bluuebunny/crossref_metadata_2025_split huggingface dataset:
Newer Pathologic Assessment Techniques for Colorectal Carcinoma
Authors: Turner Roderick R. , Li Carolyn , Compton Carolyn C. 
Published: November 2007

Abstract
The pathogenesis of colorectal carcinoma is characterized by progressive genetic abnormalities, which lead to proteomic and cellular changes that determine the cancer malignant phenotype. Phenotypic characteristics seen on histopathologic examination (e.g., tumor stage, histologic grade, and vasoinvasiveness) are essential to planning patient management and should continue to be the major focus of pathologists' efforts. Nonetheless, additional markers that improve the prognostic and predictive power of the pathologic analysis of the primary tumor have been the focus of intense research in recent years. Improved prognostic power may derive from advancements in histopathologic evaluation, more sensitive lymph node staging techniques, and specific molecular analysis methods, such as genetic tests or immunophenotypic profiles. Histopathologic improvements are needed to better standardize histologic grade determination and recognize tumor budding at the invasive front as a marker of aggressive biological behavior and an adverse parameter. Ultrastaging of mesenteric lymph nodes remains a controversial area. Genotypic studies are well developed in the areas of microsatellite instability and chromosome 18q deletion/loss of heterozygosity. Immunophenotypic studies are available in a range of areas including tumor suppressor gene/oncogene expression, proliferation/apoptosis, angiogenesis, and cell adhesion and signaling. Gene expression profiles identified by microarray techniques may help to subtype the large category of microsatellite-stable colorectal carcinoma and define immunophenotypic panels to subclassify tumors into prognostic and therapeutic groups. This brief review discusses the most promising of these approaches and evidence supporting their potential clinical utility.
New Approaches to Assessing and Treating Early-Stage Colon and Rectal Cancers: Cooperative Group Strategies for Assessing Optimal Approaches in Early-Stage Disease
Authors: Benson Al B. 
Published: November 2007

Abstract
The U.S. Gastrointestinal Intergroup (GI Intergroup), including the National Cancer Institute of Canada, has created a portfolio of clinical trials for patients with stage II and III colon and rectal cancer, integrating therapeutic strategies from recent advanced disease trials. Fluoropyrimidine-based combination therapy for metastatic disease, with either irinotecan or oxaliplatin plus bevacizumab, has resulted in significant improvement in response and disease-free and overall survival. Cetuximab and irinotecan have produced intriguing response and progression-free survival data from randomized phase II trials. Although patients with stage II and III rectal cancer are uniformly included in individual clinical trials, the GI Intergroup conducts separate trials in patients with stage II and III colon cancer, with the exception of the National Surgical Adjuvant Breast and Bowel Project (NSABP), which continues to merge both stages in their statistical designs. The U.S. chemotherapy platform for adjuvant therapy clinical trials is based on the positive adjuvant data from NSABP C-07 [FLOX with bolus 5-fluorouracil (5-FU)] and the MOSAIC trial (FOLFOX with infusional 5-FU). Three irinotecan-based adjuvant trials (one U.S. and two European) did not reach designated statistical end points. In addition, the GI Intergroup has consistently integrated molecular biological and other laboratory projects as important components of past and current trials. NSABP has recently completed accrual of patients to C-08, which is evaluating FOLFOX with or without bevacizumab in stage II/III colon cancer. E5202, the largest U.S. stage II colon cancer trial, determines patient risk by the initial evaluation of tumor 18q loss of heterozygosity and microsatellite instability status. Low-risk patients are observed, whereas high-risk patients are randomized to FOLFOX with or without bevacizumab. N0147 evaluates FOLFOX with or without cetuximab in patients with stage III disease. Two large rectal cancer trials have begun to accrue patients. NSABP R-04 compares neoadjuvant radiation with either continuous infusion 5-FU with or without oxaliplatin versus capecitabine with or without oxaliplatin. E5204 is the adjuvant comparison of FOLFOX with or without bevacizumab and is also available to NSABP R-04 patients.
Clinical Significance of Epidermal Growth Factor Receptor Protein Overexpression and Gene Copy Number Gains in Prostate Cancer
Authors: Schlomm Thorsten , Kirstein Patrick , Iwers Liv , Daniel Birte , Steuber Thomas , Walz Jochen , Chun Felix H.K. , Haese Alexander , Kollermann Jens , Graefen Markus , Huland Hartwig , Sauter Guido , Simon Ronald , Erbersdobler Andreas 
Published: November 2007

Abstract
Purpose: The epidermal growth factor receptor (EGFR) is a protein involved in the tumor progression of many cancer types and is an important therapeutic target. To determine its role in prostate cancer, we analyzed 2,497 prostate cancers on the DNA and protein level.
Experimental Design: Tissue samples from each tumor were brought into a tissue microarray and analyzed by immunohistochemistry and fluorescence in situ hybridization. A subset of cancers was also sequenced for EGFR exon 18 to 21 mutations.
Results: Detectable EGFR expression was found in 18% of cancers and was significantly associated with high grade, advanced stage, and high risk for prostate-specific antigen recurrence in univariate analysis (P &lt; 0.0001, each). Fluorescence in situ hybridization analysis with a dual-labeling probe for centromere 7 and EGFR showed increased EGFR copy number in 3.3% of cases. EGFR copy number gains were mostly due to an overrepresentation of the entire chromosome and were associated with EGFR protein expression (P &lt; 0.0001), high grade (P &lt; 0.0001), and advanced stage (P = 0.0056). Only one cancer had a high-level amplification (&gt;20 EGFR gene copies per cell). This amplification was heterogeneous, involving only ∼30% of the cancer volume. EGFR mutations were not found in 35 of the cases analyzed.
Conclusion: Increased EGFR expression is often seen in prostate cancer and is associated with poor prognosis. The significant association of EGFR copy number gains with protein expression argues for the significant role of minimal gene copy number changes for protein expression. Although EGFR expression was not an independent prognostic variable, the potential utility of anti-EGFR medications might be worth further investigation in EGFR-expressing prostate cancer.
Activation of KIF4A as a Prognostic Biomarker and Therapeutic Target for Lung Cancer
Authors: Taniwaki Masaya , Takano Atsushi , Ishikawa Nobuhisa , Yasui Wataru , Inai Kouki , Nishimura Hitoshi , Tsuchiya Eiju , Kohno Nobuoki , Nakamura Yusuke , Daigo Yataro 
Published: November 2007

Abstract
Purpose and Experimental Design: To identify molecules that might be useful as diagnostic/prognostic biomarkers and as targets for the development of new molecular therapies, we screened genes that were highly transactivated in a large proportion of 101 lung cancers by means of a cDNA microarray representing 27,648 genes. We found a gene encoding KIF4A, a kinesin family member 4A, as one of such candidates. Tumor tissue microarray was applied to examine the expression of KIF4A protein and its clinicopathologic significance in archival non–small cell lung cancer (NSCLC) samples from 357 patients. A role of KIF4A in cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of KIF4A on mammalian cells was examined using Matrigel assays.
Results: Immunohistochemical staining detected positive KIF4A staining in 127 (36%) of 357 NSCLCs and 19 (66%) of 29 small-cell lung cancers examined. Positive immunostaining of KIF4A protein was associated with male gender (P = 0.0287), nonadenocarcinoma histology (P = 0.0097), and shorter survival for patients with NSCLC (P = 0.0005), and multivariate analysis confirmed its independent prognostic value (P = 0.0012). Treatment of lung cancer cells with small interfering RNAs for KIF4A suppressed growth of the cancer cells. Furthermore, we found that induction of exogenous expression of KIF4A conferred cellular invasive activity on mammalian cells.
Conclusions: These data strongly implied that targeting the KIF4A molecule might hold a promise for the development of anticancer drugs and cancer vaccines as well as a prognostic biomarker in clinic.
Phase 2 Study of ABT-510 in Patients with Previously Untreated Advanced Renal Cell Carcinoma
Authors: Ebbinghaus Scot , Hussain Maha , Tannir Nizar , Gordon Michael , Desai Apurva A. , Knight Raymond A. , Humerickhouse Rod A. , Qian Jiang , Gordon Gary B. , Figlin Robert 
Published: November 2007

Abstract
Purpose: Angiogenesis is a characteristic of renal cell carcinoma. ABT-510 is an angiogenesis inhibitor that mimics the antiangiogenic properties of thrombospondin-1. This study was designed to assess the safety and efficacy of ABT-510 in patients with advanced renal cell carcinoma.
Experimental Design: Patients with previously untreated metastatic or unresectable renal cell carcinoma were randomized to treatment with one of two doses of ABT-510, self-administered s.c. twice daily in 28-day treatment periods without intervening rest periods. End points were progression-free survival (PFS), objective response rate, overall survival, and toxicity.
Results: The objective response rate was 4% in the 10 mg twice daily group, and there were two unconfirmed PRs in the 100 mg twice daily group. Respective median PFS was 4.2 and 3.3 months, with a 6-month PFS of 39% and 32%. Median overall survival was 27.8 months (10 mg twice daily) and 26.1 months (100 mg twice daily). The most frequent adverse events were injection site reactions (84%), fatigue (50%), headache (20%), and nausea (19%). The incidence of treatment-related, grade 3/4 adverse events was low and included three bleeding episodes (gastrointestinal hemorrhage, intracranial hemorrhage, and hemoptysis) and one thrombotic event (deep vein thrombosis). No deaths were attributed to ABT-510.
Conclusions: There was little evidence of clinical activity for ABT-510, and further evaluation as a single agent for treating advanced renal cell carcinoma is not warranted. The evidence of a favorable safety profile may justify further evaluation in combination therapy.
Schisandrin B Prevents Doxorubicin-Induced Cardiotoxicity via Enhancing Glutathione Redox Cycling
Authors: Li Ling , Pan Qiangrong , Han Weidong , Liu Zhen , Li Ling , Hu Xun 
Published: November 2007

Abstract
Purpose: The dose-cumulative cardiotoxicties and the emerging cancerous apoptotic/drug resistance are two major obstacles limiting the efficacy of anthracycline antibiotics, notably doxorubicin. We attempted to prove if schisandrin B (Sch B), a dual inhibitor of P-glycoprotein and multidrug resistance–associated protein 1, could protect against doxorubicin-induced cardiotoxicity, on the premise that Sch B is an enhancer of glutathione redox cycling that may attenuate doxorubicin-induced oxidative stress in the cardiomyocytes.
Experimental Design: Mice or rat were dosed with a single injection of doxorubicin (25 mg/kg, i.p.) with or without pretreatment of Sch B. The protective roles of Sch B against doxorubicin-induced cardiac damage were evaluated on the aspects of the release of cardiac enzymes into serum, the formation of malondialdehyde, the activation of matrix metalloproteinase, the structural damage in the left ventricles, the mortality rates, and the cardiac functions.
Results: Pretreatment of Sch B significantly attenuated doxorubicin-induced cardiotoxicities on all the aspects listed above. The underlying mechanism was associated with the effect of Sch B on maintaining the cardiomyocytic glutathione and the activities of superoxide dismutase, and the key enzymes (glutathione peroxidase, glutathione reductase, and glutathione transferase) responsible for glutathione redox cycling, which neutralized doxorubicin-induced oxidative stress.
Conclusion: To the best of our knowledge, Sch B is the only molecule ever proved to function as a cardioprotective agent as well as a dual inhibitor of P-glycoprotein and multidrug resistance–associated protein 1, which is potentially applicable to treat cancers, especially the multidrug-resistant cancers involving doxorubicin or its kin.
The Epidermal Growth Factor Receptor: A Role in Repair of Radiation-Induced DNA Damage
Authors: Chen David J. , Nirodi Chaitanya S. 
Published: November 2007

AbstractThe epidermal growth factor receptor (EGFR), which is frequently expressed in tumors of epithelial origin, is an important determinant of tumor responses to ionizing radiation. Elevated EGFR expression and activity frequently correlate with tumor resistance to radiotherapy in patients. EGFR is thought to confer tumor resistance to radiation through the activation of survival and cell proliferation pathways. Recent discoveries have identified a novel radioprotective function of EGFR which involves the radiation-induced nuclear translocation of the receptor and its interactions with the DNA-dependent protein kinase, a key component of the nonhomologous end-joining DNA repair pathway. Targeting the DNA repair function of EGFR may serve as a therapeutic model for sensitizing tumors to radiotherapy in patients.
Integrated Contextual Representation for Objects' Identities and Their Locations
Authors: Gronau Nurit , Neta Maital , Bar Moshe 
Published: November 2007

Abstract
Visual context plays a prominent role in everyday perception. Contextual information can facilitate recognition of objects within scenes by providing predictions about objects that are most likely to appear in a specific setting, along with the locations that are most likely to contain objects in the scene. Is such identity-related (“semantic”) and location-related (“spatial”) contextual knowledge represented separately or jointly as a bound representation? We conducted a functional magnetic resonance imaging (fMRI) priming experiment whereby semantic and spatial contextual relations between prime and target object pictures were independently manipulated. This method allowed us to determine whether the two contextual factors affect object recognition with or without interacting, supporting a unified versus independent representations, respectively. Results revealed a Semantic × Spatial interaction in reaction times for target object recognition. Namely, significant semantic priming was obtained when targets were positioned in expected (congruent), but not in unexpected (incongruent), locations. fMRI results showed corresponding interactive effects in brain regions associated with semantic processing (inferior prefrontal cortex), visual contextual processing (parahippocampal cortex), and object-related processing (lateral occipital complex). In addition, activation in fronto-parietal areas suggests that attention and memory-related processes might also contribute to the contextual effects observed. These findings indicate that object recognition benefits from associative representations that integrate information about objects' identities and their locations, and directly modulate activation in object-processing cortical regions. Such context frames are useful in maintaining a coherent and meaningful representation of the visual world, and in providing a platform from which predictions can be generated to facilitate perception and action.
Neurodynamics of the Prefrontal Cortex during Conditional Visuomotor Associations
Authors: Loh Marco , Pasupathy Anitha , Miller Earl K. , Deco Gustavo 
Published: November 2007

Abstract
The prefrontal cortex is believed to be important for cognitive control, working memory, and learning. It is known to play an important role in the learning and execution of conditional visuomotor associations, a cognitive task in which stimuli have to be associated with actions by trial-and-error learning. In our modeling study, we sought to integrate several hypotheses on the function of the prefrontal cortex using a computational model, and compare the results to experimental data. We constructed a module of prefrontal cortex neurons exposed to two different inputs, which we envision to originate from the inferotemporal cortex and the basal ganglia. We found that working memory properties do not describe the dominant dynamics in the prefrontal cortex, but the activation seems to be transient, probably progressing along a pathway from sensory to motor areas. During the presentation of the cue, the dynamics of the prefrontal cortex is bistable, yielding a distinct activation for correct and error trails. We find that a linear change in network parameters relates to the changes in neural activity in consecutive correct trials during learning, which is important evidence for the underlying learning mechanisms.
Functional Magnetic Resonance Imaging Evidence for Abnormalities in Response Selection in Attention Deficit Hyperactivity Disorder: Differences in Activation Associated with Response Inhibition but Not Habitual Motor Response
Authors: Suskauer Stacy J. , Simmonds Daniel J. , Fotedar Sunaina , Blankner Joanna G. , Pekar James J. , Denckla Martha B. , Mostofsky Stewart H. 
Published: November 2007

Abstract
Impaired response inhibition is thought to be a core deficit in attention deficit hyperactivity disorder (ADHD). Prior imaging studies investigating response inhibition in children with ADHD have used tasks involving different cognitive resources, thereby complicating the interpretation of their findings. In this study, a classical go/no-go task with a well-ingrained stimulus-response association (green = go; red = no-go) was used in order to minimize extraneous cognitive demands. Twenty-five children with ADHD and 25 typically developing (TD) children between the ages of 8 and 13 years and group-matched for IQ and performance on the go/no-go task were studied using event-related functional magnetic resonance imaging (fMRI). Analyses were used to examine differences in activation between the ADHD and TD groups for “go” (habitual motor response) and “no-go” (requiring inhibition of the motor response) events. Region-of-interest analyses revealed no between-group difference in activation in association with “go” events. For “no-go” events, the children with ADHD demonstrated significantly less activation than did TD controls within a network important for inhibiting a motor response to a visual stimulus, with frontal differences localized to the pre-supplementary motor area. Although blood oxygenation level-dependent fMRI data show no differences between children with ADHD and TD children in association with a habituated motor “go” response, during “no-go” events, which require selecting not to respond, children with ADHD show diminished recruitment of networks important for response inhibition. The findings suggest that abnormalities in circuits important for motor response selection contribute to deficits in response inhibition in children with ADHD and lend support to the growing awareness of ADHD-associated anomalies in medial frontal regions important for the control of voluntary actions.
Knowledge-based Correction of Flash-lag Illusion
Authors: Noguchi Yasuki , Kakigi Ryusuke 
Published: November 2007

Abstract
A flash is perceived to lag spatially behind a moving object even when the two retinal images are physically aligned (flash-lag effect, FLE). Here we show that this robust illusion can be diminished by a knowledge of letters in the observer's brain. When moving and flashed segments in the FLE made the shape of a Kanji letter (ideographic characters used in Japan), the magnitude of the illusory lag perceived by Japanese subjects was significantly reduced compared to when conventional geometric (nonletter) segments were used. This diminishment was not observed when a pseudo-Kanji letter was presented to Japanese subjects or when non-Japanese English-speakers (who do not have a knowledge of Kanji) saw a real Kanji letter, indicating that the reduction in the FLE was induced by a retrieval of the knowledge (shapes of letters) stored in the observer's brain. Furthermore, measurements of neural activities by magnetoencephalography showed that the initial brain response, in which the effect of the knowledge became evident, occurred as early as 160 msec after the appearance of the flashed segment. These results demonstrated a substantial influence of knowledge on the flash-lag illusion and further suggest a rapid response of the knowledge-based perceptual pathway in the human brain.
Perception and Understanding of Others' Actions and Brain Connectivity
Authors: Pavlova Marina , Sokolov Alexander N. , Birbaumer Niels , Krägeloh-Mann Ingeborg 
Published: November 2007

Abstract
Perception and understanding of dispositions and intentions of others through their actions are of immense importance for adaptive daily-life behavior and social communication. Here we ask whether, and, if so, how this ability is impaired in adolescents who were born premature and suffer early periventricular damage, periventricular leukomalacia (PVL) that affects brain connectivity. The visual event arrangement (EA) task was administered to PVL patients and two control groups, premature-born and term-born adolescents without brain abnormalities on a magnetic resonance imaging scan. Performance on the EA task was significantly lower in PVL patients as compared with controls. No difference was found between premature-born participants without lesions and term-born controls. Performance on the EA task was inversely related to the volumetric extent of lesions in the parieto-occipital regions of both hemispheres and, in particular, to the right temporal periventricular lesions. Whereas our earlier work reveals that compromised visual processing of biological motion, impairments in visual navigation, and other visual-perceptual disabilities in PVL patients are associated with parieto-occipital lesions, difficulties in the visual EA task solely are specifically linked to the right temporal periventricular lesions. For the first time, we show that the severity of the right temporal PVL can serve as a predictor of the ability for perception and understanding of others' actions. We assume that impairments in this ability in PVL patients are caused by disrupted brain connectivity to the right temporal cortex, a key node of the social brain.