bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-75: Concomitant use of panitumumab (Pmab) had no clinically significant effect on irinotecan (Iri) pharmacokinetics (PK)
Authors: Kennecke Hagen , Wu Chi-Yuan , Chen Eric , Infante Jeffrey , Chen Alin , Gao Bing , Smith Brian , Litten Jason , Yang Bing-Bing 
Published: February 2011

Abstract
Background: Pmab, a fully human monoclonal antibody to the epidermal growth factor receptor (EGFR), is indicated for treatment of EGFR-expressing, chemorefractory, metastatic colorectal cancer (mCRC). This study examined effects of Pmab on Iri PK when used as combination therapy in patients (pts) with mCRC.
Methods: This phase 1, open-label, multicenter, single-arm study enrolled pts with mCRC without prior exposure to an EGFR inhibitor. Pts could not have CYP3A4 inhibiting or inducing medications ≥ 2 weeks before enrollment or UGT1A1*28 TA7/7, TA7/8, and TA8/8 polymorphisms. Pts received Iri (180 mg/m2, 90-min IV infusion) on day 1 cycle 1 followed by Pmab (6 mg/kg, 60-min IV infusion) on day 4 cycle 1. After 2 weeks (day 1 cycle 2), pts received Pmab followed immediately by Iri. Pmab and Iri were administered thereafter every 2 weeks until disease progression or intolerability. Plasma samples for Iri and its active metabolite SN-38 were collected pre-dose and up to 72 hours after Iri infusion in cycles 1 and 2. Primary endpoints were Cmax and AUC of Iri (PK subset), and secondary endpoints included rates of adverse events (AEs).
Results: 28 pts enrolled; 19 of 27 pts who received treatment met PK evaluability criteria (dosed per protocol for 2 cycles with no reductions/delays). PK profiles of Iri with or without Pmab were nearly superimposable. 90% confidence intervals for the ratios of geometric means for Iri Cmax and AUC with or without Pmab were within a prespecified 0.70 to 1.43 interval, suggesting that Pmab had no impact on Iri PK. Similar results were seen for SN-38 PK. AEs were as expected for Iri plus Pmab combination therapy.
Conclusions: Pmab in combination with Iri was generally well tolerated by pts with mCRC. Pmab had no significant effects on Iri PK.PK Profiles of Iri and SN-38 Ratio of Geometric Means Point Estimate Cycle (N = 19)Geometric Mean(Cycle 2 vs Cycle 1)90% CIIri Cmax (ng/mL)115400.9800.894 - 1.074 21510 AUC0-inf (ng·hr/mL)1112000.8980.819-0.985 210100 SN-38 Cmax (ng/mL)125.90.8230.731-0.926 221.3 AUC0-inf (ng·hr/mL)1a3260.8650.773 - 0.968 2b282 aN = 17; bN = 16; CI, Confidence interval; Iri, Irinotecan
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-75.
Abstract LB-89: Claudin-11 (CLDN11): A potential marker of gastric carcinogenesis
Authors: Agarwal Rachana , Mori Yuriko , Cheng Yulan , Jin Zhe , Olaru Alexandru , Hamilton James P. , David Stefan , Selaru Florin M. , Yang Jian , Abraham John , Duncan Mark , Harmon John , Montgomery Elizabeth , Morin Patrice J. , Meltzer Stephen J. 
Published: February 2011

Abstract
Gastric cancer (GC) remains the second most-common cause of cancer deaths globally, with an overall 5-year survival rate below 20%. The poor prognosis of this cancer, due largely to delayed diagnosis, would be greatly improved by the identification of biomarkers to stratify risk and accelerate diagnosis. In search of such markers, a pilot microarray-based genome-wide search conducted by our group identified claudin-11 (CLDN11), a tight junction (TJ) protein, as a potential target of epigenetic inactivation in gastric cancers. Claudin-11 belongs to the family of claudin proteins, which contains more than 23 members. In recent years, it has been demonstrated by us and others that members of the claudin gene family are involved in various human cancers. Our data identified the CLDN11 promoter region as being heavily hypermethylated in GC tissues and cell lines. Moreover, CLDN11 mRNA was found to be expressed only in primary noncancerous gastric mucosal tissues, as well as in an immortalized normal gastric epithelial cell line, whereas it was silenced in all GC tissues and cell lines examined. Interestingly, siRNA-mediated downregulation of CLDN11 in CLDN11-expressing gastric cells was also associated with cancer-related phenotypic changes, specifically increased cell motility and invasiveness. Our recent data also demonstrates that CLDN11 methylation levels can differentiate GC from its corresponding non-cancerous normal gastric mucosae with 100% sensitivity and specificity. A deeper understanding of the timing of CLDN11 inactivation during the development and progression of gastric neoplasia will lead to the development of potential early detection and prognostic biomarkers. Further, large-scale prospective validation studies of this alteration as a predictive biomarker for GC development are warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-89.
Abstract LB-9: DNA binding distinguishes wild-type and mutant p53 activity
Authors: Ray Debolina , Gal Susannah 
Published: February 2011

Abstract
Cell cycle regulation is a function of several regulatory genes such as cyclin G, p21, etc. controlled by p53. Several other genes such as pcna, puma, noxa involved in DNA repair and apoptotic pathways are also coordinated by p53. It is thus understandable that mutations in p53 could result in de-regulation of cell cycle progression, DNA repair, apoptosis, etc. Any imbalance in the above mentioned processes normally culminates in cancer. Our present focus of study is breast cancer where the cells harbor either wild-type or mutant p53. Progression of cancer in cell lines with wild-type p53 indicates a different regulatory switch/pathway responsible for the establishment of this disease. In an effort to understand the functional effect of both wild-type and mutant p53, we have done p53 DNA binding with nuclear extracts from several breast cancer cell lines using two assays. The DNA sequences being considered as target for p53 binding are from genes involved in cell cycle regulatory pathways, DNA repair, apoptosis and p53 regulation. We have observed differences in binding of p53 to some of these gene sequences. Cell lines with wild-type p53 and functional estrogen receptor (ER) bind more to the promoter for pcna and cyclin G than cell lines with mutant p53. The binding to the promoter of the puma gene is more similar between cell lines with mutant and wild-type p53 than the other genes analyzed. We anticipate a certain trend in DNA binding based on the functional status of p53 and its interaction with other proteins such as ER. This trend of p53 binding to different gene sequences may be utilized to better understand the causes of breast cancer, its subsequent progression as well as for designing treatment protocols.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-9.
Abstract LB-91: Identification and feasibility test of novel methylation biomarkers for stool DNA-based colorectal cancer screening
Authors: An Sungwhan , Oh TaeJeong , Moon YoungHo , Kim Nayoung , Lee Seung-Hoon , Kim Nam Kyu , Chung Hyun Cheol , Oh HyunIl 
Published: February 2011

Abstract
Aberrant DNA methylation event is known to be early and frequent process in tumorigenesis and could therefore serve as a convenient biomarker for early detection of cancers. For the identification of novel methylation markers we compared each methylation profiles in super normal tissues (n=2) of healthy individuals and primary tumors and their matched normal appearing adjacent tissues (non-tumor) from colorectal cancer patients (n=12) relative to that of common reference DNA through genome-wide CpG microarray analysis following methylated DNA enrichment with a minimum size of methyl binding domain. Unsupervised hierarchical clustering of with entire methylation pattern data successfully discriminated normal, match-paired normal and primary tumors. We then statistically selected novel methylation candidates showing high frequency of methylation in primary tumor samples and intermediate in non-tumor but no methylation in supernormal tissues for early detection and confirmed in colorectal cancer cell lines by quantitative pyrosequencing-based methylation assay. For final candidates with high specificity, we selected 4 genes, GABRA1, gt-SD, gt-SI, gt-SO which showed a low methylation level in 2 healthy normal tissues. All of 4 genes appeared to be much more frequently hypermethylated in primary tumors than in non-tumor tissues in pyrosequencing assay. For the applicability into non-invasive sample we analyzed methylation status of 4 genes in stool DNAs obtained from patients with colorectal cancer (n=106) and healthy volunteers (n=10) by modified two-round nested MSP for improving analytic sensitivity. The sensitivity and specificity of each of 4 genes were estimated as 50.5% to 60.2% and 85.7% to 100%, respectively. The sensitivity of the four-gene panel was 88.7% (94/106) and its specificity was 80.0% (2/10) in detecting colorectal cancer with stool DNA. Consequently, 4 novel genes have a great potential in noninvasive stool DNA testing for colorectal cancer screening. Further large-scale clinical validation will be needed for clinical setting.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-91.
Abstract LB-96: Id1 enhances RING1b E3 ubiquitin ligase activity through the Mel-18/Bmi-1 polycomb group complex
Authors: Qian Tingting , Lee Jeong-Yeon , Kim Hyun-Jun , Kong Gu 
Published: February 2011

Abstract
The helix-loop-helix inhibitor of differentiation and DNA binding (Id1) is well-known as an oncogene in various tumors. Although it has been reported that Id-1 promotes several oncogenic processes, it is still unclear whether Id1 functions through epigenetic transcriptional regulation. In this study, we examined the effect of Id1 on polycomb group (PcG) proteins, which are crucial epigenetic gene silencers, and found that Id1 regulated the expression of Mel-18 and Bmi-1, both of which belong to PRC1 but not PRC2 complex. We also confirmed that Id1 induced Mel-18 downregulation which was mediated by the Akt pathway, and consequently upregulated the transcription of its target gene c-Myc. Using a promoter-reporter, we demonstrated that Id1 regulated Bmi-1 transcription through c-Myc binding to its E-box in the promoter. Finally, we examined the activity of E3 ligase RING1b whose catalytic activity is increased by binding with the RING finger protein Bmi-1, and found that Id1 over-expression enhanced RING1b E3 ligase activity leading to accumulation of H2A ubiquitination and ubiquitin/proteasome-mediated degradation of Geminin. Taken together, our study provided a novel link between Id1 and PcG proteins and suggested that Id1 may contribute to tumor development through PcG-mediated epigenetic regulation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-96.
Abstract LB-98: DDB1 interacts with Cdh1 and modulates the function of APCCdh1
Authors: Lv Xiao-Bin , Zeng Yi-Xin , Kang Tiebang 
Published: February 2011

Abstract
Control of cell cycle division by the anaphase promoting complex or cyclosome (APC/C) ubiquitin ligase depends on its coactivators, two WD40 repeat proteins, Cdc20 and Cdh1. APC/CCdh1 becomes active during mitotic exit and has essential targets in G1 phase by poorly understood mechanisms. In this report, we provide evidence that DDB1 (Damaged DNA-binding protein 1), a recently identified protein interacting with numerous proteins containing WD40 domains, is capable of binding with the WD40 domains of Cdh1, but not of Cdc20, through its BPA and BPC domains. Moreover, cells lacking DDB1 exhibit markedly elevated protein levels of the substrates for APC/CCdh1, and mitotic cells depleting DDB1 significantly delay mitotic exit, demonstrating that such an interaction between DDB1 and Cdh1 plays a critical role in regulating APC/CCdh1 activity. On the contrary, cells depleting Cdh1 have no effect on the UV-induced degradation of Cdt1, the main function of DDB1 as an E3 ligase. Strikingly, the APCCdh1 substrates are normal in the cells knock-down of Cul4A and CulB, which along with DDB1 forms an E3 ligase complex, indicating that DDB1 modulates the function of APCCdh1 in a manner independent on the Cul4-DDB1 complex. Taken together, DDB1 may functionally regulate the normal mitotic exit by modulating APCCdh1 activity, revealing for the first time that three E3 ligases, DDB1, Cdh1, and Skp2, may cooperate to tightly control cell cycle division.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-98.
Angiographic Vasospasm Is Strongly Correlated With Cerebral Infarction After Subarachnoid Hemorrhage
Authors: Crowley R. Webster , Medel R. , Dumont Aaron S. , Ilodigwe Don , Kassell Neal F. , Mayer Stephan A. , Ruefenacht Daniel , Schmiedek Peter , Weidauer Stephan , Pasqualin Alberto , Macdonald R. Loch 
Published: February 2011

Background and Purpose—
The long-standing concept that delayed cerebral infarction after aneurysmal subarachnoid hemorrhage results exclusively from large artery vasospasm recently has been challenged. We used data from the CONSCIOUS-1 trial to determine the relationship between angiographic vasospasm and cerebral infarction after subarachnoid hemorrhage.

Methods—
We performed a post hoc exploratory analysis of the CONSCIOUS-1 data. All patients underwent catheter angiography before treatment and 9±2 days after subarachnoid hemorrhage. CT was performed before and after aneurysm treatment, and 6 weeks after subarachnoid hemorrhage. Angiograms and CT scans were assessed by centralized blinded review. Angiographic vasospasm was classified as none/mild (0%–33% decrease in arterial diameter), moderate (34%–66%), or severe (≥67%). Infarctions were categorized as secondary to angiographic vasospasm, other, or unknown causes. Logistic regression was conducted to determine factors associated with infarction.

Results—
Complete data were available for 381 of 413 patients (92%). Angiographic vasospasm was none/mild in 209 (55%) patients, moderate in 118 (31%), and severe in 54 (14%). Infarcts developed in 6 (3%) of 209 with no/mild, 12 (10%) of 118 patients with moderate, and 25 (46%) of 54 patients with severe vasospasm. Multivariate analysis found a strong association between angiographic vasospasm and cerebral infarction (OR, 9.3; 95% CI, 3.7–23.4). The significant association persisted after adjusting for admission neurological grade and aneurysm size. Method of aneurysm treatment was not associated with a significant difference in frequency of infarction.

Conclusions—
A strong association exists between angiographic vasospasm and cerebral infarction. Efforts directed at further reducing angiographic vasospasm are warranted.
Subtherapeutic Warfarin Is Not Associated With Increased Hemorrhage Rates in Ischemic Strokes Treated With Tissue Plasminogen Activator
Authors: Vergouwen Mervyn D.I. , Casaubon Leanne K. , Swartz Richard H. , Fang Jiming , Stamplecoski Melissa , Kapral Moira K. , Silver Frank L. 
Published: February 2011

Background and Purpose—
Concern exists that preadmission warfarin use may be associated with an increased risk of intracerebral hemorrhage in patients with ischemic stroke receiving intravenous tissue plasminogen activator, even in those with an international normalized ratio <1.7. However, evidence to date has been derived from a small single-center cohort of patients.

Methods—
We used data from Phase 3 of the Registry of the Canadian Stroke Network. We compared the rates of post-tissue plasminogen activator hemorrhage, including any intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and gastrointestinal hemorrhage in patients with and without preadmission warfarin use. For those receiving warfarin, we restricted the analysis to patients with an international normalized ratio <1.7 on presentation. Secondary outcomes included functional status and mortality. Multivariate analyses were performed to adjust for other prognostic factors.

Results—
Our cohort included 1739 patients with acute ischemic stroke treated with intravenous tissue plasminogen activator of whom 125 (7.2%) were receiving warfarin before admission and had an international normalized ratio <1.7. Preadmission warfarin use was not associated with any secondary intracerebral hemorrhage (OR, 1.2; 95% CI, 0.7 to 2.2), symptomatic intracerebral hemorrhage (OR, 1.1; 95% CI, 0.5 to 2.3), or gastrointestinal hemorrhage (OR, 1.1; 95% CI, 0.2 to 5.6). Multivariate analysis showed that preadmission warfarin use was independently associated with a reduced risk of poor functional outcome (OR, 0.6; 95 CI, 0.3 to 0.9), but not with in-hospital mortality (OR, 0.6; 95% CI, 0.3 to 1.0).

Conclusions—
The results from the present study suggest that tissue plasminogen activator treatment appears to be safe in patients with acute ischemic stroke taking warfarin with an international normalized ratio <1.7 and may reduce the risk of poor functional outcome.
Genes Associated With Adult Cerebral Venous Thrombosis
Authors: Marjot Thomas , Yadav Sunaina , Hasan Nazeeha , Bentley Paul , Sharma Pankaj 
Published: February 2011

Background and Purpose—
Quantitative predictions of the risk of cerebral venous thrombosis (CVT) conferred by certain genotypes have yet to be reliably established. We conducted a comprehensive meta-analysis of all candidate genes studied to assess their genetic contribution to the etiology of CVT. We compared our findings against equivalent analyses for pediatric CVT and adult ischemic stroke.

Methods—
Databases were searched to August 2010 for all genes investigated in adult CVT, and odds ratios (ORs) for each gene-disease association were calculated. A mendelian randomization strategy was also undertaken to determine whether a causal relation to one gene could be ascertained.

Results—

We identified 26 case-control studies investigating 6 polymorphisms in 6 genes and included 1183 CVT cases and 5189 controls. Statistically significant associations with CVT were found for factor V Leiden/G1691A (OR=2.40; 95% CI, 1.75 to 3.30;
P
<0.00001) and prothrombin/G20210A (OR=5.48; 95% CI, 3.88 to 7.74;
P
<0.00001). After iterative analysis controlling for interstudy heterogeneity, methylene tetrahydrofolate reductase/C677T was also found to be significantly associated (OR=2.30; 95% CI, 1.20 to 4.42;
P
=0.02). Variants in the remaining 3 genes (Janus kinase-2, plasminogen activator inhibitor-1, and protein Z) were not significantly associated. Pooled ORs for CVT risk in adults for factor V Leiden and prothrombin were significantly greater when compared against childhood CVT and adult arterial ischemic stroke. A causal relation with methylene tetrahydrofolate reductase may exist.

Conclusions—
CVT has a genetic basis. Genes involved in the clotting cascade provide a greater level of thrombosis risk in the cerebral venous circulation compared with its arterial circulation, and a greater level of risk exists for adults compared with children.
Increased Thyroid Function and Elevated Thyroid Autoantibodies in Pediatric Patients With Moyamoya Disease
Authors: Li Hao , Zhang Zheng-Shan , Dong Zhen-Nan , Ma Mai-Juan , Yang Wei-Zhong , Han Cong , Du Ming-Mei , Liu Yun-Xi , Yang Hong , Liu Wei , Duan Lian , Cao Wu-Chun 
Published: February 2011

Background and Purpose—
The purpose of this study was to investigate whether thyroid function and thyroid autoantibodies were associated with the risk of moyamoya disease in pediatric subjects.

Methods—
Thyroid function and thyroid autoantibodies were evaluated in patients with moyamoya disease and control subjects, and their associations with moyamoya disease were estimated using multivariate analysis.

Results—
We included 114 pediatric patients and 114 healthy control subjects. The patients displayed higher prevalence of increased thyroid function and elevated thyroid autoantibodies in comparison with control subjects. These remained significant after multivariate adjustment; the ORs (95% CI) for increased thyroid function and evaluated thyroid autoantibodies were evaluated as 12.47 (1.55 to 100.51) and 4.33 (1.29 to 14.59), respectively.

Conclusions—
Increased thyroid function and elevated thyroid autoantibodies are associated with moyamoya disease and therefore monitoring of thyroid function and thyroid autoantibodies in patients with moyamoya disease is suggested, which might help to guide subsequent clinical management.
Sea Surface Temperature Biases under the Stratus Cloud Deck in the Southeast Pacific Ocean in 19 IPCC AR4 Coupled General Circulation Models
Authors: Zheng Yangxing , Shinoda Toshiaki , Lin Jia-Lin , Kiladis George N. 
Published: February 2011

Abstract
This study examines systematic biases in sea surface temperature (SST) under the stratus cloud deck in the southeast Pacific Ocean and upper-ocean processes relevant to the SST biases in 19 coupled general circulation models (CGCMs) participating in the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4). The 20 years of simulations from each model are analyzed. Pronounced warm SST biases in a large portion of the southeast Pacific stratus region are found in all models. Processes that could contribute to the SST biases are examined in detail based on the computation of major terms in the upper-ocean heat budget. Negative biases in net surface heat fluxes are evident in most of the models, suggesting that the cause of the warm SST biases in models is not explained by errors in net surface heat fluxes. Biases in heat transport by Ekman currents largely contribute to the warm SST biases both near the coast and the open ocean. In the coastal area, southwestward Ekman currents and upwelling in most models are much weaker than observed owing to weaker alongshore winds, resulting in insufficient advection of cold water from the coast. In the open ocean, warm advection due to Ekman currents is overestimated in models because of the larger meridional temperature gradient, the smaller zonal temperature gradient, and overly weaker Ekman currents.