bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-53: Paclitaxel inhibits microtubule detachment from centrosomes
Authors: Ganguly Anutosh , Yang Hailing , Cabral Fernando 
Published: February 2011

Abstract
Paclitaxel has been reported to inhibit cell division by suppressing microtubule dynamics at low concentrations that do not alter microtubule polymer levels. Although our studies confirm that paclitaxel suppresses microtubule dynamics at low concentrations, we show that suppression of dynamics is insufficient to inhibit cell proliferation. Wild-type CHO cells exhibited a dose-dependent decrease in microtubule dynamicity that reached a minimum at concentrations that had no observable effect on the ability of the cells to divide. Moreover, paclitaxel-dependent mutant cells that assemble reduced amounts of microtubule polymer and require paclitaxel for proliferation, exhibited a similar dose response for suppression of dynamics but much higher drug concentrations were needed to restore cell division. Thus, maximal suppression of microtubule dynamics neither inhibited the proliferation of wild-type cells, nor rescued cell division in paclitaxel-dependent cells. Instead, the higher concentrations of drug needed to restore mutant cell division caused the disappearance of microtubule fragments commonly seen in these cell lines. Using live cell imaging, we found that microtubule fragments are generated by detachment from microtubule organizing centers, and that paclitaxel acts to prevent this detachment, thereby raising microtubule polymer levels. We conclude that low paclitaxel concentrations act at microtubule plus ends to inhibit dynamics, but that higher concentrations are needed to inhibit cell division and prevent microtubule detachment from organizing centers.
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-53.
Abstract LB-69: Targeting CK2 with small molecule CX-4945 modulates NF-kappaB, TP53 and cell survival in head and neck squamous cell carcinoma
Authors: Kannabiran Vishnu , Friedman Jay , Lu Hai , Anderes Kenna , Chen Zhong , Van Waes Carter 
Published: February 2011

Abstract
Objective: We previously identified CK2 as an upstream kinase activating NF-kappaB and modulating TP53 mediated signaling pathways. Up regulated CK2 activity is implicated in promoting the malignant phenotype and progression of head and neck squamous cell carcinoma (HNSCC). Here, we investigate the antitumor effects of CX-4945, a selective small molecule inhibitor of CK2.
Design: The effects of CX-4945 on cell proliferation were measured by MTT assay in a panel of 9 University of Michigan squamous cell carcinoma (UM-SCC) cell lines. The half maximal inhibitory concentration (IC50) was determined in vitro. CX-4945 inhibition of cell cycle and induction of cell death were measured by DNA flow cytometry. The effects of CX-4945 on the activity of NF-kappaB, BCL-XL, and TP53 promoters were tested by the chemiluminescent reporter gene assay. The anti-tumor activity of orally administered CX-4945 was evaluated in SCID mice bearing UM-SCC-11A xenografts.
Results: The IC50 in 9 UM-SCC cell lines ranged from 3.4 µM to 11.7 µM. The UM-SCC-11A cell line used for in vivo studies had an IC50 of 4.07 µM in vitro. CX-4945 showed a concentration and time dependent cell cycle arrest in G1 and G2/M phases accompanied by a significant induction of sub-G0 cells indicating cell death. CK2 inhibition with CX-4945 downregulated the reporter activities of survival-promoting genes such as NF-kappaB and BCL-XL and up regulated the reporter activity of apoptosis-promoting gene TP53 in a concentration and time dependent manner. Furthermore, CX-4945 (75 mg/kg) showed significant tumor growth inhibition (31% (p&lt;0.05)) in UM-SCC-11A xenografts compared to the control group.
Conclusions: Inhibition of CK2 via CX-4945 reveals anti-proliferative activity and modulation of NF-kappaB activation in HNSCC cell lines. In vivo studies show significant antitumor activity in a bortezomib-resistant HNSCC xenograft model. CK2 is an unexploited target in HNSCC and CX-4945 demonstrates the potential of a therapeutic agent with this novel mechanism of action for the treatment of head and neck cancers. (Supported by NIDCD intramural project ZIA DC-000016)
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-69.
Abstract LB-71: Stage Ia vs. Ib endometrial stromal sarcoma: Does the new staging system predict survival
Authors: Garg Gunjal , Shah Jay P. , Morris Robert T. 
Published: February 2011

Abstract
Background: In 2008, a new FIGO staging system was specifically designed and approved for endometrial stromal sarcoma. Our objective was to determine the impact of this new staging system on survival in patients with stage I endometrial stromal sarcoma (ESS).
Methods: Data were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Kaplan-Meier log rank and Cox proportional hazards models were used for survival analysis and to identify possible predictors for survival.
Results: The identified cohort included 464 women, with 310 (67%) low-grade endometrial stromal sarcoma (LGESS), 96 (21%) high-grade endometrial stromal sarcoma (HGESS), and 58 (12%) unclassified ESS. LGESS compared to HGESS differed significantly with regards to the patient age (48 vs. 60 years, p&lt;0.001), tumor size (5.6 cm vs. 8.0 cm, p&lt;0.001), cervical involvement (5.2% vs. 18.8%, p&lt;0.001), myometrial invasion (62% vs. 66.6%, p=0.01), and stage IB disease (44% vs. 76%, p&lt;0.001). Similarly, compared with LGESS, a greater percentage of HGESS patients underwent lymphadenectomy (29.0% vs. 60.4%; P &lt;0.001), salpingo-oophorectomy (78.4% vs. 93.7%, p=0.001), and administration of radiotherapy (14.8% vs 50.0%; P&lt;0.001). There was no significant difference between stages IA and IB with regards to the above-mentioned demographic and clinico-pathologic variables, in both LGESS and HGESS. The 5-year overall survival was worse in HGESS than LGESS (45.4% vs. 97.2%, p&lt;0.001). The difference in 5-year overall survival between stages IA and IB was significant in LGESS (100% vs. 93.5%, p=0.003), but not in HGESS (51.4% vs. 43.5%, p=0.2). Although age (p=0.001), race (p= 0.005), stage (p=0.004) were all significant prognostic factors in LGESS, only cervical involvement (p=0.02) was a significant predictor in HGESS.
Conclusion: The new staging system is appropriate for risk stratification in LGESS. The prognosis in HGESS seems to be most influenced by the presence of cervical involvement and not by tumor size as the staging criteria would suggest.
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-71.
Abstract LB-77: A randomized double-blind placebo-controlled phase II trial of sorafenib and erlotinib or erlotinib alone in previously treated advanced non-small cell lung cancer: Correlative analyses
Authors: Spigel David R. , Burris Howard A. , Greco F. Anthony , Shipley Diana L. , Friedman Elke K. , Waterhouse David M. , Whorf Robert C. , Mitchell R. Brian , Daniel Davey B. , Zangmeister Jeffery , Hainsworth John D. 
Published: February 2011

Abstract
Background: Sorafenib is an oral multikinase inhibitor of angiogenesis and cellular proliferation which has shown preliminary activity in non-small-cell lung cancer (NSCLC). We conducted a multicenter phase II trial of erlotinib +/− sorafenib in 2nd/3rd line NSCLC.
Methods: Patients with previously treated stage IIIB/IV NSCLC were eligible (1-2 prior regimens). Additional eligibility criteria included: ECOG performance status 0-2, all NSCLC histologies, measurable disease, adequate organ function, and the absence of major cardiovascular disease. Patients with treated brain metastases and/or on stable anticoagulation were eligible. Patients were stratified according to squamous/non-squamous histology, prior bevacizumab use, and line of therapy and were randomized 2:1 to receive erlotinib 150mg orally once daily and sorafenib 400mg orally twice daily, or erlotinib and placebo. Patients were also consented for biomarker testing for epidermal growth factor receptor (EGFR) mutations, EGFR amplification, and K-ras mutations. The primary endpoint was to assess the efficacy of each arm in terms of objective response rate (ORR) and progression-free survival (PFS). The trial was designed to enroll 168 patients to demonstrate a 40% improvement on an historical 2.2 month PFS (&gt; 80%, 1-sided 0.1).
Results: 168 patients were enrolled from February 2008 to February 2009. Baseline characteristics were well-matched between cohorts (median age, 65 years; 3rd line therapy, 39%; prior bevacizumab, 36%; squamous histology, 30%). The ORRs for the sorafenib/erlotinib and erlotinib/placebo cohorts were 8.1% v. 10.9%, respectively (p=.55). However, the disease control rates (ORR + proportion of patients with stable disease) were 54.1% (sorafenib/erlotinib) v. 38.2% (erlotinib/placebo) (p=.06). The median PFS was 3.25 months (sorafenib/erlotinib) v. 1.87 months (erlotinib/placebo) (HR 0.86 [95% CI 0.60, 1.22], p=.20). 72 (44%) patients had material assessable for EGFR mutation analysis. Among the 67 patients who were found to have EGFR wild-type (WT) tumors, the median PFS was 3.25 months (sorafenib/erlotinib) v. 1.71 months (erlotinib/placebo) (HR 0.55 [95% CI 0.32, 0.96], p=.02).
Conclusions: Additional preplanned subset analyses based on histology, EGFR amplification, K-ras mutation, prior bevacizumab treatment, and line of therapy will be presented, as well as updated overall response, PFS, survival, and toxicity data.
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-77.
Abstract LB-8: Tumor suppressive functions of leucine zipper transcription factorlike 1
Authors: Qun Wei , Zhou Wen , Wang Weining , Gao Boning , Cao Jiang , Wang LinBo , liu Zhi-ping 
Published: February 2011

Abstract
Human leucine zipper transcription factor like 1 (LZTFL1) is a novel gene with unknown biological functions. It is located in the chromosome region 3p21.3, a hot spot for tumor suppressor genes. To understand the biological functions of LZTFL1, we surveyed the expression level of LZTFL1 in tumor and normal samples in tissue microarrays and a clinical archive of 84 gastric cancer specimens using immunohistochemistry. We found that LZTFL1 is expressed highly in the epithelial cells of normal tissues and is significantly down regulated in the corresponding tumor samples. The expression level of LZTFL1 correlated significantly with the survival outcomes of the patients and had significant inverse correlation with tumor metastasis. Overexpression of LZTFL1 in tumor cells inhibited anchorage-independent cell growth and cell migration in vitro, and repressed tumor growth in vivo. Furthermore, we show that LZTFL1 expression is upregulated upon epithelial cell differentiation and is graded along the crypt-villus axis of the intestine with weakest expression level in the proliferative zone of the crypt and highest expression level at the apex of the differentiation zone in the villus. Expression of LZTFL1 overlaps with that of E-cadherin at the plasma membrane. Our results indicate that LZTFL1 is a tumor suppressor and that loss of LZTFL1 expression has significant clinical outcomes. LZTFL1 expression may serve as an independent prognostic marker for survival outcome of gastric cancer patients. We propose that LZTFL1 may inhibit tumorigenesis by stabilizing E-cadherin-mediated adherens junction formation and promoting epithelial cell differentiation.
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-8.
Abstract LB-94: A non-lytic, cell-based, bioluminescent HDAC assay
Authors: Kirkland Thomas A. , Niles Andrew L. , Scurria Michael A. , Ugo Tim , Evans Nathan 
Published: February 2011

Abstract
Histone deacetylase (HDAC) class I and II enzymes play a critical role in the normal gene regulation events of development and homeostasis, but their dysregulation has been implicated in a variety of solid tumors and hematological malignancies. Broad spectrum inhibitors of HDAC Class I and II enzymes have been shown to achieve significant biological responses in otherwise refractory cancers. However, the underlying molecular mechanisms of these inhibitors have yet to be fully elucidated. Therefore, more sensitive and efficient tools are needed to rapidly identify and define modulators of HDAC activity. We have recently developed a one-step, homogeneous, luminescent assay for the detection of activity in a high-throughput format from multiple HDAC Class I and II isoforms, in cell culture, enriched or recombinant sources. This luciferase-containing, “glow-type” assay reagent measures HDAC activity in a proportional manner when the pro-luciferin peptide substrate becomes deacetylated and susceptible to lysine-specific cleavage by a developer enzyme contained within the reagent. This substrate is fully cell-permeable and can directly measure HDAC activity in living cells. We will present data demonstrating assay utility with attachment-dependent and suspension cell types using representative inhibitors from the hydroxamate, short-chain fatty acid, benzamide and cyclic peptide classes. Furthermore, we will correlate HDAC inhibition profiles with initiation of caspase activity and/or other cytotoxicity biomarkers.
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-94.
Apolipoprotein E Induces Antiinflammatory Phenotype in Macrophages
Authors: Baitsch Daniel , Bock Hans H. , Engel Thomas , Telgmann Ralph , Müller-Tidow Carsten , Varga Georg , Bot Martine , Herz Joachim , Robenek Horst , von Eckardstein Arnold , Nofer Jerzy-Roch 
Published: February 2011

Objective—
Apolipoprotein E (apoE) exerts potent antiinflammatory effects. Here, we investigated the effect of apoE on the functional phenotype of macrophages.

Methods and Results—

Human apoE receptors very-low-density lipoprotein receptor (VLDL-R) and apoE receptor-2 (apoER2) were stably expressed in RAW264.7 mouse macrophages. In these cells, apoE downregulated markers of the proinflammatory M1 phenotype (inducible nitric oxide synthase, interleukin [IL]-12, macrophage inflammatory protein-1α) but upregulated markers of the antiinflammatory M2 phenotype (arginase I, SOCS3, IL-1 receptor antagonist [IL-1RA]). In addition, M1 macrophage responses (migration, generation of reactive oxygen species, antibody-dependent cell cytotoxicity, phagocytosis), as well as poly(I:C)- or interferon-γ-induced production of proinflammatory cytokines; cyclooxygenase-2 expression; and activation of nuclear factor-κB, IκB, and STAT1, were suppressed in VLDL-R- or apoER2-expressing cells. Conversely, the suppression of the M2 phenotype and the enhanced response to poly(I:C) were observed in apoE-producing bone marrow macrophages derived from VLDL-R-deficient mice but not wild-type or low-density lipoprotein receptor–deficient mice. The modulatory effects of apoE on macrophage polarization were inhibited in apoE receptor-expressing RAW264.7 cells exposed to SB220025, a p38 mitogen-activated protein kinase inhibitor, and PP1, a tyrosine kinase inhibitor. Accordingly, apoE induced tyrosine kinase-dependent activation of p38 mitogen-activated protein kinase in VLDL-R- or apoER2-expressing macrophages. Under in vivo conditions, apoE
−/−
mice transplanted with apoE-producing wild-type bone marrow showed increased plasma IL-1RA levels, and peritoneal macrophages of transplanted animals were shifted to the M2 phenotype (increased IL-1RA production and CD206 expression).

Conclusion—
ApoE signaling via VLDL-R or apoER2 promotes macrophage conversion from the proinflammatory M1 to the antiinflammatory M2 phenotype. This effect may represent a novel antiinflammatory activity of apoE.
Intracranial Hemodynamics Is Altered by Carotid Artery Disease and After Endarterectomy
Authors: MacIntosh Bradley J. , Sideso Ediri , Donahue Manus J. , Chappell Michael A. , Günther Matthias , Handa Ashok , Kennedy James , Jezzard Peter 
Published: February 2011

Background and Purpose—
Carotid endarterectomy (CEA) has become a routine procedure to treat symptomatic carotid artery disease and reduce the risk of recurrent cerebral ischemic events. The purpose of this study was to use an arterial spin labeling dynamic magnetic resonance angiography technique to characterize intracranial hemodynamics before and after CEA.

Methods—
Thirty-seven carotid artery disease patients participated in this study, of whom 24 underwent magnetic resonance imaging before and after CEA. Seventeen control subjects spanning 5 decades underwent magnetic resonance imaging to assess age-related changes. Hemodynamic metrics (that is, relative time to peak and amplitude) were calculated with a γ-variate model. Linear regression was used to relate carotid artery disease burden to downstream hemodynamics in the circle of Willis.

Results—

Relative time to peak increased with age in controls (
P
<0.020). For patients, relative time to peak was positively correlated with percent stenosis (
P
<0.050), independent of age. At 1 day after CEA, the middle cerebral artery ipsilateral to the CEA showed significant dynamic magnetic resonance angiography changes: relative time to peak decreased (
P
<0.017) and the flow amplitude increased (
P
<0.009). No pre- versus post-CEA changes were significant in the contralateral middle cerebral artery or posterior segments.

Conclusions—
This noninvasive, arterial spin labeling–based method produced time-resolved images that were used to characterize intracranial arterial flow associated with aging, extracranial carotid artery disease, and CEA. Results demonstrate that the technique has the sensitivity to detect hemodynamic changes after CEA.
Personality Types of Otolaryngology Resident Applicants as Described by the Myers‐Briggs Type Indicator
Authors: Zardouz Shawn , German Michael A. , Wu Edward C. , Djalilian Hamid R. 
Published: February 2011

ObjectiveTo assess the personality types of applicants to a single otolaryngology residency program using the Myers‐Briggs Type Indicator. The personality types were compared with those of the general population and with physicians in other medical specialties.Study DesignCross‐sectional survey.SettingUniversity hospital.Subjects and MethodsA personality survey was emailed to 327 resident physician applicants over 2 consecutive years (2008‐2009). Analysis was accomplished by calculating prevalence estimates.ResultsOf the 327 anonymous surveys, 137 were completed (response rate = 42%). The Introverted/Sensing/Thinking/ Judging personality type was the most prevalent (14.6%), representing 13% of the general population. Prospective applicants displayed mostly Extroverted (E; 58%), Sensing (S; 54%), Thinking (T; 62%), and Judging (J; 61%) personality traits. Of the 16 personality types, statistically significant differences were found between otolaryngology resident applicants and the general population only for the Extroverted/Sensing/Thinking/ Perceiving (P =. 002) personality type after correcting for multiple comparisons. The Intuitive (N; 46%) and Feeling (F; 38%) types correlated closely with the reported personality types of those individuals in non–primary care specialties, 47% and 28%, respectively. Extroverted (E) and Thinking (T) individuals appeared to prefer surgical specialties, which occurred in 58% and 62% of the applicants, respectively. There were no significant differences between male and female applicants.ConclusionThis study examines the personality types of medical students applying to an otolaryngology residency. The results support a highly structured, data‐driven teaching preference among applicants. These results may allow for a better understanding of the personalities of medical students who are interested in otolaryngology.
Comparison of Muzzle Suppression and Ear‐Level Hearing Protection in Firearm Use
Authors: Branch Matthew Parker 
Published: February 2011

ObjectiveTo compare noise reduction of commercially available ear‐level hearing protection (muffs/inserts) to that of firearm muzzle suppressors.SettingExperimental sound measurements under consistent environmental conditions.SubjectsNone.Study Design and MethodsMuzzle suppressors for 2 pistol and 2 rifle calibers were tested using the Bruel & Kjaer 2209 sound meter and Bruel & Kjaer 4136 microphone calibrated with the Bruel & Kjaer Pistonphone using Military‐Standard 1474D placement protocol. Five shots were recorded unsuppressed and 10 shots suppressed under consistent environmental conditions. Sound reduction was then compared with the real‐world noise reduction rate of the best available ear‐level protectors.ResultsAll suppressors offered significantly greater noise reduction than ear‐level protection, usually greater than 50% better. Noise reduction of all ear‐level protectors is unable to reduce the impulse pressure below 140 dB for certain common firearms, an international standard for prevention of sensorineural hearing loss.ConclusionModern muzzle‐level suppression is vastly superior to ear‐level protection and the only available form of suppression capable of making certain sporting arms safe for hearing. The inadequacy of standard hearing protectors with certain common firearms is not recognized by most hearing professionals or their patients and should affect the way hearing professionals counsel patients and the public.
Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma
Authors: Piekarz Richard L. , Frye Robin , Prince H. Miles , Kirschbaum Mark H. , Zain Jasmine , Allen Steven L. , Jaffe Elaine S. , Ling Alexander , Turner Maria , Peer Cody J. , Figg William D. , Steinberg Seth M. , Smith Sonali , Joske David , Lewis Ian , Hutchins Laura , Craig Michael , Fojo A. Tito , Wright John J. , Bates Susan E. 
Published: February 2011

Abstract
Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL. Forty-seven patients with PTCL of various subtypes including PTCL NOS, angioimmunoblastic, ALK-negative anaplastic large cell lymphoma, and enteropathy-associated T-cell lymphoma were enrolled. All patients had received prior therapy with a median of 3 previous treatments (range 1-11); 18 (38%) had undergone stem-cell transplant. All patients were evaluated for toxicity; 2 patients discovered to be ineligible were excluded from response assessment. Common toxicities were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. Complete responses were observed in 8 and partial responses in 9 of 45 patients, for an overall response rate of 38% (95% confidence interval 24%-53%). The median duration of overall response was 8.9 months (range 2-74). Responses were observed in various subtypes, with 6 responses among the 18 patients with prior stem-cell transplant. The histone deacetylase inhibitor romidepsin has single agent clinical activity associated with durable responses in patients with relapsed PTCL. This study has been registered at clinicaltrials.gov as NCT00007345.