bluuebunny/crossref_metadata_2025_split huggingface dataset:
[18F]-3′Deoxy-3′-Fluorothymidine Positron Emission Tomography and Breast Cancer Response to Docetaxel
Authors: Contractor Kaiyumars B. , Kenny Laura M. , Stebbing Justin , Rosso Lula , Ahmad Rizvana , Jacob Jimmy , Challapalli Amarnath , Turkheimer Federico , Al-Nahhas Adil , Sharma Rohini , Coombes R. Charles , Aboagye Eric O. 
Published: October 2011

Abstract
Purpose: To establish biomarkers indicating clinical response to taxanes, we determined whether early changes in [18F]-3′deoxy-3′-fluorothymidine positron emission tomography (FLT-PET) can predict benefit from docetaxel therapy in breast cancer.
Experimental Design: This was a prospective unblinded study in 20 patients with American Joint Committee on Cancer (AJCC) stage II–IV breast cancer unresponsive to first-line chemotherapy or progressing on previous therapy. Individuals underwent a baseline dynamic FLT-PET scan followed by a scan 2 weeks after initiating the first or second cycle of docetaxel. PET variables were compared with anatomic response midtherapy (after 3 cycles).
Results: Average and maximum tumor standardized uptake values at 60 minutes (SUV60,av and SUV60,max) normalized to body surface area ranged between 1.7 and 17.0 and 5.6 and 26.9 × 10−5 m2/mL, respectively. Docetaxel treatment resulted in a significant decrease in FLT uptake (P = 0.0003 for SUV60,av and P = 0.0002 for SUV60,max). Reduction in tumor SUV60,av was associated with target lesion size changes midtherapy (Pearson R for SUV60,av = 0.64; P = 0.004) and predicted midtherapy target lesion response (0.85 sensitivity and 0.80 specificity). Decreases in SUV60,av in responders were due, at least in part, to reduced net intracellular trapping of FLT (rate constant, Ki). Docetaxel significantly reduced Ki by 51.1% (±28.4%, P = 0.0009).
Conclusion: Changes in tumor proliferation assessed by FLT-PET early after initiating docetaxel chemotherapy can predict lesion response midtherapy with good sensitivity warranting prospective trials to assess the ability to stop therapy in the event of non–FLT-PET response. Clin Cancer Res; 17(24); 7664–72. ©2011 AACR.
Polycomb Repressor Complex-2 Is a Novel Target for Mesothelioma Therapy
Authors: Kemp Clinton D. , Rao Mahadev , Xi Sichuan , Inchauste Suzanne , Mani Haresh , Fetsch Patricia , Filie Armando , Zhang Mary , Hong Julie A. , Walker Robert L. , Zhu Yuelin J. , Ripley R. Taylor , Mathur Aarti , Liu Fang , Yang Maocheng , Meltzer Paul A. , Marquez Victor E. , De Rienzo Assunta , Bueno Raphael , Schrump David S. 
Published: October 2011

Abstract
Purpose: Polycomb group (PcG) proteins are critical epigenetic mediators of stem cell pluripotency, which have been implicated in the pathogenesis of human cancers. This study was undertaken to examine the frequency and clinical relevance of PcG protein expression in malignant pleural mesotheliomas (MPM).
Experimental Design: Microarray, quantitative reverse transcriptase PCR (qRT-PCR), immunoblot, and immunohistochemistry techniques were used to examine PcG protein expression in cultured MPM, mesothelioma specimens, and normal mesothelial cells. Lentiviral short hairpin RNA techniques were used to inhibit EZH2 and EED expression in MPM cells. Proliferation, migration, clonogenicity, and tumorigenicity of MPM cells either exhibiting knockdown of EZH2 or EED, or exposed to 3-deazaneplanocin A (DZNep), and respective controls were assessed by cell count, scratch and soft agar assays, and murine xenograft experiments. Microarray and qRT-PCR techniques were used to examine gene expression profiles mediated by knockdown of EZH2 or EED, or DZNep.
Results: EZH2 and EED, which encode components of polycomb repressor complex-2 (PRC-2), were overexpressed in MPM lines relative to normal mesothelial cells. EZH2 was overexpressed in approximately 85% of MPMs compared with normal pleura, correlating with diminished patient survival. Overexpression of EZH2 coincided with decreased levels of miR-101 and miR-26a. Knockdown of EZH2 orEED, or DZNep treatment, decreased global H3K27Me3 levels, and significantly inhibited proliferation, migration, clonogenicity, and tumorigenicity of MPM cells. Common as well as differential gene expression profiles were observed following knockdown of PRC-2 members or DZNep treatment.
Conclusions: Pharmacologic inhibition of PRC-2 expression/activity is a novel strategy for mesothelioma therapy. Clin Cancer Res; 18(1); 77–90. ©2011 AACR.
A Dose-Escalation and Signal-Generating Study of the Immunocytokine L19-IL2 in Combination with Dacarbazine for the Therapy of Patients with Metastatic Melanoma
Authors: Eigentler Thomas K. , Weide Benjamin , de Braud Filippo , Spitaleri Gianluca , Romanini Antonella , Pflugfelder Annette , González-Iglesias Reinerio , Tasciotti Annaelisa , Giovannoni Leonardo , Schwager Kathrin , Lovato Valeria , Kaspar Manuela , Trachsel Eveline , Menssen Hans D. , Neri Dario , Garbe Claus 
Published: October 2011

Abstract
Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a tumor angiogenesis marker, and of human interleukin-2 (IL2). L19-IL2 delivers IL2 to the tumor site exploiting the selective expression of EDB on newly formed blood vessels. Previously, the recommended dose of L19-IL2 monotherapy was defined as 22.5 million international units (Mio IU) IL2 equivalents. In this study, safety and clinical activity of L19-IL2 in combination with dacarbazine were assessed in patients with metastatic melanoma.
Experimental Design: The first 10 studied patients received escalating doses of L19-IL2 on days 1, 3, and 5 in combination with 1 g/m2 of dacarbazine on day 1 of a 3-weekly therapy cycle. Subsequently, 22 patients received L19-IL2 at recommended dose plus dacarbazine. Up to six treatment cycles were given, followed by a maintenance regimen with biweekly L19-IL2.
Results: The recommended dose of L19-IL2 in combination with dacarbazine was defined as 22.5 Mio IU. Toxicity was manageable and reversible, with no treatment-related deaths. Twenty-nine patients were evaluable for efficacy according to Response Evaluation Criteria in Solid Tumors (RECIST). In a centralized radiology analysis, eight of 29 (28%) patients achieved a RECIST-confirmed objective response, including a complete response still ongoing 21 months after treatment beginning. The 12-month survival rate and median overall survival of the recommended dose–treated patients (n = 26) were 61.5% and 14.1 months, respectively.
Conclusions: The repeated administration of L19-IL2 in combination with dacarbazine is safe and shows encouraging signs of clinical activity in patients with metastatic melanoma. This combination therapy is currently evaluated in a randomized phase II trial with patients with metastatic melanoma. Clin Cancer Res; 17(24); 7732–42. ©2011 AACR.
Phase I Study of Topotecan, Ifosfamide, and Etoposide (TIME) with Autologous Stem Cell Transplant in Refractory Cancer: Pharmacokinetic and Pharmacodynamic Correlates
Authors: Perkins Janelle B. , Goldstein Steven C. , Dawson Jana L. , Kim Jongphil , Field Teresa L. , Partyka James S. , Fields Karen K. , Maddox Beth L. , Simonelli Christine E. , Neuger Anthony M. , Lush Richard M. , Sullivan Daniel M. 
Published: October 2011

Abstract
Purpose: To determine the maximum tolerated dose (MTD) of topotecan in combination with ifosfamide, mesna, and etoposide (TIME), followed by autologous hematopoietic cell transplant (HCT), in patients with chemotherapy-refractory malignancies.
Experimental Design: Patients were treated with (in mg/m2/d) ifosfamide 3,333, mesna 3,333, and topotecan 3.3 to 28.3 during days −8 through −6 and etoposide 500 (days −5 through −3) followed by HCT on day 0. Once MTD was defined, we expanded this dosing cohort to include patients with high-risk lymphoma due to activity seen during dose escalation. Topotecan pharmacokinetic analyses were carried out, and topoisomerase I levels and activity were measured.
Results: The topotecan MTD in this regimen was 64 mg/m2 (21.3 mg/m2/d). Mucositis was dose limiting and correlated with topotecan dose level and area under the curve (AUC). Dose level was also correlated with length of hospitalization, number of days of parenteral nutrition, and neutrophil and platelet engraftment. Topotecan AUC was significantly correlated with time to platelet recovery. The baseline peripheral blood mononuclear cell topoisomerase I level was found to be a significant positive predictor for overall and progression-free survival. Topotecan AUC was positively correlated with dose level, with a trend toward decreasing clearance with increasing dose.
Conclusion: Topotecan can be a useful drug in the high-dose setting given its activity in some malignancies when given in standard dose. Pharmacokinetic monitoring may be a valuable tool for optimizing the use of topotecan and to avoid toxicity seen with high-systemic exposures. Baseline topoisomerase I levels may have an important role in predicting topotecan efficacy. Clin Cancer Res; 17(24); 7743–53. ©2011 AACR.
Breast Cancer–Derived Bone Metastasis Can Be Effectively Reduced through Specific c-MET Inhibitor Tivantinib (ARQ 197) and shRNA c-MET Knockdown
Authors: Previdi Sara , Abbadessa Giovanni , Dalò Francesca , France Dennis S. , Broggini Massimo 
Published: October 2011

Abstract
Breast cancer exhibits a propensity to metastasize to bone, resulting in debilitating skeletal complications associated with significant morbidity and poor prognosis. The cross-talk between metastatic cancer cells and bone is critical to the development and progression of bone metastases. We have shown the involvement of the HGF/c-MET system in tumor–bone interaction contributing to human breast cancer metastasis. Therefore, disruption of HGF/c-MET signaling is a potential targeted approach to treating metastatic bone disease. In this study, we evaluated the effects of c-MET inhibition by both an oral, selective, small-molecule c-MET inhibitor, tivantinib, and a specific short hairpin RNA (shRNA) against c-MET in a mouse model of human breast cancer. Tivantinib exhibited dose-dependent antimetastatic activity in vivo, and the 120 mg/kg dose, proven to be suboptimal in reducing subcutaneous tumor growth, induced significant inhibition of metastatic growth of breast cancer cells in bone and a noteworthy reduction of tumor-induced osteolysis. shRNA-mediated c-MET silencing did not affect in vitro proliferation of bone metastatic cells, but significantly reduced their migration, and this effect was further enhanced by tivantinib. Both observations were confirmed in vivo. Indeed, more pronounced tumor growth suppression with concomitant marked decreases of lytic lesions and prolongation of survival were achieved by dual c-MET inhibition using both tivantinib and RNA interference strategies. Overall, our findings highlighted the effectiveness of c-MET inhibition in delaying the onset and progression of bone metastases and strongly suggest that targeting c-MET may have promising therapeutic value in the treatment of bone metastases from breast cancer. Mol Cancer Ther; 11(1); 214–23. ©2011 AACR.
A Polymeric Nanoparticle Encapsulated Small-Molecule Inhibitor of Hedgehog Signaling (NanoHHI) Bypasses Secondary Mutational Resistance to Smoothened Antagonists
Authors: Chenna Venugopal , Hu Chaoxin , Pramanik Dipankar , Aftab Blake T. , Karikari Collins , Campbell Nathaniel R. , Hong Seung-Mo , Zhao Ming , Rudek Michelle A. , Khan Saeed R. , Rudin Charles M. , Maitra Anirban 
Published: October 2011

Abstract
Aberrant activation of the hedgehog (Hh) signaling pathway is one of the most prevalent abnormalities in human cancer. Tumors with cell autonomous Hh activation (e.g., medulloblastomas) can acquire secondary mutations at the Smoothened (Smo) antagonist binding pocket, which render them refractory to conventional Hh inhibitors. A class of Hh pathway inhibitors (HPI) has been identified that block signaling downstream of Smo; one of these compounds, HPI-1, is a potent antagonist of the Hh transcription factor Gli1 and functions independent of upstream components in the pathway. Systemic administration of HPI-1 is challenging due to its minimal aqueous solubility and poor bioavailability. We engineered a polymeric nanoparticle from [poly(lactic-co-glycolic acid); (PLGA)] conjugated with polyethylene glycol (PEG), encapsulating HPI-1 (NanoHHI). NanoHHI particles have an average diameter of approximately 60 nm, forms uniform aqueous suspension, and improved systemic bioavailability compared with the parent compound. In contrast to the prototype targeted Smo antagonist, HhAntag (Genentech), NanoHHI markedly inhibits the growth of allografts derived from Ptch−/+; Trp53−/− mouse medulloblastomas that harbor a SmoD477G binding site mutation (P &lt; 0.001), which is accompanied by significant downregulation of mGli1 as well as bona fide Hh target genes (Akna, Cltb, and Olig2). Notably, NanoHHI combined with gemcitabine also significantly impedes the growth of orthotopic Pa03C pancreatic cancer xenografts that have a ligand-dependent, paracrine mechanism of Hh activation when compared with gemcitabine alone. No demonstrable hematologic or biochemical abnormalities were observed with NanoHHI administration. NanoHHI should be amenable to clinical translation in settings where tumors acquire mutational resistance to current Smo antagonists. Mol Cancer Ther; 11(1); 165–73. ©2011 AACR.
MUC13 Mucin Augments Pancreatic Tumorigenesis
Authors: Chauhan Subhash C. , Ebeling Mara C. , Maher Diane M. , Koch Michael D. , Watanabe Akira , Aburatani Hiroyuki , Lio Yuhlong , Jaggi Meena 
Published: October 2011

AbstractThe high death rate of pancreatic cancer is attributed to the lack of reliable methods for early detection and underlying molecular mechanisms of its aggressive pathogenesis. Although MUC13, a newly identified transmembrane mucin, is known to be aberrantly expressed in ovarian and gastro-intestinal cancers, its role in pancreatic cancer is unknown. Herein, we investigated the expression profile and functions of MUC13 in pancreatic cancer progression. The expression profile of MUC13 in pancreatic cancer was investigated using a recently generated monoclonal antibody (clone PPZ0020) and pancreatic tissue microarrays. The expression of MUC13 was significantly (P &lt; 0.005) higher in cancer samples compared with normal/nonneoplastic pancreatic tissues. For functional analyses, full-length MUC13 was expressed in MUC13 null pancreatic cancer cell lines, MiaPaca and Panc1. MUC13 overexpression caused a significant (P &lt; 0.05) increase in cell motility, invasion, proliferation, and anchorage-dependent or -independent clonogenicity while decreasing cell–cell and cell-substratum adhesion. Exogenous MUC13 expression significantly (P &lt; 0.05) enhanced pancreatic tumor growth and reduced animal survival in a xenograft mouse model. These tumorigenic characteristics correlated with the upregulation/phosphorylation of HER2, p21-activated kinase 1 (PAK1), extracellular signal-regulated kinase (ERK), Akt, and metastasin (S100A4), and the suppression of p53. Conversely, suppression of MUC13 in HPAFII pancreatic cancer cells by short hairpin RNA resulted in suppression of tumorigenic characteristics, repression of HER2, PAK1, ERK, and S100A4, and upregulation of p53. MUC13 suppression also significantly (P &lt; 0.05) reduced tumor growth and increased animal survival. These results imply a role of MUC13 in pancreatic cancer and suggest its potential use as a diagnostic and therapeutic target. Mol Cancer Ther; 11(1); 24–33. ©2011 AACR.
A 71-Gene Signature of TRAIL Sensitivity in Cancer Cells
Authors: Chen Jun-Jie , Knudsen Steen , Mazin Wiktor , Dahlgaard Jesper , Zhang Baolin 
Published: October 2011

Abstract
TNF-related apoptosis inducing ligand (TRAIL) is a promising anticancer agent because of its ability to selectively induce apoptosis in cancer cells but not in most normal cells. However, some cancer cells are resistant to TRAIL cytotoxicity thereby limiting its therapeutic efficacy. Using genome-wide mRNA expression profiles from the NCI60 panel and their differential sensitivities to TRAIL-induced apoptosis, we have identified 71 genes whose expression levels are systemically higher in TRAIL-sensitive cell lines than resistant lines. The elevated expression of the 71 genes was able to accurately predict TRAIL sensitivity in the NCI60 training set and two test sets consisting of a total of 95 human cancer cell lines. Interestingly, the 71-gene signature is dominated by two functionally related gene families—interferon (IFN)-induced genes and the MHC genes. Consistent with this result, treatment with IFN-γ augmented TRAIL-induced apoptosis. The 71-gene signature could be evaluated clinically for predicting tumor response to TRAIL-related therapies. Mol Cancer Ther; 11(1); 34–44. ©2011 AACR.
Phase II Prospective Randomized Trial of a Low-Fat Diet with Fish Oil Supplementation in Men Undergoing Radical Prostatectomy
Authors: Aronson William J. , Kobayashi Naoko , Barnard R. James , Henning Susanne , Huang Min , Jardack Patricia M. , Liu Bingrong , Gray Ashley , Wan Junxiang , Konijeti Ramdev , Freedland Stephen J. , Castor Brandon , Heber David , Elashoff David , Said Jonathan , Cohen Pinchas , Galet Colette 
Published: October 2011

AbstractPreclinical studies suggest lowering dietary fat and decreasing the ratio of omega-6 to omega-3 polyunsaturated fatty acids decreases the risk of prostate cancer development and progression. We conducted a phase II randomized trial to test the effect of decreasing dietary fat combined with decreasing the dietary omega-6:omega-3 ratio on biomarkers related to prostate cancer development and progression. Patients undergoing radical prostatectomy were randomly assigned to receive a low-fat diet with 5 grams of fish oil daily (dietary omega-6:omega-3 ratio of 2:1) or a control Western diet (omega-6:omega-3 ratio of 15:1) for four to six weeks prior to surgery. The primary endpoint was change in serum insulin-like growth factor I (IGF-1) between arms. Secondary endpoints were serum IGFBP-1, prostate prostaglandin E2 levels, omega-6:omega-3 fatty acid ratios, COX-2, and markers of proliferation and apoptosis. Fifty-five patients were randomized and 48 completed the trial. There was no treatment difference in the primary outcome. Positive secondary outcomes in the low-fat fish oil versus Western group were reduced benign and malignant prostate tissue omega-6:omega-3 ratios, reduced proliferation (Ki-67 index), and reduced proliferation in an ex vivo bioassay when patient sera was applied to prostate cancer cells in vitro. In summary, four to six weeks of a low-fat diet and fish oil capsules to achieve an omega-6:omega-3 fatty acid ratio of 2:1 had no effect on serum IGF-1 levels, though in secondary analyses, the intervention resulted in decreased prostate cancer proliferation and decreased prostate tissue omega-6:omega-3 ratios. These results support further studies evaluating reduction of dietary fat with fish oil supplementation on modulating prostate cancer biology. Cancer Prev Res; 4(12); 2062–71. ©2011 AACR.
Predictors and Implications of Stent Thrombosis in Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Palmerini Tullio , Dangas George , Mehran Roxana , Caixeta Adriano , Généreux Philippe , Fahy Martin P. , Xu Ke , Cristea Ecaterina , Lansky Alexandra J. , Stone Gregg W. 
Published: October 2011

Background—
The frequency, predictors, and consequences of stent thrombosis (ST) in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) have been incompletely studied. We sought to investigate the incidence, predictors, and clinical implications of ST occurring within 1 year after percutaneous coronary intervention in patients with NSTE-ACS.

Methods and Results—

The Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial was a large-scale, prospective, randomized trial of antithrombotic regimens in patients with NSTE-ACS. The present analysis includes 7162 patients in whom stents were implanted. At 1 year, definite/probable ST occurred in 146 patients (2.2%), including 94 definite and 52 probable events. There were 100 episodes (1.4%) of early ST (within the first 30 days) and 46 episodes (0.8%) of late ST (between 30 days and 1 year). The incidence of ST within 1 year was similar in patients treated with drug-eluting stents or bare metal stents (hazard ratio, 0.86; 95% confidence interval, 0.62–1.20;
P
=0.38) and was independent of procedural antithrombotic treatment. Patients with ST compared with those without ST had strikingly higher 1-year rates of cardiac mortality (32.4% versus 2.9%,
P
<0.0001), myocardial infarction (82.6% versus 7.6%,
P
<0.0001), and target vessel revascularization (79.6% versus 7.4%,
P
<0.0001). Independent predictors of 1-year definite/probable ST were insulin-treated diabetes mellitus, number of diseased vessels, and ST-segment deviation ≥1 mm.

Conclusions—
Compared with elective stent implantation, ST occurs with increased frequency in the first year after stent implantation in patients with NSTE-ACS, especially within the first 30 days, and is associated with marked increases in cardiac mortality and adverse events. Insulin-treated diabetes, number of diseased vessels, and dynamic ST-segment changes were independent predictors of 1-year ST in NSTE-ACS.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00093158.
The effects of tandem and conventional vacuum steaming methods on the properties of yarns
Authors: Şardağ Sibel , Özdemir Özcan 
Published: October 2011

This study was performed in order to investigate the effects of tandem and conventional vacuum steaming on the physical properties of 100% cotton and 100% viscose yarns. The yarns with different twisting coefficients and numbers were twisted and exposed to tandem and conventional vacuum steaming at different temperatures. Tenacity, unevenness, hairiness, twist liveliness, package hardness values, and spirality of knitted fabrics produced from these yarns were measured before and after vacuum steaming. The results obtained were assessed by means of COSTAT statistical analysis program. Variation analysis and SNK test were carried out at 5% (0.05) level of significance. The findings of this study indicate that the effects of vacuum steaming methods on the tenacity, unevenness, hairiness, twist liveliness and package hardness values of yarns are statistically significant. Although the effects of tandem vacuum steaming vary depending on the temperature applied and the raw material used, decreases are observed in unevenness, hairiness, twist liveliness and package hardness values of yarns.