bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temozolomide as Monotherapy Is Effective in Treatment of Advanced Malignant Neuroendocrine Tumors
Authors: Ekeblad Sara , Sundin Anders , Janson Eva Tiensuu , Welin Staffan , Granberg Dan , Kindmark Henrik , Dunder Kristina , Kozlovacki Gordana , Örlefors Håkan , Sigurd Mattias , Öberg Kjell , Eriksson Barbro , Skogseid Britt 
Published: May 2007

Abstract
Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors.
Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m2) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of O6-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n = 23) and compared with response to temozolomide.
Results: Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with O6-methylguanine DNA methyltransferase immunoreactivity in &lt;10% of nuclei, whereas four patients showed radiologic responses.
Conclusions: Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
Circulating Tumor Cells in Perioperative Esophageal Cancer Patients: Quantitative Assay System and Potential Clinical Utility
Authors: Liu Zhian , Jiang Ming , Zhao Jianhua , Ju Huangxian 
Published: May 2007

AbstractPurpose: To establish a quantitative system for evaluating the role of circulating tumor cells (CTC) in peripheral blood samples in patients who undergo surgery for treatment of esophageal cancer.Experimental Design: One hundred fifty-five peripheral blood samples from 53 esophageal cancer patients were collected before surgery (B-1), immediately after surgery (B0), and on the 3rd day postoperatively (B+3). Eighty-nine samples from 22 benign patients who underwent thoracotomy and 30 healthy volunteers were obtained as controls. A real-time reverse transcription-PCR quantitative analysis system based on carcinoembryonic antigen (CEA) mRNA gene expression was designed for detection of CTC.Results: This developed system can detect CEA mRNA-positive cells down to 3 cells per milliliter of peripheral blood. The cells in negative control groups were lower than the detection limit. The medians of 188 [95% confidence interval (95% CI), 155-498], 1513 (95% CI, 660-7,974) and 707 (95% CI, 737-3,005) CEA mRNA-positive cells per mL with the CEA-positive rates of 28.3%, 60.4%, and 42.9% in B-1, B0, and B+3 peripheral blood samples were obtained, respectively. There was statistically significant difference between B-1 and B0 (P = 0.0001) and between B-1 and B+3 (P = 0.0209). Fifty percent of patients with R &gt; 0.4 showed metastasis in 1 year after surgery, whereas the probability was only 14.3% for patients with R &lt; 0.4 (where R is CTC ratio of B+3 to B0, P = 0.043).Conclusions: Esophageal cancer operation results in tumor cells dissemination and significant increase of CTC in peripheral blood, which is related to the developed metastasis. CTC are helpful for evaluating micrometastasis and have the potential for predicting recurrence in esophageal cancer.
Disruption of Endothelial Cell Interactions with the Novel HU177 Cryptic Collagen Epitope Inhibits Angiogenesis
Authors: Cretu Alexandra , Roth Jennifer M. , Caunt Maresa , Akalu Abebe , Policarpio Desiree , Formenti Silvia , Gagne Paul , Liebes Leonard , Brooks Peter C. 
Published: May 2007

Abstract
Purpose: The importance of cellular communication with the extracellular matrix in regulating cellular invasion is well established. Selective disruption of communication links between cells and the local microenvironment by specifically targeting non-cellular matrix-immobilized cryptic extracellular matrix epitopes may represent an effective new clinical approach to limit tumor-associated angiogenesis. Therefore, we sought to determine whether the HU177 cryptic collagen epitope plays a functional role in regulating angiogenesis in vivo.
Experimental Design: We examined the expression and characterized the HU177 cryptic collagen epitope in vitro and in vivo using immunohistochemistry and ELISA. We examined potential mechanisms by which this cryptic collagen epitope may regulate angiogenesis using in vitro cell adhesion, migration, proliferation, and biochemical assays. Finally, we examined the whether blocking cellular interactions with the HU177 cryptic epitope plays a role in angiogenesis and tumor growth in vivo using the chick embryo model.
Results: The HU177 cryptic epitope was selectively exposed within tumor blood vessel extracellular matrix, whereas little was associated with quiescent vessels. An antibody directed to this cryptic site selectively inhibited endothelial cell adhesion, migration, and proliferation on denatured collagen type IV and induced increased levels of cyclin-dependent kinase inhibitor p27KIP1. Systemic administration of mAb HU177 inhibited cytokine- and tumor-induced angiogenesis in vivo.
Conclusions: We provide evidence for a new functional cryptic regulatory element within collagen IV that regulates tumor angiogenesis. These findings suggest a novel and highly selective approach for regulating angiogenesis by targeting a non-cellular cryptic collagen epitope.
Tissue Factor Expression, Angiogenesis, and Thrombosis in Pancreatic Cancer
Authors: Khorana Alok A. , Ahrendt Steven A. , Ryan Charlotte K. , Francis Charles W. , Hruban Ralph H. , Hu Ying Chuan , Hostetter Galen , Harvey Jennifer , Taubman Mark B. 
Published: May 2007

Abstract
Purpose: Hemostatic activation is common in pancreatic cancer and may be linked to angiogenesis and venous thromboembolism. We investigated expression of tissue factor (TF), the prime initiator of coagulation, in noninvasive and invasive pancreatic neoplasia. We correlated TF expression with vascular endothelial growth factor (VEGF) expression, microvessel density, and venous thromboembolism in resected pancreatic cancer.
Experimental Design: Tissue cores from a tri-institutional retrospective series of patients were used to build tissue microarrays. TF expression was graded semiquantitatively using immunohistochemistry in normal pancreas (n = 10), intraductal papillary mucinous neoplasms (n = 70), pancreatic intraepithelial neoplasia (n = 40), and resected or metastatic pancreatic adenocarcinomas (n = 130).
Results: TF expression was observed in a majority of noninvasive and invasive pancreatic neoplasia, including 77% of pancreatic intraepithelial neoplasias, 91% of intraductal papillary mucinous neoplasms, and 89% of pancreatic cancers, but not in normal pancreas. Sixty-six of 122 resected pancreatic cancers (54%) were found to have high TF expression (defined as grade ≥2, the median score). Carcinomas with high TF expression were more likely to also express VEGF (80% versus 27% with low TF expression, P &lt; 0.0001) and had a higher median MVD (8 versus 5 per tissue core with low TF expression, P = 0.01). Pancreatic cancer patients with high TF expression had a venous thromboembolism rate of 26.3% compared with 4.5% in patients with low TF expression (P = 0.04).
Conclusions: TF expression occurs early in pancreatic neoplastic transformation and is associated with VEGF expression, increased microvessel density, and possibly clinical venous thromboembolism in pancreatic cancer. Prospective studies evaluating the role of TF in pancreatic cancer outcomes are warranted.
Differential Methylation Hybridization Array of Endometrial Cancers Reveals Two Novel Cancer-Specific Methylation Markers
Authors: Zighelboim Israel , Goodfellow Paul J. , Schmidt Amy P. , Walls Ken C. , Mallon Mary Ann , Mutch David G. , Yan Pearlly S. , Huang Tim Hui-Ming , Powell Matthew A. 
Published: May 2007

AbstractPurpose: To identify novel endometrial cancer-specific methylation markers and to determine their association with clinicopathologic variables and survival outcomes.Experimental Design: Differential methylation hybridization analysis (DMH) was done for 20 endometrioid endometrial cancers using normal endometrial DNA as a reference control. Combined bisulfite restriction analysis (COBRA) was used to verify methylation of sequences identified by DMH. Bisulfite sequencing was undertaken to further define CpG island methylation and to confirm the reliability of the COBRA. The methylation status of newly identified markers and the MLH1 promoter was evaluated by COBRA in a large series of endometrioid (n = 361) and non-endometrioid uterine cancers (n = 23).Results: DMH and COBRA identified two CpG islands methylated in tumors but not in normal DNAs: SESN3 (PY2B4) and TITF1 (SC77F6/154). Bisulfite sequencing showed dense methylation of the CpG islands and confirmed the COBRA assays. SESN3 and TITF1 were methylated in 20% and 70% of endometrioid tumors, respectively. MLH1 methylation was seen in 28% of the tumors. TITF1 and SESN3 methylation was highly associated with MLH1 methylation (P &lt; 0.0001). SESN3 and TITF1 were methylated in endometrioid and non-endometrioid tumors, whereas MLH1 methylation was restricted to endometrioid tumors. Methylation at these markers was not associated with survival outcomes.Conclusions: The 5′ CpG islands for SESN3 and TITF1 are novel cancer-specific methylation markers. Methylation at these loci is strongly associated with aberrant MLH1 methylation in endometrial cancers. SESN3, TITF1 and MLH1 methylation did not predict overall survival or disease-free survival in this large cohort of patients with endometrioid endometrial cancer.
Standardizing Slide-Based Assays in Breast Cancer: Hormone Receptors, HER2, and Sentinel Lymph Nodes
Authors: Ross Jeffrey S. , Symmans W. Fraser , Pusztai Lajos , Hortobagyi Gabriel N. 
Published: May 2007

Abstract
Despite the rapid expansion of novel diagnostics designed to personalize breast cancer care, there remain several significant unmet needs for improving the accuracy and reliability of tests that are already in common daily clinical practice. For example, although immunohistochemistry has been the predominant method for measuring estrogen receptor and progesterone receptor status for over 15 years, this assay remains unstandardized and there is a widespread concern that inaccuracy in immunohistochemistry technique and interpretation is leading to an unacceptably high error rate in determining the true hormone receptor status. Similarly, there is considerable concern that both false-negative and false-positive result rates for testing for HER2 status are unacceptably high in current clinical practice. This commentary considers a variety of factors, including preanalytic conditions and slide-scoring procedures, and other variables that may be contributing to current testing error rates and why there is a great need for the standardization of these biomarker assay procedures to further enable the highest possible quality of care for newly diagnosed breast cancer patients.
Gene Expression Signature Predicts Recurrence in Lung Adenocarcinoma
Authors: Larsen Jill E. , Pavey Sandra J. , Passmore Linda H. , Bowman Rayleen V. , Hayward Nicholas K. , Fong Kwun M. 
Published: May 2007

Abstract
Purpose: Improving outcomes for early-stage lung cancer is a major research focus at present because a significant proportion of stage I patients develop recurrent disease within 5 years of curative-intent lung resection. Within tumor stage groups, conventional prognostic indicators currently fail to predict relapse accurately.
Experimental Design: To identify a gene signature predictive of recurrence in primary lung adenocarcinoma, we analyzed gene expression profiles in a training set of 48 node-negative tumors (stage I-II), comparing tumors from cases who remained disease-free for a minimum of 36 months with those from cases whose disease recurred within 18 months of complete resection.
Results: Cox proportional hazards modeling with leave-one-out cross-validation identified a 54-gene signature capable of predicting risk of recurrence in two independent validation cohorts of 55 adenocarcinomas [log-rank P = 0.039; hazard ratio (HR), 2.2; 95% confidence interval (95% CI), 1.1-4.7] and 40 adenocarcinomas (log-rank P = 0.044; HR, 3.3; 95% CI, 1.4-7.9). Kaplan-Meier log-rank analysis found that predicted poor-outcome groups had significantly shorter survival, and furthermore, the signature predicted outcome independently of conventional indicators of tumor stage and node stage. In a subset of earliest stage adenocarcinomas, generally expected to have good outcome, the signature predicted samples with significantly poorer survival.
Conclusions: We describe a 54-gene signature that predicts the risk of recurrent disease independently of tumor stage and which therefore has potential to refine clinical prognosis for patients undergoing resection for primary adenocarcinoma of the lung.
Inhibition of Poly(ADP-Ribose) Polymerase Enhances Cell Death and Improves Tumor Growth Delay in Irradiated Lung Cancer Models
Authors: Albert Jeffrey M. , Cao Carolyn , Kim Kwang Woon , Willey Christopher D. , Geng Ling , Xiao Dakai , Wang Hong , Sandler Alan , Johnson David H. , Colevas Alexander D. , Low Jennifer , Rothenberg Mace L. , Lu Bo 
Published: May 2007

Abstract
Purpose: Poly(ADP-ribose) polymerase-1 (PARP-1) is the founding member of a family of enzymes that catalyze the addition of ADP-ribose units to proteins that mediate DNA repair pathways. Ionizing radiation induces DNA strand breaks, suggesting that PARP-1 inhibition may sensitize tumor cells to radiation.
Experimental Design: We investigated the combination of PARP-1 inhibition with radiation in lung cancer models. ABT-888, a novel potent PARP-1 inhibitor, was used to explore the effects of PARP-1 inhibition on irradiated tumors and tumor vasculature.
Results: ABT-888 reduced clonogenic survival in H460 lung cancer cells, and inhibited DNA repair as shown by enhanced expression of DNA strand break marker histone γ-H2AX. Both apoptosis and autophagy contributed to the mechanism of increased cell death. Additionally, ABT-888 increased tumor growth delay at well-tolerated doses in murine models. For a 5-fold increase in tumor volume, tumor growth delay was 1 day for ABT-888 alone, 7 days for radiation alone, and 13.5 days for combination treatment. Immunohistochemical staining of tumor sections revealed an increase in terminal deoxyribonucleotide transferase–mediated nick-end labeling apoptotic staining, and a decrease in Ki-67 proliferative staining after combination treatment. Matrigel assay showed a decrease in in vitro endothelial tubule formation with ABT-888/radiation combination treatment, and von Willebrand factor staining of tumor sections revealed decreased vessel formation in vivo, suggesting that this strategy may also target tumor angiogenesis.
Conclusions: We conclude that PARP-1 inhibition shows promise as an effective means of enhancing tumor sensitivity to radiation, and future clinical studies are needed to determine the potential of ABT-888 as a radiation enhancer.
Determination of the Mechanical Properties of a Solid Elastic Medium from a Seismic Wave Propagation Using Two Statistical Estimators
Authors: Zein Samih , Canot Édouard , Erhel Jocelyne , Nassif Nabil 
Published: May 2007

In this paper, we study an inverse problem consisting in the determination of the mechanical properties of a layered solid elastic medium in contact with a fluid medium by measuring the variation of the pressure in the fluid while propagating a seismic/acoustic wave. The estimation of mechanical parameters of the solid is obtained from the simulation of a seismic wave propagation model governed by a system of partial differential equations. Two stochastic methods, Markov chain Monte Carlo with an accelerated version and simultaneous perturbation stochastic approximation, are implemented and compared with respect to cost and accuracy.
Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function
Authors: Kubach Jan , Lutter Petra , Bopp Tobias , Stoll Sabine , Becker Christian , Huter Eva , Richter Christoph , Weingarten Petra , Warger Tobias , Knop Jürgen , Müllner Stefan , Wijdenes John , Schild Hansjörg , Schmitt Edgar , Jonuleit Helmut 
Published: May 2007

AbstractCD4+CD25+Foxp3+ regulatory T cells (CD25+ Treg cells) direct the maintenance of immunological self-tolerance by active suppression of autoaggressive T-cell populations. However, the molecules mediating the anergic state and regulatory function of CD25+ Treg cells are still elusive. Using differential proteomics, we identified galectin-10, a member of the lectin family, as constitutively expressed in human CD25+ Treg cells, while they are nearly absent in resting and activated CD4+ T cells. These data were confirmed on the mRNA and protein levels. Single-cell staining and flow cytometry showed a strictly intracellular expression of galectin-10 in CD25+ Treg cells. Specific inhibition of galectin-10 restored the proliferative capacity of CD25+ Treg cells and abrogated their suppressive function. Notably, first identified here as expressed in human T lymphocytes, galectin-10 is essential for the functional properties of CD25+ Treg cells.
Small-molecule agonists of SHIP1 inhibit the phosphoinositide 3-kinase pathway in hematopoietic cells
Authors: Ong Christopher J. , Ming-Lum Andrew , Nodwell Matt , Ghanipour Ali , Yang Lu , Williams David E. , Kim Joseph , Demirjian Loutfig , Qasimi Pooran , Ruschmann Jens , Cao Li-Ping , Ma Kewei , Chung Stephen W. , Duronio Vincent , Andersen Raymond J. , Krystal Gerald , Mui Alice L.-F. 
Published: May 2007

AbstractBecause phosphoinositide 3-kinase (PI3K) plays a central role in cellular activation, proliferation, and survival, pharmacologic inhibitors targeting components of the PI3K pathway are actively being developed as therapeutics for the treatment of inflammatory disorders and cancer. These targeted drugs inhibit the activity of either PI3K itself or downstream protein kinases. However, a previously unexplored, alternate strategy is to activate the negative regulatory phosphatases in this pathway. The SH2-containing inositol-5′-phosphatase SHIP1 is a normal physiologic counter-regulator of PI3K in immune/hematopoietic cells that hydrolyzes the PI3K product phosphatidylinositiol-3,4,5-trisphosphate (PIP3). We now describe the identification and characterization of potent and specific small-molecule activators of SHIP1. These compounds represent the first small-molecule activators of a phosphatase, and are able to activate recombinant SHIP1 enzyme in vitro and stimulate SHIP1 activity in intact macrophage and mast cells. Mechanism of activation studies with these compounds suggest that they bind a previously undescribed, allosteric activation domain within SHIP1. Furthermore, in vivo administration of these compounds was protective in mouse models of endotoxemia and acute cutaneous anaphylaxis, suggesting that SHIP1 agonists could be used therapeutically to inhibit the PI3K pathway.
Generation of novel high quality HMW-GS genes in two introgression lines of Triticum aestivum/Agropyron elongatum
Authors: Liu Shuwei , Zhao Shuangyi , Chen Fanguo , Xia Guangmin 
Published: May 2007

Abstract

Background
High molecular weight glutenin subunits (HMW-GS) have been proved to be mostly correlated with the processing quality of common wheat (Triticum aestivum). But wheat cultivars have limited number of high quality HMW-GS. However, novel HMW-GS were found to be present in many wheat asymmetric somatic hybrid introgression lines of common wheat/Agropyron elongatum.

Results
To exploit how these new subunits were generated, we isolated HMW-GS genes from two sib hybrid lines (II-12 and 11-4-6) and compared them with those from their parents. The result shows that two genes of hybrid (H11-3-3 and H11-4-3) are directly introgressed from the donor parent Agropyron elongatum; one hybrid gene (H1Dx5) comes from point mutation of a parental wheat gene (1Dx2.1); two other hybrid genes (H1By8 and H1By16) are likely resulting from unequal crossover or slippage of a parental wheat gene (1By9.1); and the sixth novel hybrid gene (H1Dy12) may come from recombination between two parental genes.

Conclusion
Therefore, we demonstrate that novel HMW-GS genes can be rapidly created through asymmetric somatic hybridization in a manner similar with the evolution mechanism of these genes supposed before. We also described gene shuffling as a new mechanism of novel HMW-GS gene formation in hybrids. The results suggest that asymmetric somatic hybridization is an important approach for widening HMW-GS genebank of wheat quality improvement.
Transcriptional analysis of an immune-responsive serine protease from Indian malarial vector, Anopheles culicifacies
Authors: Rodrigues Janneth , Agrawal Neema , Sharma Anil , Malhotra Pawan , Adak Tridibes , Chauhan Virander S , Bhatnagar Raj K 
Published: May 2007

Abstract

Background
The main vector for transmission of malaria in India is the Anopheles culicifacies mosquito species, a naturally selected subgroup of which is completely refractory (R) to transmission of the malaria parasite, Plasmodium vivax;

Results
Here, we report the molecular characterization of a serine protease (acsp30)-encoding gene from A. culicifacies, which was expressed in high abundance in the refractory strain compared to the susceptible (S) strain. The transcriptional upregulation of acsp30 upon Plasmodium challenge in the refractory strain coincided with ookinete invasion of mosquito midgut. Gene organization and primary sequence of acsp30 were identical in the R and S strains suggesting a divergent regulatory status of acsp30 in these strains. To examine this further, the upstream regulatory sequences of acsp30 were isolated, cloned and evaluated for the presence of promoter activity. The 702 bp upstream region of acsp30 from the two strains revealed sequence divergence. The promoter activity measured by luciferase-based reporter assay was shown to be 1.5-fold higher in the R strain than in the S. Gel shift experiments demonstrated a differential recruitment of nuclear proteins to upstream sequences of acsp30 as well as a difference in the composition of nuclear proteins in the two strains, both of which might contribute to the relative abundance of acsp30 in the R strain;

Conclusion
The specific upregulation of acsp30 in the R strain only in response to Plasmodium infection is suggestive of its role in contributing the refractory phenotype to the A. culicifacies mosquito population.