tbuckley/cabot-search huggingface dataset:
Obese men, higher PSA nadir values after radical prostatectomy (RP), and higher biochemical recurrence (BCR) rates: Results from the SEARCH database.
Authors: T. S. Ho, W. J. Aronson, M. K. Terris, J. C. Presti, C. J. Kane, C. L. Amling, S. J. Freedland
Journal: Journal of Clinical Oncology (2011)

186 Background: Obesity is associated with risk of BCR after RP. It has been suggested this may be due to poor surgical technique and greater risk of positive margins. We examined whether obesity predicted the risk of a detectable PSA nadir after RP (as a measure of residual PSA-producing tissue left behind) and if this accounted for the greater risk of BCR in obese men in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Methods: We identified 1,011 men treated with RP from 2001 to 2010 in SEARCH who had known data for pre-operative BMI and ultrasensitive PSA nadir within 6 months after RP. The association between BMI (&lt;25, 25-29.9, and &gt;30 kg/m 2 ) and PSA nadir (0, 0.01-0.09, 0.10-0.19, and &gt;0.2) was tested using chi-squared and linear regression adjusting for clinical and pathological characteristics. A proportional hazards model was used to test the association between BMI and BCR adjusted for clinical and pathological characteristics and with and without PSA nadir. Results: Higher BMI was associated with higher PSA nadir (chi-squared, p=0.03). On multivariate analysis, obesity (p&lt;0.001) was associated with higher PSA nadir. Among men with a PSA nadir &lt;0.2 ng/ml (i.e. those who did not recur based upon PSA nadir alone), obesity was associated with BCR when not adjusted for PSA nadir (HR 1.85, 95% CI 1.19-2.89, p=0.007). Adjusting for PSA nadir attenuated, but did not eliminate this association (HR 1.65, 95% CI 1.05-2.59, p=0.03). Even among men with an undetectable PSA nadir, obesity remained significantly associated with BCR (HR 3.45, 95% CI 1.41-8.47, p=0.007). Interestingly, among men with a detectable PSA nadir, but &lt;0.2 ng/ml, obesity did not predict BCR with (HR 1.21, 95% CI 0.71-2.07, p=0.49) or without adjustment for PSA nadir (HR 1.41, 95% CI =0.82-2.41, p=0.22). Conclusions: Obese men are more likely to have a higher PSA nadir suggesting technical issues confound an ideal operation in obese men. However, the increased PSA nadir does not completely explain the higher PSA recurrence rates. These data further support the idea that obesity is biologically associated with prostate cancer progression. No significant financial relationships to disclose.
The SWI/SNF Complex Protein Snr1 Is a Tumor Suppressor in <i>Drosophila</i> Imaginal Tissues
Authors: Gengqiang Xie, Hanqing Chen, Dongyu Jia, Zhiqiang Shu, William Hunt Palmer, Yi-Chun Huang, Xiankun Zeng, Steven X. Hou, Renjie Jiao, Wu-Min Deng
Journal: Cancer Research (2016)

Abstract Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here, we use Drosophila imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades. Removal of Snr1 resulted in neoplastic tumorigenic overgrowth in imaginal epithelial tissues, whereas depletion of any other members of the SWI/SNF complex did not induce similar phenotypes. Unlike other components of the SWI/SNF complex that were detected only in the nucleus, Snr1 was observed in both the nucleus and the cytoplasm. Aberrant regulation of multiple signaling pathways, including Notch, JNK, and JAK/STAT, was responsible for tumor progression upon snr1-depletion. Our results suggest that the cytoplasmic Snr1 may play a tumor suppressive role in Drosophila imaginal tissues, offering a foundation for understanding the pivotal role of SMARCB1/hSNF5 in suppressing MRT during early childhood. Cancer Res; 77(4); 862–73. ©2017 AACR.
A major impact of the influenza seasonal epidemic on intensive care units, Réunion, April to August 2016
Authors: Laurent Filleul, Dany Bakoly Ranoaritiana, Elsa Balleydier, David Vandroux, Clémence Ferlay, Marie-Christine Jaffar-Bandjee, Julien Jaubert, Bénédicte Roquebert, Bruno Lina, Martine Valette, Bruno Hubert, Sophie Larrieu, Elise Brottet
Journal: Eurosurveillance (2016)

The 2016 seasonal influenza in Réunion in the southern hemisphere, was dominated by influenza A(H1N1)pdm09 (possibly genogroup 6B.1). An estimated 100,500 patients with acute respiratory infection (ARI) consulted a physician (cumulative attack rate 11.9%). Sixty-six laboratory-confirmed cases (65.7/100,000 ARI consultations) were hospitalised in an intensive care unit, the highest number since 2009. Impact on intensive care units was major. Correlation between severe cases was 0.83 between Réunion and France and good for 2009 to 2015.
A Comparison of Levofloxacin and Oral Third Generation Cephalosporins As Antibacterial Prophylaxis in Acute Myeloid Leukemia (AML) during Chemotherapy-Induced Neutropenia
Authors: Kristyn E. Yemm, Jason N. Barreto, Ross A. Dierkhising, Kristin C. Mara, Naseema Gangat, Pritish K. Tosh
Journal: Blood (2016)
The MMSET Gene Contributes to the Growth, Adhesion, and Tumorigencitiy of t(4;14) Multiple Myeloma Cells.
Authors: Josh Lauring, Abde M. Abukhdeir, Hiroyuki Konishi, Joseph P. Garay, John P. Gustin, Qiuju Wang, Robert J. Arceci, William Matsui, Ben H. Park
Journal: Blood (2007)
Consciousness around the time of saccadic eye movements
Authors: Bruce Bridgeman
Journal: Behavioral and Brain Sciences (2016)

Abstract During saccadic eye movements, the job of the nervous system is not to perceive a change in stimulation from the receptors, but to prevent a change from reaching consciousness. These movements occupy an intermediate range between actions that are almost always conscious, such as finger movements, and those that are never conscious, such as the smooth-muscle actions of the digestive system. Consciousness in this context requires attention to the consequences of an action.
A phase I open-label, dose-escalation study of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.
Authors: Susan Joy Littman, Daniel Monti, Andrew Newberg, Anthony Bazzan, Madhavan V. Pillai, Nancy Lewis, Charles Yeo, Mark Levine, Edith P. Mitchell
Journal: Journal of Clinical Oncology (2012)

323 Background: IV ascorbic acid (vit c) is a prodrug for steady state formation of ascorbate radical (Asc · - ) in the extracellular space resulting in sustained production of H 2 O 2 leading to selective killing of tumor cells by a pro-oxidative mechanism. In preclinical models of panc cancer pharmacologic concentrations of Asc · - with gem resulted in a synergistic cytotoxic response. We conducted a Phase I dose escalation study of IV ascorbic acid with gem plus erlotinib chemo as first line therapy in panc cancer. Methods: Patients with adv panc cancer were enrolled using a standard 3+3+3 design to assess the safety and pharmacology of IV vit c in combo with gem and erlotinib. Cohort 1 received 50 g IV vit c and subsequent cohorts were escalated by 25 g to a final dose of 100 g. Pts were given 3 infusions of vit c per week on separate days for 8 w (1 cycle). IV gem was given on day 1 (1000 mg/m 2 ) and weekly for 7 w followed by a rest week. Oral erlotinib (100 mg) was given daily for 8 w. Trt continued until disease progression or toxicity. Steady state ascorbate PK was assessed in cohorts 2 and 3. AEs were determined using NCI CTCAE v3.0. Tumor responses were assessed per RECIST. Results: Of 14 pts enrolled, 9 or 3 per cohort completed the study. Median age was 64 years. 5 pts did not complete trt (2 discontinued, 3 died). 9 pts completed at least 24 ascorbic acid trts and 1 cycle of gem/erlotinib therapy. There were 24 AEs. These included 15 non-serious AEs and 8 SAEs. The most frequent AEs were grade 1/2 thrombocytopenia. Other grade 1/2 events included anemia, hyperglycemia, abd discomfort, ascites and infection. SAEs: 2 grade 3 heme, 1 grade 3 GI, 1 grade 3 infectious and 2 grade 4 thrombosis. Plasma asc levels were 25.3 - 31.9 mm/L for pts receiving the 100g dose. 8 of the 9 pts had a reduction in the panc primary with 1 pt having no change at 8 w. For non-target lesions, 2 had PD and 7 had SD per RECIST. Conclusions: Overall safety data do not reveal AEs other than those expected in patients with metastatic panc cancer and/or treatment with gem and erlotinib. Addition of IV ascorbic acid did not increase toxicity. Preliminary efficacy results are encouraging. A phase II study is planned.
Effect of Standard Radiotherapy With Cisplatin vs Accelerated Radiotherapy With Panitumumab in Locoregionally Advanced Squamous Cell Head and Neck Carcinoma
Authors: Lillian L. Siu, John N. Waldron, Bingshu E. Chen, Eric Winquist, Jim R. Wright, Abdenour Nabid, John H. Hay, Jolie Ringash, Geoffrey Liu, Ana Johnson, George Shenouda, Martin Chasen, Andrew Pearce, James B. Butler, Stephen Breen, Eric Xueyu Chen, T. J. FitzGerald, T. J. Childs, Alexander Montenegro, Brian O'Sullivan, Wendy R. Parulekar
Journal: JAMA Oncology (2016)

The Canadian Cancer Trials Group study HN.6 is the largest randomized clinical trial to date comparing the concurrent administration of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies with radiotherapy (RT) to standard chemoradiotherapy in locoregionally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).To compare progression-free survival (PFS) in patients with LA-SCCHN treated with standard-fractionation RT plus high-dose cisplatin vs accelerated-fractionation RT plus the anti-EGFR antibody panitumumab.A randomized phase 3 clinical trial in 17 Canadian centers. A total of 320 patients were randomized between December 2008 and November 2011.Patients with TanyN+M0 or T3-4N0M0 LA-SCCHN were randomized 1:1 to receive standard-fractionation RT (70 Gy/35 over 7 weeks) plus cisplatin at 100 mg/m2 intravenous for 3 doses (arm A) vs accelerated-fractionation RT (70 Gy/35 over 6 weeks) plus panitumumab at 9 mg/kg intravenous for 3 doses (arm B).Primary end point was PFS. Due to an observed declining event rate, the protocol was amended to a time-based analysis. Secondary end points included overall survival, local and regional PFS, distant metastasis-free survival, quality of life, adverse events, and safety.Of 320 patients randomized (268 [84%] male; median age, 56 years), 156 received arm A and 159 arm B. A total of 93 PFS events occurred. By intention-to-treat, 2-year PFS was 73% (95% CI, 65%-79%) in arm A and 76% (95% CI, 68%-82%) in arm B (hazard ratio [HR], 0.95; 95% CI, 0.60-1.50; P = .83). The upper bound of the HR 95% CI exceeded the prespecified noninferiority margin. Two-year overall survival was 85% (95% CI, 78%-90%) in arm A and 88% (95% CI, 82%-92%) in arm B (HR, 0.89; 95% CI, 0.54-1.48; P = .66). Incidence of any grade 3 to 5 nonhematologic adverse event was 88% in arm A and 92% in arm B (P = .25).With a median follow-up of 46 months, the PFS of panitumumab plus accelerated-fractionation RT was not superior to cisplatin plus standard-fractionation RT in LA-SCCHN and noninferiority was not proven. Despite having negative results, HN.6 has contributed important data regarding disease control and toxic effects of these treatment strategies.clinicaltrials.gov Identifier: NCT00820248.
A nonrandomized observational trial of short-term preoperative endocrine therapy in ER-positive breast cancer to investigate change in genomic expression using the 21-gene breast cancer assay.
Authors: A. D. Bleznak, E. A. Dellers, B. Glenn-Porter, S. Kimmel, H. Chung, C. Yoshizawa, E. Burke, D. S. Davison, C. Chao
Journal: Journal of Clinical Oncology (2011)

221 Background: Preoperative systemic treatment is commonly employed for women with locally advanced breast cancer. Women with early-stage breast cancer, whose resections may be delayed for 30 to 60 days while they undergo preoperative evaluation, may benefit from receiving preoperative endocrine therapy while awaiting surgery. One rationale for not initiating such treatment is that the cancer may be rendered less chemosensitive. The 21-gene assay is a proven predictor of chemotherapy responsiveness. The objective of this study is to examine the association between recurrence score (RS) and ER, PR, and HER2 RT-PCR values in core biopsy and surgical specimens from patients treated with short term pre-operative endocrine therapy. Methods: Pre- and postmenopausal women with clinical T1-N0-M0, sonographically visible, ER-positive, HER2-negative breast cancer were eligible. Patients were treated with 4-8 weeks of preoperative endocrine therapy; letrozole if postmenopausal or tamoxifen if premenopausal. Clinical breast examination and ultrasound were conducted every two weeks, with the final ultrasound immediately prior to surgery. Tumor blocks from the core biopsy and surgical excision were submitted to Genomic Health, Inc., where RS, ER, PR, and HER2 results were obtained from each of the paired specimens. Results: Nineteen matching core biopsy and surgical specimens were available for analysis. Pearson correlation coefficients between core biopsy and excisional sample results were 0.89 for RS, 0.87 for ER, 0.72 for PR, and 0.77 for HER2. On average, small but statistically significant increases in RS and decreases in ER and PR were observed (all p &lt; 0.005 from paired t-test). No obvious associations between these markers and clinical response were observed. Conclusions: In this small, hypothesis-generating study, paired RS and RT-PCR for ER/PR/HER2 remained correlated after short-term preoperative endocrine therapy. This study provides no suggestion of decreasing chemosensitivity during preoperative endocrine therapy, but additional research is warranted to explore these findings further.
Real-life treatment of patients with advanced or metastatic renal cell carcinoma in German oncology and urology outpatient centers (RCC-Registry).
Authors: L. Mueller, P. Goebell, K. Blumenstengel, A. Lueck, M. Koska, N. Marschner
Journal: Journal of Clinical Oncology (2011)

367 Background: Until 2006, advanced or metastatic renal cell carcinoma (mRCC) patients were treated with immunomodulators such as interleukins and interferons. Multiple new targeted therapeutics, mainly signal transduction inhibitors, have been developed resulting in fundamental changes of therapeutic standards for patients with mRCC. In 2007, recruitment into the registry started in order to survey the treatment of mRCC patients, the course of disease and treatment as well as the therapeutic decision-making processes. Methods: It is intended to enroll 1,000 mRCC patients and collect data for each case for a maximum of 3 years. Over 100 oncology and urology outpatient centers in Germany are participating. Inclusion Criteria: (1) patients with metastatic or locally advanced RCC requiring antineoplastic therapy, (2) start of first palliative therapy within 1 year before enrolment, (3) age at least 18 years, and (4) Informed written consent. Results: By May 2010, 509 patients were enrolled. At the start of systemic therapy mean age were 66.2 years for male and 69.0 years for female patients, respectively. Patients have a Charlson Comorbidity Index of 1.0. More than 94% of patients had metastases at inclusion. 62.8% of the patients received sunitinib as first-line treatment, 12.0% received temsirolimus, 9.6% were treated with bevacizumab/interferon alpha, and 9.1% received sorafenib. Median duration determined using Kaplan-Meier analyses of first-line treatment with: sunitinib: 8.5 months (n=319), temsirolimus: 2.6 months (n=60), bevacizumab/interferon alpha: 4.6 months (n=49), and sorafenib: 6.7 months (n=45) whereby the duration of ongoing therapies was censored as the date of last documentation; thus the final duration might exceed the given values. After first-line treatment with sunitinib most of the patients received either sorafenib (12.4%, n=63) or temsirolimus (7.7%, n=39) in the second line. Conclusions: The registry provides an overview of the current treatment of mRCC patients in German outpatient cancer centers and shows how fast the insights of clinical studies concerning treatment of mRCC patients are transferred into current medical practice. [Table: see text]
Mechanisms of cross-talk between the diet, the intestinal microbiome, and the undernourished host
Authors: Helene Velly, Robert A. Britton, Geoffrey A. Preidis
Journal: Gut Microbes (2016)

Undernutrition remains one of the most pressing global health challenges today, contributing to nearly half of all deaths in children under five years of age. Although insufficient dietary intake and environmental enteric dysfunction are often inciting factors, evidence now suggests that unhealthy gut microbial populations perpetuate the vicious cycle of pathophysiology that results in persistent growth impairment in children. The metagenomics era has facilitated new research identifying an altered microbiome in undernourished hosts and has provided insight into a number of mechanisms by which these alterations may affect growth. This article summarizes a range of observational studies that highlight differences in the composition and function of gut microbiota between undernourished and healthy children; discusses dietary, environmental and host factors that shape this altered microbiome; examines the consequences of these changes on host physiology; and considers opportunities for microbiome-targeting therapies to combat the global challenge of child undernutrition.
Treating people right: Who goes untreated with systemic therapy for metastatic prostate cancer (mPC)?
Authors: Daniella J. Perlroth, Stephen F. Thompson, Essy Mozaffari, Yesenia Luna, Dana P. Goldman, Darius N. Lakdawalla
Journal: Journal of Clinical Oncology (2012)

125 Background: We investigated the use of systemic therapies (androgen deprivation therapy and chemotherapy) for men with mPC in the community, comparing those treated and untreated. Methods: 8,295 men diagnosed with mPC at presentation from the 2000-05 Surveillance, Epidemiology, and End Results (SEER) database were linked to Medicare claims. We excluded those diagnosed with other primary malignancies, disenrolling from Medicare Parts A or B (n=3,293), or who died within 1 month of diagnosis (n=468), leaving 4,534 patients. Treatment, service use and comorbidities were measured in Medicare claims, demographic and clinical data in SEER. We compared characteristics of patients by treatment group using univariate and logistic regression to estimate the predicted probability of receiving systemic therapies for black and nonblack patients. Differences across hospital service areas (HSAs) were computed, using logistic regression to adjust for demographic and clinical characteristics. Results: 3,657 patients (80.7%) received systemic therapy and 877 (19.3%) did not. Mean time to systemic treatment was 2.5 months. Follow up was 28.8 months for the treated, 19.2 months for the untreated. Among the treated, 20.4% received ADT and chemotherapy, 78.3% ADT only and 1.3% chemo only. Untreated patients were statistically older (78.6 versus 77.3 years), less likely to be married (48% versus 61%), and more likely residents of lower income areas and black race (26% versus 13%). The two groups scored similarly on a comorbidity index (0.51 versus 0.43). The model predicted a 66% probability of receiving systemic treatment for blacks versus 82% for whites, controlling for other factors. Systemic treatment use varied across regions from 62% to 94%. There was an 8-14% greater likelihood of receiving systemic treatment for men living in above versus below median regions. Conclusions: One in 5 men with mPC in this sample survived long enough to be treated systemically, yet was not. Untreated men with mPC are more likely to be black, unmarried and reside in low income areas, raising concerns for equal access to treatment. Some regions are better at initiating systemic treatment for men with mPC than others.
Pralatrexate Reverses the Trend to Progressive Resistance to Successive Systemic Treatment Regimens In Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL)
Authors: Owen A O'Connor, Corinne Haouin, Pier Luigi Zinzani, Christian Gisselbrecht, Francine M Foss, Kerry Joanne Savage, Barbara Pro, Lauren Pinter-Brown, Nancy L. Bartlett, Steven M Horwitz, Eric D Jacobsen, Tony Koutsoukos, Steven M. Fruchtman, Bertrand Coiffier
Journal: Blood (2010)
Can MRI accurately define tumor boundaries to guide focal salvage after radiotherapy?
Authors: D. Iupati, M. A. Haider, P. W. Chung, A. Bayley, C. Catton, M. Milosevic, R. G. Bristow, G. Morton, P. R. Warde, C. Menard
Journal: Journal of Clinical Oncology (2011)

124 Background: We evaluated the role of MRI (plus/minus biopsy) in delineating tumour boundaries for focal salvage therapy of prostate cancer recurrence after external beam radiotherapy. Methods: Patients with biochemical failure after radiotherapy were enrolled in a prospective clinical trial mapping sites of local recurrence. An integrated diagnostic MRI and interventional mapping biopsy procedure was performed under sedation in a 1.5T scanner. Patients were imaged with a pelvic coil and an endorectal coil attached to a stereotactic transperineal template assembly. Multiparametric MRI images were acquired, followed by targeted radial biopsy of suspicious regions and random sextant sampling of the normal-appearing peripheral zone. Histology maps were generated by delineation and registration of biopsy cores onto diagnostic images using point-based rigid image registration. Two independent blinded observers reviewed images offline and delineated tumours boundaries which were compared against overlaid histology maps. Coverage was considered accurate if all pathologically proven tumour sites were encompassed within delineated boundaries. Results: Of the 18 patients analysed to date, the majority (83%) were found to have local recurrence. Patients with &lt;6 informative cores were excluded, leaving 15 patients for analysis. Observers performed comparably, whereby mean MRI sensitivity, specificity, PPV and NPV for detecting tumor was 0.76, 0.7, 0.7, and 0.75. The MRI tumour boundary was accurate in 5/15 patients, and improved to 8/15 patients with addition of a 5-mm expansion margin. Targeted radial biopsies improved accuracy to 14/15 patients, by excluding false positive regions (n=2), increasing tumor volumes (n=2) or both (n=2). Random sampling biopsy was only relevant in 1 patient by detecting tumor not identified by MRI and targeted biopsy. Conclusions: MRI alone is not sufficiently accurate to define boundaries for tumor-targeted salvage even with addition of an uncertainty margin. Targeted biopsy improved both detection and delineation accuracy for recurrent tumor regions, and changed salvage therapy planning in 40% of patients. No significant financial relationships to disclose.
Outcome of HLA-Mismatched Unrelated Donor Allogeneic Stem Cell Transplantation Depends On the Intensity of the Conditioning Regimen.
Authors: Francis Ayuk, Tatjana Zabelina, Ulrike Bacher, Christine Wolschke, Heinrich Lellek, Thomas Eiermann, Rudolf Erttmann, Nicolaus Kröger, Axel R. Zander
Journal: Blood (2009)