascites production and thymic metastasis formation.
High expression of the tumor marker EpCAM is frequently associated with poor prognosis, which could well rely on the EpCAM-claudin-7 association that prohibits EpCAM-mediated cell-cell adhesion but promotes migration, proliferation, apoptosis resistance, and tumorigenicity. (Mol Cancer Res 2009;7(3):285–99)
Drought-Driven Changes in Lake Areas and Their Effects on the Surface Energy Balance of Minnesota’s Lake-Dotted Landscape
Authors: Plank Colin , Shuman Bryan 
Published: March 2009

Abstract
Open water within Minnesota constitutes 11 830 km2 and represents a significant proportion of the moisture available on the landscape. Because lakes absorb and store heat in the spring and summer, and release heat in the autumn and winter, they also play a significant role in surface energy budgets. Lake areas fluctuate significantly over time, and thus alter surface albedo and energy partitioning in the expanding and contracting lake margin. Observations of lake areas from the 1930s “Dust Bowl” drought were used to approximate the impact of changes in lake area and volume on surface energy budgets. A statewide map of lake area change constructed from historical aerial photos of 620 lakes shows trends in percent area changes that mimic trends in moisture balance. Based on the aerial photos and an analysis of lake bathymetries, the water volume removed from the land exposed around the lakes during the drought was 9.1 ± 3.0 × 109 m3. The total area of exposed land was 3300 ± 800 km2. Based on a balanced energy budget estimate, the transition from standing water to exposed land at lake margins accounted for 1.12 ± 0.31 × 1011 W of energy storage across the state. The decreased heat storage resulted in a statewide average storage flux anomaly of 0.50 ± 0.14 W m−2 with localized anomalies as high as 33.9 ± 7.1 W m−2. Large uncertainties exist, however, regarding the partitioning of the energy because of the wide range of potential albedo values for both land and water. As conditions warmed during the twentieth century, lake volumes have increased. Therefore, the assessment herein of the change in heat storage is relevant to comparisons of high regional temperatures in the 1930s and 2000s.
A Verified Estimation of the El Niño Index Niño-3.4 since 1877
Authors: Bunge Lucia , Clarke Allan J. 
Published: March 2009

Abstract
Decadal and longer time-scale variabilities of the best known El Niño–Southern Oscillation (ENSO) indexes are poorly correlated before 1950, and so knowledge of interdecadal variability and trend in ENSO indexes is dubious, especially before 1950. To address this problem, the authors constructed and compared physically related monthly ENSO indexes. The base index was El Niño index Niño-3.4, the sea surface temperature (SST) anomaly averaged over the equatorial box bounded by 5°N, 5°S, 170°W, and 120°W; the authors also constructed indexes based on the nighttime marine air temperature over the Niño-3.4 region (NMAT3.4) and an equatorial Southern Oscillation index (ESOI). The Niño-3.4 index used the “uninterpolated” sea surface temperature data from the Second Hadley Centre Sea Surface Temperature dataset (HadSST2), a dataset with smaller uncertainty and better geographical coverage than others. In constructing the index, data at each point for a given month were weighted to take into account the typical considerable spatial variation of the SST anomaly over the Niño-3.4 box as well as the number of observations at that point for that month. Missing monthly data were interpolated and “noise” was reduced by using the result that Niño-3.4 has essentially the same calendar month amplitude structure every year. This 12-point calendar month structure from April to March was obtained by an EOF analysis over the last 58 yr and then was fitted to the entire monthly time series using a least squares approach. Equivalent procedures were followed for NMAT3.4 and ESOI. The new ESOI uses Darwin atmospheric pressure in the west and is based on theory that allows for variations of the atmospheric boundary layer depth across the Pacific.
The new Niño-3.4 index was compared with NMAT3.4, the new ESOI, and with a record of δ18O from a coral at Palmyra, an atoll inside the region Niño-3.4 (Cobb et al.). Correlation coefficients between Niño-3.4 and the three monthly indexes mentioned above before 1950 are 0.84, 0.87, 0.73 and 0.93, 0.86, 0.73 for decadal time scales. These relatively high correlation coefficients between physically related but independent monthly time series suggest that this study has improved knowledge of low-frequency variability. All four indexes are consistent with a rise in Niño-3.4 SST and the weakening of the equatorial Pacific winds since about 1970.
Upper-Ocean Thermal Structure and the Western North Pacific Category 5 Typhoons. Part II: Dependence on Translation Speed
Authors: Lin I-I. , Pun Iam-Fei , Wu Chun-Chieh 
Published: March 2009

Abstract
Using new in situ ocean subsurface observations from the Argo floats, best-track typhoon data from the U.S. Joint Typhoon Warning Center, an ocean mixed layer model, and other supporting datasets, this work systematically explores the interrelationships between translation speed, the ocean’s subsurface condition [characterized by the depth of the 26°C isotherm (D26) and upper-ocean heat content (UOHC)], a cyclone’s self-induced ocean cooling negative feedback, and air–sea enthalpy fluxes for the intensification of the western North Pacific category 5 typhoons. Based on a 10-yr analysis, it is found that for intensification to category 5, in addition to the warm sea surface temperature generally around 29°C, the required subsurface D26 and UOHC depend greatly on a cyclone’s translation speed. It is observed that even over a relatively shallow subsurface warm layer of D26 ∼ 60–70 m and UOHC ∼ 65–70 kJ cm−2, it is still possible to have a sufficient enthalpy flux to intensify the storm to category 5, provided that the storm can be fast moving (typically Uh ∼ 7–8 m s−1). On the contrary, a much deeper subsurface layer is needed for slow-moving typhoons. For example at Uh ∼ 2–3 m s−1, D26 and UOHC are typically ∼115–140 m and ∼115–125 kJ cm−2, respectively. A new concept named the affordable minimum translation speed Uh_min is proposed. This is the minimum required speed a storm needs to travel for its intensification to category 5, given the observed D26 and UOHC. Using more than 3000 Argo in situ profiles, a series of mixed layer numerical experiments are conducted to quantify the relationship between D26, UOHC, and Uh_min. Clear negative linear relationships with correlation coefficients R = −0.87 (−0.71) are obtained as Uh_min = −0.065 × D26 + 11.1, and Uh_min = −0.05 × UOHC + 9.4, respectively. These relationships can thus be used as a guide to predict the minimum speed a storm has to travel at for intensification to category 5, given the observed D26 and UOHC.
Gram-positive bacteria enhance HIV-1 susceptibility in Langerhans cells, but not in dendritic cells, via Toll-like receptor activation
Authors: Ogawa Youichi , Kawamura Tatsuyoshi , Kimura Tetsuya , Ito Masahiko , Blauvelt Andrew , Shimada Shinji 
Published: March 2009

Abstract
Although numerous studies have shown a higher risk of acquiring HIV infection in the presence of other sexually transmitted diseases, the biologic mechanisms responsible for enhanced HIV acquisition are unclear. Because Langerhans cells (LCs) are suspected to be the initial HIV targets after sexual exposure, we studied whether microbial components augment HIV infection in LCs by activating Toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD) pattern recognition receptors. We found that TLR1/2 and TLR2/6 agonists dramatically enhanced both HIV susceptibility and replication in immature monocyte-derived LCs, whereas TLR3-5, TLR7-9, and NOD1,2 agonists did not significantly affect HIV infection. The same infection-enhancing effects were observed when LCs were incubated with other related bacterial components as well as with whole Gram+ bacteria. In resident LCs in human skin, TLR2 agonists also significantly increased HIV susceptibility. By contrast, TLR2 agonists and related bacterial components decreased HIV susceptibility in monocyte-derived dendritic cells (DCs). We found that TLR2 activation of LCs, but not DCs, resulted in a significant down-regulation of APOBEC3G, which is a cellular restriction factor for HIV. Given these data, we hypothesize that ligation of TLR2 by Gram+ bacterial products may underlie enhanced sexual transmission of HIV that occurs with concomitant bacterial sexually transmitted disease infections.
Common susceptibility alleles are unlikely to contribute as strongly as the FV and ABO loci to VTE risk: results from a GWAS approach
Authors: Trégouët David-Alexandre , Heath Simon , Saut Noémie , Biron-Andreani Christine , Schved Jean-François , Pernod Gilles , Galan Pilar , Drouet Ludovic , Zelenika Diana , Juhan-Vague Irène , Alessi Marie-Christine , Tiret Laurence , Lathrop Mark , Emmerich Joseph , Morange Pierre-Emmanuel 
Published: March 2009

Abstract
Venous thromboembolism (VTE) is a complex disease that has a major genetic component of risk. To identify genetic factors that may modify the risk of VTE, we conducted a genome-wide association study by analyzing approximately 317 000 single nucleotide polymorphisms (SNPs) in 453 VTE cases and 1327 controls. Only 3 SNPs located in the FV and ABO blood group genes were found associated with VTE at a genome-wide significant level of 1.7 × 10−7. Detailed analysis of these SNPs in additional cohorts of more than 1700 cases and 1400 controls revealed that the association observed at the FV locus was the result of the increased risk mediated by the FV Leiden mutation, whereas O and A2 blood groups were found to be at lower risk for VTE. Apart from the FV and ABO loci, no other locus was found strongly associated with VTE. However, using this large cohort of subjects, we were able to replicate the mild effects of 2 nonsynonymous SNPs, rs1613662 in GP6 and rs13146272 in CYP4V2, recently suspected to be associated with VTE.
Quarantine for pandemic influenza control at the borders of small island nations
Authors: Nishiura Hiroshi , Wilson Nick , Baker Michael G 
Published: March 2009

Abstract

Background
Although border quarantine is included in many influenza pandemic plans, detailed guidelines have yet to be formulated, including considerations for the optimal quarantine length. Motivated by the situation of small island nations, which will probably experience the introduction of pandemic influenza via just one airport, we examined the potential effectiveness of quarantine as a border control measure.

Methods
Analysing the detailed epidemiologic characteristics of influenza, the effectiveness of quarantine at the borders of islands was modelled as the relative reduction of the risk of releasing infectious individuals into the community, explicitly accounting for the presence of asymptomatic infected individuals. The potential benefit of adding the use of rapid diagnostic testing to the quarantine process was also considered.

Results
We predict that 95% and 99% effectiveness in preventing the release of infectious individuals into the community could be achieved with quarantine periods of longer than 4.7 and 8.6 days, respectively. If rapid diagnostic testing is combined with quarantine, the lengths of quarantine to achieve 95% and 99% effectiveness could be shortened to 2.6 and 5.7 days, respectively. Sensitivity analysis revealed that quarantine alone for 8.7 days or quarantine for 5.7 days combined with using rapid diagnostic testing could prevent secondary transmissions caused by the released infectious individuals for a plausible range of prevalence at the source country (up to 10%) and for a modest number of incoming travellers (up to 8000 individuals).

Conclusion
Quarantine at the borders of island nations could contribute substantially to preventing the arrival of pandemic influenza (or at least delaying the arrival date). For small island nations we recommend consideration of quarantine alone for 9 days or quarantine for 6 days combined with using rapid diagnostic testing (if available).
Characterization of STAT3 activation and expression in canine and human osteosarcoma
Authors: Fossey Stacey L , Liao Albert T , McCleese Jennifer K , Bear Misty D , Lin Jiayuh , Li Pui-Kai , Kisseberth William C , London Cheryl A 
Published: March 2009

Abstract

Background
Dysregulation of signal transducer and activator of transcription 3 (STAT3) has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA) tissues and cell lines. OSA in the canine population is known to exhibit a similar clinical behavior and molecular biology when compared to its human counterpart, and is often used as a model for preclinical testing of novel therapeutics. The purpose of this study was to investigate the potential role of STAT3 in canine and human OSA, and to evaluate the biologic activity of a novel small molecule STAT3 inhibitor.

Methods
To examine STAT3 and Src expression in OSA, we performed Western blotting and RT-PCR. OSA cells were treated with either STAT3 siRNA or small molecule Src (SU6656) or STAT3 (LLL3) inhibitors and cell proliferation (CyQUANT), caspase 3/7 activity (ELISA), apoptosis (Western blotting for PARP cleavage) and/or viability (Wst-1) were determined. Additionally, STAT3 DNA binding after treatment was determined using EMSA. Expression of STAT3 targets after treatment was demonstrated with Western blotting, RT-PCR, or gel zymography.

Results
Our data demonstrate that constitutive activation of STAT3 is present in a subset of canine OSA tumors and human and canine cell lines, but not normal canine osteoblasts. In both canine and human OSA cell lines, downregulation of STAT3 activity through inhibition of upstream Src family kinases using SU6656, inhibition of STAT3 DNA binding and transcriptional activities using LLL3, or modulation of STAT3 expression using siRNA, all resulted in decreased cell proliferation and viability, ultimately inducing caspase-3/7 mediated apoptosis in treated cells. Furthermore, inhibition of either Src or STAT3 activity downregulated the expression of survivin, VEGF, and MMP2, all known transcriptional targets of STAT3.

Conclusion
These data suggest that STAT3 activation contributes to the survival and proliferation of human and canine OSA cells, thereby providing a potentially promising target for therapeutic intervention. Future investigational trials of LLL3 in dogs with spontaneous OSA will help to more accurately define the role of STAT3 in the clinical setting.
Morbidity, demography and life style of Hungarian medical doctors 25 years after graduation
Authors: Rurik Imre , Kalabay László 
Published: March 2009

Az egészségügyi dolgozók életmódját, egészségi állapotát, szociális körülményeit világszerte vizsgálják. A kelet-európai országokban kevés vizsgálat történt ebben a témakörben, és még kevesebbet publikáltak. Ez a tanulmány megpróbálja összehasonlítani az orvosok egészségi állapotát, a szakmai pálya jellemzőit és néhány szociológiai tényezőt 25 évvel a diplomaszerzés után. Az eredményeket nemek között és szakmai csoportok (alapellátási, manuális, nem manuális és diagnosztikus) között hasonlították össze. A Semmelweis Orvostudományi Egyetemen 1979-ben végzett 228 orvos válaszolt a kérdőívben megadott kérdésekre. Több férfi választott manuális szakmát, míg a nők körében az alapellátási szakmák voltak népszerűbbek. A nők gyakrabban kényszerültek munkahelyük vagy szakterületük módosítására, mint a férfiak. A férfi orvosok átlagos gyerekszáma 2,26, míg a nőké 1,87 volt. A legnagyobb testsúlynövekedést az alapellátási szakmát választó férfiak és a nem manuális szakmát űző női orvosok körében regisztrálták. A magas vérnyomás és a rendszeres szűrővizsgálatok elhanyagolása gyakoribb volt a férfiak körében, akik nem mindig voltak megfelelően kezelve. A fizikai aktivitás és a sportra fordított idő jelentősen csökkent a végzés után, és a kedvelt sportok is gyakran mások voltak. A női orvosok fontosabbnak tartották a rendszeres testedzést. A dohányzás főleg a manuális szakmát űző férfiak és az alapellátásban dolgozó nők körében volt gyakoribb. A manuális szakmában dolgozók és a nem manuális szakmájú nők gyakrabban fogyasztottak alkoholt. Ha betegek voltak, a férfiak megbízhatóbban követték a kezelőorvos tanácsait. Az orvosok saját egészségi állapotukat jobbnak ítélték, mint hasonló korú betegeikét. Idegen nyelveket a férfiak nagyobb arányban beszéltek. Az évfolyamból a válaszadók 10%-a szerzett tudományos fokozatot.
Rural Perceptions of Continuing Professional Education
Authors: Jukkala Angela M. , Henly Susan J. , Lindeke Linda L. 
Published: March 2009

Background:
This study describes rural health care professionals' perceptions about professional isolation and the availability, accessibility, and relevance of continuing education.

Methods:

Registered nurses (
n
= 165) and physicians (
n
= 59) providing health care services in 26 rural hospitals in two Midwestern states participated in the study.

Results:
Rural health care providers experience barriers to accessing relevant continuing education. Although physicians reported higher levels of professional isolation than their nurse counterparts, professional isolation was identified as a concern by both provider groups.

Conclusions:
To ensure an adequate supply of knowledgeable and skillful rural health care professionals, continuing education specific to the delivery of care in rural settings is necessary. Once developed, the continuing education must be delivered in a manner that is acceptable and accessible to isolated rural providers.

J Contin Educ Nurs
2008;39(12):555–563.