tbuckley/cabot-search huggingface dataset:
194TiP eXalt3: Phase 3 randomized study comparing ensartinib to crizotinib in anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients
Authors: L. Horn, Y-L. Wu, M. Reck, C. Liang, F. Tan, K. Harrow, V. Oertel, G. Dukart, T.S.K. Mok
Journal: Journal of Thoracic Oncology (2018)
Ly6C(high)単球に由来するマクロファージの機能的に異なるサブセットを含むさまざまな腫瘍微細環境
Authors: Movahedi Kiavash, Laoui Damya, Gysemans Conny, Baeten Martijn, Stange Geert, Van Den Bossche Jan, Mack Matthias, Pipeleers Daniel, In’T Veld Peter, DE Baetselier Patrick, A Van Ginderachter Jo
Journal: Cancer Research (2010)
The prognostic impact of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite.
Authors: Jonna Berntsson, Maria Christina Svensson, Karin Leandersson, Bjorn Nodin, Agnieszka Krzyzanowska, Anders Bjartell, Jakob Eberhard, Karin Jirstrom
Journal: Journal of Clinical Oncology (2017)

47 Background: Several studies report dense infiltration of tumour-infiltrating T cells and natural killer cells to be associated with an improved prognosis in colorectal cancer (CRC); but whether these associations differ by tumour location remain unknown. This study investigated the prognostic impact of immune cell infiltration in CRC, with particular reference to the anatomical subsite of the primary tumour. Methods: Immunohistochemical expression of CD3, CD8, FoxP3, and CD56 was analysed in tissue microarrays with tumours from 557 incident CRC cases from a prospective population-based cohort. Kaplan-Meier and Cox regression analyses were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. Results: In the entire cohort, dense infiltration of all the investigated immune cells correlated significantly with an improved 5-year OS in both univariable and multivariable analysis, adjusted for age, TNM stage, differentiation grade, and vascular invasion. Dense infiltration of CD3+ and CD8+ cells were independent favourable prognostic factors for tumours in the right colon (hazard ratio [HR] = 0.53, 95 % confidence interval [CI] 0.29-0.95 and HR = 0.35, 95% CI 0.19-0.65, respectively), but not in the left colon or rectum. When microsatellite instability status was included in the adjusted model, only CD8+ cells remained an independent favourable prognostic factor in right-sided tumours. Dense infiltration of FoxP3+ cells was an independent favourable prognostic factor for tumours in the rectum (HR = 0.54, 95% CI 0.30-0.99), but not in the right or left colon. Infiltration of CD56+ cells did not carry any independent prognostic impact after stratifying for primary tumour site. Conclusions: The results from this study demonstrate that the prognostic impact of certain T cell subsets in CRC differs by primary tumour site, being most evident in right-sided tumours. These findings indicate that tumour location may be an important factor to take into consideration in therapeutic decisions, including eligibility for immunotherapy.
Subgroup analysis by baseline (BL) weight-associated parameters: A phase III study of liposomal irinotecan (nal-IRI)±5-fluorouracil/leucovorin (5-FU/LV) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based (gem) therapy.
Authors: Teresa Mercade Macarulla, Richard Hubner, Jean-Frédéric Blanc, Andrea Wang-Gillam, Chung-Pin Li, Gyorgy Bodoky, Andrew Peter Dean, Shan Yanshen, Gayle S. Jameson, Kyung-Hun Lee, Chang-Fang Chiu, Gilberto Schwartsmann, Fadi S. Braiteh, David Cunningham, Li-Tzong Chen, Daniel D. Von Hoff, Khalid Kevin Mamlouk, Floris A de Jong, Jens T. Siveke
Journal: Journal of Clinical Oncology (2018)

410 Background: We report prognostic evaluation of BL weight-associated parameters (body-mass index [BMI], body surface area [BSA] and weight) in pts with mPDAC after progression following gem-based therapy (NAPOLI-1 trial; NCT01494506). Pts received nal-IRI+5-FU/LV, nal-IRI monotherapy or 5-FU/LV in NAPOLI-1, an international, randomised, phase 3 trial; nal-IRI+5-FU/LV treatment resulted in a 45% increased median OS vs. 5-FU/LV (unstratified HR = 0.67; p = 0.012). Methods: This exploratory subgroup analysis compares outcomes by BL BMI, BSA and weight, using primary survival analysis data from the ITT population for all treatment arms combined (n = 417) and the nal-IRI+5-FU/LV arm on its own (n = 117). Results: OS and PFS were not significantly different between BL BMI, BSA and weight median subgroups in the entire NAPOLI-1 ITT population (HR range 1.06–1.15; log-rank p-value range 0.21–0.60; Table) and in the nal-IRI+5-FU/LV arm (HR range 0.94–1.19; log-rank p-value range 0.43–1.00). Conclusions: This post-hoc subgroup analysis did not detect any prognostic impact on treatment outcome by BL BMI, BSA and weight for mPDAC pts progressed following gem-based therapy. This observation rules out a treatment-independent effect. No evidence of a predictive effect on nal-IRI+5-FU/LV efficacy was found. Clinical trial information: NCT01494506. [Table: see text]
Response to: ‘Postpartum breastfeeding status’ by Betzold
Authors: Amanda M Eudy, Anna Maria Siega-Riz, Stephanie M Engel, Nora Franceschini, Annie Green Howard, Megan E B Clowse, Michelle Petri
Journal: Annals of the Rheumatic Diseases (2018)

Response to: 'Postpartum breastfeeding status' by
Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer
Authors: Janos L. Tanyi, Sara Bobisse, Eran Ophir, Sandra Tuyaerts, Annalisa Roberti, Raphael Genolet, Petra Baumgartner, Brian J. Stevenson, Christian Iseli, Denarda Dangaj, Brian Czerniecki, Aikaterini Semilietof, Julien Racle, Alexandra Michel, Ioannis Xenarios, Cheryl Chiang, Dimitri S. Monos, Drew A. Torigian, Harvey L. Nisenbaum, Olivier Michielin, Carl H. June, Bruce L. Levine, Daniel J. Powell, David Gfeller, Rosemarie Mick, Urania Dafni, Vincent Zoete, Alexandre Harari, George Coukos, Lana E. Kandalaft
Journal: Science Translational Medicine (2018)

We conducted a pilot clinical trial testing a personalized vaccine generated by autologous dendritic cells (DCs) pulsed with oxidized autologous whole-tumor cell lysate (OCDC), which was injected intranodally in platinum-treated, immunotherapy-naïve, recurrent ovarian cancer patients. OCDC was administered alone (cohort 1, n = 5), in combination with bevacizumab (cohort 2, n = 10), or bevacizumab plus low-dose intravenous cyclophosphamide (cohort 3, n = 10) until disease progression or vaccine exhaustion. A total of 392 vaccine doses were administered without serious adverse events. Vaccination induced T cell responses to autologous tumor antigen, which were associated with significantly prolonged survival. Vaccination also amplified T cell responses against mutated neoepitopes derived from nonsynonymous somatic tumor mutations, and this included priming of T cells against previously unrecognized neoepitopes, as well as novel T cell clones of markedly higher avidity against previously recognized neoepitopes. We conclude that the use of oxidized whole-tumor lysate DC vaccine is safe and effective in eliciting a broad antitumor immunity, including private neoantigens, and warrants further clinical testing.
Hepatoma cell‐secreted exosomal microRNA‐103 increases vascular permeability and promotes metastasis by targeting junction proteins
Authors: Jian‐Hong Fang, Zi‐Jun Zhang, Li‐Ru Shang, Yu‐Wei Luo, Yi‐Fang Lin, Yunfei Yuan, Shi‐Mei Zhuang
Journal: Hepatology (2018)

Increased vascular permeability facilitates metastasis. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the crosstalk between cancer and stromal cells. To date, whether and how secreted miRNAs affect vascular permeability remains unclear. Based on deep sequencing and quantitative PCR, we found that higher level of serum miR‐103 was associated with higher metastasis potential of hepatocellular carcinoma (HCC). The in vitro endothelial permeability and transendothelial invasion assays revealed that the conditioned media or exosomes derived from high miR‐103‐expressing hepatoma cells increased the permeability of endothelial monolayers, but this effect was attenuated if exosome secretion of hepatoma cells was blocked by silencing ALIX and HRS or if miR‐103 within hepatoma or endothelial cells was antagonized. Most importantly, pretreating endothelial monolayers with exosomes that were from stable miR‐103‐expressing hepatoma cells facilitated the transendothelial invasion of tumor cells, and this role of exosomes was abrogated by inhibiting miR‐103 in endothelial cells. Further in vivo analyses disclosed that mice with xenografts of stable miR‐103‐expressing hepatoma cells exhibited higher vascular permeability in tumor, higher level of exosomal miR‐103 and greater number of tumor cells in blood circulation, and increased rates of hepatic and pulmonary metastases, compared to control mice. Mechanism investigations revealed that hepatoma cell‐secreted miR‐103 could be delivered into endothelial cells via exosomes, and then attenuated the endothelial junction integrity by directly inhibiting the expression of VE‐Cadherin (VE‐Cad), p120‐catenin (p120) and zonula occludens 1. Moreover, miR‐103 could also promote tumor cell migration by repressing p120 expression in hepatoma cells. Conclusion : Hepatoma cell‐secreted exosomal miR‐103 increases vascular permeability and promotes tumor metastasis by targeting multiple endothelial junction proteins, which highlights secreted miR‐103 as a potential therapeutic target and a predictive marker for HCC metastasis. (H epatology 2018).
To track or not to track: wheeze phenotypes in preschool children
Authors: Paul L.P. Brand, André Schultz
Journal: European Respiratory Journal (2018)

We applaud the robust statistical approach used by Spycher et al. [1] to assess the temporal stability of episodic viral wheeze (EVW) and multitrigger wheeze (MTW) phenotypes in young children. They reported that in two large population-based cohort studies, children who continued to wheeze at 4 and 6 years of age showed a tendency to maintain the same phenotype from the age of 2 years. The authors' conclusion, and that of the accompanying editorial, is that the EVW and MTW phenotypes in young children are stable and track over time [2], and that these phenotypes may represent different disease entities [1, 2]. We would like to call for caution in interpreting these results because they are based on statistical probability, not on clinical differential diagnosis. Wheeze phenotypes in preschool children are insufficiently stable and valid to base treatment decisions upon <http://ow.ly/HFhd30ivJyq>
A core domain set for hidradenitis suppurativa trial outcomes: an international Delphi process
Authors: L. Thorlacius, J.R. Ingram, B. Villumsen, S. Esmann, J.S. Kirby, A.B. Gottlieb, J.F. Merola, R. Dellavalle, S.M. Nielsen, R. Christensen, A. Garg, G.B.E. Jemec
Journal: British Journal of Dermatology (2018)

There is no consensus on core outcome domains for hidradenitis suppurativa (HS). Heterogeneous outcome measure instruments in clinical trials likely leads to outcome‐reporting bias and limits the ability to synthesize evidence. To achieve global multistakeholder consensus on a core outcome set (COS) of domains regarding what to measure in clinical trials for HS. Six stakeholder groups participated in a Delphi process that included five anonymous e‐Delphi rounds and four face‐to‐face consensus meetings to reach consensus on the final COS. The aim was for a 1 : 1 ratio of patients to healthcare professionals (HCPs). A total of 41 patients and 52 HCPs from 19 countries in four continents participated in the consensus process, which yielded a final COS that included five domains: pain, physical signs, HS‐specific quality of life, global assessment and progression of course. A sixth domain, symptoms, was highly supported by patients and not by HCPs but is recommended for the core domain set. Routine adoption of the COS in future HS trials should ensure that core outcomes of importance to both patients and HCPs are collected.
232TiP Lanreotide autogel/depot in lung neuroendocrine tumours: The randomized, double-blind, placebo-controlled, international phase 3 SPINET Study
Authors: X-M. Truong Thanh, D. Reidy-Lagunes, M. Kulke, E. Wolin, S. Singh, D. Ferone, D. Hoersch, A. Houchard, M. Caplin, E. Baudin
Journal: Journal of Thoracic Oncology (2018)
Phase I clinical trial of combination imatinib and ipilimumab in patients with advanced malignancies.
Authors: Matthew Reilley, Ann Marie Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Steven Falchook, Daniel D. Karp, Sarina Anne Piha-Paul, Apostolia Maria Tsimberidou, Siqing Fu, Ralph Zinner, JoAnn Lim, Stacie A. Bean, Allison Bass, Sandra Montez, Luis M Vence, Padmanee Sharma, James Patrick Allison, Funda Meric-Bernstam, David S. Hong
Journal: Journal of Clinical Oncology (2016)

3054 Background: Imatinib mesylate can induce rapid tumor regression, inhibit tumor immunosuppressive mechanisms, and release large amounts of antigenic debris from tumor cell death with subsequent increase in tumor antigen presentation. CTLA-4 blockade and imatinib combination therapy in mouse models of GIST synergistically reduces size of tumors mediated by imatinib-dependent intratumoral accumulation of CD8+ T-cells and suppression of Treg-cells. We hypothesized that combination therapy with imatinib and ipilimumab immunotherapy would be tolerable and may synergistically enhance anti-tumor T-cell activation in patients (pts). Methods: Primary objective of the dose-escalation study (3+3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose of the combination. Eligible pts had metastatic or unresectable, solid tumors. In the expansion cohort, pts were required to have a known KIT mutation. Secondary objectives included evaluation of antitumor activity of the combination based on KIT mutation status and the predictive status of tumor-associated immune biomarkers. Results: 26 pts were dosed in the escalation portion of the study. No dose limiting toxicities were encountered. The most common grade 1 and 2 related adverse events (AEs) were nausea (57%), fatigue (50%), vomiting (46%), anorexia (35%), diarrhea, skin rash, and edema (each 27%). There were 4 (16%) grade 3 related AEs including fatigue, anemia, rash, and vomiting. There were no grade 4 AEs. The MTD was the highest planned dose level of Ipilmumab at 3mg/kg and Imatinib at 400mg twice daily. An additional 10 pts were treated at MTD. Among all pts, three responses were seen: one GIST (PR) and 2 melanoma pts (CR + PR). These responses were seen at higher dose levels. Stable disease was seen in 7 pts lasting an average of 6 months. Notably, both melanoma responders had KIT mutations; the GIST responder was wild type. Immune cell activity in tumor tissue biopsy specimens and serum is under analysis. Conclusions: In this phase I trial the combination was well tolerated. Responders in this trial suggest that this combination at MTD has antitumor activity in WT GIST and KIT-mutant melanoma and merits further investigation. Clinical trial information: NCT01738139.
Dr. Jekyll and Mr. Hyde: MAP17’s up-regulation, a crosspoint in cancer and inflammatory diseases
Authors: José M. García-Heredia, Amancio Carnero
Journal: Molecular Cancer (2018)

Inflammation is a common defensive response that is activated after different harmful stimuli. This chronic, or pathological, inflammation is also one of the causes of neoplastic transformation and cancer development. MAP17 is a small protein localized to membranes with a restricted pattern of expression in adult tissues. However, its expression is common in destabilized cells, as it is overexpressed both in inflammatory diseases and in cancer. MAP17 is overexpressed in most, if not all, carcinomas and in many tumors of mesenchymal origin, and correlates with higher grade and poorly differentiated tumors. This overexpression drives deep changes in cell homeostasis including increased oxidative stress, deregulation of signaling pathways and increased growth rates. Importantly, MAP17 is associated in tumors with inflammatory cells infiltration, not only in cancer but in various inflammatory diseases such as Barret's esophagus, lupus, Crohn's, psoriasis and COPD. Furthermore, MAP17 also modifies the expression of genes connected to inflammation, showing a clear induction of the inflammatory profile. Since MAP17 appears highly correlated with the infiltration of inflammatory cells in cancer, is MAP17 overexpression an important cellular event connecting tumorigenesis and inflammation?
Physiology and Engineering of the Graded Interfaces of Musculoskeletal Junctions
Authors: Edward D. Bonnevie, Robert L. Mauck
Journal: Annual Review of Biomedical Engineering (2018)

The connective tissues of the musculoskeletal system can be grouped into fibrous, cartilaginous, and calcified tissues. While each tissue type has a distinct composition and function, the intersections between these tissues result in the formation of complex, composite, and graded junctions. The complexity of these interfaces is a critical aspect of their healthy function, but poses a significant challenge for their repair. In this review, we describe the organization and structure of complex musculoskeletal interfaces, identify emerging technologies for engineering such structures, and outline the requirements for assessing the complex nature of these tissues in the context of recapitulating their function through tissue engineering.
Successful closure of a gastropulmonary fistula after esophagectomy using the Apollo Overstitch and endoscopic vacuum therapy
Authors: Seung-Hun Chon, Ulrich Toex, Patrick Plum, Claudia Fuchs, Robert Kleinert, Christiane Bruns, Tobias Goeser
Journal: Endoscopy (2018)

Gastropulmonary fistulas following transthoracic en bloc esophagectomy and intrathoracic gastric reconstruction (Ivor Lewis esophagectomy) are rare but life-threatening complications. Surgical management of these is difficult and associated with significant instances of morbidity and mortality [1]. One possible treatment for leaks after upper gastrointestinal surgery is endoluminal vacuum therapy (EVT) [2]. A newer treatment option is the endoscopic suturing system Apollo Overstitch [3] [4] [5]. The Overstitch is a single-use device that is placed on top of a double-channel therapeutic endoscope, which facilitates full-thickness surgical suturing in single or running technique. To our knowledge, the case presented below constitutes the first successful clinical application of a combination of Overstitch and EVT to close a gastropulmonary fistula after Ivor Lewis esophagectomy.
157P Second-line afatinib for patients with locally advanced or metastatic NSCLC harbouring common EGFR mutations: A phase IV study
Authors: S. Thongprasert, S. Geater, D. Clement, A. Abdelaziz, J. Reyer-Igama, D. Jovanovic, S. Suresh, A. Cseh, R. Gaafar
Journal: Journal of Thoracic Oncology (2018)
Patterns of metastases in malignant pleural mesothelioma in the modern era: Redefining the spread of an old disease.
Authors: Dearbhaile Catherine Collins, Anastasia Constantinidou, Raghav Sundar, Maxime Chenard-Poirier, Timothy Anthony Yap, Udai Banerji, Johann S. De Bono, Juanita Suzanne Lopez, Nina Tunariu
Journal: Journal of Clinical Oncology (2017)

8556 Background: Malignant pleural mesothelioma (MPM) has been historically documented as a locally infiltrative disease in large series from the early 1980s. With the changing landscape of cancer diagnosis and treatment, increased areas of unusual metastases have been published as case reports. With no standard second-line therapies for MPM, referral to early phase trial units is common. We report the metastatic patterns of a large cohort of MPM patients treated at the Royal Marsden Drug Development Unit (DDU). Methods: Clinical data was gathered for MPM patients referred to the DDU from 1992 to 2016. Radiographic details were collected from CT, bone scan and FDG PET imaging. Prior treatment, response, somatic mutations, clinical trial and survival data was obtained from medical records. Results: From the database, 165 evaluable patients with MPM were identified. Median age at diagnosis was 64 years (range 37–90) and 76% were male. Epithelioid MPM comprised 81% and 65% were right sided. Bone metastases were reported in 20%, with the majority lytic in nature ( Table). Peritoneal and omental disease was evident in 24% with ascites in 16%. In 11% of cases lung metastases presented as diffuse miliary-type pattern. Visceral metastases (15%) were predominantly liver (78%), but also occurred in adrenals, spleen and kidneys. Symptomatic brain metastases were recorded in 3%. Median overall survival was 24.2 months (95% CI: 20.8 - 29.2). Conclusions: This large study documents the metastatic patterns of advanced MPM in the 21 st century and highlights an increased frequency of traditionally unexpected sites of metastases. Higher than expected incidence of lytic bone metastases (20%) suggests consideration of bone imaging in advanced MPM clinical workflow and trial protocols. [Table: see text]
Abstract 15017: Nanoanalytical Analysis of Bisphosphonate-Induced Alteration of Microcalcifications Using a 3D Hydrogel Platform
Authors: Jessica L Ruiz, Joshua D Hutcheson, Luis Cardoso, Tan Pham, Sheldon Weinbaum, Elena Aikawa
Journal: Circulation (2016)

Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiP), a proposed therapy for vascular calcification, paradoxically increased risk in patients with prior acute events but decreased risk in other patients. We recently demonstrated that calcifying extracellular vesicles (EV) released by cells within the plaque aggregate and nucleate calcific mineral. We hypothesize that BiP block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the resultant risk of plaque rupture. 3D collagen hydrogels incubated with calcifying EV modeled fibrous cap calcification, serving as a platform to image mineral nucleation and test potential therapies for vascular calcification. This study visualized EV aggregation and formation of stress-inducing microcalcifications at single-EV resolution, via scanning electron microscopy. Finite element analysis (FEA) of a representative microcalcification formed in the 3D platform predicted a consequential 350% increase in fibrous cap tensile stress (Figure, red color). Energy-dispersive x-ray spectroscopy (EDS) confirmed that EV aggregates contained calcium and phosphorous. BiP (ibandronate) treatment added on day 0 decreased the size (21.5 μm 2  vs. 14.2 μm 2 ) and EDS-detected calcium (4.32% by weight (wt%) vs. 2.36 wt%) and phosphorous (4.26 wt% vs. 1.94 wt%) comprising EV aggregates measured on day 8. However, an increase in mineral was measured when BiP was added at later time points (Graph). BiP treatment altered microcalcification morphology in a time-dependent manner. These findings support our hypothesis that BiP alter EV-driven calcification, which may help explain confounding clinical data. The study confirmed that our 3D hydrogel is a viable platform to study EV-mediated mineral nucleation and evaluate potential therapies for cardiovascular calcification.