bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypermethylation of Tachykinin-1 Is a Potential Biomarker in Human Esophageal Cancer
Authors: Jin Zhe , Olaru Alexandru , Yang Jian , Sato Fumiaki , Cheng Yulan , Kan Takatsugu , Mori Yuriko , Mantzur Carmit , Paun Bogdan , Hamilton James P. , Ito Tetsuo , Wang Suna , David Stefan , Agarwal Rachana , Beer David G. , Abraham John M. , Meltzer Stephen J. 
Published: November 2007

AbstractPurpose: Our aim was to investigate whether and at what stage hypermethylation of the tachykinin-1 (TAC1) gene is associated with human esophageal neoplastic transformation.Experimental Design: TAC1 promoter hypermethylation was examined by real-time methylation-specific PCR in 258 human esophageal specimens and 126 plasma samples from patients or tissues at various stages of neoplastic evolution.Results: TAC1 hypermethylation in tissue samples showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) from normal esophagus (P &lt; 0.0001). Both frequencies and normalized methylation values of TAC1 tissue methylation were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's esophagus, EAC, and ESCC than in normal esophagus (P &lt; 0.01). The frequency of TAC1 hypermethylation increased dramatically and early during neoplastic progression, from 7.5% in normal esophagus to 55.6% in BE from patients with Barrett's metaplasia alone, 57.5% in dysplastic Barrett's esophagus, and 61.2% in EAC. There was a significant relationship between TAC1 hypermethylation and BE segment length, a known clinical risk factor for neoplastic progression. Twelve (50%) of 24 ESCC exhibited TAC1 hypermethylation. Overall patient survival correlated significantly with TAC1 methylation status in ESCC patients (mean survival, 22 versus 110 months; P = 0.0102, log-rank test), but not in EAC patients. Both mean normalized methylation values and frequency of TAC1 hypermethylation in plasma samples were significantly higher in EAC patients than in control subjects. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2′-deoxycytidine reduced TAC1 methylation and increased TAC1 mRNA expression.Conclusions: TAC1 promoter hypermethylation is a common event in both major histologic types of human esophageal carcinoma, occurs early, correlates with other progression risk factors in esophageal adenocarcinogenesis, and is a tissue biomarker of a poor prognosis in ESCC. Circulating methylated TAC1 promoter DNA also offers potential as a biomarker for the diagnosis of EAC.
Repair Capacity for UV Light–Induced DNA Damage Associated with Risk of Nonmelanoma Skin Cancer and Tumor Progression
Authors: Wang Li-E , Li Chunying , Strom Sara S. , Goldberg Leonard H. , Brewster Abenaa , Guo Zhaozheng , Qiao Yawei , Clayman Gary L. , Lee J. Jack , El-Naggar Adel K. , Prieto Victor G. , Duvic Madeleine , Lippman Scott M. , Weber Randal S. , Kripke Margaret L. , Wei Qingyi 
Published: November 2007

AbstractPurpose: To examine the role of suboptimal DNA repair capacity (DRC) for UV light–induced DNA damage in the development of nonmelanoma skin cancer (NMSC) and tumor progression.Experimental Design: We conducted a hospital-based case-control study of 255 patients with newly diagnosed NMSC [146 with basal cell carcinoma (BCC) and 109 with squamous cell carcinoma (SCC)] and 333 cancer-free controls. We collected information on demographic variables and risk factors from questionnaires, tumor characteristics from medical records, and lymphocytic DRC phenotype by the host-cell reactivation assay. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI).Results: Overall, there was a relative 16% reduction in DRC in NMSC patients compared with controls (P &lt; 0.001 for BCC and for SCC, respectively). DRC below the controls' median value was associated with increased risk significantly for BCC (OR, 1.62; 95% CI, 1.07-2.45) but borderline for SCC (OR, 1.63; 95% CI, 0.95-2.79) after adjustment for age, sex, and other assay-related covariates. When the highest tertile of controls' DRC was used as the reference, the intermediate and low DRC were associated with a statistically significant trend for increasing risk for both BCC (Ptrend = 0.007) and SCC (Ptrend = 0.020). However, patients with aggressive or multiple SCC tended to have a higher DRC than those with nonaggressive or single SCC.Conclusions: Reduced DRC is an independent risk factor for BCC and single or nonaggressive SCC but not for multiple primaries, local aggressiveness, or recurrence of NMSC.
A Contemporary Prognostic Nomogram for Men with Hormone-Refractory Metastatic Prostate Cancer: A TAX327 Study Analysis
Authors: Armstrong Andrew J. , Garrett-Mayer Elizabeth S. , Yang Yi-Chun Ou , de Wit Ronald , Tannock Ian F. , Eisenberger Mario 
Published: November 2007

Abstract
Purpose: To develop a prognostic model and nomogram using baseline clinical variables to predict death among men with metastatic hormone-refractory prostate cancer (HRPC).
Experimental Design: TAX327 was a clinical trial that randomized 1,006 men with metastatic HRPC to receive every three week or weekly docetaxel or mitoxantrone, each with prednisone. We developed a multivariate Cox model and nomogram to predict survival at 1, 2, and 5 years.
Results: Ten independent prognostic factors other than treatment group were identified in multivariate analysis: (a) presence of liver metastases [hazard ratio (HR), 1.66; P = 0.019], (b) number of metastatic sites (HR, 1.63 if ≥2 sites; P = 0.001), (c) clinically significant pain (HR, 1.48; P &lt; 0.0001), (d) Karnofsky performance status (HR, 1.39 if ≤70; P = 0.016), (e) type of progression (HR, 1.37 for measurable disease progression and 1.29 for bone scan progression; P = 0.005 and 0.01, respectively), (f) pretreatment prostate-specific antigen (PSA) doubling time (HR, 1.19 if &lt;55 days; P = 0.066), (g) PSA (HR, 1.17 per log rise; P &lt; 0.0001), (h) tumor grade (HR, 1.18 for high grade; P = 0.069), (i) alkaline phosphatase (HR, 1.27 per log rise; P &lt; 0.0001), and (j) hemoglobin (HR, 1.11 per unit decline; P = 0.004). A nomogram was developed based on this multivariate model and validated internally using bootstrap methods, with a concordance index of 0.69.
Conclusions: This multivariate model identified several new independent prognostic factors in men with metastatic HRPC, including PSA doubling time, and led to the successful development of a clinically applicable nomogram. External prospective validation may support the wider use of this prognostic baseline model for men with HRPC treated with chemotherapy.
Daily Physical-Rest Activities in Relation to Nutritional State, Metabolism, and Quality of Life in Cancer Patients with Progressive Cachexia
Authors: Fouladiun Marita , Körner Ulla , Gunnebo Lena , Sixt-Ammilon Petra , Bosaeus Ingvar , Lundholm Kent 
Published: November 2007

Abstract
Purpose: To evaluate daily physical-rest activities in cancer patients losing weight in relation to disease progression.
Experimental Design: Physical activity-rest rhythms were measured (ActiGraph, armband sensor from BodyMedia) in relation to body composition (dual-energy X-ray absorptiometry), energy metabolism, exercise capacity (walking test), and self-scored quality of life (SF-36, Hospital Anxiety and Depression Scale) in weight-losing outpatients with systemic cancer (71 ± 2 years, n = 53). Well-nourished, age-matched, and previously hospitalized non–cancer patients served as controls (74 ± 4 years, n = 8). Middle-aged healthy individuals were used as reference subjects (49 ± 5 years, n = 23).
Results: Quality of life was globally reduced in patients with cancer (P &lt; 0.01), accompanied by significantly reduced spontaneous physical activity during both weekdays and weekends compared with reference subjects (P &lt; 0.01). Spontaneous physical activity declined over time during follow-up in patients with cancer (P &lt; 0.05). However, overall physical activity and the extent of sleep and bed-rest activities did not differ between patients with cancer and age-matched non–cancer patients. Spontaneous physical activity correlated weakly with maximum exercise capacity in univariate analysis (r = 0.41, P &lt; 0.01). Multivariate analysis showed that spontaneous physical activity was related to weight loss, blood hemoglobin concentration, C-reactive protein, and to subjectively scored items of physical functioning and bodily pain (SF-36; P &lt; 0.05-0.004). Anxiety and depression were not related to spontaneous physical activity. Patient survival was predicted only by weight loss and serum albumin levels (P &lt; 0.01), although there was no such prediction for spontaneous physical activity.
Conclusions: Daily physical-rest activities represent variables which probably reflect complex mental physiologic and metabolic interactions. Thus, activity-rest monitoring provides a new dimension in the evaluation of medical and drug interventions during palliative treatment of patients with cancer.
5-Aminosalicylic Acid Given in the Remission Stage of Colitis Suppresses Colitis-Associated Cancer in a Mouse Colitis Model
Authors: Ikeda Ikuko , Tomimoto Ayako , Wada Koichiro , Fujisawa Toshio , Fujita Koji , Yonemitsu Kyoko , Nozaki Yuichi , Endo Hiroki , Takahashi Hirokazu , Yoneda Masato , Inamori Masahiko , Kubota Kensuke , Saito Satoru , Nagashima Yoji , Nakagama Hitoshi , Nakajima Atsushi 
Published: November 2007

Abstract
Purpose: The risk of colorectal cancer is increased in patients with inflammatory bowel diseases, especially those with ulcerative colitis (UC). Although 5-aminosalicylic acid (5-ASA) is widely used in the treatment of UC to suppress the colitic inflammation, no studies have been conducted to examine the chemopreventive effect of 5-ASA, given in the remission phase of colitis, against colitis-associated cancer using animal models. We therefore investigated the possible inhibition by peroxisome proliferator-activated receptor-γ (PPARγ) ligands and 5-ASA of colitis-associated colon carcinogenesis in a mouse model.
Experimental Design: A dextran sodium sulfate/azoxymethane–induced mouse colon cancer model was used, and the chemopreventive effects of 5-ASA and PPARγ ligands, given in the remission phase of colitis, against colitis-related colon carcinogenesis, were evaluated.
Results: The number of neoplasms in the mice treated with 5-ASA was significantly lower than that in the control mice. In addition, the size of the neoplasms in treated mice was also significantly smaller than that in the control mice. In contrast, no significant suppression in the number or size of the tumors was observed in the mice treated with PPARγ ligands. The proliferating cell nuclear antigen–labeling index in the tumor cells of the 5-ASA–treated mice was significantly smaller than that in the control, indicating that 5-ASA reduced tumor cell proliferation.
Conclusion: Our results revealed that 5-ASA given in the remission phase of colitis significantly suppressed the development of colitis-associated cancer in a mouse model, which indicates the clinical importance of adopting chemopreventive strategies even in UC patients in remission.
Amplicon Mapping and Expression Profiling Identify the Fas-Associated Death Domain Gene as a New Driver in the 11q13.3 Amplicon in Laryngeal/Pharyngeal Cancer
Authors: Gibcus Johan H. , Menkema Lorian , Mastik Mirjam F. , Hermsen Mario A. , de Bock Geertruida H. , van Velthuysen Marie-Louise F. , Takes Robert P. , Kok Klaas , Álvarez Marcos Cesar A. , van der Laan Bernard F.A.M. , van den Brekel Michiel W.M. , Langendijk Johannes A. , Kluin Philip M. , van der Wal Jacqueline E. , Schuuring Ed 
Published: November 2007

AbstractPurpose: Amplification of the 11q13 region is a frequent event in human cancer. The highest incidence (36%) is found in head and neck squamous cell carcinomas. Recently, we reported that the amplicon size in 30 laryngeal and pharyngeal carcinomas with 11q13 amplification is determined by unique genomic structures, resulting in the amplification of a set of genes rather than a single gene.Experimental Design: To investigate which gene(s) drive the 11q13 amplicon, we determined the smallest region of overlap with amplification and the expression levels of all genes within this amplicon.Results: Using array-based comparative genomic hybridization analysis, we detected a region of ∼1.7 Mb containing 13 amplified genes in more than 25 of the 29 carcinomas. Quantitative reverse transcription-PCR revealed that overexpression of 8 potential driver genes including, cyclin D1, cortactin, and Fas-associated death domain (FADD), correlated significantly with DNA amplification. FADD protein levels correlated well with DNA amplification, implicating that FADD is also a candidate driver gene in the 11q13 amplicon. Analysis of 167 laryngeal carcinomas showed that increased expression of FADD (P = 0.007) and Ser194 phosphorylated FADD (P = 0.011) were associated with a worse disease-specific survival. FADD was recently reported to be involved in cell cycle regulation, and cancer cells expressing high levels of the Ser194 phosphorylated isoform of FADD proved to be more sensitive to Taxol-induced cell cycle arrest.Conclusion: Because of the frequent amplification of the 11q13 region and concomitant overexpression of FADD in head and neck squamous cell carcinomas, we hypothesize that FADD is a marker to select patients that might benefit from Taxol-based chemoradiotherapy.
Identification of a Novel Cancer-Testis Antigen CRT2 Frequently Expressed in Various Cancers Using Representational Differential Analysis
Authors: Hayashi Emiko , Matsuzaki Yuriko , Hasegawa Go , Yaguchi Tomonori , Kurihara Sachiko , Fujita Tomonobu , Kageshita Toshiro , Sano Makoto , Kawakami Yutaka 
Published: November 2007

AbstractPurpose: Cancer-testis antigens are promising targets for cancer immunotherapy. Identification of additional cancer-testis antigens with frequent expression in various cancers was attempted using representational differential analysis (RDA) and immunogenicity evaluation.Experimental Design: cDNAs preferentially expressed in testis were enriched using RDA by subtraction between testis and normal tissues. Thirty clones showing cancer-testis–like expression based on EST database analysis were evaluated by reverse transcription-PCR. A potential antigen, CRT2, was identified and its expression was analyzed with a newly generated anti-CRT2 antibody. The immunogenicity of CRT2 was examined based on reactivity with serum immunoglobulin G (IgG) from cancer patients, using Western blot and ELISA analysis, and on in vitro induction of tumor-reactive CTLs from HLA-A24 transgenic mice and human peripheral blood lymphocytes.Results: CRT2 was expressed in elongated spermatids of testis among normal tissues and in various cancer cell lines and tissues. The recombinant CRT2 protein was recognized by serum IgG from patients with various cancers in Western blot and ELISA analyses. A CRT2-derived peptide was identified as an HLA-A24–restricted T-cell epitope that induced tumor-reactive CTLs.Conclusion: CRT2 was identified as a new cancer-testis antigen expressed in elongated spermatids of testis and in cancer tissues (particularly melanoma) that is recognized by serum IgG from cancer patients. An HLA-A24–restricted T-cell epitope capable of inducing tumor-reactive CTLs was identified, suggesting that CRT2 may be useful for cancer diagnosis and immunotherapy.
Transforming Growth Factor-β and the Immune Response to Malignant Disease
Authors: Teicher Beverly A. 
Published: November 2007

AbstractTransforming growth factor-β (TGF-β) is a key player in malignant disease through its actions on host tissues and cells. Malignant cells often secrete large amounts of TGF-β that act on nontransformed cells present in the tumor mass as well as distal cells in the host to suppress antitumor immune responses creating an environment of immune tolerance, augmenting angiogenesis, invasion and metastasis, and increasing tumor extracellular matrix deposition. Cells of the innate immune system contribute to the high concentrations of TGF-β found in tumor masses. In addition, dendritic cell subpopulations secreting TGF-β contribute to the generation of regulatory T cells that actively inhibit the activity of other T cells. Elevated levels of plasma TGF-β are associated with advanced stage disease and may separate patients into prognostically high-risk populations. Anti–TGF-β therapy could reverse the immunosuppressive effects of this cytokine on the host as well as decrease extracellular matrix formation, decrease angiogenesis, decrease osteolytic activity, and increase the sensitivity of the malignant cells to cytotoxic therapies and immunotherapies. Phase I clinical trials of an inhibitor of TGF-β receptor type I kinase activity and a TGF-β neutralizing antibody are under way.
Knee Valgus during Drop Jumps in National Collegiate Athletic Association Division I Female Athletes
Authors: Joseph Michael , Tiberio David , Baird Jennifer L. , Trojian Thomas H. , Anderson Jeffrey M. , Kraemer William J. , Maresh Carl M. 
Published: November 2007

Background Female athletes land from a jump with greater knee valgus and ankle pronation/eversion. Excessive valgus and pronation have been linked to risk of anterior cruciate ligament injury. A medially posted orthosis decreases component motions of knee valgus such as foot pronation/eversion and tibial internal rotation. Hypothesis We hypothesized a medial post would decrease knee valgus and ankle pronation/eversion during drop-jump landings in NCAA-I female athletes. Study Design Controlled laboratory study. Methods Knee and ankle 3-dimensional kinematics were measured using high-speed motion capture in 10 National Collegiate Athletic Association Division I female athletes during a drop-jump landing with and without a medial post. Analysis of variance was used to determine differences in posting condition, t tests were used to determine dominant-nondominant differences, and the Pearson correlation coefficient was used to determine relationships between variables. Results Significant differences were found for all measures in the posted condition. A medial post decreased knee valgus at initial contact (1.24°, P< .01) and maximum angle (1.21 °, P< .01). The post also decreased ankle pronation/eversion at initial contact (0.77°, P < .01) and maximum angle (0.95°, P = .039). Conclusion The authors have demonstrated a significant decrease in knee valgus and ankle pronation/eversion during a drop jump with a medial post placed in the athletes’ shoes. Clinical Relevance A medial post may be a potential means to decrease risk of anterior cruciate ligament injury.
Idiopathic pulmonary fibrosis: multiple causes and multiple mechanisms?
Authors: Maher T. M. , Wells A. U. , Laurent G. J. 
Published: November 2007

Idiopathic pulmonary fibrosis (IPF) is a devastating condition that carries a prognosis worse than that of many cancers.A recent classification of the idiopathic interstitial pneumonias has redefined the diagnostic criteria necessary to determine a diagnosis of IPF. The present authors believe that this redefinition is incorrect, relying as it does on subtle histological differences for the definition of separate disease categories.A further issue affecting IPF research is the polarisation of views around two competing pathogenetic hypotheses. One argues for the primacy of inflammation as the trigger that initiates fibrosis, and the other proposes that fibrosis arises as a consequence of chronic epithelial injury and failure of repair due to aberrant epithelial–mesenchymal interactions. The present authors believe that this schism is hampering understanding of IPF and skewing research priorities.It is argued here, instead, that abnormalities in multiple pathways involved in wound healing and inflammation lead to the development of idiopathic pulmonary fibrosis, and it is suggested that a new rationale for clinical classification and pathogenesis may be more productive in driving the search for novel therapies in the future.
Preliminary nanopore cheminformatics analysis of aptamer-target binding strength
Authors: Thomson Karen , Amin Iftekhar , Morales Eric , Winters-Hilt Stephen 
Published: November 2007

Abstract

Background
Aptamers are nucleic acids selected for their ability to bind to molecules of interest and may provide the basis for a whole new class of medicines. If the aptamer is simply a dsDNA molecule with a ssDNA overhang (a "sticky" end) then the segment of ssDNA that complements that overhang provides a known binding target with binding strength adjustable according to length of overhang.

Results
Two bifunctional aptamers are examined using a nanopore detector. They are chosen to provide sensitive, highly modulated, blockade signals with their captured ends, while their un-captured regions are designed to have binding moieties for complementary ssDNA targets. The bifunctional aptamers are duplex DNA on their channel-captured portion, and single-stranded DNA on their portion with binding ability. For short ssDNA, the binding is merely to the complementary strand of DNA, which is what is studied here – for 5-base and 6-base overhangs.

Conclusion
A preliminary statistical analysis using hidden Markov models (HMMs) indicates a clear change in the blockade pattern upon binding by the single captured aptamer. This is also consistent with the hypothesis that significant conformational changes occur during the annealing binding event. In further work the objective is to simply extend this ssDNA portion to be a well-studied ~80 base ssDNA aptamer, joined to the same bifunctional aptamer molecular platform.
Robust clustering in high dimensional data using statistical depths
Authors: Ding Yuanyuan , Dang Xin , Peng Hanxiang , Wilkins Dawn 
Published: November 2007

Abstract

Background
Mean-based clustering algorithms such as bisecting k-means generally lack robustness. Although componentwise median is a more robust alternative, it can be a poor center representative for high dimensional data. We need a new algorithm that is robust and works well in high dimensional data sets e.g. gene expression data.

Results
Here we propose a new robust divisive clustering algorithm, the bisecting k-spatialMedian, based on the statistical spatial depth. A new subcluster selection rule, Relative Average Depth, is also introduced. We demonstrate that the proposed clustering algorithm outperforms the componentwise-median-based bisecting k-median algorithm for high dimension and low sample size (HDLSS) data via applications of the algorithms on two real HDLSS gene expression data sets. When further applied on noisy real data sets, the proposed algorithm compares favorably in terms of robustness with the componentwise-median-based bisecting k-median algorithm.

Conclusion
Statistical data depths provide an alternative way to find the "center" of multivariate data sets and are useful and robust for clustering.