bluuebunny/crossref_metadata_2025_split huggingface dataset:
ECSA/DPPA2 is an Embryo-Cancer Antigen that Is Coexpressed with Cancer-Testis Antigens in Non–Small Cell Lung Cancer
Authors: John Thomas , Caballero Otavia L. , Svobodová Suzanne J. , Kong Alan , Chua Ramon , Browning Judy , Fortunato Sheila , Deb Siddhartha , Hsu Melinda , Gedye Craig A. , Davis Ian D. , Altorki Nasser , Simpson Andrew J. , Chen Yao-Tseng , Monk Marilyn , Cebon Jonathan S. 
Published: June 2008

Abstract
Purpose: Cancer cells recapitulate many behaviors of pluripotent embryonic cells such as unlimited proliferation, and the capacity to self-renew and to migrate. Embryo-cancer sequence A (ECSA), later named developmental pluripotency associated-2 (DPPA2), is an embryonic gene initially isolated from pluripotent human preimplantation embryos. We hypothesized that ECSA/DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy.
Experimental Design: ECSA/DPPA2 expression was examined in a panel of normal and tumor tissue by reverse transcription PCR, quantitative real-time PCR, and immunohistochemistry. A panel of 110 non–small cell lung cancers (NSCLC) were further investigated for the presence of ECSA/DPPA2 transcripts and several cancer testis antigens (CTA). Sera from 104 patients were analyzed for spontaneous ECSA/DPPA2 antibody production by ELISA and Western blot.
Results: ECSA/DPPA2 transcripts were limited to normal testis, placenta, bone marrow, thymus, and kidney but expressed in a variety of tumors most notably in 30% of NSCLC. Enrichment for CTAs in ECSA/DPPA2-positive NSCLC was observed. Immunohistochemistry confirmed nuclear and cytoplasmic localization in subpopulations of cells with coexpression of the CTA MAGE-A3. Antibodies to recombinant ECSA/DPPA2 protein were detected in the sera of 4 of 104 patients with NSCLC but not in healthy controls.
Conclusions: The restricted expression in normal tissues, expression in tumors with coexpression of CTAs, and spontaneous immunogenicity indicate that ECSA/DPPA2 is a promising target for antigen-specific immunotherapy in NSCLC.
Prognostic Significance of Defective Mismatch Repair and BRAF V600E in Patients with Colon Cancer
Authors: French Amy J. , Sargent Daniel J. , Burgart Lawrence J. , Foster Nathan R. , Kabat Brian F. , Goldberg Richard , Shepherd Lois , Windschitl Harold E. , Thibodeau Stephen N. 
Published: June 2008

Abstract
Purpose: Colon tumors with defective DNA mismatch repair (dMMR) have a well-characterized phenotype and accounts for ∼15% to 20% of sporadic colon cancer as well as those colon cancer patients with Lynch syndrome. Although the presence of dMMR seems to be a favorable prognostic marker, data suggest that these patients do not respond as well to adjuvant chemotherapy.
Experimental Design: In this study, we examined the prognostic significance of tumor MMR deficiency and the presence of a specific mutation in BRAF (V600E) in a group of patients (n = 533) who participated in a randomized prospective clinical trial through the North Central Cancer Treatment Group.
Results: Tumors with dMMR were found to be associated with higher tumor grade (P = 0.001), proximal location (P &lt; 0.0001), and improved overall and disease-free survival (P = 0.05 and 0.04, respectively). Among all cases examined, evaluation of the BRAF V600E mutation status revealed no statistically significant differences in either disease-free or overall survival. Patients were then grouped into four categories for further analysis: dMMR/BRAF(−), dMMR/BRAF(+), pMMR/BRAF(−), and pMMR/BRAF(+). The dMMR/BRAF(−) group had a significantly improved overall survival (5-year overall survival of 100% versus 73%, P = 0.002) compared with all others. The remaining three groups had very similar survival outcomes. An additional cohort of tumors previously classified as having dMMR were also tested for the BRAF V600E alteration. Results remained significant (P = 0.006) when the two groups were combined for analysis.
Conclusions: Overall, these data suggest that the underlying molecular etiology of those tumors having dMMR may influence the disease outcome in these patients.
Matrix metalloproteinase-9 Inhibition Down-Regulates Radiation-Induced Nuclear Factor-κB Activity Leading to Apoptosis in Breast Tumors
Authors: Kunigal Sateesh , Lakka Sajani S. , Joseph Pushpa , Estes Norman , Rao Jasti S. 
Published: June 2008

Abstract
Purpose: Novel strategies are needed to prevent the high mortality rates of several types of cancer. These high rates stem from tumor resistance to radiation therapy, which is thought to result from the induction of matrix metalloproteinases (MMP) and plasminogen activators. In the present study, we show that the modulation of MMP-9 expression, using adenoviral-mediated transfer of the antisense MMP-9 gene (MMP-9 adenoviral construct, Ad-MMP-9), affects breast cancer sensitivity to radiation.
Experimental Design: In the present study, we used antisense Ad-MMP-9 to down-regulate the expression of MMP-9 in MDA MB 231 breast cancer cell lines in vitro before irradiation and subsequently incubated cells in hypoxic condition. In vivo studies were done with orthotopic breast tumors, and radiosensitivity was evaluated both in vitro and in vivo.
Results: Ad-MMP-9 infection resulted in down-regulation of radiation-induced levels of hypoxia-inducible factor 1α and MMP-9 under hypoxic conditions in MDA MB 231 breast cancer cells. In addition, Ad-MMP-9, in combination with radiation, decreased levels of the transcription factors nuclear factor-κB and activator protein 1, both of which contribute to the radioresistance of breast tumors. Finally, the triggering of the Fas–Fas ligand apoptotic cascade, which resulted in the cleavage of PARP-1 and caspase-10, caspase-3, and caspase-7, signifies the efficiency of combined treatment of Ad-MMP-9 and radiation. Treatment with Ad-MMP-9 plus radiation completely regressed tumor growth in orthotopic breast cancer model.
Conclusions: In summary, integrating gene therapy (adenovirus-mediated inhibition of MMP-9) with radiotherapy could have a synergistic effect, thereby improving the survival of patients with breast cancer.
Mutant Epidermal Growth Factor Receptor in Benign, Borderline, and Malignant Ovarian Tumors
Authors: Steffensen Karina Dahl , Waldstrøm Marianne , Olsen Dorte Aalund , Corydon Thomas , Lorentzen Karen Axelgaard , Knudsen Hans Jørgen , Jeppesen Ulla , Brandslund Ivan , Jakobsen Anders 
Published: June 2008

Abstract
Purpose: Dysfunction of the epidermal growth factor (EGF) complex is essential to the growth and development of many human tumors. Overexpression of the EGF receptor (EGFR) is a characteristic finding in a considerable number of solid tumors and often signalizes poor prognosis. There is a major disagreement among researchers about both the frequency and possible clinical importance of EGFR overexpression in ovarian cancer. The type III variant of EGFR (EGFRvIII) is a mutant with a deletion. Contrary to the wild-type, it is constitutively active. EGFRvIII has not been found in normal tissue, and consequently, it is an attractive tumor-specific candidate for molecular targeted treatment. The literature dealing with this mutation in ovarian cancer has been very sparse.
Experimental Design: Tissue from 225 patients who underwent surgery for a pelvic mass was collected consecutively. The samples included 99 ovarian/peritoneal/tuba cancers, 17 ovarian borderline tumors, 66 benign ovarian tumors, 15 other cancer types, 24 normal ovarian biopsies, and 4 miscellaneous. The presence of EGFRvIII was investigated both by PCR analyses for EGFRvIII gene expression and with protein analysis by Western blots.
Results: None of the tissue samples was positive for the EGFRvIII mutation neither at the mRNA level nor at the protein level.
Conclusions: The EGFRvIII mutation seems to be very rare in ovarian tissue. Our data indicate that EGFRvIII is not a part of the malignant phenotype in ovarian cancer and should not be pursued as a therapeutic target for treatment of this disease.
Evaluation of the Pharmacodynamic Effects of MGCD0103 from Preclinical Models to Human Using a Novel HDAC Enzyme Assay
Authors: Bonfils Claire , Kalita Ann , Dubay Marja , Siu Lillian L. , Carducci Michael A. , Reid Gregory , Martell Robert E. , Besterman Jeffrey M. , Li Zuomei 
Published: June 2008

Abstract
Purpose: The pharmacodynamic properties of MGCD0103, an isotype-selective inhibitor of histone deacetylase (HDAC), were evaluated in preclinical models and patients with a novel whole-cell HDAC enzyme assay.
Experimental Design: Boc-Lys(ε-Ac)-AMC, a HDAC substrate with fluorescent readout, was found to be cell permeable and was used to monitor MGCD0103-mediated HDAC inhibition in cultured cancer cells in vitro, in peripheral WBC ex vivo, in mice in vivo, and in human patients.
Results: MGCD0103 inhibited HDAC activity in several human cancer cell lines in vitro and in human peripheral WBC ex vivo in a dose-dependent manner. Unlike suberoylanilide hydroxamic acid, the HDAC inhibitory activity of MGCD0103 was time dependent and sustained for at least 24 hours following drug removal in peripheral WBC ex vivo. Inhibitory activity of MGCD0103 was sustained for at least 8 hours in vivo in mice and 48 hours in patients with solid tumors. HDAC inhibitory activity of MGCD0103 in peripheral WBC correlated with induction of histone acetylation in blood and in implanted tumors in mice. In cancer patients, sustained pharmacodynamic effect of MGCD0103 was visualized only by dose-dependent enzyme inhibition in peripheral WBC but not by histone acetylation analysis.
Conclusions: This study shows that MGCD0103 has sustained pharmacodynamic effects that can be monitored both in vitro and in vivo with a cell-based HDAC enzyme assay.
AP1-Dependent Galectin-1 Expression Delineates Classical Hodgkin and Anaplastic Large Cell Lymphomas from Other Lymphoid Malignancies with Shared Molecular Features
Authors: Rodig Scott J. , Ouyang Jing , Juszczynski Przemyslaw , Currie Treeve , Law Kenneth , Neuberg Donna S. , Rabinovich Gabriel A. , Shipp Margaret A. , Kutok Jeffery L. 
Published: June 2008

Abstract
Purpose: Galectin-1 (Gal1) is an immunomodulatory glycan-binding protein regulated by an AP1-dependent enhancer in Hodgkin Reed-Sternberg cells. We recently found that Reed-Sternberg cell Gal1 promotes the immunosuppressive T-helper 2/T-regulatory cell–skewed microenvironment in classical Hodgkin lymphoma (cHL). We sought to investigate whether the coordinate expression of activated AP1 pathway components and Gal1 serves as a diagnostic signature of cHL. In addition, because there are common signaling and survival pathways in cHL and additional non–Hodgkin lymphomas, we also evaluated whether the AP1/Gal1 signature is shared by other molecularly or morphologically related lymphomas.
Experimental Design: We evaluated 225 cases of primary cHL and non–Hodgkin lymphoma for evidence of a functional AP1/Gal1 signature by immunohistochemical techniques.
Results: Gal1 is selectively expressed by malignant Reed-Sternberg cells in &gt;90% of primary cHLs, and Gal1 expression is concordant with the activated AP1 component, c-Jun. In contrast, diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and another Hodgkin-related entity, nodular lymphocyte–predominant Hodgkin lymphoma, do not express Gal1. However, anaplastic large cell lymphoma (ALCL), consistently expresses both Gal1 and its transcriptional regulator, c-Jun. The presence of activated c-Jun, indicative of functional AP1 activity, was confirmed by phospho-c-Jun immunostaining in cHL and ALCL.
Conclusions: These findings establish a functional AP1 signature that includes Gal1 expression in cHL and ALCL and suggests a common mechanism for tumor immunotolerance in these diseases. In addition, the combination of Gal1 and c-Jun serve as diagnostic biomarkers that delineate cHL and ALCL from other lymphomas with shared morphologic and/or molecular features.
Gly82Ser Polymorphism of the Receptor for Advanced Glycation End Products Is Associated with an Increased Risk of Gastric Cancer in a Chinese Population
Authors: Gu Haijuan , Yang Li , Sun Qingmin , Zhou Bo , Tang Naping , Cong Rihong , Zeng Ying , Wang Bin 
Published: June 2008

Abstract
Purpose: It has been shown that the expression of the receptor for advanced glycation end products (RAGE) is closely associated with invasion and metastasis in gastric cancer. A Gly82Ser polymorphism in exon 3 of RAGE gene was identified and thought to have an effect on the functions of its protein. Therefore, the goal of the present study was to investigate whether the polymorphism is involved in the development or progression of gastric cancer.
Experimental Design: In the hospital-based case-control study, the RAGE genotypes were determined using PCR-RFLP in 566 individuals (283 gastric cancer patients and 283 age- and sex-matched controls).
Results: The distribution of genotype was significantly different between cases and controls (P = 0.038). Compared with the wild-type 82Gly/Gly carriers, subjects with the variant genotypes (82Gly/Ser and 82Ser/Ser) had a significantly higher risk of gastric cancer (adjusted odds ratio, 1.47; 95% confidence interval, 1.05-2.06). Moreover, the elevated gastric cancer risk was especially evident in younger individuals (ages ≤58 years), nonsmokers, and rural subjects. Further analyses revealed that the variant genotypes were associated with adjacent organ invasion in the subanalysis of gastric cancer patients.
Conclusions: Our findings indicate that the RAGE Gly82Ser polymorphism may confer not only an increased risk of gastric cancer but also with invasion of gastric cancer in the Chinese population.
Genetic Polymorphism in EGF Is Associated with Prostate Cancer Aggressiveness and Progression-Free Interval in Androgen Blockade–Treated Patients
Authors: Teixeira Ana L. , Ribeiro Ricardo , Cardoso Diana , Pinto Daniela , Lobo Francisco , Fraga Avelino , Pina Francisco , Calais-da-Silva Fernando , Medeiros Rui 
Published: June 2008

Abstract
Purpose: Most prostate cancer patients develop resistance to androgen deprivation treatment, resulting in hormone resistance. Epidermal growth factor (EGF) activates several pro-oncogenic intracellular pathways inducing proliferation, differentiation, and tumorigenesis in epithelial cells. The EGF-EGF receptor pathway seems to be especially relevant in hormone-resistant prostate cancer stage. A single nucleotide polymorphism G&gt;A in +61 locus of EGF gene has been described, in which A homozygous carriers express significantly less EGF protein compared with G allele carriers. Our purpose was to investigate the potential prognostic and predictive role of EGF functional genetic variant +61 G&gt;A in prostate cancer patients submitted to androgen blockade therapy (ABT).
Experimental Design: We conducted a case-control study in prostate cancer patients treated with ABT (n = 123) and in healthy controls without evidence of cancer (n = 152). Cumulatively, a follow-up study (median follow-up, 37 months) was undertaken to evaluate response to ABT therapy in prostate cancer patients. EGF +61 G&gt;A genotypes were detected by PCR-RFLP.
Results: We found increased risk in G carriers, after age-adjusted regression analysis, for being diagnosed with Gleason ≥7 and with metastatic disease compared with control group (CG; age-adjusted odds ratio, 3.37, P = 0.004 and age-adjusted odds ratio, 2.61, P = 0.043, respectively). Kaplan-Meier survival analysis and log-rank test showed an influence of EGF +61 G&gt;A polymorphism in time to relapse during ABT (P = 0.018).
Conclusions: EGF functional polymorphism may contribute to earlier relapse in ABT patients, supporting the involvement of EGF as an alternative pathway in hormone-resistant prostatic tumors. Furthermore, our results lend support to EGF-EGF receptor pathway as an additional therapeutic target during hormonal treatment.
‘Speech-Smile’, ‘Speech-Laugh’, ‘Laughter’ and Their Sequencing in Dialogic Interaction
Authors: Kohler Klaus J. 
Published: June 2008

Abstract
Laughing is examined auditorily and acoustico-graphically, on the basis of exemplary speech data from spontaneous German dialogues, as pulmonic air stream modulation for communicative functions, paying attention to fine phonetic detail in interactional context. These phonetic case descriptions of laughing phenomena in speaker interaction in a small corpus have as their goal to create an awareness of the phonetic and functional parameters that need to be considered in the future acquisition, acoustic analysis and statistical evaluation of large spontaneous databases.
Spectral Integration of Dynamic Cues in the Perception of Syllable-Initial Stops
Authors: Fox Robert Allen , Jacewicz Ewa , Feth Lawrence L. 
Published: June 2008

Abstract
The present experiments examine the potential role of auditory spectral integration and spectral center of gravity (COG) effects in the perception of initial formant transitions in the syllables [da]-[ga] and [t<sup>h</sup>a]-[k<sup>h</sup>a]. Of interest is whether the place distinction for stops in these syllables can be cued by a ‘virtual F3 transition’ in which the percept of a frequency transition is produced by a dynamically changing COG. Listeners perceived the virtual F3 transitions comparably with actual F3 transitions although the former were less salient a cue. However, in a separate experiment, static ‘virtual F3 bursts’ were not as effective as actual F3 bursts in cueing the alveolar-velar place distinction. These results indicate that virtual F3 transitions can provide phonetic information to the perceptual system and that auditory spectral integration (completed by the central auditory system) may play a significant role in speech perception.
Sensitivity of Low-Level Winds Simulated by the WRF Model in California’s Central Valley to Uncertainties in the Large-Scale Forcing and Soil Initialization
Authors: Michelson Sara A. , Bao Jian-Wen 
Published: May 2008

Abstract
The sensitivity of the Weather and Research Forecasting (WRF) model-simulated low-level winds in the Central Valley (CV) of California to uncertainties in the atmospheric forcing and soil initialization is investigated using scatter diagrams for a 5-day period in which meteorological conditions are typical of those associated with poor-air-quality events during the summer in the CV. It is assumed that these uncertainties can be approximated by two independent operational analyses. First, the sensitivity is illustrated using scatter diagrams and is measured in terms of the linear regression of the output from two simulations that differ in either the atmospheric forcing or the soil initialization. The spatial variation of the sensitivity is then investigated and is linked to the dominant low-level flows within the CV. The results from this case study suggest that the WRF-simulated low-level winds in the northern CV [i.e., the Sacramento Valley (SV)] are more sensitive to the uncertainties in the atmospheric forcing than to those in the soil initialization in the typical weather conditions during the summer that are prone to poor air quality in the CV. The simulated low-level winds in the southernmost part of the San Joaquin Valley (SJV) are more sensitive to the uncertainties in the soil initialization than they are in the SV. In the northern SJV, the simulated low-level winds are overall more sensitive to the uncertainties in the large-scale upper-level atmospheric forcing than to those in the soil initialization. This spatial variation in sensitivity reflects the important roles that the large-scale forcing, specified by the lateral boundary conditions and the local forcing associated with the soil state, play in controlling the low-level winds in the CV.
Tropical Pacific Forcing of North American Medieval Megadroughts: Testing the Concept with an Atmosphere Model Forced by Coral-Reconstructed SSTs*
Authors: Seager Richard , Burgman Robert , Kushnir Yochanan , Clement Amy , Cook Ed , Naik Naomi , Miller Jennifer 
Published: May 2008

Abstract
The possible role that tropical Pacific SSTs played in driving the megadroughts over North America during the medieval period is addressed. Fossil coral records from the Palmyra Atoll are used to derive tropical Pacific SSTs for the period from a.d. 1320 to a.d. 1462 and show overall colder conditions as well as extended multidecadal La Niña–like states. The reconstructed SSTs are used to force a 16-member ensemble of atmosphere GCM simulations, each with different initial conditions, with the atmosphere coupled to a mixed layer ocean outside of the tropical Pacific. Model results are verified against North American tree ring reconstructions of the Palmer Drought Severity Index. A singular value decomposition analysis is performed using the soil moisture anomaly simulated by another 16-member ensemble of simulations forced by global observed SSTs for 1856–2004 and tree ring reconstructions of the Palmer Drought Severity Index for the same period. This relationship is used to transfer the modeled medieval soil moisture anomaly (relative to the modern simulation) into a model-estimated Palmer Drought Severity Index. The model-estimated Palmer Drought Severity Index reproduces many aspects of both the interannual and decadal variations of the tree ring reconstructions, in addition to an overall drier climate that is drier than the tree ring records suggest. The model-estimated Palmer Drought Severity Index simulates two previously identified “megadroughts,” a.d. 1360–1400 and a.d. 1430–60, with a realistic spatial pattern and amplitude. In contrast, the model fails to produce a period of more normal conditions in the early fifteenth century that separated these two megadroughts. The dynamical link between tropical SSTs and the North American megadroughts is akin to that operating in modern droughts. The model results are used to argue that the tropical Pacific played an active role in driving the megadroughts. However, the match between simulated and reconstructed hydroclimate is such that it is likely that both the coral-reconstructed SST anomalies contain significant errors and that SST anomalies in other basins also played a role in driving hydroclimate variations over North America during the late medieval period.