tbuckley/cabot-search huggingface dataset:
Primary tumor location and expression of mir-664 as a combined biomarker for bevacizumab effectiveness in metastatic colorectal cancer.
Authors: Mogens Karsboel Boisen, Christian Dehlendorff, Dorte Linnemann, Jim S. Larsen, Kell Oesterlind, Joergen Hansen, Svend Erik Nielsen, Per Pfeiffer, Line Schmidt Tarpgaard, Niels Henrik Hollander, Nina Keldsen, Torben Hansen, Brita Bjerregaard Jensen, Estrid Vilma Solyom Hoegdall, Benny Vittrup Jensen, Julia S. Johansen
Journal: Journal of Clinical Oncology (2013)

3572 Background: We aimed to identify tissue microRNAs (miRs) that could predict outcome for patients with metastatic colorectal cancer (mCRC) treated with first line bevacizumab (BEV) and chemotherapy (CT) but not for patients treated with CT alone. Methods: Patients with mCRC treated with first line capecitabine and oxaliplatin (CT) with or without BEV at ten hospitals were identified and data was extracted retrospectively. Formalin-fixed paraffin-embedded tissue samples from primary tumors were collected and RNA was purified from 3 x 10 µm sections, without micro-dissection. miR expression was measured using Applied Biosystems TaqMan Custom LDA cards profiling 22 selected miRs in duplicate. The 22 miRs were selected from a previous discovery study profiling 754 miRs. miR expression was related to time to disease progression (TTP) and overall survival (OS) in multivariate analyses using Cox proportional hazards models with adjustment for age, prior adjuvant treatment, and no. of metastatic sites. We have previously found that patients with primary tumors originating in the sigmoid colon and rectum (S+R) experienced a better outcome than patients with other primary tumor locations (caecum to descending colon) when treated with BEV, so our analyses were stratified by primary tumor location. Results: miR expression was measured in samples from 399 patients: 155 samples from the original CT+BEV discovery study, 119 samples from a new CT+BEV cohort, and 125 samples from a CT alone cohort. Expression of miR-664 showed a significant positive association with increasing TTP, OS, and response rate (RR), but only in the cohort of patients with sigmoid colon- and rectal primary tumors treated with CT+BEV (n=183). Conclusions: We have identified a subgroup of patients with mCRC that are likely to benefit from BEV addition to first line CT using the combined information of location of the primary tumor and expression level of miR-664. [Table: see text]
Storing up problems for the future
Authors: Fiona Godlee
Journal: BMJ (2017)

The chancellor of the exchequer’s announcement of more funds for social care in England is welcome. The money falls short of what’s needed, but it will help stabilise social care, says Chris Ham (doi:10.1136/bmj.j1281), and will free up 2000-3000 hospital beds for casualty admissions or for elective surgery.

But the overall picture is very far from rosy. The prolonged underfunding of the NHS is now biting hard, says a King’s Fund report published this week (doi:10.1136/bmj.j1328). After more than five years of austerity, …
PREDICTORS OF MORTALITY IN ACUTE MYOCARDIAL INFARCTION PATIENTS WITH UNPROTECTED LEFT MAIN CORONARY ARTERY DISEASE
Authors: Seung-Woon Rha, Sung Hun Park, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Min Shim, Jun Hyuk Kang, Woo Hyeun Kim, Eun Jin Park, Jah Yeon Choi, Sunki Lee, Hu Li, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2017)
Sarcoligo: Impact of local ablative treatment of oligometastatic sarcomas on overall survival.
Authors: Juliette Thariat, Laurence Moureau-Zabotto, Nicolas Penel, Antoine Italiano, Jacques-Olivier Bay, Marie-Pierre Sunyach, Pascaline Boudou-Rouquette, Sébastien Salas, Christine Le Maignan, Marie Ducassou, Kais Aldabbagh, Nicolas Isambert, Elsa Kalbacher, Qiong Pan, Patricia Pautier, Hussam Hijazi, François Bertucci, Antoine Thyss
Journal: Journal of Clinical Oncology (2012)

10042 Background: 40-50% of sarcomas become metastatic. Median survival of metastatic patients has improved over time. The probably multifactorial reasons for such improvement are not fully clear. Noteworthy, for patients with a controlled primary and a limited number of lung metastases, complete resection of their metastases yields survival rates of up to 40% at three years. Advances in surgery, radiotherapy and radiofrequency have fostered the use of local treatments for various metastatic sites (lung, liver, spine...). Methods: A multicentric retrospective study of the Groupe Sarcome Francais (GSF-GETO); approved by the nationally-review board and ethical committee, was conducted to assess the impact of local ablative treatment on overall survival. Patients who had had oligometastases (any site, 1-5 synchronous metastases) at diagnostic or during the course of disease between 2000 and 2010 were included. Results: Median age of the 243 oligometastatic sarcoma patients was 53 years-old (11-86). Patients had grade I, II and III in 7.5%, 29.6% and 63.3% of cases, respectively with various histologies. 69% of patients underwent local ablative treatment of metastases. Median follow-up was 59 months (4-212) for living patients. Median overall survival was 51 months (1-348). On univariate analysis, grade, histology, absence of chemotherapy, local ablative treatment (surgery, irradiation, radiofrequency or chemoembolisation) correlated with survival but not age or site of oligometastasis. On multivariate analyses, grade (hazard ratio HR 0.12 [CI95 0.3-0.6]) and local ablative treatment (HR 3.8 [CI95 2.1-7.1]) remained significant. Conclusions: Local ablative treatment of metastases is associated with better survival in sarcoma patients with oligometastatic disease. The role of the locoregional treatment of metastases and its impact on quality of life should be assessed prospectively.
Phase I study of concurrent high-dose three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC)
Authors: I. Sekine, M. Sumi, Y. Ito, H. Nokihara, N. Yamamoto, H. Kunitoh, Y. Ohe, T. Tamura
Journal: Journal of Clinical Oncology (2009)

7546 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. Methods: Eligible patients (unresectable stage III NSCLC, age ≥ 20 years, PS 0–1, V 20 ≤ 30%) received cisplatin (80mg/m 2 day 1) and vinorelbine (20mg/m 2 days 1 and 8) repeated every 4 weeks for 3–4 cycles. The dose of 3D-CRT was 66 Gy in 33 fractions, 72 Gy in 36 fractions, and 78 Gy in 39 fractions at levels 1–3, respectively. The dose-limiting toxicity (DLT), defined as grade ≥3 esophagitis, pneumonitis, myelitis, dermatitis and heart injury, and early stop of protocol treatment, was evaluated in 6–12 patients at each level. Results: Of the 17, 16 and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled into levels 1–3, respectively, of the study. A total of 26 patients were excluded because of V 20 &gt; 30% (n=10), overdose to the esophagus (n=8) and brachial plexus (n=2), comorbidity (n=3), or patient refusal (n=3). There were 26 men and 5 women with a median (range) age of 60 (41–75) years. Of these, 23 (74%) had adenocarcinoma and 20 (65%) had stage IIIA disease. The full planned dose of radiotherapy could be administered in all the patients, and more than 80% of the patients received 3–4 cycles of chemotherapy. Grade 3–4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, grade 3 esophagitis and grade 3 pulmonary toxicity were noted in one, two and one patients, respectively. DLT was noted in 17% of the patients at each level. Two (6%) complete and 27 (87%) partial responses were obtained. In a preliminary survival analysis, the median progression-free and overall survivals were determined to be 15.0 months and 37.6 months, respectively. Conclusions: At the level of 78Gy, only 25% of the patients assessed for eligibility were actually eligible. Toxicity was relatively mild up to 78 Gy in this highly selective patient group. Thus, we determined that the recommended dose of 3D-CRT administered concurrently with cisplatin and vinorelbine chemotherapy was 72Gy. [Table: see text]
Effects of Renal Function on the Pharmacokinetics of Panobinostat in Patients with Advanced Cancer: A Phase I Study
Authors: Sunil Sharma, Emile Voest, Nicole Hagner, P.O. Witteveen, Martijn Lolkema, Neeraj Agarwal, Sue-zette Valera, Jason Li, Derek Mires, Maria Grazia Porro, Margaret M. Woo, Dagmar Hess
Journal: Blood (2011)
Serum/Glucocorticoid-Regulated Kinase 1 (SGK1) Is a Prominent Target Gene of the Transcriptional Response to Cytokines In Multiple Myeloma and Supports the Growth of Myeloma Cells
Authors: Unn-Merete Fagerli, Thorsten Stühmer, Toril Holien, Randi Utne Holt, Ove Bruland, Manik Chatterjee, John Shaughnessy, Stephan Mathas, Anders Sundan, Ralf C Bargou, Bernd Dörken, Magne Borset, Martin Janz
Journal: Blood (2010)
ON-TREATMENT LDL-C LEVELS WHEN ALIROCUMAB DOSE IS DECREASED FROM 150 TO 75 MG EVERY 2 WEEKS IN PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: RESULTS FROM ODYSSEY OLE
Authors: Michel Farnier, John Guyton, Gisle Langslet, Robert Dufour, Marie Baccara-Dinet, Chantal Din-Bell, Garen Manvelian, G. Kees Hovingh
Journal: Journal of the American College of Cardiology (2017)
A dye-assisted paper-based point-of-care assay for fast and reliable blood grouping
Authors: Hong Zhang, Xiaopei Qiu, Yurui Zou, Yanyao Ye, Chao Qi, Lingyun Zou, Xiang Yang, Ke Yang, Yuanfeng Zhu, Yongjun Yang, Yang Zhou, Yang Luo
Journal: Science Translational Medicine (2017)

A paper-based assay for rapid and reliable blood grouping uses dye-based color changes as a visual readout to identify distinct blood components.
Up-regulation of LFA-1 allows liver-resident memory T cells to patrol and remain in the hepatic sinusoids
Authors: H. A. McNamara, Y. Cai, M. V. Wagle, Y. Sontani, C. M. Roots, L. A. Miosge, J. H. O’Connor, H. J. Sutton, V. V. Ganusov, W. R. Heath, P. Bertolino, C. G. Goodnow, I. A. Parish, A. Enders, I. A. Cockburn
Journal: Science Immunology (2017)

Liver-resident CD8+ T cells are highly motile cells that patrol the vasculature and provide protection against liver pathogens. A key question is: how can these liver CD8+ T cells be simultaneously present in the circulation and tissue-resident? Because liver-resident T cells do not express CD103 - a key integrin for T cell residence in epithelial tissues - we investigated other candidate adhesion molecules. Using intra-vital imaging we found that CD8+ T cell patrolling in the hepatic sinusoids is dependent upon LFA-1-ICAM-1 interactions. Interestingly, liver-resident CD8+ T cells up-regulate LFA-1 compared to effector-memory cells, presumably to facilitate this behavior. Finally, we found that LFA-1 deficient CD8+ T cells failed to form substantial liver-resident memory populations following Plasmodium or LCMV immunization. Collectively, our results demonstrate that it is adhesion through LFA-1 that allows liver-resident memory CD8+ T cells to patrol and remain in the hepatic sinusoids.
ATRIAL FIBRILLATION (AF) AND ATRIAL FLUTTER (AFL) PREVALENCE AND CHARACTERISTICS FOR PERSONS WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV+) AND MATCHED UNINFECTED CONTROLS
Authors: Jes Sanders, Alexandra Steverson, Anna Pawlowski, Daniel Schneider, Prasanth Nannapaneni, Sanjiv Shah, Chad J. Achenbach, Donald Lloyd-Jones, Matthew Feinstein
Journal: Journal of the American College of Cardiology (2017)
Peripheral Laser for Recalcitrant Macular Edema Owing to Retinal Vein Occlusion: The WAVE Trial
Authors: Charles C. Wykoff, William C. Ou, Rui Wang, David M. Brown, Cassandra Cone, Deneva Zamora, Ryan T. Le, Min Sagong, Kang Wang, SriniVas R. Sadda
Journal: Ophthalmology (2017)
Von Willebrand Factor (VWF) Regulates Angiogenesis: Studies in Blood-Derived Endothelial Progenitor Cells From Von Willebrand's Disease Patients and VWF-Deficient Mice
Authors: Richard D Starke, Koralia Paschalaki, Francesco Ferraro, Thomas A J McKinnon, Nicola H Dryden, Elspeth Payne, Dorian O Haskard, Alun D Hughes, Daniel Cutler, Michael Laffan, Anna Maria Randi
Journal: Blood (2011)
Vitamin D (vD) deficiency (def) in breast cancer (BC) patients (pts)
Authors: C. A. Presant, L. Bosserman
Journal: Journal of Clinical Oncology (2007)

11082 Background: Vitamin D metabolism is important for maintaining bone health and perhaps cancer prevention. Prior studies have reported vD def in 88% of brca pts (Lonning et al ASCO 2006 abst 554), and 79% of women (Chlebowski et al ASCO 2006 abst 6) . Methods: In order to determine the frequency of vD def, we studied 41 consecutive brca pts. Levels of vD were correlated with clinical features. Pts were classified as vD def if 25OH D &lt;20, 1.25 diOH D &lt;14, or D3 &lt;20. Insufficiency (ins) of vD was 25OH D 20–29. Results: 8 pts had vD def (19.5%). This was more common in young pts &lt;60 (37.5%) compared to older pts (8%) (p4) in 5/6 pts &lt;60 and 5/7 older pts. vD def did not correlate with bone disease: 25% def in pts without bone disease, 17% in pts with osteopenia, and 17% in pts with osteoporosis. In older pts, vD was normal in 12/14 pts on anastrazole, and in 7/11 pts not on anastrazole, indicating no relation of anastrazole to vD def. Bisphosphonate (bis) usage was slightly higher in older pts (60%) versus younger pts (38%) but not significantly (p&lt;0.2). While only 19% of pts on bis had vD ins or def, 50% of pts not on bis had ins or def vD (p&lt;0.05). Although only 5% of pts on bis had vD def, 30% of pts not taking bis had vD def (p&lt;0.05). Conclusions: In brca pts, vD def is less than reported, but still frequent. All brca pts should be tested for vD periodically. VD def may be less frequent in pts on bis, and confirmatory trials should be performed. VD levels should also be monitored even if pts report taking vD. VD def or ins should be treated and monitored by oncologists. Since vD may be related to cancer incidence, and to bone disease, all brca trials collecting data on bone events, bone density, and second cancers should also report relationship to vD levels in individual study participants. No significant financial relationships to disclose.
MyD88/CD40-based costimulation to enhance survival and proliferation of chimeric antigen receptor (CAR)-modified T cells.
Authors: Aaron E Foster, Peter Chang, Pei-Yi Lin, Jeannette Crisostomo, Aruna Mahendravada, An Lu, Mariam Khalil, Kevin Mark Slawin, David Spencer
Journal: Journal of Clinical Oncology (2015)

3064 Background: Treatment of B cell malignancies with CAR-modified T cells has shown remarkable efficacy, but clinical responses in solid tumors have been limited due to poor T cell persistence and expansion. We examined whether incorporation of unconventional signaling elements, derived from the “universal” toll-like receptor adaptor molecule, MyD88, and the TNF family member, CD40, into CARs could improve T cell survival, proliferation and antitumor efficacy. Methods: Bicistronic vectors encoding inducible Caspase-9 (iCasp9) and CD19- or Her2-targeted CARs incorporating various costimulatory domains (e.g., CD28, 4-1BB, MyD88/CD40) were generated and used to transduce T cells. CAR-T cells were assessed for antitumor function in tumor coculture assays using CD19+ (Raji and Daudi) cells or Her2+ (SK-BR-3) tumor cells. Efficacy was monitored in immunodeficient (NSG) mice engrafted with tumor cell lines followed by i.v. CAR-T cell injection. In vivo T cell proliferation, as well as elimination via iCasp9 after i.p. injection of rimiducid, was measured using bioluminescent imaging (BLI). Tumor burden was also assessed by BLI or caliper measurements. Results: All CAR constructs could be stably expressed in T cells (30-90% CAR expression). MC costimulation resulted in greatly increased IL-2 production compared to CARs with alternative costimulation (~2500 pg/mL and ~200 pg/mL for MC and CD28.41BB, respectively). This correlated with enhanced T cell proliferation and corresponded to better tumor elimination in coculture assays (99% elimination at a 1:1 E:T ratio within 14 days). MC costimulation also enhanced the efficacy of CAR-T therapy in CD19+ and Her2+ tumor models, respectively, compared to control CARs. Furthermore, T cells transduced with MC-encoding CARs could be rapidly eliminated in vivo (within 1 day) via iCasp9 following rimiducid administration. Conclusions: MyD88/CD40 represents a potent, new T cell costimulatory molecule for CAR-T cells, resulting in robust IL-2 production, improved survival and proliferation, increased antitumor activity against CD19+ and Her2+ tumors in vitro and in vivo, while retaining a high safety profile through the iCasp9 suicide gene.
MYOCARDIAL HEMORRHAGE AFTER CORONARY ISCHEMIA-REPERFUSION LEADS TO AN IRON-MEDIATED, SELF-PERPETUATING LOOP OF FOAM CELL AND CEROID ACCUMULATION
Authors: Ivan Cokic, Kolja Wawrowsky, Avinash Kali, Hsin-Jung Yang, Richard Tang, Joseph Francis, Rohan Dharmakumar
Journal: Journal of the American College of Cardiology (2017)
PCSK9 VARIANTS AND NEUROCOGNITIVE IMPAIRMENT: DATA FROM THE REASONS FRO GEOGRAPHIC AND RACIAL DIFFERENCES IN STROKE (REGARDS) STUDY
Authors: Matthew Mefford, Robert Rosenson, Mary Cushman, Michael Farkouh, Leslie McClure, Virginia Wadley, Monika Safford, Ransi Somaratne, Keri Monda, Emily Levitan
Journal: Journal of the American College of Cardiology (2017)
Prolonged radiation duration in women with cervical cancer: A population-based analysis of associated factors and impact on survival.
Authors: Ana Isabel Tergas, Alfred I. Neugut, Ling Chen, Sharyn Nan Lewin, William M. Burke, Dawn L. Hershman, Jason Dennis Wright
Journal: Journal of Clinical Oncology (2014)

6518 Background: The National Comprehensive Cancer Network recommends that radiotherapy (RT) for treatment of locally advanced cervical cancer (LACC) finish within 8 weeks (wks). Although RT duration is a proposed national quality metric, there is little data supporting this in the era of concurrent chemotherapy. We examined factors associated with prolonged RT duration and its impact on survival in women with LACC treated with primary chemoradiation. Methods: Women reported in the National Cancer Database with stage IB2-IVA cervical cancer from 2003-2011 who received external beam RT, brachytherapy, and chemotherapy were analyzed. RT duration was modeled dichotomously (≤ or > 8 wks) and categorically (6-8, 9-10, >10 wks). Multivariable logistic regression was used to determine factors associated with prolonged RT duration (defined as >8 wks). Impact of RT duration on survival was examined using Kaplan-Meier analysis and Cox proportional hazards models. Results: Of the 7,209 women identified, 3,401 (47.1%) completed RT within 8 wks; 2,159 (29.9%) and 1,649 (22.9%) completed RT in 9-10 and >10 wks, respectively. Stage, race, insurance, comorbidity, diagnosis year, facility location, and neighborhood rurality/urbanicity were associated with prolonged RT on multivariable analysis. Black women (OR 1.22; 95% CI 1.07– 1.40), Medicaid recipients (OR 1.20; 95% CI 1.06 - 1.35), and rural residents (OR 1.84; 95% CI 1.24 - 2.73) were more likely to have prolonged RT. There was no survival difference for RT duration ≤8 vs. >8 wks. However, RT duration >10 wks was associated with inferior survival times (log rank p-value 0.002). Compared to those completing RT within 8 wks, adjusted hazard ratios for death for the 9-10 wks group and the >10 wks group were 0.90 (95% CI 0.78 – 1.03) and 1.1 (95% CI 0.95 - 1.26), respectively. Conclusions: Sociodemographic factors are important predictors of radiotherapy duration for cervical cancer. Impact of radiation duration on survival is marginal and only seen with duration >10 wks, bringing to question its use as a quality metric. Further research is needed to support the recommendation of radiation duration to not exceed 8 weeks in the era of concurrent chemoradiation.
A phase I study of ARQ 197 in combination with temsirolimus in advanced solid tumors.
Authors: Christos Kyriakopoulos, Jill Kolesar, Jens C. Eickhoff, Jennifer Heideman, Glenn Liu, Kari Braun Wisinski
Journal: Journal of Clinical Oncology (2015)

2554 Background: A wide variety of human cancers exhibit dysregulated c-Met activity that has implications in oncogenesis. Phosphorylation of c-Met results in activation of the PI3K/AKT/mTOR pathway. Combined blockade of c-Met and mTOR pathways has shown efficacy in preclinical studies. ARQ 197 (tivantinib) is a c-Met inhibitor and temsirolimus is a selective mTOR inhibitor. We aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), adverse events (AEs), clinical activity and pharmacokinetic (PK) parameters of the above combination. Methods: This open-label phase I study used a 3 + 3 dose escalation design. Patients (pts) in cohorts of 3 were treated with escalating doses of ARQ 197 (120-360 mg tablets orally twice daily) and temsirolimus (20 mg IV weekly) followed by dose expansion at MTD. Separate cohorts were planned for poor and extensive ARQ 197 metabolizers based on CYP2C19 genotypes. Cycles were 28 days besides cycle 1 that was 35 days to allow for PK analysis. Results: 21 pts (median age 57 [range 29-71]) were enrolled for dose escalation. All were extensive CYP2C19 metabolizers. The most common types of cancer were colorectal (6 pts), ovarian (4 pts), renal (2 pts) and pancreatic (2 pts). In the dose escalation cohort, 16/21 pts were evaluable per protocol. They remained on study for a median of 73.6 days (range 15-296). The MTD was ARQ 197 240 mg bid and temsirolimus 20 mg once weekly. DLTs included grade (gr) 4 neutropenia (2 pts; 1 with gr 3 febrile neutropenia) and gr 3 abdominal pain (1 pt). The most common AEs at least possibly related to therapy included: fatigue (62%; gr 1-2 in 12 pts, gr 3 in 1 pt), anemia (48%; gr 2 in 9 pts, gr 3 in 1 pt), nausea (48%; gr 1-2 in 9 pts, gr 3 in 1 pt), vomiting (48%; gr 1-2 in 9 pts, gr 3 in 1 pt) and diarrhea (48%; gr 1-2 in 9 pts, gr 3 in 1 pt). 1 pt with ovarian cancer had a confirmed partial response and remained on study for 9 months. A second pt with ovarian cancer has stable disease and remains on study at 5 months. 4 of 6 pts have been enrolled to the dose expansion cohort and are in cycle 1. Data from the dose expansion will be presented. Conclusions: The combination of ARQ 197 with temsirolimus appears to be well tolerated with evidence of clinical activity. The MTD expansion and PK analysis are ongoing. Clinical trial information: NCT01625156.
PROGNOSTIC IMPLICATIONS OF LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN IN STAGE 4 AND 5 CHRONIC KIDNEY DISEASE PATIENTS
Authors: Liselotte C.R. Hensen, Kathleen Goossens, Joris Rotmans, Johan Jukema, Victoria Delgado, Jeroen Bax
Journal: Journal of the American College of Cardiology (2017)