bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sorafenib Inhibits the Imatinib-Resistant KIT
T670I Gatekeeper Mutation in Gastrointestinal Stromal Tumor
Authors: Guo Tianhua , Agaram Narasimhan P. , Wong Grace C. , Hom Glory , D'Adamo David , Maki Robert G. , Schwartz Gary K. , Veach Darren , Clarkson Bayard D. , Singer Samuel , DeMatteo Ronald P. , Besmer Peter , Antonescu Cristina R. 
Published: August 2007

Abstract
Purpose: Resistance is commonly acquired in patients with metastatic gastrointestinal stromal tumor who are treated with imatinib mesylate, often due to the development of secondary mutations in the KIT kinase domain. We sought to investigate the efficacy of second-line tyrosine kinase inhibitors, such as sorafenib, dasatinib, and nilotinib, against the commonly observed imatinib-resistant KIT mutations (KITV654A, KITT670I, KITD820Y, and KITN822K) expressed in the Ba/F3 cellular system.
Experimental Design: In vitro drug screening of stable Ba/F3 KIT mutants recapitulating the genotype of imatinib-resistant patients harboring primary and secondary KIT mutations was investigated. Comparison was made to imatinib-sensitive Ba/F3 KIT mutant cells as well as Ba/F3 cells expressing only secondary KIT mutations. The efficacy of drug treatment was evaluated by proliferation and apoptosis assays, in addition to biochemical inhibition of KIT activation.
Results: Sorafenib was potent against all imatinib-resistant Ba/F3 KIT double mutants tested, including the gatekeeper secondary mutation KITWK557-8del/T670I, which was resistant to other kinase inhibitors. Although all three drugs tested decreased cell proliferation and inhibited KIT activation against exon 13 (KITV560del/V654A) and exon 17 (KITV559D/D820Y) double mutants, nilotinib did so at lower concentrations.
Conclusions: Our results emphasize the need for tailored salvage therapy in imatinib-refractory gastrointestinal stromal tumors according to individual molecular mechanisms of resistance. The Ba/F3 KITWK557-8del/T670I cells were sensitive only to sorafenib inhibition, whereas nilotinib was more potent on imatinib-resistant KITV560del/V654A and KITV559D/D820Y mutant cells than dasatinib and sorafenib.
AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models
Authors: Davies Barry R. , Logie Armelle , McKay Jennifer S. , Martin Paul , Steele Samantha , Jenkins Richard , Cockerill Mark , Cartlidge Sue , Smith Paul D. 
Published: August 2007

Abstract
Constitutive activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) signaling pathway in human cancers is often associated with mutational activation of BRAF or RAS. MAPK/ERK kinase 1/2 kinases lie downstream of RAS and BRAF and are the only acknowledged activators of ERK1/2, making them attractive targets for therapeutic intervention. AZD6244 (ARRY-142886) is a potent, selective, and ATP-uncompetitive inhibitor of MAPK/ERK kinase 1/2. In vitro cell viability inhibition screening of a tumor cell line panel found that lines harboring BRAF or RAS mutations were more likely to be sensitive to AZD6244. The in vivo mechanisms by which AZD6244 inhibits tumor growth were investigated. Chronic dosing with 25 mg/kg AZD6244 bd resulted in suppression of growth of Colo-205, Calu-6, and SW-620 xenografts, whereas an acute dose resulted in significant inhibition of ERK1/2 phosphorylation. Increased cleaved caspase-3, a marker of apoptosis, was detected in Colo-205 and Calu-6 but not in SW-620 tumors where a significant decrease in cell proliferation was detected. Chronic dosing of AZD6244 induced a morphologic change in SW-620 tumors to a more differentiated phenotype. The potential of AZD6244 in combination with cytotoxic drugs was evaluated in mice bearing SW-620 xenografts. Treatment with tolerated doses of AZD6244 and either irinotecan or docetaxel resulted in significantly enhanced antitumor efficacy relative to that of either agent alone. These results indicate that AZD6244 has potential to inhibit proliferation and induce apoptosis and differentiation, but the response varies between different xenografts. Moreover, enhanced antitumor efficacy can be obtained by combining AZD6244 with the cytotoxic drugs irinotecan or docetaxel. [Mol Cancer Ther 2007;6(8):2209–19]
Rapamycin inhibits multiple stages of c-Neu/ErbB2–induced tumor progression in a transgenic mouse model of HER2-positive breast cancer
Authors: Mosley Jonathan D. , Poirier John T. , Seachrist Darcie D. , Landis Melissa D. , Keri Ruth A. 
Published: August 2007

Abstract
Amplification of the HER2 (ErbB2, c-Neu) proto-oncogene in breast cancer is associated with poor prognosis and high relapse rates. HER2/ErbB2, in conjunction with ErbB3, signals through the Akt/phosphatidylinositol 3-kinase pathway and leads to the activation of mammalian target of rapamycin (mTOR), a critical mRNA translation regulator that controls cell growth. Gene expression analysis of mammary tumors collected from mouse mammary tumor virus-c-Neu transgenic mice revealed that mRNA levels of several mTOR pathway members were either up-regulated (p85/phosphatidylinositol 3-kinase and p70S6 kinase) or down-regulated (eIF-4E-BP1) in a manner expected to enhance signaling through this pathway. Treatment of these mice with the mTOR inhibitor rapamycin caused growth arrest and regression of primary tumors with no evidence of weight loss or generalized toxicity. The treatment effects were due to decreased proliferation, associated with reduced cyclin D1 expression, and increased cell death in primary tumors. Whereas many of the dead epithelial cells had the histopathologic characteristics of ischemic necrosis, rapamycin treatment was not associated with changes in microvascular density or apoptosis. Rapamycin also inhibited cellular proliferation in lung metastases. In summary, data from this preclinical model of ErbB2/Neu-induced breast cancer show that inhibition of the mTOR pathway with rapamycin blocks multiple stages of ErbB2/Neu-induced tumorigenic progression. [Mol Cancer Ther 2007;6(8):2188–97]
Thallium-201 SPECT predicts response to intensity-modulated radiation therapy for recurrent oral squamous cell carcinoma
Authors: Lee J. K. , Liu W. S. , Lin Y. S. , Liu J. T. , Chang L. P. , Chou M. C. , Huang W. S. 
Published: August 2007

SummaryThe aim of this study was designed to investigate the usefulness of thallium-201 single photon emission computed tomography (SPECT) in predicting response of intensitymodulated radiation therapy (IMRT) for recurrent oral squamous cell carcinoma (OSCC). Patients, methods: Thirty-one patients with histologically proven recurrent OSCC were recruited. Before IMRT, all patients underwent SPECT at 15 min and 120 min after intravenous injection 111 MBq of thallous chloride (201Tl). Tumour uptake was measured with the semiquantitative early ratio (ER), delayed ratio (DR), and retention index (RI). The patients were classified into responder (complete response and partial response) and non-responder (stable disease and progressive disease) groups according to the tumour response evaluated by the Response Evaluation Criteria in Solid Tumors guidelines. Results: As comparing DR and RI between the two groups, both parameters were significantly higher in the responder group. When a DR of 1.75 was used as a cutoff value for the responders, the receiver operating characteristic (ROC) analyses revealed sensitivity and specificity of 79% and 75%, respectively. At a cutoff value for the responders of a RI of 78.5%, the ROC analyses showed sensitivity and specificity of 95% and 83%, respectively. Conclusion: Our results suggest that 201Tl-SPECT, as measured by the DR or RI has clinical potential in predicting response of IMRT for patients with recurrent OSCC. The ROC curve analyses further suggest that RI may be superior to DR in distinguishing responders from non-responders.
Guideline for radioiodine therapy for benign thyroid diseases (version 4)
Authors: Dressler J. , Grünwald F. , Leisner B. , Moser E. , Reiners Chr. , Schicha H. , Schneider P. , Schober O. , Dietlein M. ,   für die Deutsche Gesellschaft für Nuklearmedizin (DGN)
Published: August 2007

SummaryVersion 4 of the guideline for radioiodine therapy for benign thyroid diseases includes an interdisciplinary consensus on decision making for antithyroid drugs, surgical treatment and radioiodine therapy. The quantitative description of a specific goiter volume for radioiodine therapy or operation was cancelled. For patients with nodular goiter with or without autonomy, manifold circumstances are in favor of surgery (suspicion on malignancy, large cystic nodules, mediastinal goiter, severe compression of the trachea) or in favor of radioiodine therapy (treatment of autonomy, age of patient, co-morbidity, history of prior subtotal thyroidectomy, profession like teacher, speaker or singer). For patients with Graves' disease, radioiodine therapy or surgery are recommended in the constellation of high risk of relapse (first-line therapy), persistence of hyperthyroidism or relapse of hyperthyroidism. After counseling, the patient gives informed consent to the preferred therapy. The period after radioiodine therapy of benign disorders until conception of at least four months was adapted to the European recommendation.
The Other Rabī': Biographical Traditions and the Development of Early Shāfi'ī Authority
Authors: Jaques R. Kevin 
Published: August 2007

AbstractThis article examines the biographical traditions that developed around al-Rabī b. Sulaymān al-Jīzī (d. 256/872) who, by the Mamlūk period, was widely viewed as a disciple of Muhammad b. Idrīs al-Shāfi'ī (d. 204/820). Against this view, I demonstrate that scholars working in the 4th/10th century depicted al-Jīzī as a follower of the Mālikī movement in Egypt. These scholars also suggested that some traditions transmitted by al-Rabī' b. Sulaymān al-Murādī (d. 270/884) were mistakenly attributed to al-Jīzī. By the 5th/11th century, new legal ideas had surfaced that conflicted with those said to have been transmitted by al-Murādī from al-Shāfi'ī. In order to save al-Murādī's reputation as the faithful and trustworthy transmitter of al-Shāfi'ī's final legal views, al-Jīzī was reinvented as a companion of al-Shāfi'ī so that legal ideas that conflicted with those found in the Kitāb al-umm could be attributed to him instead of al-Murādī.
Judicial Practice in Islamic Criminal Law In Nigeria—a Tentative Overview
Authors: Weimann Gunnar 
Published: August 2007

AbstractUniquely, in Nigeria Islamic Criminal Law was introduced in the framework of a secular federal constitution. In 2000 and 2001, twelve Northern states adopted legislation on the hadd offences and the Islamic law on homicide and bodily harm. Reliable statistics on the number of cases tried under the new laws are unavailable. Based on information from the media and human rights organisations, I present roughly 125 criminal cases tried before Nigerian Sharī'a courts between 2000 and 2004. This sample shows that Sharī'a was particularly enforced in states dominated by the Hausa. In religiously mixed states, the bid to introduce Sharī'a became part of the religious groups' competition for hegemony and access to public resources, with violent consequences. The expectations which many Muslims attached to the introduction of Sharī'a were inflated. Its impact on the security of life and property, the fight against corruption and the promotion of good governance has probably been minimal.
Judicial Activism and Islamic Family Law: A Socio-Legal Evaluation of Recent Trends in Bangladesh
Authors: Hoque Ridwanul , Khan MD. Morshed Mahmud 
Published: August 2007

AbstractThis article critically examines instances of judicial activism in the field of Islamic family law in Bangladesh in an attempt to assess this judicial trend. Seeing 'judicial activism' mainly as an enlightened application of ijtihād and also as society-specific application of statutes based on, or related to sharī'ah, we highlight the justice-ameliorative role of this concept. The authors argue that judicial activism has led to the amelioration of the status of women in Bangladesh as compared to a traditional construction of the sharī'ah, and that judges have adequate authority and legitimacy to develop Islamic family law to ensure better justice in the home. We conclude that modernist judicial reform is not only desirable but also inevitable in the current South Asian socio-legal milieu, where legislative passivity vis-à-vis Islamic family law prevails.
"Learning to Speak Horse": The Culture of "Natural Horsemanship"
Authors: Birke Lynda 
Published: August 2007

AbstractThis paper examines the rise of what is popularly called "natural horsemanship" (NH), as a definitive cultural change within the horse industry. Practitioners are often evangelical about their methods, portraying NH as a radical departure from traditional methods. In doing so, they create a clear demarcation from the practices and beliefs of the conventional horse-world. Only NH, advocates argue, properly understands the horse. Dissenters, however, contest the benefits to horses as well as the reliance in NH on disputed concepts of the natural. Advocates, furthermore, sought to rename technologies associated with riding while simultaneously condemning technologies used in conventional training (such as whips). These contested differences create boundaries and enact social inclusion and exclusion, which the paper explores. For horses, the impact of NH is ambiguous: Depending on practitioners, effects could be good or bad. However, for the people involved, NH presents a radical change—which they see as offering markedly better ways of relating to horses and a more inclusive social milieu.
Imaging Extinction: Disclosure and Revision in Photographs of the Thylacine (Tasmanian tiger)
Authors: Freeman Carol 
Published: August 2007

AbstractThe thylacine was a shy and elusive nonhuman animal who survived in small numbers on the island of Tasmania, Australia, when European settlers arrived in 1803. After a deliberate campaign of eradication, the species disappeared 130 years later. Visual and verbal constructions in the nineteenth century labeled the thylacine a ferocious predator, but photographs of individuals in British and American zoos that were used to illustrate early twentieth-century zoological works presented a very different impression of the animal. The publication of these photographs, however, had little effect on the relentless progress of extermination. This essay focuses on the relationship between photographs of thylacines and the process of extinction, between images and words, and between pictures of dead animals and live ones. The procedures, claims, and limitations of photography are crucial to the messages generated by these images and to the role they played in the representation of the species. This essay explains why the medium of photography and pleas for preservation could not save the thylacine.
How Ravens Came to the Tower of London
Authors: Sax Boria 
Published: August 2007

AbstractAccording to popular belief, Charles II of England (reigned 1660-1685) once heard a prophecy that if ravens left the Tower of London it would "fall," so he ordered that the wings of seven ravens in the Tower be trimmed. Until recently, this claim was not challenged even in scholarly literature. There are, however, no allusions to the Tower Ravens before the end of the nineteenth century. The ravens, today meticulously cared for by Yeoman Warders, are largely an invented tradition, designed to give an impression of continuity with the past. This article examines the few known references, both graphic and textual, to the Tower Ravens through 1906. It concludes that the ravens were originally brought in to dramatize the alleged site of executions at the Tower. Although not accorded great significance at first, legends that would eventually make the ravens mascots of Britain began outside of the Tower.
Nematodes of the order Rhabditida from Tehran province, Iran. The genus Acrobeles von Linstow, 1877 with description of A. iranicus sp. n.
Authors: Shokoohi Ebrahim , Abolafia Joaquín , Zad Javad 
Published: August 2007

AbstractA new species of the genus Acrobeles is described from natural areas in Tehran province, Iran. Acrobeles iranicus sp. n. is characterised by having a body 400–441 μ m long in females, 'double' cuticle with rows of interannular punctations, lateral field with two incisures, labial probolae 9–12 μ m long, pharyngeal corpus slightly fusiform and 2–4 times isthmus length, postuterine sac 5–15 μ m or 0.2–0.5 times as long as body diam. and bearing larger cells in its proximal part and conical female tail (31–36 μ m, c = 11.5–13.6, c′ = 2.3–2.9). In addition, Iranian populations of another three previously known species are studied: A. andalusicus, A. complexus and A. singulus, the third species having the male described for the first time. Descriptions, measurements and illustrations, including SEM photographs, are provided for all four species.
Tenuidraconema tongaense n. sp. (Nematoda: Draconematidae), a new free-living marine nematode from a seamount in the southwest Pacific Ocean
Authors: Rho Hyun Soo , Min Won Gi , Kim Dong Sung 
Published: August 2007

Abstract
A new species of free-living marine draconematid nematode, Tenuidraconema
tongaense n. sp., is described. This new species was collected from shallow
subtidal dead corals and detritus from a seamount in a hydrothermal area off
the Tonga Islands, southwest Pacific Ocean. Tenuidraconema tongaense n. sp.
differs from the known species of the genus by the following combination of
characters: longer body (1060-1265 μ m), position of 12 cephalic adhesion
tubes (anterior six cephalic adhesion tubes inserted on rostrum and
posterior six adhesion tubes inserted on anterior body annule in male; all
12 cephalic adhesion tubes inserted on rostrum in female), number of
posterior sublateral adhesion tubes (11 in male, 12 in female) and posterior
subventral adhesion tubes (9-11 in male, 10-11 in female) with somatic setae
intermingled between the two anteriormost sublateral adhesion tubes, longer
spicule length (43-50 μ m), and slender body (a = 41.1-48.6 in male and
29.4-35.1 in female). A pictorial key and a dichotomous identification key
for males and females are provided for the species. A table comparing the
major differential diagnostic characteristics of the species of
Tenuidraconema is presented.
The effect of five composts of different origin on the survival and reproduction of Globodera rostochiensis
Authors: Renčo Marek , D'Addabbo Trifone , Sasanelli Nicola , Papajová Ingrid 
Published: August 2007

AbstractFive composts of different origin (C1: fresh olive pomace, straw, chicken manure and urea; C2: fresh olive pomace, cow manure, lettuce residues, straw and sawdust; C3: sewage sludge and municipal green residues; C4: grass, leaves, tree branches and soil; C5: by-product from penicillin production (mycelium), straw and sawdust, were tested for the control of the cyst nematode, Globodera rostochiensis, on potato in pot experiments. Composts were mixed with the nematode-infested soil at the rates of 1.0, 2.5, 5.0 and 10.0% w/w. A significant reduction in the number of eggs and juveniles was observed at all concentrations of the tested composts; compost from olive pomace mixed with urea resulted in the greatest decrease.
The embryonic cell lineage of the nematode Halicephalobus gingivalis (Nematoda: Cephalobina: Panagrolaimoidea)
Authors: Houthoofd Wouter , Borgonie Gaëtan 
Published: August 2007

AbstractThis paper describes the nearly complete embryonic cell lineage of the terrestrial nematode, Halicephalobus gingivalis, up to somatic muscle contraction, resulting in the formation of 536 cells, of which 24 undergo programmed cell death. Halicephalobus gingivalis has a 94% lineage homology with both Caenorhabditis elegans and Pellioditis marina, and a fate homology of only 86% and 78%, respectively. Although H. gingivalis belongs to a different superfamily than C. elegans and P. marina, its cell lineage is remarkably consistent with them. Variations in the fate distribution of cells among the different species were only observed at the end of the cell lineage. The data presented here show that the polyclonal cell specification is much more widespread in clades 9 and 10 and is not a highly derived trait that is specifically linked to the fast development of the model organism C. elegans.
Reliability of PCR-based techniques for detection and discrimination of plant-parasitic nematodes of sugarcane
Authors: Berry Shaun , Fargette Mireille , Morand Serge , Cadet Patrice 
Published: August 2007

Abstract
In order to develop diagnostic tools for plant-parasitic nematodes of
sugarcane in South Africa, this work investigated the potential biodiversity
of these nematodes in the amount of nucleic acid available, the
discrimination of species by a PCR-based method (targeting the ITS1 region)
and the effect of some experimental conditions on their detection or
discrimination. The ITS1 amplified fragment varied in size, ranging from 400
bp (Meloidogyne javanica) to 1200 bp (Longidorus pisi, Paratrichodorus
minor, Xiphinema elongatum, Xiphinema zulu). Some species discrimination was
possible by discernible differences in ITS1 amplified fragment sizes. The
potential, as well as shortcomings (inhibitions, competition) of this
approach are assessed and further steps/outcomes discussed. Part of the work
also focused on DNA extraction. Nematode genomic nucleic acid was extracted
from five nematode species (Pratylenchus zeae, Helicotylenchus dihystera,
Meloidogyne javanica, Xiphinema elongatum and Paratrichodorus lobatus) and
we discuss the significant differences obtained between species in the
amount of nucleic acid extracted. There were also marked differences in the
quantity and quality of nucleic acid extracted from nematode suspensions
originating from soils, depending on the extraction buffer used.
How do nematodes get their sweets? Solute supply to sedentary plant-parasitic nematodes
Authors: Hofmann Julia , Grundler Florian 
Published: August 2007

AbstractSedentary cyst and root-knot nematodes withdraw large amounts of solutes from feeding structures induced in host roots. The feeding structures are specialised cells with a high metabolic activity and a tremendous capacity in translocation of nutrients. The required nutrients are provided by the plant transport systems – water and inorganic solutes from the xylem, assimilates such as sugars and amino acids from the phloem. Here we discuss the available data on the mechanisms by which nutrients are translocated into the nematode feeding sites. The interaction between Heterodera schachtii and Arabidopsis thaliana serves as a model system for cyst nematodes. In this case sufficient data are available to propose a conclusive concept for the mechanisms of nutrient flow: basically, in the early stages of nematode development syncytia are symplasmically isolated, so that transport proteins are responsible for the nutrient supply. Later, connections to the phloem via plasmodesmata are established, so that developing females are well supplied with assimilates. The interactions of root-knot nematodes with their hosts share a number of similarities but the data currently available are not sufficient to draw similar conclusions. As nutrient supply and functionality of feeding structures are the basis of biotrophic parasitism of sedentary nematodes, it is tempting to unravel the mechanisms by which both plant and nematodes influence each other via nutrient fluxes.