bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower Admission Hemoglobin Levels Are Associated With Longer Symptom Duration in Acute ST‐Elevation Myocardial Infarction
Authors: Shacham Yacov , Leshem‐Rubinow Eran , Ben‐Assa Eyal , Roth Arie , Steinvil Arie 
Published: October 2013

ABSTRACTBackgroundAn acute‐phase response in patients with acute myocardial infarction could contribute to the development of anemia.HypothesisAn association may exist between symptom duration, hemoglobin (Hb) concentration and serum C‐reactive protein (CRP) values in patients presenting to an emergency department (ED) with acute ST‐segment elevation myocardial infarction (STEMI).MethodsA retrospective analysis was conducted on consecutive male STEMI patients who were admitted to our medical center's ED from January 2008 to November 2012 and had presented within the first 12 hours after the onset of chest pain. Hemoglobin concentration and serum CRP levels were determined from blood samples taken prior to any drug or fluid administration. Analyses of variance were used to determine interactions between selected time‐to‐presentation cutoffs and admission Hb and CRP concentrations. Patients with other reasons known to cause elevation of inflammatory markers, anemia, or bleeding diathesis were excluded.ResultsThe study population comprised 718 patients whose mean age was 61 ± 12 years (range, 27–96 years). Blood was drawn for Hb and CRP measurements directly upon admission. Patients who presented to the ED within 3 hours of symptom onset had higher Hb concentrations (P = 0.048) and lower serum CRP levels (P < 0.001) compared with those who presented after a longer interval from symptom onset.ConclusionsLonger symptom duration is associated with a lower admission Hb level and an early rise in the CRP level of male patients with acute STEMI.
Safe‐Dose Thrombolysis Plus Rivaroxaban for Moderate and Severe Pulmonary Embolism: Drip, Drug, and Discharge
Authors: Sharifi Mohsen , Bay Curt , Schwartz Frederic , Skrocki Laura 
Published: October 2013

ABSTRACTBackgroundThrombolysis, though very effective, has not been embraced as routine therapy for symptomatic pulmonary embolism (PE) except in very severe cases. Rivaroxaban recently has been approved for the treatment of venous thromboembolism (VTE). There are no data on the combined use of thrombolysis and rivaroxaban in PE.Hypothesis“Safe dose” thrombolysis (SDT) plus new oral anticoagulants are expected to become an appealing, safe and effective approach in the treatment of moderate and severe PE in the near future, thereby drastically reducing hospitalization time.MethodsOver a 12‐month period, 98 consecutive patients with symptomatic PE were treated by a combination of SDT and rivaroxaban. The SDT was started in parallel with unfractionated heparin and given in 2 hours. Heparin was given for a total of 24 hours and rivaroxaban started at 15 or 20 mg daily 2 hours after termination of heparin infusion.ResultsThere was no bleeding due to SDT. Recurrent VTE occurred in 3 patients who had been switched to warfarin. No patient on rivaroxaban developed VTE. Two patients died of cancer at a mean follow‐up of 12 ± 2 months. The pulmonary artery systolic pressure dropped from 52.8 ± 3.9 mm Hg before to 32 ± 4.4 mm Hg within 36 hours of SDT (P < 0.001). The duration of hospitalization for patients presenting primarily for PE was 1.9 ± 0.2 days.Conclusions“Safe dose” thrombolysis plus rivaroxaban is highly safe and effective in the treatment of moderate and severe PE, leading to favorable early and intermediate‐term outcomes and early discharge.
Tetrahydroisoquinolinone‐Based Steroidomimetic and Chimeric Microtubule Disruptors
Authors: Leese Mathew P. , Jourdan Fabrice L. , Major Meriel R. , Dohle Wolfgang , Hamel Ernest , Ferrandis Eric , Fiore Ann , Kasprzyk Philip G. , Potter Barry V. L. 
Published: October 2013

AbstractA structure–activity relationship (SAR) translation strategy was used for the discovery of tetrahydroisoquinoline (THIQ)‐based steroidomimetic and chimeric microtubule disruptors based upon a steroidal starting point. A steroid A,B‐ring‐mimicking THIQ core was connected to methoxyaryl D‐ring ring mimics through methylene, carbonyl and sulfonyl linkers to afford a number of steroidomimetic hits (e.g., 7‐methoxy‐2‐(3‐ methoxybenzyl)‐6‐sulfamoyloxy‐1,2,3,4‐tetrahydroisoquinoline (20 c) GI50=2.1 μM). Optimisation and control experiments demonstrate the complementary SAR of this series and the steroid derivatives that inspired its design. Linkage of the THIQ‐based A,B‐mimic with the trimethoxyaryl motif prevalent in colchicine site binding microtubule disruptors delivered a series of chimeric molecules whose activity (GI50=40 nM) surpasses that of the parent steroid derivatives. Validation of this strategy was obtained from the excellent oral activity of 7‐methoxy‐6‐sulfamoyloxy‐2‐(3,4,5‐trimethoxybenzyl)‐1,2,3,4‐tetrahydroisoquinoline (20 z) relative to a benchmark steroidal bis‐ sulfamate in an in vivo model of multiple myeloma.
De Novo Design, Synthesis and Evaluation of Benzylpiperazine Derivatives as Highly Selective Binders of Mcl‐1
Authors: Ding Xiao , Li Yan , Lv Li , Zhou Mi , Han Li , Zhang Zhengxi , Ba Qian , Li Jingquan , Wang Hui , Liu Hong , Wang Renxiao 
Published: October 2013

AbstractConsiderable efforts have been made to the development of small‐molecule inhibitors of antiapoptotic B‐cell lymphoma 2 (Bcl‐2) family proteins (such as Bcl‐2, Bcl‐xL, and Mcl‐1) as a new class of anticancer therapies. Unlike general inhibitors of the entire family, selective inhibitors of each member protein can hopefully reduce the adverse side effects in chemotherapy treatments of cancers overexpressing different Bcl‐2 family proteins. In this study, we designed four series of benzylpiperazine derivatives as plausible Bcl‐2 inhibitors based on the outcomes of a computational algorithm. A total of 81 compounds were synthesized, and their binding affinities to Bcl‐2, Bcl‐xL, and Mcl‐1 measured. Encouragingly, 22 compounds exhibited binding affinities in the micromolar range (Ki<20 μM) to at least one target protein. Moreover, some compounds were observed to be highly selective binders to Mcl‐1 with no detectable binding to Bcl‐2 or Bcl‐xL, among which the most potent one has a Ki value of 0.18 μM for Mcl‐1. Binding modes of four selected compounds to Mcl‐1 and Bcl‐xL were derived through molecular docking and molecular dynamics simulations. It seems that the binding affinity and selectivity of these compounds can be reasonably interpreted with these models. Our study demonstrated the possibility for obtaining selective Mcl‐1 inhibitors with relatively simple chemical scaffolds. The active compounds identified by us could be used as lead compounds for developing even more potent selective Mcl‐1 inhibitors with potential pharmaceutical applications.
Intermittent versus continuous erlotinib with concomitant modified “XELOX” (q3W) in first‐line treatment of metastatic colorectal cancer
Authors: Ma Brigette B. Y. , Chan Stephen L. , Ho Wing M. , Lau Wilson , Mo Frankie , Hui Edwin P. , Chan Charles , Poon Annette , Dattatray Rasalkar D. , Wong S. C. Cesar , To Ka F. , King Ann D. , Ahuja Anil , Chan Anthony T. C. 
Published: October 2013

BACKGROUNDThis study evaluated the activity of 2 schedules of erlotinib in combination with chemotherapy, and the prognostic significance of serum amphiregulin (AREG) and transforming growth factor alpha (TGFa) in metastatic colorectal cancer.METHODSA total of 60 untreated patients were randomized to a “continuous” (CON; erlotinib 100 mg daily) or an “intermittent” (INT; erlotinib 150 mg on alternate day on day 2 to 14, then 150 mg daily on days 15 to 21) schedule of erlotinib with a modified XELOX (capecitabine plus oxaliplatin) regimen. Serum levels of AREG and TGFa were determined serially.RESULTSBaseline characteristics were similar between the 2 arms. Of the 58 patients evaluated for response, there was a nonsignificant trend toward a slightly higher overall response rate in the INT arm (66.7%) versus the CON arm (56.7%). At a median follow‐up of 2.8 years, the median overall survival was 18.8 months (95% confidence interval = 11.3‐22.9 months) and 20.7 months (95% confidence interval = 12.5‐31 months, P = .19) for the CON and INT arm, respectively. KRAS mutation did not predict drug response. The 2 arms did not differ significantly in toxicity. Baseline serum TGFa was an independent predictor of progression‐free survival, whereas a drop in serum TGFa and AREG levels following 3 to 4 cycles of treatment were associated with shorter progression‐free survival and overall survival, respectively.CONCLUSIONSThe intermittent erlotinib schedule was associated with a higher response rate, although this is not statistically significant. Serum TGFa and AREG levels have prognostic significance in erlotinib‐treated patients with colorectal cancer, and further studies are warranted. Cancer 2013;119:4145–4153. © 2013 American Cancer Society.
TRAIL receptor agonist conatumumab with modified FOLFOX6 plus bevacizumab for first‐line treatment of metastatic colorectal cancer
Authors: Fuchs Charles S. , Fakih Marwan , Schwartzberg Lee , Cohn Allen L. , Yee Lorrin , Dreisbach Luke , Kozloff Mark F. , Hei Yong‐jiang , Galimi Francesco , Pan Yang , Haddad Vincent , Hsu Cheng‐Pang , Sabin Antony , Saltz Leonard 
Published: October 2013

BACKGROUNDIn patients with previously untreated metastatic colorectal cancer (mCRC), we conducted a phase 1b/randomized phase 2 trial to define the safety, tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with conatumumab, an investigational, fully human monoclonal IgG1 antibody that specifically activates death receptor 5 (DR5).METHODSTwelve patients were enrolled in a phase 1b open‐label dose‐escalation trial of conatumumab with mFOLFOX6/bev; thereafter, 190 patients were randomized 1:1:1 to receive mFOLFOX6/bev in combination with 2 mg/kg conatumumab, 10 mg/kg conatumumab, or placebo. Therapy cycles were repeated every 2 weeks until disease progression or the occurrence of unacceptable toxicity.RESULTSIn phase 1b, conatumumab with mFOLFOX6/bev was tolerated without apparent added toxicity over mFOLFOX6/bev alone. In phase 2, conatumumab with mFOLFOX6/bev did not confer a benefit in progression‐free survival when compared with placebo with mFOLFOX6/bev. Toxicity was similar in all treatment arms. Following treatment, similar increases in circulating caspase‐3 levels were observed in all arms.CONCLUSIONSConatumumab with mFOLFOX6/bev did not offer improved efficacy over the same chemotherapy with placebo in first‐line treatment of patients with mCRC. These data do not support further development of conatumumab in advanced CRC. Cancer 2013;119:4290–4298. © 2013 American Cancer Society.
Associations among prognostic understanding, quality of life, and mood in patients with advanced cancer
Authors: El‐Jawahri Areej , Traeger Lara , Park Elyse R. , Greer Joseph A. , Pirl William F. , Lennes Inga T. , Jackson Vicki A. , Gallagher Emily R. , Temel Jennifer S. 
Published: October 2013

BACKGROUNDPatients' perception of their prognosis has an impact on their decisions about medical care. However, the relations between prognostic understanding and quality of life (QoL) and mood are unknown. The objectives of this study were to assess perceptions of prognosis and preferences for prognostic information among patients with advanced cancer and to explore the associations of prognostic understanding with QoL and mood.METHODSFifty patients were assessed within 6 to 12 weeks of initiating chemotherapy for advanced gastrointestinal cancers. A 13‐item questionnaire was used to assess patients' information preferences, perceptions of their prognosis and goal of therapy, and communication about end‐of‐life care. The Functional Assessment of Cancer Therapy‐General and the Hospital Anxiety and Depression Scale were used to assess QoL and mood, respectively.RESULTSFifty of 62 (80%) consecutive, eligible patients were enrolled. Thirty‐eight of 50 patients (75%) wanted to know as many details as possible about their cancer diagnosis and treatment. However, 25 of 50 patients (50%) stated that the goal of therapy was to “cure their cancer,” and only 10 of 49 patients (22%) reported having a discussion about end‐of‐life preferences with their oncologist. Patients who acknowledged their illness as terminal reported lower QoL (P = .005) and higher anxiety (P = .003) compared with those who did not perceive themselves as being terminally ill.CONCLUSIONSAlthough patients desired detailed information about their illness, half incorrectly perceived their cancer as curable. Accurate prognostic understanding was associated with lower QoL and worse anxiety. Interventions to improve patients' prognostic understanding while providing adequate psychosocial support are warranted. Cancer 2014;120:278–285. © 2013 American Cancer Society.
The cross‐talk between estrogen receptor and peroxisome proliferator‐activated receptor gamma in thyroid cancer
Authors: Chu Ryan , van Hasselt Andrew , Vlantis Alexander C. , Ng Enders K. W. , Liu Shirley Y. W. , Fan Michael Dahua , Ng Siu Kwan , Chan Amy B. W. , Liu Zhimin , Li Xin‐ying , Chen George G. 
Published: October 2013

BACKGROUNDEstrogen receptor (ER) and peroxisome proliferator‐activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied.METHODSThe impact of ER over‐expression or down‐expression by DNA/small interfering RNA (siRNA) transfection, ERα agonists, and the ERβ agonist diarylpropiolnitrile (DPN) on PPARγ expression/activity was examined in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells. The effects of PPARγ modulation by rosiglitazone (RTZ), a PPARγ ligand, and of PPARγ siRNA on ER expression were determined. Cellular functions reflected by cell proliferation and migration were assayed. Apoptosis was analyzed by terminal deoxynucleotidyl transferase dUTP nick‐end labeling, and apoptotic‐related proteins were evaluated by Western blot analysis.RESULTSPPARγ protein and activity were reduced by the over‐expression of either ERα or ERβ, whereas repression of ERα or ERβ increased PPARγ expression. The administration of RTZ counteracted the effects of ER and also reduced their expression, particularly in PTC cells. Moreover, knockdown of PPARγ increased ER expression and activity. Functionally, ERα activation offset the inhibitory effect of PPARγ on cellular functions, but ERβ activation aggregated it and induced apoptosis, particularly in PTC cells. Finally, the interaction between ERβ and PPARγ enhanced the expression of proapoptotic molecules, such as caspase‐3 and apoptosis‐inducing factor.CONCLUSIONSThis study provides evidence supporting a cross‐talk between ER and PPARγ. The reciprocal interaction between PPARγ and ERβ significantly inhibits the proliferation and migration of thyroid cancer cells, providing a new therapeutic strategy against thyroid cancer. Cancer 2014;120:142–153. © 2013 American Cancer Society.
Changes in plasma vascular endothelial growth factor at 8 weeks after sorafenib administration as predictors of survival for advanced hepatocellular carcinoma
Authors: Tsuchiya Kaoru , Asahina Yasuhiro , Matsuda Shuya , Muraoka Masaru , Nakata Toru , Suzuki Yuichiro , Tamaki Nobuharu , Yasui Yutaka , Suzuki Shoko , Hosokawa Takanori , Nishimura Takashi , Ueda Ken , Kuzuya Teiji , Nakanishi Hiroyuki , Itakura Jun , Takahashi Yuka , Kurosaki Masayuki , Enomoto Nobuyuki , Izumi Namiki 
Published: October 2013

BACKGROUNDA new predictive biomarker for determining prognosis in patients with hepatocellular carcinoma (HCC) who receive sorafenib is required, because achieving a reduction in tumor size with sorafenib is rare, even in patients who have a favorable prognosis. Vascular endothelial growth factor (VEGF) receptor is a sorafenib target. In the current study, the authors examined changes in plasma VEGF concentrations during sorafenib treatment and determined the clinical significance of VEGF as a prognostic indicator in patients with HCC.METHODSPlasma VEGF concentrations were serially measured in 63 patients with advanced HCC before and during sorafenib treatment. A plasma VEGF concentration that decreased >5% from the pretreatment level at 8 weeks was defined as a “VEGF decrease.” An objective tumor response was determined using modified Response Evaluation Criteria in Solid Tumors 1 month after the initiation of therapy and every 3 months thereafter.RESULTSPatients who had a VEGF decrease at week 8 (n = 14) had a longer median survival than those who did not have a VEGF decrease (n = 49; 30.9 months vs 14.4 months; P = .038). All patients who had a VEGF decrease survived for >6 months, and the patients who had both a VEGF decrease and an α‐fetoprotein response (n = 6) survived during the observation period (median, 19.7 months; range, 6.5‐31.0 months). In univariate analyses, a VEGF decrease, radiologic findings classified as progressive disease, and major vascular invasion were associated significantly with 1‐year survival; and, in multivariate analysis, a VEGF decrease was identified as an independent factor associated significantly with survival.CONCLUSIONSA plasma VEGF concentration decrease at 8 weeks after starting sorafenib treatment may predict favorable overall survival in patients with advanced HCC. Cancer 2014;120:229–237. © 2013 American Cancer Society.
Suicide ideation and associated mortality in adult survivors of childhood cancer
Authors: Brinkman Tara M. , Zhang Nan , Recklitis Christopher J. , Kimberg Cara , Zeltzer Lonnie K. , Muriel Anna C. , Stovall Marilyn , Srivastava Deo Kumar , Sklar Charles A. , Robison Leslie L. , Krull Kevin R. 
Published: October 2013

BACKGROUNDAdult survivors of childhood cancer are at risk for suicide ideation, although longitudinal patterns and rates of recurrent suicide ideation are unknown. This study investigated the prevalence of late report (ie, after initial assessment) and recurrent suicide ideation in adult survivors of childhood cancer, identified predictors of suicide ideation, and examined associations among suicide ideation and mortality.METHODSParticipants included 9128 adult survivors of childhood cancer and 3082 sibling controls enrolled in the Childhood Cancer Survivor Study who completed a survey question assessing suicide ideation on one or more occasions between 1994 and 2010. Suicide ideation was assessed using the Brief Symptom Inventory‐18 instrument. Mortality data was ascertained from the National Death Index.RESULTSSurvivors were more likely to report late (odds ratio [OR] = 1.9, 95% confidence interval [CI] = 1.5‐2.5) and recurrent suicide ideation (OR = 2.6, 95% CI = 1.8‐3.8) compared to siblings. Poor physical health status was associated with increased risk of suicide ideation in survivors (late report: OR = 1.9, 95% CI = 1.3‐2.7; recurrent: OR = 1.9, 95% CI = 1.2‐2.9). Suicide ideation was associated with increased risk for all‐cause mortality (hazard ratio = 1.3, 95% CI = 1.03‐1.6) and death by external causes (hazard ratio = 2.4, 95% CI = 1.4‐4.1).CONCLUSIONSAdult survivors of childhood cancer are at risk for late‐report and recurrent suicide ideation, which is associated with increased risk of mortality. Routine screening for psychological distress in adult survivors appears warranted, especially for survivors who develop chronic physical health conditions. Cancer 2014;120:271–277. © 2013 American Cancer Society.
Underutilization of radiation therapy in patients with glioblastoma
Authors: Aizer Ayal A. , Ancukiewicz Marek , Nguyen Paul L. , Shih Helen A. , Loeffler Jay S. , Oh Kevin S. 
Published: October 2013

BACKGROUNDRandomized trials have demonstrated that radiation improves survival in patients with glioblastoma. The purpose of this study was to characterize the risk factors and impact of omission of radiation therapy in such patients.METHODSThe Surveillance, Epidemiology, and End Results (SEER) program was used to identify 22,777 patients diagnosed with glioblastoma between 1988 and 2007. Multivariable logistic regression was employed to identify predictors associated with omission of radiation. Cox regression was used to characterize the impact of omitting radiation on all‐cause mortality.RESULTSAmong the entire cohort, 16,863 of 22,777 patients (74%) received radiation, whereas 5914 of 22,777 patients (26%) did not. Factors associated with omission of radiation included older age (OR = 1.048 per year increase, 95% CI = 1.046‐1.051, P < .001), lower annual income (OR = 0.93 per $10,000 increase, 95% CI = 0.90‐0.96, P < .001), African American race (reference = white, OR = 1.19, 95% CI = 1.03‐1.37, P = .02), Hispanic race (OR = 1.34, 95% CI = 1.19‐1.50, P < .001), Asian American race (OR = 1.24, 95% CI = 1.04‐1.48, P < .001), unmarried status (OR = 1.71, 95% CI = 1.60‐1.83, P < .001), and subtotal resection/biopsy (OR = 1.82, 95% CI = 1.69‐1.96, P < .001). The use of radiation was significantly associated with improved overall survival (2‐year survival: 14.6% versus 4.2%, P < .001; adjusted HR = 2.09, 95% CI = 2.02‐2.16, P < .001). When the population was restricted to patients < 50 years old, these findings remained largely unchanged.CONCLUSIONSRadiation therapy is associated with survival benefit in patients with glioblastoma, and sociodemographic factors play a significant role in the underutilization of radiation. The underlying causes for these disparities in care require further research. Cancer 2014;120:238–243. © 2013 American Cancer Society.
Combined lenalidomide, low‐dose dexamethasone, and rituximab achieves durable responses in rituximab‐resistant indolent and mantle cell lymphomas
Authors: Ahmadi Tahamtan , Chong Elise A. , Gordon Amanda , Aqui Nicole A. , Nasta Sunita D. , Svoboda Jakub , Mato Anthony R. , Schuster Stephen J. 
Published: October 2013

BACKGROUNDLenalidomide is an immunomodulatory drug with effects on the immune system that may enhance antibody‐dependent cell‐mediated cytotoxicity and reverse tumor‐induced immune suppression. Furthermore, single‐agent lenalidomide has therapeutic activity in relapsed/refractory B‐cell lymphomas. These immunologic effects potentially may enhance the action of rituximab.METHODSTo test the efficacy of lenalidomide combined with rituximab, the authors conducted a phase 2 trial of lenalidomide, low‐dose dexamethasone, and rituximab in patients who had rituximab‐resistant, relapsed/refractory, indolent B‐cell or mantle cell lymphomas. Patients received two 28‐day treatment cycles of lenalidomide 10 mg daily and dexamethasone 8 mg once weekly (part I). During cycle 3, 4 weekly doses of rituximab 375 mg/m2 were administered with lenalidomide‐dexamethasone (part II). After the part II response assessment, stable or responding patients continued to receive lenalidomide‐dexamethasone.RESULTSTwenty‐seven patients with follicular (n = 18), mantle cell (n = 5), small lymphocytic (n = 3), and marginal zone (n = 1) lymphomas started therapy; 3 of 27 patients discontinued therapy because of adverse events and were not evaluable for response. For 24 patients, the overall response rate after part I was 29% (4 patients had a complete response [CR] or CR unconfirmed, and 3 patients had a partial response), and the overall response rate after part II was 58% (8 patients had a CR, and 6 patients had a partial response). For 27 patients, at a median follow‐up of 12.2 months, the median progression‐free survival was 23.7 months.CONCLUSIONSThe combination of lenalidomide, low‐dose dexamethasone, and rituximab achieved high response rates with durable responses in patients with rituximab‐resistant, indolent B‐cell and mantle cell lymphomas. Overall response rate increased from 29% after two 28‐day cycles of lenalidomide and low‐dose dexamethasone to 58% after the addition of rituximab, suggesting that lenalidomide can overcome resistance to rituximab. Cancer 2014;120:222–228. © 2013 American Cancer Society.