tbuckley/cabot-search huggingface dataset:
A novel microRNA-based treatment approach for malignant pleural mesothelioma.
Authors: Glen Reid, Marcella Pel, Michaela Kirschner, Yuen Yee Cheng, Nancy Mugridge, Jocelyn Weiss, Marissa Williams, Casey Wright, Sonja Klebe, Himanshu Brahmbhatt, Jennifer MacDiarmid, Nico Van Zandwijk
Journal: Journal of Clinical Oncology (2013)

7586 Background: Malignant pleural mesothelioma (MPM) is recalcitrant to treatment and new approaches are needed. The microRNA miR-16 has been implicated as a tumor suppressor in a range of cancer types, and restoration of miR-16 expression has been shown to inhibit tumor cell proliferation. The miR-16 status in MPM is largely unknown. Methods: MicroRNA expression was analysed by TaqMan-based RT-qPCR in 10 MPM cell lines and 60 tumour specimens consisting of archival blocks from patients undergoing surgery. MicroRNA expression was restored in vitro using mimics corresponding to the sequence of the mature microRNA, and effects on proliferation and target genes were assessed with standard methods. Human xenograft-bearing mice were treated with miR-16 mimics packaged in minicells targeted with EGFR-specific antibodies. Results: Expression of miR-16 was consistently down-regulated in MPM cell lines and MPM tumor specimens as were the co-expressed miR-15a and miR-15b. A decrease of 2- to 5-fold in miR-16 expression was found when MPM cell lines were compared with the normal mesothelial cell line MeT-5A. When tumor specimens were compared with normal pleura, the down-regulation of miR-16 was in the order of 10-fold. Using synthetic miR-16 mimics to restore miR-16 expression in MPM cell lines led to time- and dose-dependent growth inhibition in a panel of MPM cell lines but did not affect growth of MeT-5A. Growth inhibition correlated with cell cycle arrest and concordant down-regulation of miR-16 target genes including Bcl-2 and CCND1. In a series of experiments with nude mice bearing MPM (MSTO-H211) xenografts, intravenous administration of miR-16 mimics packaged in minicells led to consistent and dose-dependent inhibition of tumor growth. Conclusions: Restoring miR-16 expression represents a novel approach to treatment for MPM. Preparations are being made to test miR-16 packaged in minicells as a new treatment approach for patients with recurrent MPM and NSCLC.
<i>NM 23-H1</i> gene expression of a migration suppressor in gastric lymphoma.
Authors: Il Kim
Journal: Journal of Clinical Oncology (2017)

39 Background: We previously describedthat the NDPK-A(nucleoside diphosphate kinase A) contributes variably to the migration of cancer cell. To investigate the role of the NDPK-A in gastric lymphoma, we evaluated the expression of NDPK-A in two different cancer cell lines of the same gastric lymphoma patient. Methods: The primary cell line of gastric lymphoma, RF-1, was cultured from the primary gastric lymphoma site, and the other cell line RF-48 was metastasized to the peritoneum of the same patient after 6 months. We have generated stable gastric lymphoma transfectants, pIRES-NDPKA-GFP-neo, that constitutively over-express transfected and vector form of NDPK-A, in addition to a reporter, green fluorescent protein(GFP). The transfected gastric lymphoma cell migration assay was performed 24-well modified chemotaxis chambers with FluroBloc membrane. Results: In regard to the migration rate of the gastric lymphoma cell lines, RF-1 vector was 75.8±7.5%, RF-1 transfected was 54.4±12.3%, RF-48 vector was 84.7±15.4%, RF-48 transfected type was 62.3±9.2%, RF-48 migrated better than RF-1, and the vector type migrated better than the transfected type. NDPK-A was presented more in RF-1 than RF-48, and presented more in the transfected type than the vector type, and concerning the migration rate, RF-48 migrated better than RF-1, and the vector type migrated better than the transfected type. Conclusions: Concerning NM 23-H1 gene encodes the NDPK-A in gastric lymphomas, more abundant was NDPK-A, poorer was migration, and thus it played a role of the suppressor of migration. Our analysis of pooled data found that NDPK-A acts as a migration suppressor in gastric lymphoma.
ANÁLISIS DE LA RENTABILIDAD DE LA EBUS Y EUS COMBINADAS EN LA ESTADIFICACIÓN EN EL CÁNCER DE PULMÓN SIN AFECTACIÓN MEDIASTÍNICA APARENTE
Authors: A Velasco Guardado, A Álvarez Delgado, M Iglesias Heras, R Cordovilla, J Feito Pérez, M González Jose, M López Zubizarreta
Journal: Endoscopy (2015)

Introducción: En el cáncer de pulmón no microcítico (CPNM) cuando en el estudio de extensión con PET-TC no presenta alteraciones mediastínicas y presenta uno de los siguientes criterios: tumor central, tumor del sulcus, tumor de baja captación y/o afectación N1; se indica la realización de un estudio ecoendoscópico con PAAF.
Pacritinib versus best available therapy for the treatment of myelofibrosis irrespective of baseline cytopenias (PERSIST-1): an international, randomised, phase 3 trial
Authors: Ruben A Mesa, Alessandro M Vannucchi, Adam Mead, Miklos Egyed, Anita Szoke, Aleksandr Suvorov, Janos Jakucs, Andrew Perkins, Ritam Prasad, Jiri Mayer, Judit Demeter, Peter Ganly, Jack W Singer, Huafeng Zhou, James P Dean, Peter A te Boekhorst, Jyoti Nangalia, Jean-Jacques Kiladjian, Claire N Harrison
Journal: The Lancet Haematology (2017)
Factors affecting communication patterns between oncology staff and bereaved families: A cross-sectional study.
Authors: Tal Granot, Shlomit Perry, Noa Gordon, Shulamith Rizel, Salomon M. Stemmer
Journal: Journal of Clinical Oncology (2014)

e20509 Background: The perceptions surrounding the role of the oncology staff in supporting families of deceased patients have evolved with the transition to an interdisciplinary cancer-care approach. The goal of this study was to investigate the interactions between oncology professionals and bereaved families. Methods: This was a cross-sectional study. All oncology staff members at the Davidoff Center (Petah Tikva, Israel) were given a questionnaire including 39 statements relating to communications with bereaved families. Responses were measured using a 5-point Likert scale. Results: Of the 155 Davidoff Center staff members, 107 (69%) filled questionnaires with <20% missing data and were included in the analysis (α=0.799; corrected, α=0.821). The respondents included 37 (38%) physicians, 49 (50%) nurses, 8 (8%) social workers, and 4 (4%) psychologists. The median age was 45.1 yrs, 90% were Jewish, and 63% had ≥10 yrs of oncology experience. Most respondents thought it was important to contact bereaved families (73%), that such interaction provided closure to the staff (79%), and that it was professionally appropriate (82%). Approximately half (51%) indicated that they contact >50% of the families of their deceased patients. Contacting bereaved families was considered to be within the responsibility of the physicians (88%), nurses (81%), or social workers (87%). The main barriers for contacting bereaved families were emotional overload (68%) and lack of time (63%); 60% indicated a need for additional communication tools to aid them in bereavement follow up. In a multivariate analysis, profession (physician vs nurse), primary workplace (inpatient vs outpatient setting) and ethnicity (Jewish vs Muslim) were significant variables regarding the importance of contacting bereaved families as well as with actually contacting them. Other factors (eg, age, gender, marital status, years of oncology experience, number of dying patients treated monthly) were mostly nonsignificant. Conclusions: Perspectives regarding bereavement actions differ significantly across medical professions, work settings, and ethnicities. Additional guidance/education regarding bereavement actions is warranted.
Impact on MPN Symptoms and Quality of Life of Front Line Pegylated Interferon Alpha-2a Vs. Hydroxyurea in High Risk Polycythemia Vera and Essential Thrombocythemia: Results of Myeloproliferative Disorders Research Consortium (MPD-RC) 112 Global Phase III Trial
Authors: Ruben A. Mesa, Heidi E. Kosiorek, John Mascarenhas, Josef T. Prchal, Alessandro Rambaldi, Dmitriy Berenzon, Abdulraheem Yacoub, Claire N. Harrison, Mary Frances McMullin, Alessandro M. Vannucchi, Joanne Ewing, Casey L. O'Connell, Jean-Jacques Kiladjian, Adam J. Mead, Elliott F. Winton, David S. Leibowitz, Valerio De Stefano, Murat O. Arcasoy, Craig M. Kessler, Rosalind Catchatourian, Damiano Rondelli, Richard T. Silver, Andrea Bacigalupo, Arnon Nagler, Marina Kremyanskaya, Lonette Sandy, Mohamed E. Salama, Vesna Najfeld, Joseph Tripodi, Rona Singer Weinberg, Raajit K. Rampal, Ronald Hoffman, Amylou C. Dueck
Journal: Blood (2018)
Correlation of target motion with the dosimetric variance on breast and OAR during whole breast radiotherapy with 4D-CT.
Authors: Jianbin Li, Wei Wang
Journal: Journal of Clinical Oncology (2012)

e11521 Background: To explore the correlation between the respiration-induced target motion and volume variation with the dosimetric variance on breast and OAR during free breathing. Methods: Seventeen patients after breast conserving surgery underwent respiration-synchronized 4DCT simulation scans during free breathing. The treatment planning constructed using the end inspiration (EI) scan, then copied and applied to the other respiratory phases and the dose distribution was calculated separately. To evaluate the dose–volume histograms parameters for the PTV, ipsilateral lung and heart. Results: During free breathing, the CTV motion vector was 2.09 ± 0.74 mm, and the volume variation was 3.05 ± 0.94%. There was no correlation between the volume variation of CTV and target/OAR dosimetric variation (|r| = 0.39 ~ 0.48). In anteroposterior (AP), superoinferior (SI) and vector directions,the CTV movement correlated well with the mean PTV dose, conformal index (CI), and the lung volume receiving high dose (V 20 , V 30 , V 40 , and V 50 ) (|r| = 0.651 ~ 0.975); in SI and vector directions, the CTV displacement only correlated with the heart volume receiving &gt;5Gy (V 5 ) (r = -0.795, 0.687). The lung volume variation and the lung volume receiving high dose correlated reasonably well (r = 0.655 ~ 0.882), and the correlation only exist between the heat volume variation and the V 5 of heart (r = -0.701). Conclusions: Target movement correlated well with the target/OAR dosimetric variation in certain directions, indicating that whole breast IMRT assisted with breathing control or respiratory-adapted gated treatment will promote the accuracy of dose delivery during radiotherapy. To minimize lung irradiation, gated treatment maybe most precise if centered at end expiration.
Prevention of stent migration: Which option would patients prefer?
Authors: Yin Zhang, Yun Zhuang, Yang Wang, Jianping Chen
Journal: Endoscopy (2017)

We read with great interest the article by Ngamruengphong et al. “Endoscopic suturing for the prevention of stent migration in benign upper gastrointestinal conditions: a comparative multicenter study” [1]. The authors introduced an endoscopic suturing device (OverStitch; Apollo Endosurgery, Austin, Texas, USA) for the prevention of stent migration in patients with benign upper gastrointestinal diseases. After stent deployment, the endoscopic suturing device bites through the stent and esophageal mucosa to complete the suture. Compared with the patients who did not undergo stent fixation, the stent migration rate was lower in the endoscopic suturing group (33 % vs. 16 %; P = 0.03), suggesting that endoscopic suturing decreases the migration rate of fully covered metal stents.
Poster Session 3: Cost-Effectiveness; HCV: Diagnostics, Epidemiology, and Natural History
Journal: Hepatology (2014)

889Amal protocol to define candidacy for down-staging, 27.5% did not.No specific threshold in terms of number and size of tumors was used to define candidacy for down-staging by 42.5% of programs.Portal vein tumor thrombus was not a contra-indication to down-staging for 27.5% of programs.Most programs (84%) did not use a specific alpha fetoprotein (AFP) threshold to determine down-staging candidacy.For those programs which used an AFP threshold, this ranged from 400 to 5000.Almost all programs (97%) used the Milan Criteria to define down-staging success.A period of observation to demonstrate stability after successful down-staging was not required by 30%.When a period of stability was required, this ranged from 1 to 9 months, with 3 months being most common.Most programs considered trans-arterial radio-embolization as a down-staging modality, but chemo-embolization remained the dominant modality in all but a single program.Overall, most respondents expressed neutral feelings towards each of these practices, although 25% felt that use of the Milan Criteria to define successful down-staging was too restrictive.Conclusions: Practices vary across the country in terms of defining candidacy for down-staging, and for defining success of down-staging.Despite the range of practices, most individual practitioners reported comfort with the practice pattern at their own institution.Data on the efficacy of down-staging should be interpreted in the context of this wide range of down-staging practices.
Tuning formulation of multipeptide vaccination for melanoma patients at high risk of relapse
Authors: J. Baurain, N. Van Baren, M. Marchand, Y. Humblet, J. Machiels, P. G. Coulie
Journal: Journal of Clinical Oncology (2006)

18014 Background: Vaccination with MAGE peptides is followed by tumor regression in 10–20% of metastatic melanoma patients with detectable disease, mostly those with only SC or lymph node metastases. Anti-vaccine cytolytic T lymphocyte (CTL) responses have been observed in about 50% of the regressor patients, suggesting that these vaccines were poorly immunogenic. Recent reports have documented convincing CTL responses in patients vaccinated with peptides administered in a water-in-oil emulsion with Montanide, a clinical grade incomplete Freund’s adjuvant. After SC injection, this vaccine stimulates a local inflammation which could help to the recruitment of peptide presenting cells. Considering the absence of an effective treatment to prevent relapses of cutaneous melanoma, we applied this vaccination modality in an adjuvant setting. Methods and Results: We vaccinated 14 HLA-A2 melanoma patients with no evidence of disease but at high risk of relapse, with 4 antigenic peptides (MAGE-3.A2, NA17.A2, Tyrosinase.A2 and gp100.A2) emulsified in Montanide ISA51. Seven patients received 5 vaccinations, every 3 weeks, consisting of 4 injections of 900 μg of one peptide and 1 ml Montanide. Seven other patients received the same vaccines but with 300 μg of each peptide. Toxicity was limited to grade II, at the injection sites. Two thirds of the patients mounted a CTL response to peptide gp100.A2, and 50% to peptide NA17.A2. The lower doses of peptides were as immunogenic as the higher. Conclusions: These encouraging results indicate that this simple vaccination modality is not toxic and clearly immunogenic. We wish to formally assess the role of the immunological adjuvant Montanide in these CTL responses by vaccinating a third group of patients with the same 4 antigenic peptides without Montanide. We will also vaccinate with a mix of the 4 peptides and Montanide all injected at one site, as this will reduce the number of injections and could facilitate immunological helper effects of each peptide on the others. Finally, depending on the immunological results obtained with these two additional cohorts of patients, the best modality will be used in a larger study to evaluate clinical efficacy. No significant financial relationships to disclose.
A first-in-human study of the dual ROCK I/II inhibitor, AT13148, in patients with advanced cancers.
Authors: Dionysios Papadatos-Pastos, Rajiv Kumar, Timothy Anthony Yap, Ruth Ruddle, Shaun Decordova, Paul Jones, Gavin Halbert, Michelle D Garrett, Robert McLeod, Zoe Backholer, Karen E Swales, Florence I. Raynaud, Johann Sebastian De Bono, Udai Banerji
Journal: Journal of Clinical Oncology (2015)

2566 Background: AT13148 is a first-in-class, orally bioavailable, dual ROCK I/II inhibitor, which potently inhibits ROCK I/II (6, 4 nM), PKA (3 nM), AKT (38 nM) and p70S6K (8 nM). Broad anti-cancer activity has been demonstrated in a number of pre-clinical models. Methods: Patients (pts) with advanced solid tumors were enrolled into successive dose escalation cohorts of a minimum of three and maximum of six patients. AT13148 was dosed orally on days (D) 1, 3 and 5 of every week. Pharmacokinetic (PK) parameters were assessed and pre- and post-tumor biopsies, platelet-rich plasma (PRP) and hair follicles were analysed to evaluate target inhibition of AKT (p-AKT, p-S6K and p-GSK3B) and PKA (p-VASP). Results: 30 pts (16 male, 14 female) were treated with AT13148. Dose escalation started at 5 mg with doubling through 6 cohorts (10, 20, 40, 80 and 160 mg). Following the appearance of grade 2/3 toxicities in pts dosed at 160 mg (hypotension, headache and diarrhea), further dose doubling was not considered and the dose was increased by 50% to 240 mg. Thus far, at this dose there was one DLT of elevated liver enzymes which was reversible on treatment withdrawal. The cohort is currently being expanded to 6 pts. The most common drug-related toxicities in the study so far have been nausea, anorexia, headache and hypotension. PK analysis showed a dose proportional increase in AUC (382-13382 nM.h) and Cmax (21-450 nM) up to 160 mg (r2 = 0.98) on the first dose. Preliminary PD analyses in PRP have shown a ≥ 88% increase in p-AKT from baseline at cycle 1 D 15-22 (p ≤ 0.01) in the 160 mg cohort, a 17-21% decrease in pGSK3B from baseline at 6 h and 48 h post-dose (p ≤ 0.03) in the 160 mg cohort, and a 45% decrease in p-VASP from baseline at 48 h post-dose (p = 0.004) in the 80 mg cohort. Conclusions: AT13148 was administered orally on D 1, 3 and 5/week in an intermittent schedule and has currently reached a dose of 240 mg. At this dose there have been predictable tolerable 'on target' toxicities and dose escalation is ongoing. Clinical trial information: NCT01585701. Clinical trial information: NCT01585701.
Comparison of survival for left-sided KRASwt mCRC patients treated with anti-EGFR based therapy as compared to right-sided mCRC.
Authors: Lubos B. Petruzelka, Radka Obermannova, Karel Hejduk, Lenka Ostrizkova, Lenka Zdrazilova-Dubska, Dagmar Brancikova, Beatrix Bencsikova, Rostislav Vyzula, Michal Vocka
Journal: Journal of Clinical Oncology (2017)

763 Background: Anti-EGFR-antibody-based treatment is a standard of care in patients with RASwt metastatic colorectal cancer (mCRC). Right-sided mCRC is associated with frequent presence of KRAS mutation and with worse prognosis. Here we show the clinical outcome of 1 st , 2 nd , and 3 rd -line anti-EGFR therapy in KRASwt mCRC patients in the context of primary tumor location. Methods: Data from 3 national comprehensive cancer centers in the Czech Republic were collected prospectively from 01/2009 to 03/2016. A retrospective analysis of outcomes of 567 pts with KRASwt mCRC treated with anti-EGFR was performed. Right-sided colon was defined as coecum, ascending colon and transverse; while left-sided contains the splenic flexure, descending and sigmoid colon. The group of metastatic rectal cancer was analyzed separately. The primary objective was assessment of OS and PFS in 1 st , 2 nd , and 3 rd -line treatment of mCRC. OS and PFS were calculated using the Kaplan-Meier method and statistical significance was assessed using the log-rank test. Results: Right-sided tumor location was in 125 pts (22.0%), left-sided in 231 (40.7%) and rectal in 211 (37.2%). Median OS and PFS in months with 95% CI and log-rank test p-value are shown in a table. Conclusions: KRASwt mCRC patients with primary tumor in left-sided colon and rectum have comparable clinical outcome when treated with anti-EGFR-based therapy. In metastatic disease, primary right-sided KRASwt carcinoma is associated with short PFS and OS across all anti-EGFR-based treatment lines. The work was partially supported by Czech Ministry of Helth project no. 16-31966A and Technology Agency of the Czech Republic no. TA04010838. [Table: see text]
Treatment ofpatients (pts) with HER2- metastatic breast cancer (MBC) with <i>nab</i>-paclitaxel (<i>nab</i>-P) in the clinical practice setting—Results of a US Oncology survey.
Authors: Debra A. Patt, Paula Richardson, Debra Rembert, Deyanira Corzo, Clara Chen
Journal: Journal of Clinical Oncology (2014)

e12008 Background: Different dosages/schedules of nab-P (ie, 260 mg/m2 q3w, 100 mg/m2 qw, and 150 mg/m2 qw) have been assessed in phase 2/3 trials of MBC. However, limited information exists on the use of nab-P in the community setting. Here we report on experience with nab-P for the treatment of HER2− MBC and pt characteristics that impact nab-P treatment patterns in the community practice setting. Methods: From 9/6 to 10/21, 2013, US Oncology network physicians completed 30-question, web-based surveys on nab-P utilization, toxicity frequency, management, and duration. Responses were analyzed categorically by pt characteristics and proportional nab-P utilization. High (H) nab-P users were defined as those with ≥ 33% of HER2− pts who received nab-P. Results: 104/428 responded; 84% were from large practices (≥ 16 oncologists) and 56% were H nab-P users. For first- and second-line treatment, 100 mg/m2 qw (51% and 58%) was the most common starting dosage/schedule followed by 125 mg/m2 qw (22% and 14%), while 150 mg/m2 qw (4% and 2%) and 260 mg/m2 q3w (14% and 7%) were selected less often. Common factors affecting choice of nab-P monotherapy for H and less experienced users included comorbidities/performance status (PS; 86% vs 76%), quality of prior taxane response (67% vs 76%), steroid intolerance/contraindications/hypersensitivity (48% vs 59%), predominant visceral metastases (55% vs 43%), and age (43% vs 59%). Qw dosing was preferred for pts with select aggressive disease characteristics (ie, triple-negative MBC, short disease-free interval, predominant visceral metastases), poor PS, history of peripheral neuropathy (PN), and for elderly pts; q3w nab-P was generally used in pts ≤ 50 y and pts with good PS. Respondents reported 29% of pts had dose-limiting PN. Dose-limiting PN and neutropenia were the most common safety-related reasons for discontinuation of nab-P. Conclusions: In the community practice setting, 100 mg/m2 qw nab-P is the most commonly used starting dosage for pts with HER2− MBC, including those with aggressive disease characteristics. Consistent with phase 2/3 trials, PN and neutropenia were common dose-limiting toxicities.