tbuckley/cabot-search huggingface dataset:
Phase 1/2 study of durvalumab and tremelimumab as monotherapy and in combination in patients with unresectable hepatocellular carcinoma (HCC).
Authors: Ghassan K. Abou-Alfa, Bruno Sangro, Michael Morse, Andrew X. Zhu, Richard D. Kim, Ann-Lii Cheng, Masatoshi Kudo, Yoon-Koo Kang, Stephen L. Chan, Joyce Antal, Jillian Boice, Feng Xiao, Shannon R. Morris, Johanna Bendell
Journal: Journal of Clinical Oncology (2016)

TPS3103 Background: No approved standard-of-care treatment options exist for patients with unresectable HCC who progress on, are intolerant to, or have refused sorafenib therapy. The PD-1/PD-L1 pathway is an important immune checkpoint used by tumor cells to block antitumor responses. Durvalumab is a selective, high-affinity human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 (IC50 0.1 nM) and CD80 (B7.1; IC50 0.04 nM). Tremelimumab is an IgG2 monoclonal antibody that inhibits CTLA-4. Tremelimumab monotherapy can induce objective tumor remission with a favorable safety profile in patients with HCC.1Targeting both PD-L1 and CTLA-4 pathways provides nonredundant pathway blockade of critical immune checkpoints. Methods: This phase 1/2, multicenter, open-label, randomized study evaluates the safety, tolerability, and antitumor activity of durvalumab and tremelimumab each as monotherapy (20 and 10 mg/kg Q4W, respectively) and in combination (20 and 1 mg/kg Q4W, respectively) in patients with unresectable HCC with or without concomitant viral hepatitis B or hepatitis C infection who have progressed on, are intolerant to, or have refused treatment with sorafenib. Key exclusion criteria are prior exposure to immune-mediated therapy, hepatic encephalopathy, active or prior documented gastrointestinal variceal bleed, and any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer. The primary objective is to assess the safety and tolerability of durvalumab and tremelimumab each as monotherapy and in combination. Key secondary objectives are to evaluate clinical outcomes (including objective response rate, duration of response, and overall survival) and describe the pharmacokinetics, pharmacodynamics (including PD-L1 expression), and immunogenicity of durvalumab and tremelimumab as monotherapy and in combination. Recruitment is ongoing. 1. Sangro B, et al. J Hepatol. 2013;59:81-8. Clinical trial information: NCT02519348.
Detrimental Effect of Hypercholesterolemia on High-Density Lipoprotein Particle Remodeling in Pigs
Authors: Teresa Padró, Judit Cubedo, Sandra Camino, Maria Teresa Béjar, Soumaya Ben-Aicha, Guiomar Mendieta, Joan Carles Escolà-Gil, Rafael Escate, Manuel Gutiérrez, Laura Casani, Lina Badimon, Gemma Vilahur
Journal: Journal of the American College of Cardiology (2017)
Microwave ablation and radiofrequency ablation for the treatment of hepatocellular carcinoma: Result of the first prospective randomized controlled trial
Authors: Violi Naïk Vietti, Rafael Duran, Boris Guiu, Christophe Aubé, Jean-Pierre Cercueil, Pierre Bize, Isabelle Pache, Pierre Deltenre, Jean-François Knebel, Alban Denys
Journal: Annals of Oncology (2017)
Діагностика та корекція порушень травлення в практиці сімейного лікаря
Authors: Yu.I. Reshetilov, S.M. Dmitrieva, N.M. Protsenko, Ye.Yu. Vasylchenko, L.P. Kuznetsov, T.V. Bogoslav, N.P. Guz, O.F. Tsaprika
Journal: GASTROENTEROLOGY (2020)

У статті надано результати дослідження аероіонів повітря, що видихається, у 310 пацієнтів із поєднаною патологією органів травлення. Наведено новий неінвазивний метод діагностики та індивідуалізації комплексного лікування хворих, зокрема дієтотерапії. Обґрунтовано підбір продуктів харчування згідно з основними електрохімічними характеристиками. Оцінено перспективи використання методу аероіонного тестування в клінічній практиці як технології первинного скринінгу та неінвазивного контролю результатів лікування.
KEYNOTE-183: A randomized, open-label phase 3 study of pembrolizumab in combination with pomalidomide and low-dose dexamethasone in refractory or relapsed and refractory multiple myeloma (rrMM).
Authors: Jatin J. Shah, Sundar Jagannath, María-Victoria Mateos, Antonio Palumbo, Uma Kher, Patricia Maria Marinello, Jesus San Miguel
Journal: Journal of Clinical Oncology (2016)

TPS8070 Background: Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, leading to antitumor immune response. In the phase 1 KEYNOTE-023 trial of pembrolizumab + lenalidomide and low-dose dexamethasone, the treatment combination had an acceptable safety profile and promising preliminary efficacy in patients with rrMM, supporting further evaluation of pembrolizumab in these patients. The randomized, open-label, multicenter, phase 3 KEYNOTE-183 study (NCT02576977) was designed to compare the efficacy of pomalidomide and low-dose dexamethasone with or without pembrolizumab in patients with rrMM. Methods: Eligible patients must be aged ≥ 18 years, have confirmed diagnosis of MM with measurable disease, have had ≥ 2 lines of prior treatment, and are refractory to their last line of therapy. Patients must have been previously exposed to an immunomodulatory drug such as lenalidomide or thalidomide and a proteasome inhibitor such as bortezomib or carfilzomib, and be refractory or relapsed/refractory to one or both. Patients will be randomized 1:1 to receive pomalidomide 4 mg daily on days 1-21 and low-dose dexamethasone 40 mg daily on days 1, 8, 15, and 22 of repeated 28-day cycles, with or without pembrolizumab 200 mg every 3 weeks. Stratification will be based on the number of prior lines of treatment (2 vs ≥ 3) and disease status (refractory vs sensitive to lenalidomide). Treatment will continue until progressive disease or unacceptable toxicity. Response will be assessed every 28 days by Clinical Adjudication Committee blinded central review and investigator review based on International Myeloma Working Group response criteria. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. Primary end point is to be progression-free survival; secondary end points are to include overall survival, overall response rate and safety and tolerability. Enrollment in KEYNOTE-183 is ongoing; ~300 patients are to be enrolled. Clinical trial information: NCT02576977.
Breast cancer chemoprevention in primary care: Assessing readiness for change.
Authors: Haiyun Wang, Sharon Larson, Claire Frances Snyder, Victor G. Vogel, Lester Kirchner, Ying Maggie Zeng, Haiyan Sun, Xiaowei Sherry Yan
Journal: Journal of Clinical Oncology (2016)

1547 Background: Despite FDA approval of medications for breast cancer risk reduction and professional organizations’ (ASCO, USPSTF & NCCN) chemoprevention recommendations, chemoprevention use has not increased substantially. Barriers and facilitators to primary care providers’ (PCP) incorporation of breast cancer chemoprevention could inform efforts to increase uptake. Methods: We conducted an online survey of PCPs’ regarding awareness and use of breast cancer chemoprevention, and perceived barriers/solutions. All eligible PCPs at Geisinger Health System (family physicians, internists, residents, physician assistants, nurse practitioners) who practice ≥ one-half day per week in a family practice, internal medicine or OB-GYN outpatient clinic were invited to participate via email (four attempts total). Results: Of 492 invited providers, 195 (40%) participated (mean age 41 years, 61% female, 70% MD/DO, 45% ≥ 10 years in practice). Of the 195 participants, 74 (38%) used the Gail model for breast cancer risk assessment and 16 (8%) used Tamoxifen or Raloxifene for breast cancer prevention in the past year. Providers who used the Gail model were more likely to have made a breast cancer diagnosis in the past year (72% vs. 53%; p = .01). Providers who ever prescribed chemoprevention were older (mean age 49 vs. 40 years), were more likely to be in practice ≥ 10 years (75% vs 42%; p = .03), and to have diagnosed breast cancer in the past year (100% vs. 57%; p = .001). Barriers to incorporating breast cancer chemoprevention in primary care most commonly reported were lack of knowledge about chemoprevention drugs (75%), unaware of chemoprevention guidelines (67%), and inability to identify high risk women (62%). Only 41% perceived time constraints as a barrier. If risk assessment tools could be integrated to facilitate identification of high risk women, PCPs (85%) prefer referring appropriate women to a high-risk breast clinic to managing breast cancer prevention themselves. Conclusions: PCPs infrequently assess breast cancer risk and rarely prescribe chemoprevention drugs for risk reduction. PCP education on breast cancer prevention and establishing high-risk breast clinics may improve breast cancer chemoprevention uptake.
Absence of driver mutations in persistent polyclonal B-cell lymphocytosis with binucleated lymphocytes
Authors: Bruno Tesson, Sarah Huet, Béatrice Grange, Laurent Jallades, Lucile Baseggio, Pascale Felman, Alexandra Traverse-Glehen, Jean-Pierre Magaud, Jean-Christophe Lega, Christine Bole-Feysot, Gilles Salles, Evelyne Callet-Bauchu, Pierre Sujobert
Journal: Blood (2017)
Increased IgE<sup>+</sup> B Cells in Sputum, but Not Blood, Bone Marrow, or Tonsils, after Inhaled Allergen Challenge in Subjects with Asthma
Authors: John-Paul Oliveria, Brittany M. Salter, Jonathan MacLean, Shweta Kotwal, Ashley Smith, Jeffrey M. Harris, Heleen Scheerens, Roma Sehmi, Gail M. Gauvreau
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Emergence of quinolone-resistant Escherichia coli at a comprehensive cancer center
Authors: K. V. Rolston, E. Coyle, R. Prince
Journal: Journal of Clinical Oncology (2007)

19623 Background: Quinolone prophylaxis is recommended in high-risk neutropenic patients. Although effective in reducing the frequency of febrile episodes and documented gram-negative infections, this approach can lead to the emergence of resistant organisms. Surveillance studies looking for changes in resistance patterns at institutions that care for high-risk patients are also recommended. Methods: Our institution has participated in the meropenem yearly susceptibility test information collection (MYSTIC) program since 2000. The susceptibility of E. coli isolates from our cancer patients to quinolones (ciprofloxacin and levofloxacin) and broad-spectrum agents often used in empiric antimicrobial regimens in such patients, was determined. These studies were conducted by JMI Laboratories, Iowa, USA, and combined results as well as results of each participating institution were provided. CLSI designated breakpoints for susceptibility were used. Ribotyping and PFGE studies were performed on recent isolates. Results: Table 1 documents the declining susceptibility of E. coli isolates to the quinolones. In 2006 only 40.7% were quinolone susceptible compared to 84.2% in 2000 (p = 0.0032). All E. coli isolates remain susceptible to the carbapenems (meropenem, imipenem, ertapenem) and 95.5% remain susceptible to cefepime, ceftazidime, piperacillin-tazobactam, and the aminoglycosides. Twenty-one resistant E. coli isolates underwent ribotyping. Fourteen isolates showed identical ribotype and similar PFGE patterns suggesting the presence of an endemic clone. The other 7 isolates showed variability in their molecular patterns. Conclusions: Quinolone resistance among E. coli strains isolated from cancer patients has increased substantially. Fortunately these isolates remain susceptible to most broad-spectrum beta-lactams and aminoglycosides. Effective infection control methods need to be implemented and enforced in order to reduce the spread of these organisms in high risk patients. No significant financial relationships to disclose. [Table: see text]
Sensitivity of Ibrutinib Exposed Chronic Lymphocytic Leukemia B-Cells to Inhibition of Axl Receptor Tyrosine Kinase
Authors: Sutapa Sinha, Justin C Boysen, Kari G. Chaffee, Brian F Kabat, Susan L. Slager, Sameer A. Parikh, Charla R Secreto, Tait D. Shanafelt, Jose F. Leis, Steven L. Warner, David J. Bearss, Asish K Ghosh, Neil E. Kay
Journal: Blood (2016)
Dissecting human gliomas by single-cell RNA sequencing
Authors: Itay Tirosh, Mario L Suvà
Journal: Neuro-Oncology (2017)

Diffuse gliomas are the most common human primary brain tumors and remain incurable. They are complex entities in which diverse genetic and nongenetic effects determine tumor biology and clinical course. Our current understanding of gliomas in patients is primarily based on genomic and transcriptomic methods that have profiled them as bulk, providing critical information yet masking the diversity of cells within each tumor. Recent advances in single-cell DNA and RNA profiling have paved the way to studying tumors at cellular resolution. Here, we review initial studies deploying single-cell analysis in clinical glioma samples, with a focus on RNA expression profiling. We highlight how these studies provide new insights into glioma biology, tumor heterogeneity, cancer cell lineages, cancer stem cell programs, the tumor microenvironment, and glioma classification.
Abstract 81: End-Stage Human Failing Heart Increases Functional Cardiac Progenitor Cells
Authors: Rachana Mishra, David Simpson, Sudhish Sharma, Evan Colletti, Sunjay Kaushal
Journal: Circulation Research (2012)

Background: Human cases of end-stage heart failure provide the rare opportunity to test whether the cells within these hearts exhibit different phenotypic characteristics than those in healthy hearts. We tested whether the failing heart, as it reverses to a well-known fetal reprogramming state, also compensates by increasing the number of functional cardiac progenitor cells. Methods and Results: We examined samples from end-stage human failing hearts and also normal human hearts to quantitate the expression of various cardiac progenitor markers, by immunofluorescence, flow cytometry and RT-PCR. We further tested whether the cardiac progenitor cells were functional in a rodent model of myocardial infarction. All the failing end-stage hearts (N=13) reversed to a fetal state by switching their myosin heavy chain isoforms from beta to alpha. Additionally, atrial natriuretic factor was increased. Compared to normal congenital myocardium, failing end-stage hearts had a 2 to 5 fold increase in the number of C-kit+ and ISL-1+ cardiac progenitor cells (P&lt;0.5). The numbers of cardiac progenitor cells was highest in the right atria as compared to other chambers of the end-stage heart. Cardiac progenitor cells isolated from failing hearts expressed several stemness markers that were upregulated compared to normal human hearts. FACS and IF analysis demonstrated significantly (P&lt;0.5) higher c-kit expression in CDCs derived from end stage patients compare to normal congenital myocardium. Also, there was a tendency for increased FLK1 and Sca-1 expression in CM patients respectively. Transplanted cardiac progenitor cells from end-stage hearts promoted greater myocardial regeneration and functional improvement in the infarcted rat myocardium than transplanted cardiac progenitor cells derived from normal congenital patients (EF=57+3 vs. 41.5±3, P&lt;0.05). Conclusion: Our results show an increase of progenitor cells within the end-stage heart that have the functional potential to regenerate the myocardium. Stimulating the differentiation and increasing the population of cardiac progenitor cells may provide a novel therapeutic strategy for these end-stage hearts.
Development of automated laser capture microdissection for cancer biomarker discovery
Authors: Xiaohui Man, Lee Yee Choong, Huiyin Lee, Jia Pei Ho, Poh Kuan Chong, Wai Fun Jacklyn Kong, Yoon Pin Lim
Journal: Clinical Cancer Research (2007)

A73  Laser capture microdissection (LCM) is a recent development that enables the enrichment of specific cell types for subsequent molecular analysis and biomarker discovery efforts thus overcoming the problem of tissue heterogeneity. However, conventional LCM is manual and recognition of cells of interest is still a considerable bottleneck. Hence, automated identification of specific target cells for subsequent laser capture and analysis is desirable. Here, we described the development of an automated Cellenger-assisted LCM system and used it for proteomics of clinical breast tumors. Cellenger rule sets for automated recognition of breast cancer cells was developed and target tumor cells were microdissected by using LCM on toluidine blue stained frozen sections of breast cancer. Captured samples were subsequently analyzed using liquid chromatography-based mass spectrometry. Cellenger automates the otherwise manual and tedious detection of tumor cells during LCM and makes acquisition of tumor cells by LCM automated and efficient. The adaptation of automated LCM to proteomic technologies should also yield accurate insights into the pathobiology of breast cancer and have implications in biomarker discovery for early detection and prognostication.
Trabectedin for advanced soft tissue sarcoma: Ten-year real-life perspective.
Authors: Sivan Shamai, Ofer Merimsky
Journal: Journal of Clinical Oncology (2017)

11060 Background: Trabectedin is a marine - derived chemotherapy, which lately received FDA approval for use in anthracycline resistant advanced soft tissue sarcoma (STS), especially liposarcoma and leiomyosarcoma (L-sarcomas). Methods: We report our ten-year real-life experience with trabectedin, 1.5mg/m2/d c.i.v. q3w till progression, regarding safety and efficacy in a cohort of 86 patients (24-83y). Liposarcoma was the diagnosis in 46% , leiomyosarcoma in 43%. Results: A total of 703 cycles of Trabectedin were given, with a median of five cycles per patient (range 1-59). Median overall survival (mOS) was 11 months for liposarcoma patients (range 1-63), and 15 months for leiomyosarcoma patients (range 1-35). There was no statistically significant difference in progression free survival (PFS), when stratified according to previous treatment lines given. Trabectedin exhibited a favorable safety profile, with only 22% requiring dose reductions. Grade 3 and more toxicity were noted in 25% of the patients, mostly myelosuppression. There was no treatment related death. Conclusions: In contrast to former trials, our retrospective data represents real life experience with Trabectedin, and includes patients with diverse age, histology, performane status, prior treatments and tumor burden. The group includes 10 patients (11.6%) who received Trabectedin as first line (Either due to congestive heart failure or to rapid progression following adjuvant Doxorubicin and Ifosfamide), 10 patients (11.6%) were above age 70, nine (10.5%) had histologies other than liposarcoma or leiomyosarcoma, and 23 (26.7%) had ECOG PS of 2 or higher. Trabectedin is a safe and effective drug in advanced high grade STS. Further research is needed to identify which patients will benefit most.
Efficient Skin Temperature Sensor and Stable Gel‐Less Sticky ECG Sensor for a Wearable Flexible Healthcare Patch
Authors: Yuki Yamamoto, Daisuke Yamamoto, Makoto Takada, Hiroyoshi Naito, Takayuki Arie, Seiji Akita, Kuniharu Takei
Journal: Advanced Healthcare Materials (2017)

Wearable, flexible healthcare devices, which can monitor health data to predict and diagnose disease in advance, benefit society. Toward this future, various flexible and stretchable sensors as well as other components are demonstrated by arranging materials, structures, and processes. Although there are many sensor demonstrations, the fundamental characteristics such as the dependence of a temperature sensor on film thickness and the impact of adhesive for an electrocardiogram (ECG) sensor are yet to be explored in detail. In this study, the effect of film thickness for skin temperature measurements, adhesive force, and reliability of gel‐less ECG sensors as well as an integrated real‐time demonstration is reported. Depending on the ambient conditions, film thickness strongly affects the precision of skin temperature measurements, resulting in a thin flexible film suitable for a temperature sensor in wearable device applications. Furthermore, by arranging the material composition, stable gel‐less sticky ECG electrodes are realized. Finally, real‐time simultaneous skin temperature and ECG signal recordings are demonstrated by attaching an optimized device onto a volunteer's chest.
Precision Approach in Cancer Care
Authors: Rebecca Voelker
Journal: JAMA (2017)

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Etude randomisée comparant la mucosectomie par ligature à la mucosectomie avec capuchon pour les résections endoscopiques fragmentées des carcinomes épidermoïdes superficiels de l’œsophage
Authors: G Rahmi
Journal: Endoscopy (2016)

Le cancer de l’œsophage est associé à un très mauvais pronostic avec une survie globale à 5 ans d’environ 10 % dans les registres européens. Grâce au développement récent des techniques en endoscopie digestive, il est possible de diagnostiquer ce cancer sous une forme précoce accessible à un traitement mini-invasif comme la résection par mucosectomie ou la dissection sous-muqueuse. Actuellement, la mucosectomie est largement utilisée, notamment dans les pays occidentaux. Deux techniques sont disponibles: l’utilisation d’un système de ligature élastique ou d’un capuchon transparent fixé au bout de l’endoscope.