bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Markers of Subclinical Disease for Ewing Family Tumors from Gene Expression Profiling
Authors: Cheung Irene Y. , Feng Yi , Danis Karen , Shukla Neerav , Meyers Paul , Ladanyi Marc , Cheung Nai-Kong V. 
Published: December 2007

Abstract
Purpose: Targeting subclinical disease in the bone marrow is particularly relevant in metastatic Ewing family tumors (EFT) where cure is difficult. Genome-wide expression arrays can uncover novel genes differentially expressed in tumors over normal marrow/blood, which may have potentials as markers of subclinical disease.
Experimental Design: Gene expression array data were obtained on 28 EFT tumors using the Affymetrix U133 gene chip and compared with 10 normal blood samples. Ten genes with high tumor to blood ratios were identified. Quantitative reverse transcription-PCR was done to study (a) the dynamic range of detection of rare tumor cells, (b) the gene expression in normal blood/marrow samples, (c) the gene expression among EFT tumors, and (d) the detection and prognostic impact of marker positivity in histology-negative diagnostic marrows of EFT patients.
Results: Five of 10 genes (i.e., six-transmembrane epithelial antigen of the prostate 1 [STEAP1], cyclin D1 [CCND1], NKX2-2 transcription factor [NKX2-2], plakophilin 1 [PKP1], and transmembrane protein 47 [TMEM47]) were chosen for further analyses based on their steep linear dynamic range in detecting tumor cells seeded in normal mononuclear cells and on their homogeneous expression among EFT tumors. Prognostic effect was evaluated in 35 histology-negative diagnostic marrows. Marker negativity of STEAP1, CCND1, or NKX2-2, as well as three markers in combination, was strongly correlated with patient survival as well as survival without new metastases.
Conclusions: This gene expression array-based approach identified novel markers that may be informative at diagnosis for risk group assessment. Their clinical utility needs to be tested in large patient cohorts.
Gain of 1q Is a Potential Univariate Negative Prognostic Marker for Survival in Medulloblastoma
Authors: Lo Ken C. , Ma Changxing , Bundy Brian N. , Pomeroy Scott L. , Eberhart Charles G. , Cowell John K. 
Published: December 2007

Abstract
Purpose: Tumor risk stratification during diagnosis is paramount for children with medulloblastomas, primarily because very young patients (&lt;3 years) suffer cognitive deficits from radio- and chemotherapy sequelae. Thus, distinguishing tumors that are biologically more aggressive is essential for medulloblastoma management to maximize the delay in radiation treatment without adversely affecting survival outcome. In this context, current strategies for risk assessment, which are based on clinical parameters, remain unsatisfactory.
Experimental Design: Array-based comparative genomic hybridization (aCGH) was used to identify chromosomal copy number abnormalities in a cohort of 49 medulloblastoma tumors. Based on the karyotypes generated from aCGH analysis, each tumor was scored for copy number abnormalities, and the log-rank test was used to evaluate whether any cytogenetic events were associated with survival.
Results: A single copy gain of 1q was shown to be a negative prognostic marker for survival in medulloblastomas with high statistical significance (P &lt; 0.0001, log-rank test).
Conclusion: A gain of 1q provides a potential means of predicting overall survival in medulloblastoma.
Prognostic Role of HuR in Hereditary Breast Cancer
Authors: Heinonen Mira , Fagerholm Rainer , Aaltonen Kirsimari , Kilpivaara Outi , Aittomäki Kristiina , Blomqvist Carl , Heikkilä Päivi , Haglund Caj , Nevanlinna Heli , Ristimäki Ari 
Published: December 2007

Abstract
Purpose: HuR is an mRNA-binding protein that enhances the stability of certain transcripts and can regulate their translation. Elevated cytoplasmic expression of HuR protein has been linked to carcinogenesis and is associated with reduced survival in breast, ovarian, and gastric adenocarcinomas.
Experimental Design: Here, we have explored the relevance of HuR in familial breast cancer. Tumor samples were collected from patients with identified BRCA1 (n = 51) or BRCA2 (n = 47) mutations or familial non-BRCA1/2 cases (n = 525), and analyzed by immunohistochemistry.
Results: Among familial non-BRCA1/2 breast cancer patients, cytoplasmic HuR protein expression was present in 39.4% of the cases and was associated with estrogen receptor negativity, progesterone receptor negativity, p53 positivity, high tumor grade, and ductal type of the tumor. In multivariate analysis, cytoplasmic HuR expression was an independent marker of reduced survival in the non-BRCA1/2 group along with tumor size &gt;2 cm, lymph node metastasis, and high histologic grade. In patients with BRCA1 or BRCA2 mutations, cytoplasmic HuR expression was more frequent (62.7% for BRCA1 and 61.7% for BRCA2) than in the non-BRCA1/2 group, but in BRCA-mutated subgroups cytoplasmic HuR expression did not associate with survival.
Conclusions: Our results show that HuR is an important prognostic factor in familial breast cancer patients and may contribute to carcinogenesis in this disease.
Notch-1 Mutations Are Secondary Events in Some Patients with T-Cell Acute Lymphoblastic Leukemia
Authors: Mansour Marc R. , Duke Veronique , Foroni Letizia , Patel Bella , Allen Christopher G. , Ancliff Phil J. , Gale Rosemary E. , Linch David C. 
Published: December 2007

Abstract
Purpose: Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in &gt;50% of patients. In murine models of T-ALL, Notch-1 activation can both directly initiate leukemia and cooperate secondarily to other primary events. Whether acquisition of Notch-1 mutations is an early initiating event or a secondary event in the pathogenesis of human T-ALL is unclear.
Experimental Design: We used denaturing high-performance liquid chromatography, sequencing, and fragment analysis to analyze Notch-1 mutational status and mutant level in 62 patients at presentation as well as 16 matched presentation-relapse samples.
Results: We detected Notch-1 mutations in 47 patients (76%). Seven of these were low-level mutations (quantified at ≤10%), despite high blast counts, suggesting that they were acquired as a secondary event in a subclone. Of 16 matched presentation-relapse samples studied, 7 were wild-type at both presentation and relapse. Five of nine mutant-positive patients at presentation relapsed with the same mutation(s) at the same high level. Four patients had evidence of a change in mutant at relapse. One lost a PEST mutation and became wild-type. Two others lost mutations at relapse but acquired different mutations, despite unchanged T-cell receptor rearrangements, suggesting that the latter event predated the acquisition of the Notch-1 mutation. One relapsed with a secondary T-cell leukemia and different Notch mutation.
Conclusions: These results suggest that Notch-1 mutations can sometimes be acquired as secondary events in leukemogenesis and must be used cautiously as solitary minimal residual disease markers.
Sequential Influences of Leukemia-Specific and Genetic Factors on P-Glycoprotein Expression in Blasts from 817 Patients Entered into the National Cancer Research Network Acute Myeloid Leukemia 14 and 15 Trials
Authors: Seedhouse Claire H. , Grundy Martin , White Paul , Li Yun , Fisher Janet , Yakunina Darya , Moorman Anthony V. , Hoy Terence , Russell Nigel , Burnett Alan , Pallis Monica 
Published: December 2007

Abstract
Purpose: P-glycoprotein (Pgp) is a major prognostic factor for chemotherapy failure in acute myeloid leukemia (AML). This study compared the influence of genetic and leukemia-specific factors on Pgp.
Experimental Design: Eight hundred and seventeen samples were studied prospectively for Pgp protein expression and function and G1199A, G2677T, and C3435T polymorphisms in the encoding gene ABCB1.
Results: Age, low WBC count, high bcl-2, secondary AML and myelodysplastic syndrome, and adverse cytogenetics all correlated strongly with high Pgp (MRK16) protein expression. However, ABCB1 3435TT homozygosity was negatively correlated with Pgp. Pgp protein is only expressed in 41% of samples such that the negative effect of the polymorphism was not seen at baseline Pgp levels but was marked in the upper 41% of samples (MRK16 Δmean fluorescence intensity of 75th centile sample = 9 units for TT variant samples and 26 units for CC/CT; P = 0.003). However, no association was found between genetic factors and Pgp function using rhodamine 123 accumulation.
Conclusions: The genetic polymorphism 3435TT (which results in unstable mRNA) has a significant effect on Pgp expression, but this is only seen in ∼40% of cases in which mRNA and protein are detectable. Moreover, leukemia-specific factors, such as low WBC count and poor risk cytogenetics, have a much greater effect than genetic polymorphisms on Pgp expression in AML blasts.
Circulating Tumor Cell Number and Prognosis in Progressive Castration-Resistant Prostate Cancer
Authors: Danila Daniel C. , Heller Glenn , Gignac Gretchen A. , Gonzalez-Espinoza Rita , Anand Aseem , Tanaka Erika , Lilja Hans , Schwartz Lawrence , Larson Steven , Fleisher Martin , Scher Howard I. 
Published: December 2007

Abstract
Purpose: The development of tumor-specific markers to select targeted therapies and to assess clinical outcome remains a significant area of unmet need. We evaluated the association of baseline circulating tumor cell (CTC) number with clinical characteristics and survival in patients with castrate metastatic disease considered for different hormonal and cytotoxic therapies.
Experimental Design: CTC were isolated by immunomagnetic capture from 7.5-mL samples of blood from 120 patients with progressive clinical castrate metastatic disease. We estimated the probability of survival over time by the Kaplan-Meier method. The concordance probability estimate was used to gauge the discriminatory strength of the informative prognostic factors.
Results: Sixty-nine (57%) patients had five or more CTC whereas 30 (25%) had two cells or less. Higher CTC numbers were observed in patients with bone metastases relative to those with soft tissue disease and in patients who had received prior cytotoxic chemotherapy relative to those who had not. CTC counts were modestly correlated to measurements of tumor burden such as prostate-specific antigen and bone scan index, reflecting the percentage of boney skeleton involved with tumor. Baseline CTC number was strongly associated with survival, without a threshold effect, which increased further when baseline prostate-specific antigen and albumin were included.
Conclusions: Baseline CTC was predictive of survival, with no threshold effect. The shedding of cells into the circulation represents an intrinsic property of the tumor, distinct from extent of disease, and provides unique information relative to prognosis.
Phase I Evaluation of CDP791, a PEGylated Di-Fab′ Conjugate that Binds Vascular Endothelial Growth Factor Receptor 2
Authors: Ton N.C. , Parker G.J.M. , Jackson A. , Mullamitha S. , Buonaccorsi G.A. , Roberts C. , Watson Y. , Davies K. , Cheung S. , Hope L. , Power F. , Lawrance J. , Valle J. , Saunders M. , Felix R. , Soranson J.A. , Rolfe L. , Zinkewich-Peotti K. , Jayson G.C. 
Published: December 2007

Abstract
Purpose: Specific blocking of vascular endothelial growth factor receptor 2 (VEGFR-2) is a novel therapeutic approach. Here, we report the first phase I clinical trial evaluation of CDP791, a PEGylated di-Fab′ conjugate that binds VEGFR-2.
Experimental Design: Cohorts of patients received CDP791 at doses between 0.3 and 30 mg/kg every 3 weeks for the initial two doses.
Results: The compound was well tolerated with no dose-limiting toxicity. Dose-related hypertension was observed in patients receiving CDP791 10 mg/kg or more and several patients on the higher doses developed infusion-related cutaneous hemangiomata arising 28 to 106 days after the first drug administration and resolving 3 weeks after cessation. Biopsy and histologic evaluation showed that CDP791-bound VEGFR-2 is non-phosphorylated, suggesting that the drug is biologically active. Concentrations of CDP791 considered biologically relevant were sustained for 3 weeks when doses of 10 mg/kg or more were administered. Although no reductions in vascular permeability were recorded using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), there was a significant dose level–related reduction in tumor growth. While challenging the recent dogma that active VEGF inhibitors should modulate DCE-MRI measurements of vascular permeability, this highlights the potential of serial three-dimensional tumor measurements to detect tumor growth arrest. Twelve patients received drug for more than two treatments, although no partial or complete responses were seen.
Conclusion: The data show that CDP791 is biologically active and well tolerated, achieving appropriate plasma concentrations when administered at 10 mg/kg or more every 3 weeks.
Anti–Mesothelin Immunotoxin SS1P in Combination with Gemcitabine Results in Increased Activity against Mesothelin-Expressing Tumor Xenografts
Authors: Hassan Raffit , Broaddus V. Courtney , Wilson Shannon , Liewehr David J. , Zhang Jingli 
Published: December 2007

Abstract
Purpose: To determine the antitumor activity of the anti–mesothelin immunotoxin SS1P in combination with gemcitabine against mesothelin-expressing tumor xenografts.
Experimental Design: The in vitro activity of SS1P in combination with gemcitabine against the mesothelin-expressing cell line A431/K5 was evaluated using cytotoxicity and apoptosis assays. The antitumor activity of this combination was evaluated in nude mice bearing A431/K5 tumor xenografts. Tumor-bearing mice were treated with different doses and schedules of gemcitabine alone, SS1P alone (0.2 mg/kg i.v. every other day × three doses), or with both agents together, and tumor volumes were measured over time.
Results: In vitro studies failed to show the synergy of SS1P plus gemcitabine against the mesothelin-expressing A431/K5 cells. In contrast, in the in vivo setting, there was a marked synergy when SS1P was combined with gemcitabine for the treatment of mesothelin-expressing tumor xenografts. This synergy was present using different doses and schedules of gemcitabine administration. In mice treated with fractionated doses of gemcitabine in combination with SS1P, complete tumor regression was observed in all mice and was long-lasting in 60% of the animals. Also, this antitumor activity was specific to SS1P because HA22, an immunotoxin targeting CD22 not expressed on A431/K5 cells, did not increase the efficacy of gemcitabine.
Conclusions: SS1P in combination with gemcitabine results in marked antitumor activity against mesothelin-expressing tumors. This combination could be potentially useful for the treatment of human cancers that express mesothelin and are responsive to gemcitabine therapy.
The old authorities in South African practice
Authors: Farlam Ian 
Published: December 2007

AbstractThe old authorities have been quoted in, and relied on by, the courts of the Cape and subsequently in the other territories making up the Republic of South Africa from the foundation of the colony by the Dutch East India Company in the middle of the seventeenth century. By the end of the nineteenth century not only were the main authorities extensively quoted in the courts but the doctrines they contained were being incorporated in the textbooks that were being written. And that is still the position. It is not likely that the new generation of judges to be appointed in the next few decades will frequently consult the old authorities for guidance but the civil component of the law, already anchored in the judgments of the courts and the textbooks, will forever be part of the law. When the old authorities are consulted, it is likely that those used will primarily be those available in English translation.
Gerechtelijke nationale cultuur en haar blinde vlek: de mercuriales en gelegenheidsredes van Charles Faider als procureur-generaal bij het Hof van Cassatie (1871–1885)
Authors: Delbecke Bram 
Published: December 2007

AbstractThis article sketches the attitude of the Belgian liberal magistrate and politician Charles Faider towards the constitutional civil liberties and freedoms. One can discover an interesting paradox by comparing his opening speeches and his acts as a politician. In the speeches he gave as procureur-général at the Cour de cassation, Faider consequently emphasised the beneficiary effects of the liberal 1831 Belgian Constitution. In his discourse, the Belgian magistrates were the best guards of the splendid future of the nation, because they fully understood the age-old national tradition of civil liberties. However, as a politician, he did not hesitate to limit the constitutional rights and liberties. Due to the political pressure of Napoleon III, he limited the freedom of the press by outlawing insulting foreign heads of state. The gap between his discourse and his practice is the perfect expression of an interesting paradox: in the 19th-century Belgian nation state, liberty and national identity profoundly influenced each other, but at the same time restricted their mutual possibilities, because the overall image of a free but responsable nation had to be maintained.
A dynamic model of simulating stress distribution in the distal femur after total knee replacement
Authors: Shi J F , Wang C J , Laoui T , Hart W , Hall R 
Published: December 2007

The aim of this study has been to develop a dynamic model of the knee joint after total knee replacement (TKR) to analyse the stress distribution in the distal femur during daily activities. Using MSC/ADAMS and MSC/MARC software, a dynamic model of an implanted knee joint has been developed. This model consists of the components of the knee prosthesis as well as the bones and ligaments of the knee. The femur, tibia, fibula, and patella have been modelled as mixed cortico-cancellous bone. The distal part of femur has been modelled as a flexible body with springs used to simulate the ligaments positioned at their anatomical insertion points. With this dynamic model a gait cycle was simulated. Stress shielding was identified in the distal femur after TKR, which is consistent with other investigators' results. Interestingly, higher stresses were found in the bone adjacent to the femoral component peg. This dynamic model can now be used to analyse the stress distribution in the distal femur with different load conditions. This will help to improve implant designs and will allow comparison of prostheses from different manufacturers.
Quantification of the coupled motion that occurs with axial rotation and lateral bending of the head-neck complex: An experimental examination
Authors: Senouci M , FitzPatrick D , Quinlan J F , Mullett H , Coffey L , McCormack D 
Published: December 2007

The vertebrae of the cervical spine exhibit out-of-plane or coupled motion during axial rotation and lateral bending. Quantifying the range of motion (ROM) of this occurrence can aid the understanding of cervical spine injury mechanisms and disorders, as well as the development of new treatment methods. Previous studies have formulated ratios to describe coupled motion obtained from in-vitro examinations. The aim of the present study was to use in-vivo test data to develop mathematical relationships to quantify the coupled motion that occurs with axial rotation and lateral bending of the head-neck complex. Using a three-dimensional motion analyser it was possible to trace the coupling effect throughout the full range of unrestricted head-neck motion. Values for primary and coupled ROMs were obtained, showing no significant difference between male and female primary ROMs but a small disparity between male and female coupled ROMs. Regression equations were found to quantify coupled motion throughout the range of axial rotation and lateral bending. The present experimental study also examines the range of horizontally fixed axial rotation of the head to determine the minimum amount of coupled lateral bending that takes place, which has not been measured previously.
Can cobalt levels estimate in-vivo wear of metal-on-metal bearings used in hip arthroplasty?
Authors: Khan M , Kuiper J H , Richardson J B 
Published: December 2007

High levels of cobalt and chromium ions are detected in the blood and urine of patients with metal-on-metal (MoM) hip replacement. These elements are released as a result of wear at the bearing surfaces. Wear rates depend on a multitude of factors, which include the bearing geometry, carbon content, manufacturing processes, lubrication, speed and direction of sliding of the surfaces, pattern of loading, and orientation of the components. In-vivo wear of MoM bearings cannot be reliably measured on X-rays because no distinction can be made between the bearing surfaces. Hip simulator studies have shown that wear rates are higher during the initial bedding-in phase and subsequently drop to very low levels. Accordingly, metal ion levels would be expected to decrease with the use of the bearing, measured as implantation time following surgery. However, several clinical studies have found that metal ion levels either gradually rise or fluctuate instead of decreasing to lower levels. Moreover, hip simulator studies predict that large-diameter bearings have lower wear rates than small-diameter bearings. In clinical studies, however, metal levels in patients with large-diameter bearings are unexpectedly higher than those in patients with small-diameter bearings. As a consequence, high cobalt ion levels in patients do not necessarily imply that their MoM bearings produce much wear debris at the time that their levels were measured; it may simply be due to accumulation of wear debris from the preceding time. Exercise-related cobalt rise may overcome this limitation and give a better assessment of the current wear status of a MoM bearing surface than a measure of cobalt levels only.
A Facile KF/Al2O3-mediated, One-pot Synthesis of Symmetrical Trithiocarbonates from Alkyl Halides and Carbon Disulfide
Authors: Movassagh Barahman , Soleiman-Beigi Mohammad , Nazari Mohammad 
Published: December 2007

Abstract
A facile, efficient, and convenient method has been developed for the one-pot synthesis of symmetrical trithiocarbonates from carbon disulfide and various alkyl halides in the presence of KF/Al2O3 in DMF at room temperature.
Observation of Arsenic Transfer in Leaf Tissue of Hyperaccumulator Fern by Utilizing Synchrotron Radiation Micro-XRF Imaging
Authors: Kitajima Nobuyuki , Kashiwabara Teruhiko , Fukuda Naoki , Endo Satoshi , Hokura Akiko , Terada Yasuko , Nakai Izumi 
Published: December 2007

Abstract
We have directly observed the early process of arsenic transfer in the leaf tissue of hyperaccumulator fern (Pteris vittata L.) within 12 h after the arsenic feeding, by utilizing a synchrotron radiation micro-XRF imaging. This study visually revealed for the first time that arsenic transferred from the root to the marginal part of the leaf within 1 h after feeding. Arsenic accumulated in the region of the vascular bundle and transferred to the paraphysis prior to the sporangium.
Solvo-thermal Preparation of Cadmium Telluride Nanoparticles from a Novel Single Source Molecular Precursor
Authors: Selvakumar D , Tripathi Santosh Kumar , Singh Rajendra , Nasim M 
Published: December 2007

Abstract
A convenient solvo-thermal route has been developed for the preparation of cadmium telluride nanoparticles using a novel single source molecular precursor. The X-ray diffraction pattern confirms the face-centered-cubic structure and average diameter of the nanocrystallite is calculated to be 29.5 nm. SEM image clearly shows the needle-like structure which is further supported by TEM image where agglomerated nanoparticles are clearly seen.