tbuckley/cabot-search huggingface dataset:
Chemotherpay and Dendritic Cell Vaccine in Patient with Metastatic Melanoma: Phase II Prospective Randomized Trial
Authors: I.V. Samoylenko, T.N. Zabotina, I.N. Mikhaylova, G.Z. Chkadua, O.V. Korotkova, K. Baryshnikov, L.V. Demidov
Journal: Annals of Oncology (2012)
P-0082 Dose Escalation of the HDAC Inhibitor Resminostat in Combination Treatment with Sorafenib in Patients with Hepatocellular Carcinoma
Authors: Tom Ganten, Marcus-Alexander Wörns, Jens Siveke, Matthias Dollinger, Max Scheulen, Henning Wege, Anna Mais, Bernhard Hauns, Stefan Henning, Bernd Hentsch, Marius Horger, Ulrich Lauer, Michael Bitzer
Journal: Annals of Oncology (2012)
Graphene and other 2D materials: a multidisciplinary analysis to uncover the hidden potential as cancer theranostics
Authors: Laura Fusco, Arianna Gazzi, Guotao Peng, Yuyoung Shin, Sandra Vranic, Davide Bedognetti, Flavia Vitale, Acelya Yilmazer, Xinliang Feng, Bengt Fadeel, Cinzia Casiraghi, Lucia Gemma Delogu
Journal: Theranostics (2020)

Cancer represents one of the main causes of death in the world; hence the development of more specific approaches for its diagnosis and treatment is urgently needed in clinical practice. Here we aim at providing a comprehensive review on the use of 2-dimensional materials (2DMs) in cancer theranostics. In particular, we focus on graphene-related materials (GRMs), graphene hybrids, and graphdiyne (GDY), as well as other emerging 2DMs, such as MXene, tungsten disulfide (WS2), molybdenum disulfide (MoS2), hexagonal boron nitride (h-BN), black phosphorus (BP), silicene, antimonene (AM), germanene, biotite (black mica), metal organic frameworks (MOFs), and others. The results reported in the scientific literature in the last ten years (>200 papers) are dissected here with respect to the wide variety of combinations of imaging methodologies and therapeutic approaches, including drug/gene delivery, photothermal/photodynamic therapy, sonodynamic therapy, and immunotherapy. We provide a unique multidisciplinary approach in discussing the literature, which also includes a detailed section on the characterization methods used to analyze the material properties, highlighting the merits and limitations of the different approaches. The aim of this review is to show the strong potential of 2DMs for use as cancer theranostics, as well as to highlight issues that prevent the clinical translation of these materials. Overall, we hope to shed light on the hidden potential of the vast panorama of new and emerging 2DMs as clinical cancer theranostics.
Fortis-M, a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Oral Talactoferrin Alfa with Best Supportive Care in Patients with Advanced Non-Small Cell Lung Cancer Following Two or More Prior Regimens- by the Fortis-M Study Group
Authors: S.S. Ramalingam, J. Crawford, A. Chang, C. Manegold, R. Perez-Soler, J. Douillard, N. Thatcher, F. Barlesi, T.K. Owonikoko, Y. Wang, P. Pultar, J. Zhu, R. Malik, G. Giaccone
Journal: Annals of Oncology (2012)
Long-term outcomes of IMiD-based trials in patients with immunoglobulin light-chain amyloidosis: a pooled analysis
Authors: Rahma Warsame, Betsy LaPlant, Shaji K. Kumar, Kristina Laumann, Gabriela Perez Burbano, Francis K. Buadi, Morie A. Gertz, Robert A. Kyle, Martha Q. Lacy, David Dingli, Nelson Leung, Suzanne R. Hayman, Prashant Kapoor, Yi L. Hwa, Amie Fonder, Miriam Hobbs, Wilson I. Gonsalves, Taxiarchis Kourelis, John Lust, Stephen J. Russell, Steven Zeldenrust, Yi Lin, Eli Muchtar, Ronald S. Go, S. Vincent Rajkumar, Angela Dispenzieri
Journal: Blood Cancer Journal (2020)

Abstract Rarity of light-chain amyloidosis (AL) makes randomized studies challenging. We pooled three phase II studies of immunomodulatory drugs (IMiDs) to update survival, toxicity, and assess new response/progression criteria. Studies included were lenalidomide-dexamethasone (Len-Dex) ( n = 37; years: 2004–2006), cyclophosphamide-Len-Dex ( n = 35; years: 2007–2008), and pomalidomide-Dex ( n = 29; years: 2008–2010) trial. Primary endpoint was hematologic response. Overall survival (OS) was calculated from registration to death and progression-free survival (PFS) was calculated from registration to progression or death. Hematologic, cardiac, and renal response/progression was assessed using the modern criteria. Analysis included 101 patients, with a median age of 65 years, 61% male, 37 newly diagnosed (ND), and 64 relapsed/refractory (RR). Median follow-up was 101 months (range 17–150) and 78% of patients died. OS and PFS for pooled cohort were 31 and 15 months, respectively. Forty-eight patients achieved a hematologic response; for ND, 10 patients (28%) achieved ≥VGPR (very good partial response) and 8 (14%) among the RR. Only cardiac stage was prognostic for OS. Common grade ≥3 toxicities were hematologic, fatigue, and rash, and were similar among studies. Hematologic and renal responses occurred more frequently and rapidly using modern response criteria; cardiac response was less frequent but occurred quickly. IMiDs can result in long progression-free intervals/survival with tolerable toxicities. The new response/progression criteria were rapid and allows for tailoring therapy.
W B Stewart
Authors: Alastair Noble
Journal: BMJ (2020)

W B Stewart (“Bryce”) was proud to be born on a tea plantation in Assam in the days of the British Empire. His early upbringing was severely disrupted by the second world war. An only child, he was sent first to Scotland and then to America to be cared for by relatives and returned to Scotland only when the war ended.

After Glasgow University, where he was …
Identification of Endoglin (CD105) as an Epigenetically Regulated Candidate Tumour Suppressor Gene in Lung Cancer
Authors: K. O'Leary, A. Shia, V. Haley, F. Cavicchioli, A. Comino, P. Vanella, M. Wischnewsky, T. Crook, C. Lo Nigro, P. Schmid
Journal: Annals of Oncology (2012)
Population Based Evaluation of Chemotherapy Use After First Line Gefitinib in Epidermal Growth Factor Receptor (EGFR) Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
Authors: C. Mariano, I. Bosdet, D. Ionescu, A. Karsan, S. Sun, N. Murray, B. Melosky, J. Laskin, C. Ho
Journal: Annals of Oncology (2012)
Systematic review of human gut resistome studies revealed variable definitions and approaches
Authors: Jeffery Ho, Yun Kit Yeoh, Nilakshi Barua, Zigui Chen, Grace Lui, Sunny H Wong, Xiao Yang, Martin CW Chan, Paul KS Chan, Peter M Hawkey, Margaret Ip
Journal: Gut Microbes (2020)

In this review, we highlight the variations of gut resistome studies, which may preclude comparisons and translational interpretations. Of 22 included studies, a range of 12 to 2000 antibiotic resistance (AR) genes were profiled. Overall, studies defined a healthy gut resistome as subjects who had not taken antibiotics in the last three to 12 months prior to sampling. In studies with de novo assembly, AR genes were identified based on variable nucleotide or amino acid sequence similarities. Different marker genes were used for defining resistance to a given antibiotic class. Validation of phenotypic resistance in the laboratory is frequently lacking. Cryptic resistance, collateral sensitivity and the interaction with repressors or promotors were not investigated. International consensus is needed for selecting marker genes to define resistance to a given antibiotic class in addition to uniformity in phenotypic validation and bioinformatics pipelines.
Hierarchical assembly of nanostructured coating for siRNA-based dual therapy of bone regeneration and revascularization
Authors: Helin Xing, Xing Wang, Gao Xiao, Zongmin Zhao, Shiquan Zou, Man Li, Joseph J. Richardson, Blaise L. Tardy, Liangxia Xie, Satoshi Komasa, Joji Okazaki, Qingsong Jiang, Guodong Yang, Junling Guo
Journal: Biomaterials (2020)
Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease
Authors: Ethan R. Roy, Baiping Wang, Ying-wooi Wan, Gabriel Chiu, Allysa Cole, Zhuoran Yin, Nicholas E. Propson, Yin Xu, Joanna L. Jankowsky, Zhandong Liu, Virginia M.-Y. Lee, John Q. Trojanowski, Stephen D. Ginsberg, Oleg Butovsky, Hui Zheng, Wei Cao
Journal: Journal of Clinical Investigation (2020)

Type I interferon (IFN) is a key cytokine that curbs viral infection and cell malignancy. Previously, we demonstrated a potent IFN immunogenicity of nucleic acid–containing (NA-containing) amyloid fibrils in the periphery. Here, we investigated whether IFN is associated with β-amyloidosis inside the brain and contributes to neuropathology. An IFN-stimulated gene (ISG) signature was detected in the brains of multiple murine Alzheimer disease (AD) models, a phenomenon also observed in WT mouse brain challenged with generic NA-containing amyloid fibrils. In vitro, microglia innately responded to NA-containing amyloid fibrils. In AD models, activated ISG-expressing microglia exclusively surrounded NA+ amyloid β plaques, which accumulated in an age-dependent manner. Brain administration of rIFN-β resulted in microglial activation and complement C3-dependent synapse elimination in vivo. Conversely, selective IFN receptor blockade effectively diminished the ongoing microgliosis and synapse loss in AD models. Moreover, we detected activated ISG-expressing microglia enveloping NA-containing neuritic plaques in postmortem brains of patients with AD. Gene expression interrogation revealed that IFN pathway was grossly upregulated in clinical AD and significantly correlated with disease severity and complement activation. Therefore, IFN constitutes a pivotal element within the neuroinflammatory network of AD and critically contributes to neuropathogenic processes.
High Expression of Truncated GLI3 is Associated with Poor Overall Survival in Patients with Non-Small-Cell Lung Cancer
Authors: X.-Y. Bai, J.-Y. Lin, X.-C. Zhang, Z. Xie, H.-h. Yan, Z.-H. Chen, C.-R. Xu, S.-J. An, G.-M. Sheng, Y.-L. Wu
Journal: Annals of Oncology (2012)
The Usefulness of G8 Evaluation in Therapeutic Decision and Prediction of Tolerance in Locally Advanced or Metastatic Squamous Cell Head and Neck Cancer (SCCHN) Patients Older Than 65 Years
Authors: S.M. Ilie, I. Ruginescu, E. Saada, F.R. Ferrand, A. Schilf, F. Janot, J. Guigay
Journal: Annals of Oncology (2012)
Updated Efficacy, Biomarker, and Exposure-Response Data from a Phase 2 Study of Rilotumumab (R) Plus Epirubicin, Cisplatin, and Capecitabine (ECX) in Gastric (G) or Esophagogastric Junction (EGJ) Cancer
Authors: I. Davidenko, T. Iveson, R.C. Donehower, S. Tjulandin, A. Deptala, Y. Jiang, M. Zhu, K.S. Oliner, S. Dubey, E. Loh
Journal: Annals of Oncology (2012)
P53 Expression in Node-Positive Breast Cancer Patients Receiving Docetaxel-Based Adjuvant Chemotherapy
Authors: H.J. An, H.-J. Lee, G. Gong, K.-P. Kim, J.-H. Ahn, K.H. Jung, J.E. Kim, B.H. Son, S.-H. Ahn, S.-B. Kim
Journal: Annals of Oncology (2012)
Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response
Authors: Lu-Yu Yang, Qin Luo, Lu Lu, Wen-Wei Zhu, Hao-Ting Sun, Ran Wei, Zhi-Fei Lin, Xiang-Yu Wang, Chao-Qun Wang, Ming Lu, Hu-Liang Jia, Jin-Hong Chen, Ju-Bo Zhang, Lun-Xiu Qin
Journal: Journal of Hematology & Oncology (2020)

The propensity of the activated neutrophils to form extracellular traps (NETs) is demonstrated in multiple inflammatory conditions. In this study, we investigated the roles of NETs in metastasis of hepatocellular carcinoma (HCC) and further explored the underlying mechanism of how NETs affect metastasis as well as the therapeutic value.The neutrophils were isolated from the blood of human HCC patients and used to evaluate the formation of NETs. The expression of NET markers was detected in tumor specimens. A LPS-induced NET model was used to investigate the role of NETs on HCC metastasis. RNA-seq was performed to identify the key molecular event triggered by NETs, and their underlying mechanism and therapeutic significance were explored using both in vitro and in vivo assays.NET formation was enhanced in neutrophils derived from HCC patients, especially those with metastatic HCCs. NETs trapped HCC cells and subsequently induced cell-death resistance and enhanced invasiveness to trigger their metastatic potential, which was mediated by internalization of NETs into trapped HCC cells and activation of Toll-like receptors TLR4/9-COX2 signaling. Inhibition of TLR4/9-COX2 signaling abrogated the NET-aroused metastatic potential. A combination of DNase 1 directly wrecking NETs with anti-inflammation drugs aspirin/hydroxychloroquine effectively reduced HCC metastasis in mice model.NETs trigger tumorous inflammatory response and fuel HCC metastasis. Targeting NETs rather than neutrophils themselves can be a practice strategy against HCC metastasis.
The patient who reports a drug allergy
Authors: Robin Ferner, Patricia McGettigan
Journal: BMJ (2020)

### What you need to know

What should clinicians do when a patient gives a history of a “drug allergy”? If it really is an allergy—an immunological reaction—or a serious adverse drug reaction (ADR), then patients risk serious harm unless they avoid the drug. But often, patients and healthcare professionals use “drug allergy” to mean any suspected ADR. Accepting a “drug allergy” at face value can unnecessarily deprive the patient of a potentially useful treatment. It may directly cause harm: patients labelled “allergic to penicillin” are more likely to become infected with methicillin resistant Staphylococcus aureus or Clostridiodes difficile , for instance.1

In some cases it may be safe for a patient to take, perhaps in a lower dose, a drug that caused an ADR. Here we offer a guide to help patients and practitioners when the issue of “drug allergy” arises.

A scheme for assessing a patient who describes a drug allergy, based on our experience, is set out in figure 1. Begin by trying to establish if the harm was caused by medication, or something else. If it was an ADR, consider whether the reaction was serious, whether it was likely to be a true allergy, and whether it might have been related to the dose.



Fig 1 
An algorithm to guide decisions when a patient reports a “drug allergy”



When taking a drug history, it is better to ask: “Have you had a bad experience with any medicines or drugs?” rather than enquiring about drug allergy (see box 1 for definitions). If the patient volunteers a “drug allergy,” a detailed …
Circadian Regulator CLOCK Recruits Immune-Suppressive Microglia into the GBM Tumor Microenvironment
Authors: Peiwen Chen, Wen-Hao Hsu, Andrew Chang, Zhi Tan, Zhengdao Lan, Ashley Zhou, Denise J. Spring, Frederick F. Lang, Y. Alan Wang, Ronald A. DePinho
Journal: Cancer Discovery (2020)

Glioblastoma (GBM) is a lethal brain tumor containing a subpopulation of glioma stem cells (GSC). Pan-cancer analyses have revealed that stemness of cancer cells correlates positively with immunosuppressive pathways in many solid tumors, including GBM, prompting us to conduct a gain-of-function screen of epigenetic regulators that may influence GSC self-renewal and tumor immunity. The circadian regulator CLOCK emerged as a top hit in enhancing stem-cell self-renewal, which was amplified in about 5% of human GBM cases. CLOCK and its heterodimeric partner BMAL1 enhanced GSC self-renewal and triggered protumor immunity via transcriptional upregulation of OLFML3, a novel chemokine recruiting immune-suppressive microglia into the tumor microenvironment. In GBM models, CLOCK or OLFML3 depletion reduced intratumoral microglia density and extended overall survival. We conclude that the CLOCK-BMAL1 complex contributes to key GBM hallmarks of GSC maintenance and immunosuppression and, together with its downstream target OLFML3, represents new therapeutic targets for this disease. SIGNIFICANCE: Circadian regulator CLOCK drives GSC self-renewal and metabolism and promotes microglia infiltration through direct regulation of a novel microglia-attracting chemokine, OLFML3. CLOCK and/or OLFML3 may represent novel therapeutic targets for GBM.This article is highlighted in the In This Issue feature, p. 327.
Recent progress of hypoxia-modulated multifunctional nanomedicines to enhance photodynamic therapy: opportunities, challenges, and future development
Authors: Yixin Sun, Dongyang Zhao, Gang Wang, Yang Wang, Linlin Cao, Jin Sun, Qikun Jiang, Zhonggui He
Journal: Acta Pharmaceutica Sinica B (2020)

Hypoxia, a salient feature of most solid tumors, confers invasiveness and resistance to the tumor cells. Oxygen-consumption photodynamic therapy (PDT) suffers from the undesirable impediment of local hypoxia in tumors. Moreover, PDT could further worsen hypoxia. Therefore, developing effective strategies for manipulating hypoxia and improving the effectiveness of PDT has been a focus on antitumor treatment. In this review, the mechanism and relationship of tumor hypoxia and PDT are discussed. Moreover, we highlight recent trends in the field of nanomedicines to modulate hypoxia for enhancing PDT, such as oxygen supply systems, down-regulation of oxygen consumption and hypoxia utilization. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of PDT.
Parental desire and fertility preservation in assigned male at birth transgender people living in Belgium
Authors: Justine Defreyne, Judith Van Schuylenbergh, Joz Motmans, Kelly Tilleman, Guy T’Sjoen
Journal: International Journal of Transgender Health (2020)

Introduction: Transgender people who chose to proceed with gender affirming hormonal and/or surgical therapy, may face reduced options for fulfilling their parental desire in the future. The ideas and concerns of adult transgender people regarding fertility preservation and parental desire have never been reported in a large, non-clinical sample of assigned male at birth (AMAB) transgender people.Methods: A web-based survey on fertility and parenthood in (binary and non-binary) transgender people was conducted in Belgium. AMAB people were selected for this analysis.Results: We included 254 AMAB persons, of which 196 (77.2%) self-identified as transgender women (TW), 14 (5.5%) as cross-dressers and 44 (17.3%) as gender non-binary (GNB) people. Fifty-five (21.6%) respondents had a current/future parental desire, parental desire was already fulfilled in 81 (31.9%) and not present in 57 people (22.4%) (other: 19.2%). TW were more likely to express a parental desire, compared to GNB people and cross-dressers (P = 0.004). In total, 196 AMAB people previously sought medical assistance, of which 30 (15.3%) considered the loss of fertility due to the transitioning process undesirable. The majority (68.2%) did not want fertility preservation (FP). Fourteen people (9.8%) had proceeded with FP. The main reasons not to proceed with FP included not feeling the need (70; 68.0%), not desiring a genetic link with (future) child(ren) (20; 19.4%) and having to postpone hormone treatment (15; 14.6%). TW were more likely to have a parental desire and to have cryopreserved or to consider cryopreserving gametes, compared to GNB people.Conclusion: Parental desire and FP use were lower in the current non-clinical sample than in previous research on clinical samples. This can possibly be explained by the barriers transgender people face when considering fertility options, including postponing hormone therapy. Also, GNB persons have different needs for gender affirming treatment and FP.
Using Perivascular Fat Attenuation Index to Monitor Coronary Inflammation in Patients With Psoriasis—Reply
Authors: Youssef A. Elnabawi, Charalambos Antoniades, Nehal N. Mehta
Journal: JAMA Cardiology (2020)

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VEGF-a-induced Treg Proliferation, A Novel Mechanism of Tumor Immune Escape in Colorectal Cancer: Effects of Anti-VEGF/VEGFR Therapies
Authors: M. Terme, S. Pernot, E. Marcheteau, O. Colussi, F. Sandoval, N. Benhamouda, E. Tartour, J. Taieb
Journal: Annals of Oncology (2012)
mHealth and wearable technology should replace motor diaries to track motor fluctuations in Parkinson’s disease
Authors: M. Kelley Erb, Daniel R. Karlin, Bryan K. Ho, Kevin C. Thomas, Federico Parisi, Gloria P. Vergara-Diaz, Jean-Francois Daneault, Paul W. Wacnik, Hao Zhang, Tairmae Kangarloo, Charmaine Demanuele, Chris R. Brooks, Craig N. Detheridge, Nina Shaafi Kabiri, Jaspreet S. Bhangu, Paolo Bonato
Journal: npj Digital Medicine (2020)

Accurately monitoring motor and non-motor symptoms as well as complications in people with Parkinson's disease (PD) is a major challenge, both during clinical management and when conducting clinical trials investigating new treatments. A variety of strategies have been relied upon including questionnaires, motor diaries, and the serial administration of structured clinical exams like part III of the MDS-UPDRS. To evaluate the potential use of mobile and wearable technologies in clinical trials of new pharmacotherapies targeting PD symptoms, we carried out a project (project BlueSky) encompassing four clinical studies, in which 60 healthy volunteers (aged 23-69; 33 females) and 95 people with PD (aged 42-80; 37 females; years since diagnosis 1-24 years; Hoehn and Yahr 1-3) participated and were monitored in either a laboratory environment, a simulated apartment, or at home and in the community. In this paper, we investigated (i) the utility and reliability of self-reports for describing motor fluctuations; (ii) the agreement between participants and clinical raters on the presence of motor complications; (iii) the ability of video raters to accurately assess motor symptoms, and (iv) the dynamics of tremor, dyskinesia, and bradykinesia as they evolve over the medication cycle. Future papers will explore methods for estimating symptom severity based on sensor data. We found that 38% of participants who were asked to complete an electronic motor diary at home missed ~25% of total possible entries and otherwise made entries with an average delay of >4 h. During clinical evaluations by PD specialists, self-reports of dyskinesia were marked by ~35% false negatives and 15% false positives. Compared with live evaluation, the video evaluation of part III of the MDS-UPDRS significantly underestimated the subtle features of tremor and extremity bradykinesia, suggesting that these aspects of the disease may be underappreciated during remote assessments. On the other hand, live and video raters agreed on aspects of postural instability and gait. Our results highlight the significant opportunity for objective, high-resolution, continuous monitoring afforded by wearable technology to improve upon the monitoring of PD symptoms.
O-0028 Adjuvant Folfox4 +/- Cetuximab in KRAS Wild-Type Patients with Resected Stage III Colon Cancer Results from the Petacc8 Intergroup Trial
Authors: Julien Taieb, Josep Tabernero, Enrico Mini, Fabien Subtil, Gunnar Folprecht, Jean-Luc Van Laethem, Josef Thaler, John Bridgewater, Evaristo Sanches, Lone Nørgård Petersen, Philippe Rougier, Laurence Collette, Michel Praet, Cécile Girault, Martina Schneider, Pierre Squifflet, Pierre Laurent-Puig, Eric Van Cutsem, Laurent Bedenne, Come Lepage
Journal: Annals of Oncology (2012)