tbuckley/cabot-search huggingface dataset:
Phase 1b Dose Escalation Study Of Oral Quisinostat, a Histone Deacetylase Inhibitor (HDACi), In Combination With Velcade (Bortezomib) and Dexamethasone For Patients With Relapsed Multiple Myeloma (MM)
Authors: Philippe Moreau, Thierry Facon, Cyrille Touzeau, Lotfi Benboubker, Martine Delain, Julie Badamo-Dotzis, Charles Phelps, Christopher Doty, Hans Smit, Nele Fourneau, Ann Forslund, Peter Hellemans, Xavier Leleu
Journal: Blood (2013)
Abstract 13720: High Serum Levels of Thrombospondin-2 Correlate with Poor Prognosis of Patients with Heart Failure with Preserved Ejection Fraction
Authors: Yuichi Kimura, Yasuhiro Izumiya, Shinsuke Hanatani, Yoshiro Onoue, Satoshi Araki, Hisao Ogawa
Journal: Circulation (2014)

Introduction: Thrombospondin-2 (TSP-2) is highly expressed in hypertensive heart. Interstitial fibrosis is frequently observed in hypertensive heart, and it is a characteristic feature of heart failure with preserved ejection fraction (HFpEF). Hypothesis: High TSP-2 serum levels reflect disease severity and can predict poor prognosis of patients with HFpEF. Methods: Serum TSP-2 levels were measured by ELISA in 150 patients with HFpEF. HFpEF was defined as clinical signs or symptom of HF, left ventricular ejection fraction &gt;50%, B-type natriuretic peptide (BNP) &gt;100 pg/ml or E/e’ &gt;15. The endpoints of this study were mortality rate, HF-related hospitalization, stroke and non-fatal myocardial infarction. Results: The median serum TSP-2 level was 19.2 (14.4-26.0) ng/ml in all study participants. Serum TSP-2 levels correlated with the New York Heart Association (NYHA) functional class. Then the patients were divided into high and low TSP-2 groups based on the median value. Pulmonary capillary wedge pressure, and circulating levels of BNP and high-sensitivity cardiac troponin T were significantly higher in the high TSP-2 group than low TSP-2 group. Whereas, cardiac index was significantly lower in the high TSP-2 group. Kaplan-Meier survival curve showed high risk of adverse cardiovascular events in the high TSP-2 group, and that the combination of high TSP-2 and high BNP (&gt;100 pg/ml) was associated with the worst event-free survival rate. Univariate Cox proportional hazard analysis showed that high levels of TSP-2, NYHA functional class, presence of atrial fibrillation, high levels of BNP, left atrium dilatation were associated with future adverse events. Stepwise multivariate Cox proportional hazard analysis identified BNP (ln(BNP)) (hazard ratio [HR]: 1.98; confidence interval [CI]: 1.26-3.10, p=0.003) and TSP-2 (HR: 2.59; CI: 1.09-6.14, p=0.031) as independent predictors of risk of death and cardiovascular events. Conclusions: Circulating TSP-2 correlates with disease severity in patients with HFpEF. TSP-2 is a potentially useful predictor of future adverse cardiovascular events in patients with HFpEF.
Effects of a Provincial-Wide Implementation of Screening for Distress on Healthcare Professionals' Confidence and Understanding of Person-Centered Care in Oncology
Authors: Rie Tamagawa, Shannon Groff, Jennifer Anderson, Sarah Champ, Andrea Deiure, Jennifer Looyis, Peter Faris, Linda Watson
Journal: Journal of the National Comprehensive Cancer Network (2016)

Although published studies report that screening for distress (SFD) improves the quality of care for patients with cancer, little is known about how SFD impacts healthcare professionals (HCPs).This quality improvement project examined the impact of implementing the SFD intervention on HCPs' confidence in addressing patient distress and awareness of person-centered care.This project involved pre-evaluation and post-evaluation of the impact of implementing SFD. A total of 254 HCPs (cohort 1) were recruited from 17 facilities across the province to complete questionnaires. SFD was then implemented at all cancer care facilities over a 10-month implementation period, after which 157 HCPs (cohort 2) completed post-implementation questionnaires. At regional and community care centers, navigators supported the integration of SFD into routine practice; therefore, the impact of navigators was examined.HCPs in cohort 2 reported significantly greater confidence in managing patients' distress and greater awareness about person-centered care relative to HCPs in cohort 1. HCPs at regional and community sites reported greater awareness in person-centeredness before and after the intervention, and reported fewer negative impacts of SFD relative to HCPs at tertiary sites. Caring for single or multiple tumor types was an effect modifier, with effects observed only in the HCPs treating multiple tumors.Implementation of SFD was beneficial for HCPs' confidence and awareness of person-centeredness. Factors comprising different models of care, such as having site-based navigators and caring for single or multiple tumors, influenced outcomes.
Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer
Authors: Mingzhu Yin, Xia Li, Shu Tan, Huanjiao Jenny Zhou, Weidong Ji, Stefania Bellone, Xiaocao Xu, Haifeng Zhang, Alessandro D. Santin, Ge Lou, Wang Min
Journal: Journal of Clinical Investigation (2016)

Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage-like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM. Moreover, EGF secreted by TAMs activated EGFR on tumor cells, which in turn upregulated VEGF/VEGFR signaling in surrounding tumor cells to support tumor cell proliferation and migration. Pharmacological blockade of EGFR or antibody neutralization of ICAM-1 in TAMs blunted spheroid formation and ovarian cancer progression in mouse models. These findings suggest that EGF secreted from TAMs plays a critical role in promoting early transcoelomic metastasis of ovarian cancer. As transcoelomic metastasis is also associated with many other cancers, such as pancreatic and colon cancers, our findings uncover a mechanism for TAM-mediated spheroid formation and provide a potential target for the treatment of ovarian cancer and other transcoelomic metastatic cancers.
Usefulness of Combination of QRS-score on Admission and ST-resolution after Reperfusion for Predicting Aborted Myocardial Infarction
Authors: Nakama Yasuharu, Ishihara Masaharu, Inoue Ichiro, Kawagoe Takuji, Shimatani Yuji, Miura Fumiharu, Dai Kazuoki, Otani Takayuki, Ikenaga Hiroki, OI Kuniomi, Nakamura Masayuki, Kishimoto Shinji, Sumimoto Youji
Journal: Circulation (2012)
Clonal Evolution In Aplastic Anemia Is Driven By Chromosomal Instability Rather Than Mutations In Myeloid Malignancy Candidate Gene
Authors: Bogdan Dumitriu, Xingmin Feng, Yasutaka Ueda, Sachiko Kajigaya, Danielle Townsley, Jun Zsu, Yoshi Wakabayashi, Yanqin Yang, Delong Liu, Neal S. Young
Journal: Blood (2013)
Corrigendum to “The incidence of cholelithiasis after sleeve gastrectomy and its association with weight loss: A two-centre retrospective cohort study” [Int. J. Surg. 30 (2016) 13–18]
Authors: Wuttiporn Manatsathit, Pornchai Leelasinjaroen, Hussein Al-Hamid, Susanna Szpunar, Abdelkader Hawasli
Journal: International Journal of Surgery (2016)
Phase I randomized phase II trial of gemcitabine, erlotinib, and cixutumumab versus gemcitabine plus erlotinib as first-line treatment in patients with metastatic pancreatic cancer (SWOG-0727).
Authors: Philip Agop Philip, Bryan H. Goldman, Ramesh K. Ramanathan, Heinz-Josef Lenz, Andrew M. Lowy, Robert P. Whitehead, Syma Iqbal, Rakesh Gaur, Jacqueline K. Benedetti, C. D. Blanke
Journal: Journal of Clinical Oncology (2012)

198 Background: Targeting a single pathway in pancreatic adenocarcinoma (PAC) did not impact the natural history of this molecularly complex disease. Epidermal growth factor receptor (EGFR) targeting with erlotinib marginally improved the outcome of patients with advanced disease. We tested the hypothesis that if the EGFR and IGF-1R pathways are simultaneously blocked then progression free survival (PFS) would be significantly improved by abrogating reciprocal signaling. Methods: S0727 was a phase I/randomized phase II (RP2) study testing the anti-IGF-1R monoclonal antibody cixutumumab combined with erlotinib and gemcitabine in patients with metastatic PAC. The control arm was erlotinib plus gemcitabine. The primary endpoint of the RP2 portion of the study was PFS. Eligibility included patients with untreated metastatic disease, performance status 0/1, fasting blood glucose less than institutional upper limit of normal, and willingness to provide tissue and blood specimens for correlative studies. Results: In Phase I portion (n=10) safety of cixutumumab 6 mg/kg IV/wk, erlotinib 100 mg/day orally and gemcitabine 1000 mg/m 2 IV D 1,8, and 15 of a 28-day cycle was established. In the RP2 portion (n=124) 114 eligible patients (median age 63) were included. On the cixutumumab arm, 59% of patients were female vs. 41% on control arm. Median PFS and overall survival were 4 and 7 months, respectively, in both arms. Four patients on cixutumumab remain on treatment; sensitivity analyses show no impact on the conclusions. Major grade 3 and 4 toxicities were (cixutumumab/control) elevation of transaminases (12%/6%), fatigue (24%/21%), gastrointestinal (35%/28%), and hematologic (53%/39%). Grade 3/4 hyperglycemia was seen in 27% of patients on cixutumumab. Grade 3 or 4 kin toxicity was similar in both arms of the study (&lt; 5%). Five treatment-related deaths were reported: 2 cardiac on each arm, 1 pulmonary on cixutumumab. Conclusions: IGF-1R inhibitor cixutumumab did not improve the progression free or overall survival in patients with metastatic PAC treated with erlotinib and gemcitabine in a molecularly unselected population.
MST1-dependent vesicle trafficking regulates neutrophil transmigration through the vascular basement membrane
Authors: Angela R.M. Kurz, Monika Pruenster, Ina Rohwedder, Mahalakshmi Ramadass, Kerstin Schäfer, Ute Harrison, Gabriel Gouveia, Claudia Nussbaum, Roland Immler, Johannes R. Wiessner, Andreas Margraf, Dae-Sik Lim, Barbara Walzog, Steffen Dietzel, Markus Moser, Christoph Klein, Dietmar Vestweber, Rainer Haas, Sergio D. Catz, Markus Sperandio
Journal: Journal of Clinical Investigation (2016)

Neutrophils need to penetrate the perivascular basement membrane for successful extravasation into inflamed tissue, but this process is incompletely understood. Recent findings have associated mammalian sterile 20-like kinase 1 (MST1) loss of function with a human primary immunodeficiency disorder, suggesting that MST1 may be involved in immune cell migration. Here, we have shown that MST1 is a critical regulator of neutrophil extravasation during inflammation. Mst1-deficient (Mst1-/-) neutrophils were unable to migrate into inflamed murine cremaster muscle venules, instead persisting between the endothelium and the basement membrane. Mst1-/- neutrophils also failed to extravasate from gastric submucosal vessels in a murine model of Helicobacter pylori infection. Mechanistically, we observed defective translocation of VLA-3, VLA-6, and neutrophil elastase from intracellular vesicles to the surface of Mst1-/- neutrophils, indicating that MST1 is required for this crucial step in neutrophil transmigration. Furthermore, we found that MST1 associates with the Rab27 effector protein synaptotagmin-like protein 1 (JFC1, encoded by Sytl1 in mice), but not Munc13-4, thereby regulating the trafficking of Rab27-positive vesicles to the cellular membrane. Together, these findings highlight a role for MST1 in vesicle trafficking and extravasation in neutrophils, providing an additional mechanistic explanation for the severe immune defect observed in patients with MST1 deficiency.
Combination Therapy with the Histone Deacetylase Inhibitor Vorinostat Plus the Novel Aurora Kinase A Inhibitor MK-5108 Leads to Enhanced Lymphoma Cell Death Due to Acetylation of p53 and Repression of c-Myc, hTERT, and miRNA Levels.
Authors: Leo Kretzner, Anna Scuto, Kowolik Claudia, Richard Jove, Stephen J Forman, Yun Yen, Mark Kirschbaum
Journal: Blood (2009)
Is Recovery of Gonadal function possible in Very Long-Term Adult Male Survivors of Hodgkin's Lymphoma?
Authors: Wendy van Dorp, Ivana van der Geest, Joop Laven, Wim C.J. Hop, Sebastian J.C.M.M. Neggers, Andrica de Vries, Rob Pieters, Marry M. van den Heuvel
Journal: Blood (2012)
Endosomal pH modulation by peptide-gold nanoparticle hybrids enables potent anti-inflammatory activity in phagocytic immune cells
Authors: Hong Yang, Lisa Kozicky, Aabida Saferali, Shan-Yu Fung, Nicole Afacan, Bing Cai, Reza Falsafi, Erin Gill, Mingyao Liu, Tobias R. Kollmann, R.E.W. Hancock, Laura M. Sly, Stuart E. Turvey
Journal: Biomaterials (2016)
Intramammary lymph node metastases are an independent predictor in breast cancer outcomes
Authors: J. Shen, K. K. Hunt, N. Q. Mirza, S. Krishnamurthy, S. E. Singletary, H. M. Kuerer, F. Meric-Bernstam, B. Feig, M. I. Ross, G. V. Babiera
Journal: Journal of Clinical Oncology (2004)

615 Background: Breast cancer patients with intramammary lymph node (intraMLN) metastases are treated as having stage II disease, even in the absence of axillary nodal involvement. However, little is known about the true clinical significance of these lymph nodes. The purpose of this study was to determine the clinical relevance of intraMLN and what role they play in breast cancer outcomes. Methods: Between 1983–2003, 196 intraMLN specimens were identified in our pathology database. 130 were found in association with a primary breast malignancy. Data on clinical and pathologic features were collected, and then evaluated by univariate and multivariate analysis for locoregional recurrence (LRR), distant recurrence (DR), disease-free survival (DFS), and disease-specific survival (DSS). The median follow-up was 36 months. Results: The median age of patients was 53 years (range: 27–84). 24 patients (18%) had intraMLN identified pre-operatively by either mammography or ultrasound. The remainder were found during the pathologic examination of breast specimens. The incidence of intraMLN metastasis was 28% (n=36) and these were distributed across all T stages (T1-T4). The majority (83%) of patients with intraMLN metastases had axillary metastases. However, isolated intraMLN metastases were seen in 6 patients (5%). Univariate analysis revealed the presence of intraMLN metastasis to be associated with a poorer 5-year DFS (54% vs. 89%, p = .001) and 5-year DSS (66% vs. 90%, p = .001). On multivariate analysis, intraMLN involvement remained an independent predictor of DFS (risk ratio 2.33, p = 0.03) and DSS (risk ratio 5.32, p = .002). Conclusions: Intramammary lymph node metastases appear to be an independent predictor of poor outcome. Identification of an intraMLN with pre-operative imaging should prompt further histologic work-up. In addition, the identification of a positive intraMLN by lymphatic mapping may help identify a high-risk group of patients who warrant further axillary lymph node evaluation, despite an otherwise clinically negative axilla. No significant financial relationships to disclose.
Permissive Conditions for Evolution of PNH Clones Are Characterized by Overproduction of IFN-γ by Clonal CD4 and CD8 T Cells, Fas-L by CTLs, and Promoted by Immunogenetic Background
Authors: Michael Clemente, Heather Cazzolli, Anna Jankowska, Christine O’Keefe, Bianca Serio, Susan Nyland, Marcin Wlodarski, PK Epling-Burnette, Thomas Loughran, Alan List, Ronald Paquette, Jaroslaw Maciejewski
Journal: Blood (2008)
Oxygen in the ICU
Authors: Niall D. Ferguson
Journal: JAMA (2016)

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Pemetrexed (P) alone or in combination with platinum for malignant pleural mesothelioma (MPM): Efficacy and toxicity of the International Expanded Access Program (EAP) in Spanish patients (p)
Authors: T. Moran, J. González-Larriba, J. Montesinos, J. Delgado, B. Massutí, G. López-Vivanco, J. López-Picazo, A. Peiró, L. G. Paz-Ares, R. Rosell
Journal: Journal of Clinical Oncology (2008)

19038 Background: A landmark phase III study reported a significant survival benefit for P+cisplatin (cis) versus cis alone in MPM (Vogelzang et al. JCO 2003). EAP provided access to P alone or P plus a platinum for 3311 MPM p in 13 countries. Safety and efficacy data for Spanish p are summarized in this abstract. Methods: From Feb 2003 to May 2005, 225 advanced MPM p were enrolled at 26 sites in Spain. P 500 mg/m2 was given alone or in combination with either cis 75 mg/m2 or carboplatin (Cb) AUC 5 once every 21 days with standard pre-medication (vitamin B12, folic acid, and dexamethasone). Results: 221 MPM p were evaluable for safety and 180 (113 chemonaïve; 67 pre-treated) for efficacy. Median age, 60 yrs (range: 25–89); 78.7% male; 73.3%, Karnofsky score ≥80. Response rate: 27% in the P group, 27.5% in the P+cis group and 30.4% in the P+Cb group, with a clinical benefit rate of 51.4%, 65.5% and 78.6%, respectively. Median time to progression (TTP): 6.9 months (m) in the P group and 8 m in the P+cis group. Median survival (MS): 14.1 m in the P group and 13.4 m in the P+cis group (figure). Neither TTP nor MS could be estimated in the P+Cb group due to high censoring rate. 1-year survival: 67.2% for the P group, 57.1% for the P+cis group, and 62.8% for the P+Cb group. Hematological toxicity was tolerable. Conclusions: Treatment with P plus a platinum resulted in improved survival in MPM compared to cis or Cb alone, with a manageable toxicity, supporting the findings of the phase III study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Oncology
Treatment of Advanced Neuroendocrine Tumours: Final Results of the Ukinets and Ncri Randomised Phase 2 Net01 Trial
Authors: T. Meyer, M. Caplin, N. Reed, W. Qian, S. Lao-Sirieix, G. Armstrong, J. Valle, D. Tablot, D. Cunningham, P. Corrie
Journal: Annals of Oncology (2012)
The Sphingosine-1-Phosphate Modulator FTY720 Targets Multiple Myeloma via the CXCR4/CXCL12 Pathway
Authors: Katia Beider, Evgenia Rosenberg, Hanna Bitner, Avichai Shimoni, Merav Leiba, Maya Koren-Michowitz, Elena Ribakovsky, Shiri Klein, Devorah Olam, Lola Weiss, Hanna Wald, Michal Abraham, Eithan Galun, Amnon Peled, Arnon Nagler
Journal: Clinical Cancer Research (2016)

Purpose: To explore the functional consequences of possible cross-talk between the CXCR4/CXCL12 and the sphingosine-1-phosphate (S1P) pathways in multiple myeloma (MM) cells and to evaluate the effect of S1P targeting with the FTY720 modulator as a potential anti-MM therapeutic strategy.Experimental Design and Results: S1P targeting with FTY720 induces MM cell apoptosis. The combination of FTY720 with the SPHK1 inhibitor SKI-II results in synergistic inhibition of MM growth. CXCR4/CXCL12-enhanced expression correlates with reduced MM cell sensitivity to both FTY720 and SKI-II inhibitors, and with SPHK1 coexpression in both cell lines and primary MM bone marrow (BM) samples, suggesting regulative cross-talk between the CXCR4/CXCL12 and SPHK1 pathways in MM cells. FTY720 was found to directly target CXCR4. FTY720 profoundly reduces CXCR4 cell-surface levels and abrogates the CXCR4-mediated functions of migration toward CXCL12 and signaling pathway activation. Moreover, FTY720 cooperates with bortezomib, inducing its cytotoxic activity and abrogating the bortezomib-mediated increase in CXCR4 expression. FTY720 effectively targets bortezomib-resistant cells and increases their sensitivity to bortezomib, promoting DNA damage. Finally, in a recently developed novel xenograft model of CXCR4-dependent systemic MM with BM involvement, FTY720 treatment effectively reduces tumor burden in the BM of MM-bearing mice. FTY720 in combination with bortezomib demonstrates superior tumor growth inhibition and abrogates bortezomib-induced CXCR4 increase on MM cells.Conclusions: Altogether, our work identifies a cross-talk between the S1P and CXCR4 pathways in MM cells and provides a preclinical rationale for the therapeutic application of FTY720 in combination with bortezomib in patients with MM. Clin Cancer Res; 23(7); 1733-47. ©2016 AACR.
A phase II study of arsenic trioxide (ATO) in patients with metastatic melanoma
Authors: A. A. Tarhini, J. M. Kirkwood, W. E. Gooding, J. J. Stuckert, S. S. Agarwala
Journal: Journal of Clinical Oncology (2007)

8569 Background: Arsenic trioxide (ATO) is a promising new agent in the treatment of both solid and hematologic tumors. ATO cytotoxicity and apoptosis induction has been demonstrated in vitro with numerous human cancer cell lines including human melanoma. Methods: We conducted a safety and efficacy single arm study of ATO in patients (18 years or older) with inoperable AJCC stage IV melanoma. One cycle consisted of a loading dose of 0.32 mg/kg/day for 4 days in week 1, followed by 0.25 mg/kg/day twice per week for 6 weeks, followed by 1 week of rest for a total cycle length of 8 weeks when response assessment was performed. Results: A total of 21 patients (5 females and 16 males) were accrued with a median age of 63.8 years (range 32.9 - 81.6). All patients had metastatic melanoma including AJCC stage IV M1a (2), M1b (6) and M1c (13). ECOG performance included 0 (11) and 1 (10). One patient had metastatic choroidal melanoma and 20 had cutaneous melanoma. Twenty patients had received prior therapy including chemotherapy (17), immunotherapy (11) and radiation (3). Six patients completed 1 cycle, seven 2 cycles, one 3 cycles, one 4 cycles and two 5 cycles of ATO. Four patients did not complete the first cycle and are not evaluable for response. Possible treatment related Grade 3/4 toxicities included one case of idiopathic thrombocytopenic purpura and one case of elevated LDH. Among 17 evaluable patients, 1 (6%) had partial response lasting 7 months, 8 (47%) had disease stabilization after 1 cycle, but all eventually progressed. A total of 19 patients have died and 2 are alive at a median follow up of 17.5 weeks. Median time to progression is 14 weeks, 95% CI (9, 38) and median survival is 52.9 weeks, 95% CI (14.4, 66.1). Conclusions: ATO as a single agent is well tolerated with modest activity in metastatic melanoma that may be enhanced in combination with other agents that induce apoptosis. No significant financial relationships to disclose.