bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathological analysis of oxyphilic granular hepatocytes and hepatocellular mitochondria in chronic hepatitis C
Authors: Tanikawa Ken , Kage Masayoshi , Komuta Mina , Nakashima Osamu , Yano Hirohisa , Yatsuhashi Hiroshi , Kojiro Masamichi 
Published: April 2007

Aim:  Oxyphilic granular hepatocyte (OGH) results from hepatocellular changes associated with chronic hepatitis. The histopathological significance of OGH has not been clarified.Methods:  The subjects consisted of two groups of patients with hepatitis C: one group of patients who had undergone liver biopsy 3.8 times on average, and were followed for 8 years on average, and one group of hepatocellular carcinoma (HCC) patients who had undergone hepatectomy. The following items were examined: frequency of OGH, relationship between OGH and the degree of fibrosis and inflammation; amount of mitochondria in resected tissues; activity of mitochondrial enzymes; relationship between the development of HCC and OGH; and relationship between the duration of infection and OGH in the post‐transfusion patients.Results:  The incidence of OGH was 35.3% in liver biopsy patients and 46.9% in resected patients. A higher stage of fibrosis was associated with a higher frequency of OGH. Not only OGH but also hepatocyte mitochondria in the peripheral zone increased with the progression of fibrosis. Hepatocytes with or without increased mitochondria were randomly distributed. The mitochondrial enzyme activity was increased in hepatocytes with increased mitochondria. In the post‐transfusion patients, a longer duration of infection and a higher stage of fibrosis were associated with a higher frequency of OGH. A high percentage of patients with OGH developed HCC.Conclusion:  Mitochondrial changes are important histological findings related to the progression of liver lesions and the possible development of HCC.
Kinematic Design of a 5-DOF Hybrid Robot with Large Workspace/Limb–Stroke Ratio
Authors: Liu Haitao , Huang Tian , Mei Jianping , Zhao Xueman , Chetwynd Derek G. , Li Meng , Jack Hu S. 
Published: April 2007

Abstract
This paper deals with the conceptual and kinematic designs of a 5-degree of freedom (DOF) reconfigurable hybrid robot. The robot is composed of a 2-DOF parallel spherical mechanism that is serially connected with a 3-DOF open loop kinematic chain via a prismatic joint. Somewhat similar to the well-known Tricept robot, this design has the merit that a relatively large workspace/limb–stroke ratio can be achieved thanks to the decomposition of the motions of the output link into the 2-DOF rotation and 1-DOF translation. As with the Tricept, the robot is well suited for use as a plug-and-play module to configure different machines. The dimensional synthesis of the 2-DOF spherical parallel mechanism is carried out by the monotonical analysis of the design variables versus a global conditioning index represented by the mean of the minimum singular value of the Jacobian, leading to the solution of two nonlinear equations due to the limb length constraint and nearly axial symmetry requirement of the kinematic performance. The results of the dimensional synthesis are given via examples.
β-Lactam Resistance in
Haemophilus parasuis
Is Mediated by Plasmid pB1000 Bearing
bla
ROB-1
Authors: San Millan Alvaro , Escudero Jose Antonio , Catalan Ana , Nieto Silvia , Farelo Fidel , Gibert Magdalena , Moreno Miguel Angel , Dominguez Lucas , Gonzalez-Zorn Bruno 
Published: April 2007

ABSTRACT

β-Lactam resistance in
Haemophilus parasuis
is an emerging phenomenon that has not yet been characterized from a molecular perspective. Clinical high-level β-lactam-resistant isolates from Spain bore a novel plasmid, pB1000, expressing a functionally active ROB-1 β-lactamase. Pulsed-field gel electrophoresis was applied for the first time to
H. parasuis
and showed that β-lactam resistance is due to clonal spread of a resistant strain, BB1018, bearing pB1000.
Prophylactic Effect of Dietary Seaweed Fucoidan against Enteral Prion Infection
Authors: Doh-ura Katsumi , Kuge Tomoko , Uomoto Miyuki , Nishizawa Keiko , Kawasaki Yuri , Iha Masahiko 
Published: April 2007

ABSTRACT
Dietary seaweed fucoidan delays the onset of disease of enterally infected mice with scrapie when given orally for 6 days after infection, but not when given before the infection. This effect was not modified at a tested fucoidan dose range and appeared to reach the maximum level at a concentration of 2.5% or less in feed. Daily uptake of fucoidan might be prophylactic against prion diseases caused by ingestion of prion-contaminated materials, although further evaluation of its pharmacology remains to be done.
An Extension of Gregus Fixed Point Theorem
Authors: Olaleru JO , Akewe H 
Published: April 2007

AbstractLet "Equation missing" be a closed convex subset of a complete metrizable topological vector space "Equation missing" and "Equation missing" a mapping that satisfies "Equation missing" for all "Equation missing", where "Equation missing", "Equation missing", "Equation missing", "Equation missing", "Equation missing", and "Equation missing". Then "Equation missing" has a unique fixed point. The above theorem, which is a generalization and an extension of the results of several authors, is proved in this paper. In addition, we use the Mann iteration to approximate the fixed point of "Equation missing".
On Fuzzy "Equation missing" -Contractive Mappings in Fuzzy Metric Spaces
Authors: Miheţ Dorel 
Published: April 2007

AbstractWe answer into affirmative an open question raised by A. Razani in 2005. An essential role in our proofs is played by the separation axiom in the definition of a fuzzy metric space in the sense of George and Veeramani.
Androgen-Independent Growth and Tumorigenesis of Prostate Cancer Cells Are Enhanced by the Presence of PKA-Differentiated Neuroendocrine Cells
Authors: Deeble Paul D. , Cox Michael E. , Frierson Henry F. , Sikes Robert A. , Palmer Jodie B. , Davidson Robert J. , Casarez Eli V. , Amorino George P. , Parsons Sarah J. 
Published: April 2007

Abstract
The neuroendocrine status of prostatic adenocarcinomas is considered a prognostic indicator for development of aggressive, androgen-independent disease. Neuroendocrine-like cells are thought to function by providing growth and survival signals to surrounding tumor cells, particularly following androgen ablation therapy. To test this hypothesis directly, LNCaP cells were engineered to inducibly express a constitutively activated form of the cyclic AMP–dependent protein kinase A catalytic subunit (caPKA), which was previously found upon transient transfection to be sufficient for acquisition of neuroendocrine-like characteristics and loss of mitotic activity. Clonal cells that inducibly expressed caPKA enhanced the growth of prostate tumor cells in anchorage-dependent and anchorage-independent in vitro assays as well as the growth of prostate tumor xenografts in vivo, with the greatest effects seen under conditions of androgen deprivation. These results suggest that neuroendocrine-like cells of prostatic tumors have the potential to enhance androgen-independent tumor growth in a paracrine manner, thereby contributing to progression of the disease. [Cancer Res 2007;67(8):3663–72]
Coordinated Regulation of Pathways for Enhanced Cell Motility and Chemotaxis Is Conserved in Rat and Mouse Mammary Tumors
Authors: Wang Weigang , Wyckoff Jeffrey B. , Goswami Sumanta , Wang Yarong , Sidani Mazen , Segall Jeffrey E. , Condeelis John S. 
Published: April 2007

Abstract
Correlating tumor cell behavior in vivo with patterns of gene expression has led to new insights into the microenvironment of tumor cells in the primary tumor. Until now, these studies have been done with cell line–derived tumors. In the current study, we have analyzed, in polyoma middle T oncogene (PyMT)–derived mammary tumors, tumor cell behavior and gene expression patterns of the invasive subpopulation of tumor cells by multiphoton-based intravital imaging and microarray-based expression profiling, respectively. Our results indicate that the patterns of cell behavior that contribute to invasion and metastasis in the PyMT tumor are similar to those seen previously in rat MTLn3 cell line–derived mammary tumors. The invasive tumor cells collected from PyMT mouse mammary tumors, like their counterparts from rat xenograft mammary tumors, are a population that is relatively nondividing and nonapoptotic but chemotherapy resistant and chemotactic. Changes in the expression of genes that occur uniquely in the invasive subpopulation of tumor cells in the PyMT mammary tumors that fall on the Arp2/3 complex, capping protein and cofilin pathways show a pattern like that seen previously in invasive tumor cells from the MTLn3 cell line–derived tumors. These changes predict an enhanced activity of the cofilin pathway, and this was confirmed in isolated invasive PyMT tumor cells. We conclude that changes in gene expression and their related changes in cell behavior, which were identified in the invasive tumor cells of cell line–derived tumors, are conserved in the invasive tumor cells of PyMT-derived mouse mammary tumors, although these tumor types have different genetic origins. [Cancer Res 2007;67(8):1–6]
In vitroandIn vivoMolecular Evidence for Better Therapeutic Efficacy of ABT-627 and Taxotere Combination in Prostate Cancer
Authors: Banerjee Sanjeev , Hussain Maha , Wang Zhiwei , Saliganan Allen , Che Mingxin , Bonfil Daniel , Cher Michael , Sarkar Fazlul H. 
Published: April 2007

AbstractBone is the key metastatic site for prostate cancer. Endothelin 1 (ET-1) produced abundantly by prostate cancer cells binds to its receptor present on bone marrow stromal cells and favors osteoblastic response during bone metastases of prostate cancer. This suggests that interrupting ET-1 interaction with its endothelin A (ETA) receptor could be useful for inhibiting prostate cancer bone metastasis and, as such, may enhance the therapeutic activity of docetaxel (Taxotere), the most commonly used drug for the treatment of metastatic prostate cancer. Therefore, the goal of our study was to obtain preclinical data supporting our hypothesis that the combined use of ETA receptor antagonist (ABT-627; Atrasentan) with Taxotere will be superior in inducing apoptosis in vitro and inhibiting tumor growth in vivo in a SCID-hu model of experimental bone metastasis induced by C4-2b prostate cancer cells. In vitro studies were done on a panel of prostate cancer cell lines to understand the molecular basis of combination therapy, and we found that the combination was more effective in the inhibition of cell viability and induction of apoptosis in LNCaP and C4-2b cells (androgen receptor positive) but not in PC-3 cells. These results were correlated with inactivation of Akt/nuclear factor-κB and its target genes. For in vivo studies, the therapeutic regimen was initiated when the tumor began showing signs of growth and treatment was continued for 5 weeks. Tumor volume and serum prostate-specific antigen were used as terminal index to evaluate the therapeutic advantage of combination therapy relative to a single regimen and untreated control. At termination, we found a 90% reduction in tumor volume by combination treatment relative to the untreated control group. Most importantly, the antitumor activity was associated with the down-regulation of molecular markers in tumor tissues that were similar to those observed in vitro. [Cancer Res 2007;67(8):3818–25]
Enhanced Antitumor Activity of T Cells Engineered to Express T-Cell Receptors with a Second Disulfide Bond
Authors: Cohen Cyrille J. , Li Yong F. , El-Gamil Mona , Robbins Paul F. , Rosenberg Steven A. , Morgan Richard A. 
Published: April 2007

AbstractAdoptive transfer of genetically T-cell receptor (TCR)–modified lymphocytes has been recently reported to cause objective cancer regression. However, a major limitation to this approach is the mispairing of the introduced chains with the endogenous TCR subunits, which leads to reduced TCR surface expression and, subsequently, to their lower biological activity. We here show that it is possible to improve TCR gene transfer by adding a single cysteine on each receptor chain to promote the formation of an additional interchain disulfide bond. We show that cysteine-modified receptors were more highly expressed on the surface of human lymphocytes compared with their wild-type counterparts and able to mediate higher levels of cytokine secretion and specific lysis when cocultured with specific tumor cell lines. Furthermore, cysteine-modified receptors retained their enhanced function in CD4+ lymphocytes. We also show that this approach can be employed to enhance the function of humanized and native murine receptors in human cells. Preferential pairing of cysteine-modified receptor chains accounts for these observations, which could have significant implications for the improvement of TCR gene therapy. [Cancer Res 2007;67(8):3898–903]
Degrasyn Activates Proteasomal-Dependent Degradation of c-Myc
Authors: Bartholomeusz Geoffrey , Talpaz Moshe , Bornmann William , Kong Ling-Yuan , Donato Nicholas J. 
Published: April 2007

Abstract
c-Myc is a highly unstable transcription factor whose deregulation and increased expression are associated with cancer. Degrasyn, a small synthetic molecule, induces rapid degradation of c-Myc protein in MM-1 multiple myeloma and other tumor cell lines. Destruction of c-Myc by degrasyn requires the presence of a region of c-Myc between amino acid residues 316 and 378 that has not previously been associated with c-Myc stability. Degrasyn-induced degradation of c-Myc depends on proteasomes but is independent of the degron regions previously shown to be important for ubiquitin-mediated targeting and proteasomal destruction of the protein. Degrasyn-dependent c-Myc proteolysis is not mediated by any previously identified c-Myc regulatory mechanism, does not require new protein synthesis, and does not depend on the nuclear localization of c-Myc. Degrasyn reduced c-Myc levels in A375 melanoma cells and in A375 tumors in nude mice, and this activity correlated with tumor growth inhibition. Together, these results suggest that degrasyn reduces the stability of c-Myc in vitro and in vivo through a unique signaling process that uses c-Myc domains not previously associated with c-Myc regulation. [Cancer Res 2007;67(8):3912–8]
Phase I Study of Aerosolized SLIT Cisplatin in the Treatment of Patients with Carcinoma of the Lung
Authors: Wittgen Bart P.H. , Kunst Peter W.A. , van der Born Kasper , van Wijk Atie W. , Perkins Walter , Pilkiewicz Frank G. , Perez-Soler Roman , Nicholson Susan , Peters Godefridus J. , Postmus Pieter E. 
Published: April 2007

Abstract
Purpose: To investigate the safety and pharmacokinetics of aerosolized Sustained Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung carcinoma.
Experimental Design: Phase I, dose-escalating study of SLIT Cisplatin given in two sessions daily. Safety data, including laboratory variables, adverse events, pulmonary function tests, and radiographic imaging, were collected and analyzed for all patients to determine toxicity. Pharmacokinetic monitoring was done during the first course.
Results: Seventeen patients and one tracheostomy patient on compassionate use received treatment. Aerosolized cisplatin was well tolerated. No dose-limiting toxicity was observed at the maximum delivered dose. Safety data showed no hematologic toxicity, nephrotoxicity, ototoxicity, or neurotoxicity. Most common adverse events were nausea (64.7%), vomiting (47.1%), dyspnea (64.7%), fatigue (64.7%), and hoarseness (47.1%). Pharmacokinetic data showed very low plasma platinum levels only with the longest repeated inhalations. Common Toxicity Criteria grade 2 decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide after one course occurred both in two patients and grade one decrease in forced expiratory volume in one second and diffusing lung capacity for carbon monoxide in six and five patients, respectively. Direct airway deposition via the tracheostomy resulted in clinical deterioration after two cycles best described as bronchitis, completely reversible within days. Overall response: stable disease in 12 patients and progressive disease in 4 patients (one patient received one cycle).
Conclusions: Aerosolized liposomal cisplatin was found to be feasible and safe.
Multiplex Analysis of Serum Cytokines in Melanoma Patients Treated with Interferon-α2b
Authors: Yurkovetsky Zoya R. , Kirkwood John M. , Edington Howard D. , Marrangoni Adele M. , Velikokhatnaya Lyudmila , Winans Matthew T. , Gorelik Elieser , Lokshin Anna E. 
Published: April 2007

Abstract
Purpose: Interferon (IFN)-α2b is the only Food and Drug Administration–approved treatment for operable high-risk melanoma that has been shown to significantly and durably prolong relapse-free survival (RFS) of patients with stage IIB-III melanoma. Development of reliable serum assays may contribute to the development of methods for earlier detection of melanoma and the selection of patients who may be most susceptible to current available interventions with IFNα.
Experimental Design: A powerful high-throughput xMAP multiplex immunobead assay technology (Luminex Corp., Austin, TX) was used to simultaneously test 29 cytokines, chemokines, angiogenic as well as growth factors, and soluble receptors in the sera of 179 patients with high-risk melanoma and 378 healthy individuals.
Results: Serum concentrations of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-12p40, IL-13, granulocyte colony-stimulating factor, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β, IFNα, tumor necrosis factor (TNF)-α, epidermal growth factor, vascular endothelial growth factor (VEGF), and TNF receptor II were found to be significantly higher in patients with resected high-risk melanoma compared with healthy controls. Bayesian Network algorithm classification of the data offered 90% sensitivity at 98% specificity with 96.5% of melanoma patients distinguished from healthy individuals. IFN-α2b therapy resulted in a significant decrease of serum levels of immunosuppressive and tumor angiogenic/growth stimulatory factors (VEGF, epidermal growth factor, and hepatocyte growth factor) and increased levels of antiangiogenic IFN-γ inducible protein 10 (IP-10) and IFN-α. Pretreatment levels of proinflammatory cytokines IL-1β, IL-1α, IL-6, TNF-α, and chemokines MIP-1α and MIP-1β were found to be significantly higher in the serum of patients with longer RFS values of 1 to 5 and &gt;5 years when compared with patients with shorter RFS of &lt;1 year.
Conclusion: These data show that multiplexed analysis of serum biomarkers is useful for the evaluation of prognostic markers of clinical outcome and potential predictive markers of response to IFN-α2b in patients with high-risk operable melanoma.
Predicting Hepatocellular Carcinoma by Detection of Aberrant Promoter Methylation in Serum DNA
Authors: Zhang Yu-Jing , Wu Hui-Chen , Shen Jing , Ahsan Habibul , Tsai Wei Yann , Yang Hwai-I , Wang Li-Yu , Chen Shu-Yuan , Chen Chien-Jen , Santella Regina M. 
Published: April 2007

Abstract
Purpose: Most hepatocellular carcinomas (HCC) are diagnosed at an advanced stage. Hypermethylation of CpG islands in promoter regions is now recognized as an important early event in carcinogenesis and detection of methylated DNA has been suggested as a potential biomarker for early detection of cancer. There are no studies on epigenetic changes in samples from HCC patients before diagnosis. We explored the possible diagnostic value of aberrant promoter hypermethylation of three tumor suppressor genes in serum DNA for early detection of HCC.
Experimental Design: Aberrant promoter hypermethylation was investigated in DNA isolated from the serum of 50 HCC patients who provided repeated blood samples before diagnosis and 50 controls enrolled in a cancer screen program in Taiwan. Methylation-specific PCR was used to determine the methylation status of p16, p15, and ras association domain family 1A (RASSF1A).
Results: Among cases, aberrant methylation was found in serum DNA 1 to 9 years before clinical HCC diagnosis. RASSF1A had the highest frequency of hypermethylation with 35 (70%) cases having at least one positive sample compared with 22 (44%) for p16 and 12 (22%) for p15. Six subjects were hypermethylation negative for all three genes. For the 50 controls, promoter hypermethylation was found in three and two subjects for RASSF1A and p16, respectively; none had methylation of p15. A receiver operating characteristic curve that included clinical risk factors (age, HBsAg status, anti–hepatitis C virus status, smoking, and alcohol status) and hypermethylation biomarkers gave an overall predictive accuracy of 89% with sensitivity and specificity 84% and 94%, respectively.
Conclusions: The analysis of epigenetic changes on RASSF1A, p16, and p15 tumor suppressor genes in serum DNA may be a valuable biomarkers for early detection in populations at high risk of HCC.
Effect of Epidermal Growth Factor Receptor Inhibitor Class in the Treatment of Head and Neck Cancer with Concurrent Radiochemotherapy In vivo
Authors: Feng Felix Y. , Lopez Carlos A. , Normolle Daniel P. , Varambally Sooryanarayana , Li Xiaoxin , Chun Patrick Y. , Davis Mary A. , Lawrence Theodore S. , Nyati Mukesh K. 
Published: April 2007

Abstract
Purpose: To optimally integrate epidermal growth factor receptor (EGFR) inhibitors into the clinical treatment of head and neck cancer, two important questions must be answered: (a) does EGFR inhibition add to the effects of radiochemotherapy, and (b) if so, which method of inhibiting EGFR is superior (an EGFR antibody versus a small molecule tyrosine kinase inhibitor)? We designed an in vivo study to address these questions.
Experimental Design: Nude mice with UMSCC-1 head and neck cancer xenografts received either single, double, or triple agent therapy with an EGFR inhibitor (either cetuximab or gefitinib), gemcitabine, and/or radiation for 3 weeks. Tumor volumes and animal weights were measured for up to 15 weeks. Immunoblotting and immunofluorescent staining were done on tumors treated with either cetuximab or gefitinib alone.
Results: The addition of an EGFR inhibitor significantly delayed the tumor volume doubling time, from a median of 40 days with radiochemotherapy (gemcitabine and radiation) alone, to 106 days with cetuximab and 66 days with gefitinib (both P &lt; 0.005). Cetuximab resulted in significantly less weight loss than gefitinib. Immunoblot analysis and immunofluorescent staining of tumors show that although levels of phosphorylated AKT and extracellular signal–regulated kinase were decreased similarly in response to cetuximab or gefitinib, cetuximab caused prolonged suppression of pEGFR, pSTAT3, and BclXL compared with gefitinib.
Conclusions: EGFR inhibition, particularly with cetuximab, improves the effectiveness of radiochemotherapy in this model of head and neck cancer. The correlation of response with prolonged suppression of EGFR, STAT3, and BclXL offers the possibility that these may be candidate biomarkers for response.