tbuckley/cabot-search huggingface dataset:
Antiprostate-specific membrane antigen (PSMA)-based radioimmunotherapy: A combined analysis of radiolabeled-J591 studies.
Authors: N. H. Akhtar, D. M. Nanus, J. Osborne, S. Vallabhajosula, H. Beltran, L. Tyrell, K. Nadeau, S. J. Goldsmith, N. H. Bander, S. T. Tagawa
Journal: Journal of Clinical Oncology (2011)

136 Background: J591 is a monoclonal antibody which selectively binds the external domain of PSMA with high affinity. Two phase I trials of radiolabeled-J591 have been published; two additional studies have been completed. 90 Y is a beta-emitting particle optimal for tumor lesions 28-42 mm in size; 177 Lu is best suited for lesions 1-3 mm in diameter [O'Donoghue J Nuc Med 1995]. Methods: With WCMC IRB approval, long-term follow-up of 4 clinical trials and the ongoing studies was analyzed. Prospectively collected data were supplemented with retrospective additions when necessary. Median survival (OS) was calculated by Kaplan- Meier methodology. Results: Between 10/00 and 7/10, 132 pts with metastatic CRPC received radiolabeled J591 (103 received 177 Lu-J591, 29 90 Y-J591) with a median follow-up of 68.5 months (mo). Median age 70.3 yrs; all progressed after multiple lines of hormonal therapy, 41.7% received prior chemo, 48.5% received post-J591 chemo. Median Halabi nomogram score for the group was 146 (range 97- 196). OS for the entire group was 16.7 mo [95% CI 13.8, 19.7]. 26 (19.7%) experienced &gt; 30% PSA decline, with OS of 22.4 mo (vs 13.6 mo for those with any PSA increase, p=0.08; p=0.006 at phase II doses). Pts receiving 177 Lu-J591 had more 30% PSA declines than 90 Y-J591 (21.3% vs 6.9%, p=0.06). 37.9% had measurable disease; those who received 90 Y-J591 were more likely to have measurable response than 177 Lu-J591 [p=0.04]. All objective tumor responses also had significant PSA declines. Of 15 pts with baseline and follow-up CTC counts (CellSearch methodology), 12 (80%) became or remained favorable at follow-up; 3 became or remained unfavorable. Conclusions: Radiolabled J591 is tolerable and efficacious. As predicted based upon their physical properties, 177 Lu-J591 appears more effective for lower volume disease, with objective responses in larger volume disease only with 90 Y-J591. Current trials utilizing 177 Lu-J591 focus on predictive biomarkers, dose fractionation to improve tolerance and efficacy, combination with chemotherapy, and “salvage radioimmunotherapy” to delay the onset of metastases in men with progressive biochemical (micrometastatic) disease best suitable for 177 Lu-J591. [Table: see text]
Impairment of Myeloid Dendritic Differentiation and Role in the Support of Splenic Dysmegakaryopoiesis in Patients with Primary Myelofibrosis
Authors: Christophe Desterke, Bernadette Guerton, Sophie Amsellem, Agnes Charpentier, Brigitte Dupriez, Jean-Loup Demory, Christophe Martinaud, Jean-Jacques Lataillade, Julien Giron-Michel, Bruno Azzarone, Marie-Caroline Le Bousse-Kerdiles
Journal: Blood (2012)
DIVAN: accurate identification of non-coding disease-specific risk variants using multi-omics profiles
Authors: Li Chen, Peng Jin, Zhaohui S. Qin
Journal: Genome biology (2016)

Understanding the link between non-coding sequence variants, identified in genome-wide association studies, and the pathophysiology of complex diseases remains challenging due to a lack of annotations in non-coding regions. To overcome this, we developed DIVAN, a novel feature selection and ensemble learning framework, which identifies disease-specific risk variants by leveraging a comprehensive collection of genome-wide epigenomic profiles across cell types and factors, along with other static genomic features. DIVAN accurately and robustly recognizes non-coding disease-specific risk variants under multiple testing scenarios; among all the features, histone marks, especially those marks associated with repressed chromatin, are often more informative than others.
Defining molecular determinants of sensitivity to EGFR inhibition in urothelial carinoma.
Authors: W. Y. Kim, T. Hadzic, S. A. Heathcote, D. T. Gammons, K. Rathmell, Y. E. Whang, P. A. Godley, M. E. Nielsen, E. Wallen, R. Pruthi
Journal: Journal of Clinical Oncology (2011)

268 Background: Activation of EGFR in cancer patients has been shown to correlate with tumor proliferation, angiogenesis, and metastasis. EGFR inhibition has been shown to be clinically beneficial in several solid tumors and appears to be a tractable therapeutic target. EGFR is over-expressed in bladder cancer and a phase II trial of neoadjuvant erlotinib in patients with muscle invasive bladder cancer suggests possible clinical activity. We therefore hypothesized that we could define molecular correlates to predict response to EGFR inhibition. Methods: Correlative tumor samples derived from a phase II trial of neoadjuvant erlotinib in muscle invasive urothelial carcinoma of the bladder were analyzed to define molecular determinants of response to EGFR inhibition. The effect of silencing a candidate molecular predictor of resistance to EGFR inhibition, HRAS, was assessed by changes in the IC50 of T24 cells (harbor mutant HRAS) expressing short hairpin RNAs to HRAS or a control shRNA. Results: Analysis of the gene expression profiles of TURB-T (pretreatment) samples show that tumors from non-pT0 patients had significantly elevated levels of HRAS relative to tumors from pT0 patients. Furthermore, knock-down of HRAS in T24 cells enhanced the sensitivity of these cells to erlotinib. Conclusions: Elevated HRAS expression is correlated with a lack of response to erlotinib in vivo and silencing of HRAS in T24 cells results in enhanced sensitivity to erlotinib in vitro. Further molecular analyses are ongoing. No significant financial relationships to disclose.
Prostaglandin E2, Tumor Necrosis Factor α, and Pro-opiomelanocortin Genes as Potential Mediators of Cancer Pain in Cutaneous Squamous Cell Carcinoma of Organ Transplant Recipients
Authors: Sara Regina Frauenfelder, Sandra Nicole Freiberger, Jan Nico Bouwes Bavinck, Koen D. Quint, Roel Genders, Andreas L. Serra, Günther F. L. Hofbauer
Journal: JAMA Dermatology (2016)

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Perioperative morbidity and mortality in patients treated by radical cystectomy: A multi-institutional retrospective study.
Authors: N. Takada, T. Abe, S. Maruyama, A. Sazawa, N. Shinohara, T. Seki, M. Togashi, K. Nonomura
Journal: Journal of Clinical Oncology (2011)

270 Background: It is well known that radical cystectomy is associated with comparatively high perioperative morbidity and mortality. In the present study, we collected data of perioperative outcomes from Hokkaido University Graduate School of Medicine and our teaching hospitals and assessed the complications and death rate within 90 days after radical cystectomy. Methods: We collected clinical data of 970 patients undergoing radical cystectomy for nonmetastatic bladder cancer in 21 institutions between 1999 and 2009. We then assessed 90-day complications and death after radical cystectomy. The complications were classified according to the modified Clavien classification. Over 40 variables were included in the analysis, including age, ASA score, BMI, comorbidity, neoadjuvant chemotherapy, clinical stage, type of urinary diversion, operative time, estimated blood loss, transfusion, and hospital stay. Statistical analysis was performed utilizing Student's t-tests, chi-square tests, and logistic regression analysis. Results: The median patient age was 70 (range, 25-91) years old. 62.5% of patients had an ASA score≥2. Regarding the urinary diversion, ileal conduit was performed in 523 (53.6%) patients, neobladder in 178 (18.4%), ureterocutaneostomy in 255 (26.3%). Median operative time was 399 (range, 100-927) minutes. Median hospital stay was 39 (0-364) days. Regarding the complications, 660 (68%) patients experienced at least one complication and death rate within 90 days after surgery was 1.34% (n=13), respectively. Of the complications, 34.1% was classified as grade 1, 41.5% as grade 2, 20.1% as grade 3, 1.1% as grade 4, 1.2% as grade 5. Multivariate analysis identified age≥70 (odds ratio 1.41), urinary diversion utilizing intestine (OR 1.58) and operative time ≥ 400 (OR 1.54) were independent risk factors. Conclusions: Death rate was 1.34%, which was compatible to reports form western high- volume centers. About two-thirds of the patients experienced at least one complication, although they were mostly classified as grade 2 or less. Age, urinary diversion, and operative time were significant risk factors for perioperative complications after radical cystectomy. No significant financial relationships to disclose.
Post-treatment resistance analysis of hepatitis C virus from phase II and III clinical trials of ledipasvir/sofosbuvir
Authors: David Wyles, Hadas Dvory-Sobol, Evguenia S. Svarovskaia, Brian P. Doehle, Ross Martin, Nezam H. Afdhal, Kris V. Kowdley, Eric Lawitz, Diana M. Brainard, Michael D. Miller, Hongmei Mo, Edward J. Gane
Journal: Journal of Hepatology (2016)
ESE3 Inhibits Pancreatic Cancer Metastasis by Upregulating E-Cadherin
Authors: Tiansuo Zhao, Wenna Jiang, Xiuchao Wang, Hongwei Wang, Chen Zheng, Yang Li, Yan Sun, Chongbiao Huang, Zhi-bo Han, Shengyu Yang, Zhiliang Jia, Keping Xie, He Ren, Jihui Hao
Journal: Cancer Research (2016)

The ETS family transcription factor ESE3 is a crucial element in differentiation and development programs for many epithelial tissues. Here we report its role as a tumor suppressor in pancreatic cancer. We observed drastically lower ESE3 expression in pancreatic ductal adenocarcinomas (PDAC) compared with adjacent normal pancreatic tissue. Reduced expression of ESE3 in PDAC correlated closely with an increase in lymph node metastasis and vessel invasion and a decrease in relapse-free and overall survival in patients. In functional experiments, downregulating the expression of ESE3 promoted PDAC cell motility and invasiveness along with metastasis in an orthotopic mouse model. Mechanistic studies in PDAC cell lines, the orthotopic mouse model, and human PDAC specimens demonstrated that ESE3 inhibited PDAC metastasis by directly upregulating E-cadherin expression at the level of its transcription. Collectively, our results establish ESE3 as a negative regulator of PDAC progression and metastasis by enforcing E-cadherin upregulation. Cancer Res; 77(4); 874-85. ©2016 AACR.
The Triterpenoids 2-cyano-3,12-dioxooleana-1,9-dien-28-oic Acid (CDDO) and Their Imidazole (CDDO-Im) and Dinitrile Derivatives (DI-CDDO) Elicit Apoptosis through a Novel Mitochondrial Pathway.
Authors: Paul Brookes, Andrew Tompkins, Kimberly Morse, Shannon Hilchey, Suhail Salim, Denise Ray, Richard Phipps, Steven H. Bernstein
Journal: Blood (2005)
Prognostic Analysis of Refractory Anemia in Adult Patients with Myelodysplasric Syndrome in China.
Authors: Xiao-qin Wang, Zi-xing Chen, Shu-chang Chen, Guo-wei Lin, Mei-rong Ji, Jian-ying Liang, Dan-dan Liu, De-gao Li, Yan Ma
Journal: Blood (2007)
Prognostic Impact of Elevated Serum Ferritin at Diagnosis of Diffuse Large B-Cell Lymphoma Treated In the Rituximab Era
Authors: Herve Ghesquieres, Ferlay Céline, Lachenal Florence, Nicolas-Virlizier Emmanuelle, Domnisoru Izabella-Irina, Rey Philippe, Gargi Thérèse, Chassagne-Clement Catherine, Favier Bertrand, Biron Pierre, Sebban Catherine, Jean-Yves Blay
Journal: Blood (2010)
Tumor response and adaptation to CYP17 inhibition in prostate cancer: Induction of steroidogenesis and androgen receptor splice variants.
Authors: E. A. Mostaghel, B. Marck, A. M. Matsumoto, P. Nelson, R. Vessella, S. R. Plymate, R. B. Montgomery
Journal: Journal of Clinical Oncology (2011)

18 Background: Abiraterone is a novel inhibitor of the steroidogenic enzyme CYP17 and suppresses tumor growth in patients with castration-resistant prostate cancer (CRPC). The efficacy of abiraterone in suppressing tumor androgens or mechanisms of resistance to abiraterone are not known. Methods: Human CRPC xenografts LuCaP 23 and LuCaP 35 grown in castrated male mice were treated with abiraterone to determine effects on tumor growth and tumor androgen levels. Tumor gene expression measurements were obtained to delineate mechanisms of abiraterone resistance. Results: Abiraterone i.p. for 21 days improved survival (time to tumor size 750 mm 3 ) vs vehicle control (VC) in LuCaP 35 (HR 3.8 [95% CI 3.1-53.7] median survival 39 vs 18 days) and LuCap 23 (HR 2.4 [1.43-10.24] median survival 24 vs. 14 days). Greater anti-tumor activity correlated with superior tumor androgen suppression. Tumor testosterone was strongly suppressed in both LuCaP35 (0.20 + 0.24 vs VC 0.69 + 0.36 pg/mg) and LuCaP 23 (0.07 + 0.11 vs VC 0.49 + 0.22 pg/mg). DHT levels were also markedly suppressed in LuCaP35 (1.17 + 1.46 vs VC 3.49 + 1.81pg/mg). In contrast, DHT levels in LuCap23 were unchanged early (day 7-21) and only partially suppressed at longer time points (VC 5.73 + 1.88; early 5.31 + 2.69; late 2.82 + 2.27 pg/mg). Expression of the abiraterone target CYP17 was upregulated in both xenografts (LuCaP23 2.5 fold, p&lt;0.0001; LuCap35 2.9 fold, p=0.028). Overall, LuCap23 appeared resistant to suppression of tumor androgens due to induction of steroidogenic transcripts (including STAR, CYP11, HSD3B1 and AKR1C3) without statistically significant increases in androgen receptor (AR). In contrast, LuCap35 demonstrated strong induction of transcripts for AR and AR splice variants (AR 3.8 fold, p&lt;0.0001, V7 AR splice variant 3.7 fold, p&lt;0.0001), with induction of steroidogenic transcripts only at late time points. Conclusions: Abiraterone treatment suppressed intratumoral androgen levels and reduced growth of CRPC xenografts. Abiraterone resistance may occur through upregulation of the abiraterone target CYP17, and/or the induction of AR and AR splice variants that confer ligand-independent AR trans-activation. [Table: see text]
Identification of LMO2 Transcriptome and Interactome in Diffuse Large B-Cell Lymphoma by Integrated Experimental and Computational Approach
Authors: Elena Cubedo, Andrew J. Gentles, Chuanxin Huang, Yasodha Natkunam, Shruti Bhatt, Xiaoyu Jiang, Xiaoqing Lu, Isabel Romero-Camarero, Sylvia K. Plevritis, Jose A Martinez-Climent, Isidro Sanchez-Garcia, Ari Melnick, Izidore S Lossos
Journal: Blood (2011)
Metacognition and conscious experience
Authors: Bennett L Schwartz, Ali Pournaghdali
Journal: Behavioral and Brain Sciences (2016)

Abstract Morsella et al. focus on the conscious nature of sensation. However, also critical to an understanding of consciousness is the role of internally generated experience, such as the content of autobiographical memory or metacognitive experiences. For example, tip-of-the-tongue states are conscious feelings that arise when recall fails. Internally driven experiences drive us to action and therefore are consistent with the current approach.
Molecular and Functional Characterization of Two Novel Missense Mutations in Iron Transport Protein Causing Hypochromic Microcytic Anemia and Hemosiderosis
Authors: Rekha Athiyarath, Neeraj Arora, Rayaz Ahmed, Biju George, Mammen Chandy, Alok Srivastava, Eunice Sindhuvi Edison
Journal: Blood (2012)
Prevention of hospital-acquired bloodstream infections through chlorhexidine gluconate-impregnated washcloth bathing in intensive care units: a systematic review and meta-analysis of randomised crossover trials
Authors: Elsa Afonso, Koen Blot, Stijn Blot
Journal: Eurosurveillance (2016)

We assessed the impact of 2% daily patient bathing with chlorhexidine gluconate (CHG) washcloths on the incidence of hospital-acquired (HA) and central line-associated (CLA) bloodstream infections (BSI) in intensive care units (ICUs). We searched randomised studies in Medline, EMBASE, Cochrane Library (CENTRAL) and Web of Science databases up to April 2015. Primary outcomes were total HABSI, central line, and non-central line-associated BSI rates per patient-days. Secondary outcomes included Gram-negative and Gram-positive BSI rates and adverse events. Four randomised crossover trials involved 25 ICUs and 22,850 patients. Meta-analysis identified a total HABSI rate reduction (odds ratio (OR): 0.74; 95% confidence interval (CI): 0.60–0.90; p = 0.002) with moderate heterogeneity (I 2 = 36%). Subgroup analysis identified significantly stronger rate reductions (p = 0.01) for CLABSI (OR: 0.50; 95% CI: 0.35–0.71; p &lt; 0.001) than other HABSI (OR: 0.82; 95% CI: 0.70–0.97; p = 0.02) with low heterogeneity (I 2 = 0%). This effect was evident in the Gram-positive subgroup (OR: 0.55; 95% CI: 0.31–0.99; p = 0.05), but became non-significant after removal of a high-risk-of-bias study. Sensitivity analysis revealed that the intervention effect remained significant for total and central line-associated HABSI. We suggest that use of CHG washcloths prevents HABSI and CLABSI in ICUs, possibly due to the reduction in Gram-positive skin commensals.
Safety and efficacy of ketoconazole (K) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Contemporary experience and prognostic indicators.
Authors: M. A. Eisenberger, P. Huang, V. J. Sinibaldi, M. A. Carducci, S. R. Denmeade, E. S. Antonarakis, J. J. Kim, D. Keizman
Journal: Journal of Clinical Oncology (2011)

e15007 Background: Intracrine conversion of adrenal androgens to testosterone play an important role in CRPC progression. Treatments (tx) that block adrenal steroid synthesis have shown significant clinical benefits in mCRPC. Aim: To evaluate contemporary data on safety and efficacy associated with K in mCRPC. Methods: All/unselected mCRPC pts progressing on GnRH-a and antiandrogens (AA) treated with K were retrospectively analyzed. Pts were maintained on gonadal suppression, discontinued AA, and received K 200 - 400 mg t.i.d. until disease progression or dose-limiting toxicity (DLT). Initial 600mg/d dose was escalated to 1200mg/d if a PSA decrease was not seen at 3 months (mos) or if a subsequent disease progression was observed (optional). Follow up included hematological/chemical profile q 3 mos, scans upon clinical (physical exam/symptoms) or biochemical progression (PSA increase ≥ 25% and ≥2ng/ml from nadir). A multivariate cox regression model was used to identify variables significantly associated with disease progression. Results: From 1999-2010 (mean follow up 5-129 mos), 114 m-CRPR pts were treated with K 200mg (n=82, 72%) or 400mg (n=32, 28%) tid. Most common grade 3/4 tox events (n=23) were fatigue, abdominal discomfort, nausea, and dizziness. 9 pts (8%) had DLT (fatigue n=7, hepatotoxicity/thrombocytopenia n=1). 61/114 (54%) had ≥ 50% PSA decline. Overall median time to progression (TTP) was 8 mos (range 1-129 ). 14 pts remain progression free > 7 mos (range 7-129). Significant prognostic factors (Table) were response to prior AA (≥6 vs. <6 mos), pre-tx PSADT (≥3 vs. <3 mos) and extent of disease (limited-axial skeleton and/or nodal vs extensive- appendicular skeleton and/or visceral). Conclusions: K is effective and safe in m-CRPC. Prior response to AA, pre-tx PSADT, and extent of disease are associated with TTP and further supports a therapeutic role for suppressing adrenal androgens in m-CRPC. Factor TTP (mos), HR, p value Response to prior AA of ≥6 vs. <6 mos duration 18 vs. 3, 3.522, 0.0019 Pre-tx PSADT ≥3 vs. <3 ms 16 vs. 4, 1.725, 0.049 Limited vs. extensive metastatic disease 19 vs. 5, 2.12, 0.018
Treatment of Antigen-Presenting Cells with Histone Deacetylase Inhibitors Represents a Novel Strategy To Overcome CD4+ T-Cell Tolerance: Divergent Effects on the IL10 and IL-12 Promoter.
Authors: Hongwei Wang, Fengdong Cheng, P. Horna, I.V. Suarez, Jian Wu, A.P. Atadja, E. Seto, K. Wright, K. Bhalla, E.M. Sotomayor
Journal: Blood (2005)
The Role of ADAMTS13-Specific Circulating Immune Complexes in Prediction of Recurrence of Acquired Thrombotic Thrombocytopenic Purpura
Authors: Barbara Ferrari, Carla Valsecchi, Silvia Pontiggia, Ilaria Mancini, Luca Andrea Lotta, Danijela Mikovic, Giovanna Meloni, Flora Peyvandi
Journal: Blood (2014)
Mixed Chimerism at Three Months after Allogeneic Hematopoietic Stem Cell Transplantation Is a Significant Predictor of Disease Relapse in High-Risk Acute Myeloid Leukemia Patients in First Complete Remission
Authors: Mauricette Michallet, Mohamad Sobh, Hélène Labussière-wallet, Marie Balsat, Caroline Lejeune, Isabelle Mollet, Philippe Moskovtchenko, Xavier Thomas, Fiorenza Barraco, Valérie Mialou, Valérie Dubois, Franck E. Nicolini
Journal: Blood (2015)
Neoadjuvant chemoradiation and intraoperative electron irradiation for locally unresectable/borderline resectable pancreas adenocarcinoma.
Authors: Jonathan Ben Ashman, Adyr A Moss, Matthew D. Callister, Kunam S Reddy, David C Mulligan, Leonard L. Gunderson, Mitesh J. Borad
Journal: Journal of Clinical Oncology (2012)

327 Background: The use of preoperative therapy for pancreatic cancer remains controversial. This study reviews our experience using neoadjuvant chemotherapy and chemoradiation (CRT) followed by surgery with intraoperative electron irradiation (IOERT) for patients with borderline resectable (BR) or unresectable (UR) tumors. Methods: A retrospective review identified 48 patients (pts) with primary BR/UR pancreas adenocarcinoma treated with preop CRT with intent to proceed to curative surgery with IOERT. Seventeen patients did not undergo attempted resection and are excluded (disease progression, 12; medically inoperable, 3; declined surgery, 2). Thirty-one patients proceeded to resection attempt and are the subject of this analysis. Kaplan-Meier survival analysis was performed using log rank test for significance. Median follow up was 19 months (mo). Results: Complete resection (R0) was achieved in 11 pts, R1 in 5, and R2 or not resected (IOERT alone) in 15 patients. Twenty-six pts died (23 of disease, 2 unrelated causes, 1 uncertain). Median overall survival (OS) was 19 mo for all pts. Local progression was detected in only 5 patients (16%) while distant disease developed in 24 (77%). Resection status significantly correlated with OS; R0/R1 patients had a median survival of 23 mo vs. 10 mo for R2/unresected tumors (p = 0.002). Three-year OS was 35% vs. 0%, respectively. Survival was not influenced by tumor location, CA19-9 baseline or response, tumor size, or initial judgment of resectability (BR vs. UR). BR tumors were resectable after neoadjuvant therapy in 9 of 11 patients (R0, 8; R1, 1) while 8 of 20 initially UR tumors underwent resection (R0, 3; R1, 4; R2, 1). Conclusions: Neoadjuvant therapy combined with IOERT has the possibility to improve patient selection for surgical resection and to optimize local therapy. Although the prognosis for locally advanced pancreatic cancer remains poor, survival was superior among patients for whom R0 or R1 resection was achieved. Distant metastasis remained the dominant pattern of failure, and novel systemic agents are needed. Prospective evaluation of the impact of neoadjuvant chemotherapy, CRT, and IOERT is warranted.
Indoor development of Aedes aegypti in Germany, 2016
Authors: Helge Kampen, Stephanie Jansen, Jonas Schmidt-Chanasit, Doreen Walther
Journal: Eurosurveillance (2016)

In spring 2016, a German traveller returning from Martinique cultivated imported plant offsets in her home, and accidentally bred Aedes aegypti . Thirteen adult mosquito specimens submitted for identification and the traveller were tested for Zika, dengue and chikungunya virus infections, with negative results. The detection of Ae. aegypti by the ‘Mueckenatlas’ project demonstrates the value of this passive surveillance scheme for potential public health threats posed by invasive mosquitoes in Germany.