tbuckley/cabot-search huggingface dataset:
Oncologists practice with opioids in cancer pain
Authors: M. El-Foudeh, S. A. Alsirafy, A. Hassan, M. Hidayetullah
Journal: Journal of Clinical Oncology (2006)

18602 Background: The majority of cancer patients are mostly under the care of their primary oncologists for both active and symptom management. Pain is the most feared symptom in cancer patients. In general, it is highly prevalent and under treated. Barriers to adequate pain management still exist even among specialized care givers. Improper opioid utilization is one of main factors within those impediments. The pattern of opioid prescription among oncologists in a specialized hospital was examined on referral to a palliative care unit within the same institution. Methods: Over a period of six months (between Dec. 2003 and June 2004) 290 cancer patients were referred to the section of palliative medicine from different medical specialties within the same institution. The medical records of 233 (80%) were analyzed, 116(50%) were referred from oncology specialists (radiation, medical &amp; hematology oncology), 76 referred patients fulfilled the study criteria. On referral; all eligible patients had to be on opioids for pain. The pattern of opioid prescription by oncologists in this group of patients with reference to the currently available guidelines was examined. Results: The following results were found: Pain was inadequately controlled in 71% patients. Although, the majority of the patients 92% were able to utilize the oral route, it was only used in 36% of patients. The first strong regular opioid was the standard morphine in only 46% of patients. Breakthrough opioid was prescribed to most patients (91%). However, dose and interval were outside the general guidelines in 44% &amp; 81% respectively. Laxatives were not prescribed in half of the patients Conclusions: Opioids are the principal effective, relatively simple and practical drugs in pain relief. Yet, within specialized care providers as shown in this study, opioid utilization was unsatisfactory. More understanding of pain assessment, better opioid utilization and more knowledge of opioid pharmacology still warranted. No significant financial relationships to disclose.
TCRα rearrangements identify a subgroup of NKL-deregulated adult T-ALLs associated with favorable outcome
Authors: P Villarese, C Lours, A Trinquand, S Le Noir, M Belhocine, L Lhermitte, A Cieslak, M Tesio, A Petit, M LeLorch, S Spicuglia, N Ifrah, H Dombret, A W Langerak, N Boissel, E Macintyre, V Asnafi
Journal: Leukemia (2017)
Down-regulated miR-23a Contributes to the Metastasis of Cutaneous Melanoma by Promoting Autophagy
Authors: Weinan Guo, Huina Wang, Yuqi Yang, Sen Guo, Weigang Zhang, Yu Liu, Xiuli Yi, Jingjing Ma, Tao Zhao, Lin Liu, Zhe Jian, Ling Liu, Gang Wang, Tianwen Gao, Qiong Shi, Chunying Li
Journal: Theranostics (2017)

Melanoma is among the most aggressive tumors, and the occurrence of metastasis leads to a precipitous drop in the patients' survival. Therefore, identification of metastasis-associated biomarkers and therapeutic targets will contribute a lot to improving melanoma theranostics. Recently, microRNAs (miRNAs) have been implicated in modulating cancer invasion and metastasis, and are proved as potential non-invasive biomarkers in sera for various tumors. Here, we reported miR-23a as a novel metastasis-associated miRNA that played a remarkable role in modulating melanoma invasive and metastatic capacity and was of great value in predicting melanoma metastasis and prognosis. We found that serum miR-23a level was significantly down-regulated in metastatic melanoma patients and highly correlated with poor clinical outcomes. In addition, miR-23a level was also remarkably decreased in metastatic melanoma tissues and cell lines. Furthermore, overexpressed miR-23a suppressed the invasive and migratory property of melanoma cells by abrogating autophagy through directly targeting ATG12. Specially, miR-23a-ATG12 axis attenuated melanoma invasion and migration through autophagy-mediated AMPK-RhoA pathway. Finally, the overexpression of miR-23a prevented melanoma metastasis in vivo. Taken together, our findings demonstrate that the metastasis-associated miR-23a is not only a potential biomarker, but also a valuable therapeutic target for melanoma.
Impact of obesity on quality of life in patients with advanced heart failure
Authors: LS Evangelista, K Dracup, C Westlake, Erickson, MA Hamilton
Journal: Circulation (2004)

Supplement Ill Circulation Vol 110, No 17 October 26, 2004 Clinical Science P .000) as weU as with depression (p ressive symptoms) between obese (BMI ~30, n-154) and non-obese (BMI <30, n=195) patients were condUcied ID delerrlllle if body mm 1ndel (BMO ildependently predicts OOL 11 patients with adYanced Hf. Participants completed the Minnesota living With Heart Fanure Question· nalre and Beel< Depression Inventory and performed the six-minute walk test Bivariate analyses were performed between the variables al interest. Stepv.-i.se linear regression was used to detennine the independent contribution al BMI lD OOL Significance level for all analyses was set at p<0.05. RESULTS: Obese and non-obese patients had similar demographic characteristics (age, 54.2:!:11.5 vs 57.1:!:13.2 years; predominantly male, 77.4% vs 79.9 ; Caucasian, 73.3'11. vs. 70.7'4; and married, 64'4 vs. 63'4). The emotlOOal and depression scores were were significantly w01se In obese compared to non·obese patients (p< .005): statistical differences were not observed In total OOL and physical scores BMI was significantly correlated with all 3 scales of OOL (total p• .006; physical, ps .002; and mental,
Social capital and cognitive decline in the aftermath of a natural disaster: a natural experiment from the 2011 Great East Japan Earthquake and Tsunami
Authors: Hiroyuki Hikichi, Toru Tsuboya, Jun Aida, Yusuke Matsuyama, Katsunori Kondo, S V Subramanian, Ichiro Kawachi
Journal: The Lancet Planetary Health (2017)

We examined prospectively whether social capital mitigates the adverse effects of natural disaster on cognitive decline.The baseline for our study was established seven months before the 2011 Great East Japan Earthquake and Tsunami in a survey of older community-dwelling adults who lived 80 kilometers west of the epicenter (59.0% response rate). Approximately two and a half years after the disaster, the follow-up survey gathered information about personal experiences of disaster as well as incidence of cognitive disability (82.1% follow-up rate). Our primary outcome was cognitive disability (measured on an 8-level scale) assessed by in-home assessment.The experience of housing damage was associated with risk of cognitive impairment (coefficient = 0.04, 95% confidence interval: 0.02 to 0.06). Factor analysis of our analytic sample (n = 3,566) established two sub-scales of social capital: a cognitive dimension (perceptions of community social cohesion) and a structural dimension (informal socializing and social participation). Fixed effects regression showed that informal socializing and social participation buffered the risk of cognitive decline resulting from housing damage.Informal socializing and social participation may prevent cognitive impairment following natural disaster.National Institutes of Health (R01AG042463-04), the Japan Society for the Promotion of Science, the Japanese Ministry of Health, Labour and Welfare and the Japanese Ministry of Education, Culture, Sports, Science and Technology.
ISIS-FXIRx, A Novel and Specific Antisense Inhibitor of Factor XI, Caused Significant Reduction in FXI Antigen and Activity and Increased aPTT without Causing Bleeding in Healthy Volunteers
Authors: Que Liu, Claudette Bethune, Esmat Dessouki, John Grundy, Brett P. Monia, Sanjay Bhanot
Journal: Blood (2011)
Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with metastatic breast cancer (mBC).
Authors: Lajos Pusztai, Jon Chung, Lauren Young, Alexa Betzig Schrock, Ryan Hartmaier, Garrett Michael Frampton, Laurie M. Gay, Phil Stephens, Vincent A. Miller, Siraj Mahamed Ali, Jeffrey S. Ross, Linda T. Vahdat, Joyce O'Shaughnessy
Journal: Journal of Clinical Oncology (2017)

1016 Background: Clonal evolution during progression to and treatment of mBC highlights the importance of genomic profiling of recent samples to guide clinical decision making. We undertook this study to characterize genomic alterations (GA) in ctDNA from pts with mBC during the course of clinical care. Methods: Hybrid-capture based genomic profiling of 62 genes (FoundationACT) was performed on ctDNA from 255 BC pts. The fraction of ctDNA in the blood was estimated using the maximum somatic allele frequency (MSAF) for each sample. Results: 168 pts were ER+ [16 HER2+, 134 HER2(-), 18 HER2 unknown (unk)]; 51 were ER(-) [7 HER2+, 38 triple negative (TNBC), 6 HER2 unk]; 36 were ER unk; 95% were stage 4. For pts with treatment information, 90% had prior chemotherapy and 90% ER+ pts had prior aromatase inhibitor therapy (AI). ≥1 GA was reported in 78% of all cases and in 88% of cases with evidence of ctDNA in the blood (MSAF &gt;0). For 226 cases with MSAF &gt;0, an average of 2.7 GA/case were reported. The most common GA for ER+ pts were in TP53 (44%), PIK3CA (39%), ESR1 (36%), CDH1 (11%), KRAS (10%) and ERBB2 ( HER2, 9%). 101 ESR1 GA were identified in 61 pts [54 ER+, 7 ER unk], including 4 HER2+ pts. For ER+ pts with treatment information: 37% (22/60) with prior AI had ESR1 GA; all pts with ESR1 GA had prior AI. 24 pts had &gt;1 ESR1 GA, with instances of GA in cis. Frequent ESR1 GA were Y537S/N (n=47), D538G (n=29) and E380Q (n=7); rearrangement (n=3) and amplification (n=1) were also detected. Concurrent GA with ESR1 were found in PIK3CA (41%), FGFR1 (13%), BRCA1/2 (5%), HER2 (5%) and AKT1 (3%). In ER(-) pts, the most common GA were in TP53 (74%), PIK3CA (17%), NF1 (11%), BRCA1 (9%) and EGFR (9%). HER2 activating mutation occurred in 3% of cases that were HER2(-) by prior testing. Kinase fusions in FGFR2/3 (3 ER+) and EGFR (1 TNBC) were observed. Conclusions: In this study, evidence of ctDNA in the blood was observed in 89% of cases. PIK3CA and ESR1 GA frequencies were similar to those reported in previous studies of ctDNA from ER+ pts after AI. Diverse ESR1 GA and co-occurring GA suggest therapeutic approaches for AI refractory ER+ mBC. Our results demonstrate that genomic profiling of ctDNA may be a complementary approach to tissue-based genomic testing for pts with mBC.
Assessment of ESR1 and ERBB2 mutations in estrogen receptor positive (ER+) metastatic breast cancers (MBC).
Authors: Gargi D. Basu, Tracey White, Janine R LoBello, Ahmet Kurdoglu, Jeffrey M. Trent, Matthew J Halbert, Thomas Royce, Joyce O'Shaughnessy
Journal: Journal of Clinical Oncology (2017)

1040 Background: Mutations (mut) in ESR1 have been reported in ER+ breast cancers (BC) as an acquired resistance mut to aromatase inhibitor (AI) therapy. Acquired ERBB2 mut have also been reported in MBC patients (pts) that cause activated ERBB2 signaling. The emergence of acquired secondary mut presents challenges in effective treatment approaches. Methods: Comprehensive genomic profiling was performed on 83 BC samples with 48 metastatic; 34 primary samples. Targeted next-generation sequencing was performed on 562 cancer associated genes in paired tumor and blood DNA (germline) samples. Results: ESR1-mut were found in 23%(11/48) of ER+ MBC tissues with no mut detected in primary ER+ BCs. Mutations-D538G, Y537S and E380Q in the ligand binding domain of ER were the most common alterations, found in 54.5%, 18% and 18% of ESR1 mut samples, respectively. An ER+ HER2- liver biopsy obtained after 20 mos on AI + everolimus had ESR1-D538G and TSC2 structural event. Protein array showed high expression of androgen receptor (AR) and p-AR and activation of ERBB1/2/3, p-SRC and p-4EBP1 in this sample. Further, a functionally uncharacterized ESR1 mut was found in ER+, HER2+ and a triple negative MBC tissue (the primary BC had been ER+). Mut in PI3K pathway (PIK3CA, ARID1A, TSC1/2, PTEN) were present in 8/11 samples with ESR1 mut. Activating mut in ERBB2 were found in 3/83 samples; all 3 were in ER+ MBC samples with one case harboring mut in both ERBB2 and ESR1 (E380Q – uncertain degree of constitutive activity). Interestingly, a BC sample with ER+ HER2- liver met harbored both ERBB2 (V777L) and ERBB3 (E928G) mut; this pt responded well to trastuzumab/pertuzumab (HP) therapy. A pt with ER+ HER2-ERBB2- L755S mut met to gallbladder found after 7 mos on letrozole/palbociclib therapy responded well to HP and T-DM1 therapy. All 3 ERBB2-mut cancers had a CDH1 frameshift mut suggesting enrichment in pretreated lobular MBCs (Ross J. CCR, 2013). Conclusions: This study shows a 23% and 6% ESR1 and ERBB2 mut rate in MBC samples. No ESR1 and ERBB2 mut were present in primary BC samples. Our findings suggest that pts with lobular MBC should be monitored for acquired ERBB2 mut, and that ERBB2 mut may not arise in BCs which harbor known constitutively active ESR1 mut.
Abstract 13128: Antithrombotic Therapy and Outcomes after ICD Implantation: An Analysis from the Linked NCDR-CMS Claims Database
Authors: Hamid Ghanbari, Brahmajee Nallamothu, Yongfei Wang, Jeptha Curtis
Journal: Circulation (2013)

Background: Atrial fibrillation (AF) is a common arrhythmia in patients who receive implantable cardioverter defibrillators (ICDs). Post-procedural management of anticoagulation is challenging, par...
Immediate complete lymph node dissection does not improve melanoma survival, study finds
Authors: Michael McCarthy
Journal: BMJ (2017)

Immediate complete lymph node dissection in patients with melanoma and sentinel node metastases did not increase melanoma specific survival, a large randomised trial has found.1

Currently, sentinel node biopsy is often recommended for patients undergoing surgery for melanoma, to determine whether the cancer has metastasised. If metastases are found, immediate removal of the remaining regional lymph nodes—called complete lymph node dissection—is generally advised. However, it has not been clear whether this approach was beneficial.

The international Multicenter Selective Lymphadenectomy Trial (MSLT-II) randomly assigned 1934 patients with clinically localised melanoma but a tumour positive sentinel …
Metabolomics Identifies Metabolic Markers of Maturation in Human Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Vijesh J. Bhute, Xiaoping Bao, Kaitlin K. Dunn, Kylie R. Knutson, Eric C. McCurry, Gyuhyung Jin, Wei-Hua Lee, Sarah Lewis, Akihiro Ikeda, Sean P. Palecek
Journal: Theranostics (2017)

Cardiovascular disease is a leading cause of death worldwide.Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold immense clinical potential and recent studies have enabled generation of virtually pure hPSC-CMs with high efficiency in chemically defined and xeno-free conditions.Despite these advances, hPSC-CMs exhibit an immature phenotype and are arrhythmogenic in vivo, necessitating development of strategies to mature these cells.hPSC-CMs undergo significant metabolic alterations during differentiation and maturation.A detailed analysis of the metabolic changes accompanying maturation of hPSC-CMs may prove useful in identifying new strategies to expedite hPSC-CM maturation and also may provide biomarkers for testing or validating hPSC-CM maturation.In this study we identified global metabolic changes which take place during long-term culture and maturation of hPSC-CMs derived from three different hPSC lines.We have identified several metabolic pathways, including phospholipid metabolism and pantothenate and Coenzyme A metabolism, which showed significant enrichment upon maturation in addition to fatty acid oxidation and metabolism.We also identified increases in glycerophosphocholine and the glycerophosphocholine:phosphocholine ratio as potential metabolic biomarkers of maturation.These biomarkers were also affected in a similar manner during murine heart development in vivo.These results support that hPSC-CM maturation is associated with extensive metabolic changes in metabolic network utilization and understanding the roles of these metabolic changes has the potential to develop novel approaches to monitor and expedite hPSC-CM maturation.
CLIA validation of a novel HER2 FISH test involving image-based cell-sorting to recover pure tumor cell populations from formalin fixed paraffin embedded tissue.
Authors: Farideh Z. Bischoff, Amanda Gerber, Valeria Sero, Aditi Khurana, Marc Ting, Judy Webb, Cynthe Sims, Suman Verma, Gianni Medoro, Nicolò Manaresi, Shelly Gunn, Mathew Moore, Philip Cotter
Journal: Journal of Clinical Oncology (2017)

e12519 Background: The use of the DEPArray™ system to prepare pure tumor cell populations for more reliable and accurate downstream molecular sequence analysis has been previously demonstrated. To formally evaluate the utility of the DEPArray™ for sample preparation prior to molecular testing, we conducted a CLIA validation study to investigate the analytical performance of the instrument as well as accuracy in determining HER2 status in FFPE tumor specimens using a standard FISH assay. Methods: An initial cohort consisting of 93 FFPE samples (68 from Breast and 25 from Stomach) were selected based on defined inclusion criteria (tumor type and tumor content). For each sample, a single 50µm FFPE scroll was dissociated and then stained using fluorescently labeled Vimentin and Cytokeratin markers to distinguish between putative stromal and tumor populations, respectively. Following separation of these populations on the DEPArray™, a minimum of 100 single cells from each population was recovered and used for subsequent HER2 FISH testing. In addition, an H&amp;E of each sample was evaluated by a Pathologist to confirm the presence of tumor content. Single-cell HER2-FISH analysis was then performed on the DEPArray™ processed samples to assess the number of signals present for each of the chromosome 17 and HER2 loci. Results were compared to the conventional tissue section FISH score. Results: Of the 93 specimens, 80 samples met pre-analytical acceptability criteria that were also confirmed by conventional methods to be either HER2-positive (n = 43) or HER2-negative (n = 37). Overall, a 95% concordance between HER2 results derived from the conventional as compared to the DEPArray™ method was observed. In addition, the instrument performance in terms of reproducibility and reliability was reported as 100%. Conclusions: DEPArray™ for preparation of FFPE-derived tumor cells was analytically validated and shown to yield high confidence in performing HER2-FISH analysis on recovered pure tumor cells. Current strategies to establish clinical utility and efficacy of this approach are underway for cases characterized as equivocal for HER2 or indeterminate by FISH.
Comparison of prostate cancer identified in biopsies performed in testosterone-treated hypogonadal men, untreated hypogonadal men, and eugonadal men in a single urological office.
Authors: Ahmad Haider, Karim Sultan Haider
Journal: Journal of Clinical Oncology (2015)

e16034 Background: The lower-than-expected incidence of prostate cancer (PCa) in hypogonadal men receiving long-term treatment with testosterone undecanoate (TU) was published earlier this year (Haider et al., J Urol 2015; 193: 80-86). In this study, we investigated the incidence of PCa in relation to the number of biopsies in hypogonadal patients with or without testosterone treatment in comparison with eugonadal men from a single urology office. Methods: 340 men with testosterone ≤ 12.1 nmol/L received TU 1000 mg every 12 weeks for up to 7 years. Prostate volume (PV) and PSA were measured and digital rectal examination (DRE)/ transrectal ultrasound (TRUS) performed before treatment initiation, every 3-6 months during the first year and then regularly every 6 month. In case of suspected PCa, 53 biopsies were performed between 2004 and 2013 in this group. In the same period of time, 314 biopsies were performed in hypogonadal patients without testosterone treatment, and 584 biopsies in eugonadal patients. The patients not on testosterone treatment were examined regularly in annual intervals. Results: Of the53 biopsies performed in testosterone-treated hypogonadal patients, 5 (9.4%) were positive and 48 (90.6%) negative. In hypogonadal patients without testosterone treatment, 314 biopsies were performed. Of these, 111 (35.4%) were positive and 203 (64.6%) negative. In eugonadal patients, 584 biopsies were performed. Of these, 263 (40.4%) were positive and 321 (55%) negative. In total, 951 prostate biopsies were performed in our practice from 2004 through 2013, of which 379 (39.9%) were positive and 572 (60.1%) negative. Conclusions: Long-term treatment with TU in hypogonadal men undergoing regular monitoring according to guidelines of the European Association of Urology (EAU) does not increase the incidence of PCa. Unexpectedly, the proportion of positive biopsies was markedly higher in patients not receiving testosterone. These findings require further prospective, controlled studies.
Designing food structure and composition to enhance nutraceutical bioactivity to support cancer inhibition
Authors: David Julian McClements, Hang Xiao
Journal: Seminars in Cancer Biology (2017)

Many types of bioactive molecules found in foods ("nutraceuticals") have been shown to exert anticancer activities, including curcumin, resveratrol, polyphenols, sulforaphane, anthocyanins, genistein, quercetin and lycopene. The potential health benefits of nutraceuticals are often not realized because of their poor water solubility, chemical instability, adverse taste profile, and low oral bioavailability. Carefully designed food matrices are being developed to overcome these problems. Nutraceuticals can be isolated from their natural environment, and then incorporated into functional foods, often with the help of delivery systems (such as emulsions, nanoemulsions, liposomes, biopolymer nanoparticles, and microgels). Alternatively, the stability and bioavailability of nutraceuticals can be improved by leaving them in their natural environment, but ingesting them with a specially designed "excipient food". The structure and composition of an excipient food is controlled so as to enhance the bioaccessibilty, stability, and absorption of the nutraceuticals in the gastrointestinal tract. This review article provides an overview of some of the most important anticancer nutraceuticals found in foods, then highlights the main factors impacting their bioaccessibility, absorption and transformation. Finally, it describes different types of delivery systems and excipient systems that can be used to improve the overall bioavailability of anticancer nutraceuticals.
Transplantation from Matched Unrelated and Haploidentical Donor in Pediatric Severe Aplastic Anemia: Experience with TCR Alpha/Beta and CD19 Depletion As Graft Processing Method
Authors: Daria Shasheleva, Larisa Shelikhova, Zhanna Shekhovtsova, Dmitriy Balashov, Pavel Trakhtman, Elena Boyakova, Elena Raykina, Elena Kurnikova, Alexey Kazachenok, Varvara Briliantova, Anna Bogoyavlenskaya, Maria Ilyushina, Svetlana Kozlovskaya, Galina Novichkova, Michael Maschan, Alexey Maschan
Journal: Blood (2016)