tbuckley/cabot-search huggingface dataset:
Abstract P1-18-24: Trastuzumab Emtansine (T-DM1): No radiosensitizing effect in vitro on HER2-positive breast cancer cells (study in vitro)
Authors: Fabien Mignot, Youlia Kirova, Pierre Verrelle, Marie-Paule Teulade-Fichou, Frédérique Megnin-Chanet
Journal: Cancer Research (2020)

Abstract Purpose/Objective(s): To determine the effects of concurrent irradiation and T-DM1 on HER2-positive breast cancer cell lines. Materials/Methods: Five human breast cancer cell lines (in vitro study) presenting various levels of HER2 expression were used to determine the potential therapeutic effect of T-DM1 combined with radiation. The toxicity of T-DM1 was assessed using CellTiter-Glo® assays and cell cycle analysis was performed by flow cytometry after BrdU incorporation. HER2 cells were irradiated at different dose levels after exposure to T-DM1. Survival fractions were determined by cell survival after 5 population doubling times. Results: The results revealed that T-DM1 induced significant lethality due to the intracellular action of DM1 on the cell cycle with significant G2/M phase blocking. Even after a short time incubation, the potency of T-DM1 was maintained and even enhanced over time, with a higher rate of cell death. After irradiation alone, the D10 (dose required to achieve 10% cell survival) was significantly higher for high HER2-expressing cell lines than for low HER2-expressing cells, with a linearly increasing relationship. In combination with irradiation, using conditions that allow cell survival, T-DM1 does not induce a radiosensitivity, both effects are strictly additive. Conclusion: Although intrinsic HER2 expression is a factor of radioresistance, the results indicated that T-DM1 is not a radiation-sensitizer under the experimental conditions of this study. However, further investigations are needed, in particular in vivo studies before reaching a final conclusion. Citation Format: Fabien Mignot, Youlia Kirova, Pierre Verrelle, Marie-Paule Teulade-Fichou, Frédérique Megnin-Chanet. Trastuzumab Emtansine (T-DM1): No radiosensitizing effect in vitro on HER2-positive breast cancer cells (study in vitro) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-24.
Abstract #1955: Reduced circulating IGF-I leads to differential stress resistance and enhances cancer treatment
Authors: Changhan Lee, Lizzia Raffaghello, Fernando Safdie, Min Wei, Federica Madia, Edoardo Parrella, David Hwang, Pinchas Cohen, Giovanna Bianchi, Valter Longo
Journal: Cancer Research (2009)

Traditional chemotherapeutic agents are designed to preferentially kill cancer cells, but collateral damage to normal cells is inevitable. This limits chemotherapy efficacy and leads to serious side effects such as myelosuppression, gastrointestinal damage, and fatigue. In order to overcome toxicity, chemoprotectants such as amifostine, glutathione, mesna, and dexrazoxane have been investigated, but have been shown to provide limited protection. Recently, we reported that short-term starvation (STS) provides protection to the host but not, or much less, to cancer cells. Because fasting would have limited clinical applications, we investigated the role of pathways implicated in the beneficial effect of calorie restriction on aging and stress resistance in differential stress resistance (DSR). Fasting is known to lower circulating insulin-like growth factor-I (IGF-I), which is primarily regulated by growth hormone (GH) and nutrition. Under normal conditions, GH directly controls the production of IGF-I, but during starvation, several changes in the GH/IGF-I axis occur as a result of physiological adaptation to fasting. In humans, IGF-I levels decrease dramatically in response to short-term fasting (36-72 hours) despite increased GH secretion. In rodents, fasting (24-72 hours) decreases both GH and IGF-I production. Organisms deficient in the GH/IGF-I pathway have also been shown to be long-lived and resistant to multiple types of stress. Here we studied the effect of manipulating the level and signaling activity of GH/IGF-I in the regulation of resistance to chemotherapy in non-transformed mammalian cells and mice. Mice with an 80% reduction in circulating IGF-I levels (LID) were treated with 4 different chemotherapy drugs: etoposide, cyclophosphamide, 5-FU, and doxorubicin. LID mice were protected against high doses of three out of four chemotherapy drugs tested. When injected with a highly aggressive melanoma (B16-fluc) followed by two cycles of high dose doxorubicin treatment, all control mice died from either the tumor or the chemotherapy but 60% of LID mice remained cancer free after 90 days. Reduced level or activity of the IGF-I receptor (IGF-IR) protected primary rat glia and mouse embryonic fibroblasts but not several cancer cell lines against chemotherapy drugs. In summary, we provide evidence for the role of a reduction in circulating IGF-I in protecting the host but not cancer cells against chemotherapy toxicity.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1955.
Circular RNA-protein interactions: functions, mechanisms, and identification
Authors: Anqing Huang, Haoxiao Zheng, Zhiye Wu, Minsheng Chen, Yuli Huang
Journal: Theranostics (2020)

Circular RNAs (circRNAs) are covalently closed, endogenous RNAs with no 5′ end caps or 3′ poly(A) tails.These RNAs are expressed in tissue-specific, cell-specific, and developmental stage-specific patterns.The biogenesis of circRNAs is now known to be regulated by multiple specific factors; however, circRNAs were previously thought to be insignificant byproducts of splicing errors.Recent studies have demonstrated their activity as microRNA (miRNA) sponges as well as protein sponges, decoys, scaffolds, and recruiters, and some circRNAs even act as translation templates in multiple pathophysiological processes.CircRNAs bind and sequester specific proteins to appropriate subcellular positions, and they participate in modulating certain protein-protein and protein-RNA interactions.Conversely, several proteins play an indispensable role in the life cycle of circRNAs from biogenesis to degradation.However, the exact mechanisms of these interactions between proteins and circRNAs remain unknown.Here, we review the current knowledge regarding circRNA-protein interactions and the methods used to identify and characterize these interactions.We also summarize new insights into the potential mechanisms underlying these interactions.
Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses
Authors: Jesse M. Jaynes, Rushikesh Sable, Michael Ronzetti, Wendy Bautista, Zachary Knotts, Abisola Abisoye-Ogunniyan, Dandan Li, Raul Calvo, Myagmarjav Dashnyam, Anju Singh, Theresa Guerin, Jason White, Sarangan Ravichandran, Parimal Kumar, Keyur Talsania, Vicky Chen, Anghesom Ghebremedhin, Balasubramanyam Karanam, Ahmad Bin Salam, Ruksana Amin, Taivan Odzorig, Taylor Aiken, Victoria Nguyen, Yansong Bian, Jelani C. Zarif, Amber E. de Groot, Monika Mehta, Lixin Fan, Xin Hu, Anton Simeonov, Nathan Pate, Mones Abu-Asab, Marc Ferrer, Noel Southall, Chan-Young Ock, Yongmei Zhao, Henry Lopez, Serguei Kozlov, Natalia de Val, Clayton C. Yates, Bolormaa Baljinnyam, Juan Marugan, Udo Rudloff
Journal: Science Translational Medicine (2020)

Solid tumors elicit a detectable immune response including the infiltration of tumor-associated macrophages (TAMs). Unfortunately, this immune response is co-opted into contributing toward tumor growth instead of preventing its progression. We seek to reestablish an antitumor immune response by selectively targeting surface receptors and endogenous signaling processes of the macrophage subtypes driving cancer progression. RP-182 is a synthetic 10-mer amphipathic analog of host defense peptides that selectively induces a conformational switch of the mannose receptor CD206 expressed on TAMs displaying an M2-like phenotype. RP-182-mediated activation of this receptor in human and murine M2-like macrophages elicits a program of endocytosis, phagosome-lysosome formation, and autophagy and reprograms M2-like TAMs to an antitumor M1-like phenotype. In syngeneic and autochthonous murine cancer models, RP-182 suppressed tumor growth, extended survival, and was an effective combination partner with chemo- or immune checkpoint therapy. Antitumor activity of RP-182 was also observed in CD206high patient-derived xenotransplantation models. Mechanistically, via selective reduction of immunosuppressive M2-like TAMs, RP-182 improved adaptive and innate antitumor immune responses, including increased cancer cell phagocytosis by reprogrammed TAMs.
Abstract P5-05-11: Novel small molecule STAT3 inhibitors induce apoptosis and suppress cell migration and tumor growth in triple-negative breast cancer cells
Authors: Li Pan, Xiang Chen, Shengling Fu, Chenglong Li, Hui-Wen Lo, Jiayuh Lin
Journal: Cancer Research (2020)

Abstract Persistent STAT3 signaling is frequently detected in many cancer types and thus could potentially serve as a viable therapeutic target. In this study, we tested two novel small STAT3 inhibitors, LLY17 and LLL12B in triple-negative breast cancer cells, which frequently express persistent STAT3 phosphorylation. LLY17 and LLL12B selectively inhibited IL-6-mediated induction of STAT3 phosphorylation but no effect on IFN-γ mediated induction of STAT1 phosphorylation. LLY17 and LLL12B induced apoptosis in triple-negative breast cancer cells but exhibited minimal toxicity toward normal mammary epithelial cells. RNAi attenuation experiments confirmed the requirement of STAT3 for LLY17 and LLL12B-mediated inhibition of cell viability in triple-negative breast cancer cells. LLY17 and LLL12B inhibited STAT3 phosphorylation in human and murine triple-negative breast cancer cells. In addition, LLY17 and LLL12B inhibited cell migration of human and murine triple-negative breast cancer cells. Furthermore, LLY17 and LLL12B suppressed tumor growth and STAT3 phosphorylation of triple-negative breast cancer cells in vivo in a mammary fat pad murine syngeneic mouse model. Together, our findings suggest that targeting persistent STAT3 signaling pathway by novel oral bioavailable small molecules LLY17 and LLL12B may be a potential approach for the therapy of triple-negative breast cancer. Citation Format: Li Pan, Xiang Chen, Shengling Fu, Chenglong Li, Hui-Wen Lo, Jiayuh Lin. Novel small molecule STAT3 inhibitors induce apoptosis and suppress cell migration and tumor growth in triple-negative breast cancer cells [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-05-11.
Clifton Paget Lowther
Authors: Johanna Lowther
Journal: BMJ (2020)

Clifton Paget Lowther (“Tony”) was born in Glasgow and studied medicine at Glasgow University. After qualifying he undertook two years of national service with the Royal Army Medical Corps, based in Liverpool. He returned to Glasgow to take up junior training posts in the brand new NHS and to marry Jean Miller McDougall, whom he had met at the outbreak of war in 1939. He published papers in haematology, passed his Glasgow College Membership and then moved to Edinburgh to continue his training in cardiology under Richard W D Turner.

He carried out cardiology research at the Western General Infirmary in Edinburgh alongside Arthur Kitchin, who became a lifelong friend and cardiologist. He was involved with the first successful mitral valvotomy in Scotland and also investigated various sympathetic ganglion blockers as possible treatments of hypertension.

The story …
Hemoglobin concentration of young men at residential altitudes between 200 and 2000m mirrors Switzerland's topography
Authors: Kaspar Staub, Martin Haeusler, Nicole Bender, Irina Morozova, Patrick Erik Eppenberger, Radoslaw Panczak, Marcel Zwahlen, Dominik J Schaer, Marco Valentino Maggiorini, Silvia Ulrich, Norina N Gassmann, Martina Ulrike Muckenthaler, Frank Rühli, Max Gassmann
Journal: Blood (2020)
Erratum: Corrigendum: Statistical colocalization of genetic risk variants for related autoimmune diseases in the context of common controls
Authors: Mary D Fortune, Hui Guo, Oliver Burren, Ellen Schofield, Neil M Walker, Maria Ban, Stephen J Sawcer, John Bowes, Jane Worthington, Anne Barton, Steve Eyre, John A Todd, Chris Wallace
Journal: Nature Genetics (2015)
Abstract P3-08-54: Pattern of hepatic metastasis as a prognostic index in breast cancer liver metastasis
Authors: Jieun Lee, Moon Hyung Choi, Ahwon Lee, Sung Hak Lee
Journal: Cancer Research (2020)

Abstract Background Liver is one of a common site of metastasis in metastatic breast cancer, and associated with visceral crisis in breast cancer. The clinical course and prognosis of breast cancer with liver metastasis (BCLM) is quite different with other solid cancers presenting with liver metastasis. BCLM patients frequently develop hepatic failure due to liver metastasis, but there are no clinicopathologic or radiologic parameters estimating the prognosis of BCLM during their clinical course. In this study, we analyzed the relationship of radiologic, clinicopathologic characteristics and survival outcomes in BCLM patients. Methods Between January 2009 to May 2019, 156 BCLM patients were analyzed. Baseline and final abdomen CT scan or liver MRI during treatment was reviewed by experienced radiologist. The pattern of liver metastasis was classified as oligometasis (3 or less metastatic lesions), non-confluent mass formation, confluent mass formation, infiltrative and pseudocirrhosis pattern. Clinicopathologic characteristics including child-pugh score (CPS) and survival outcomes including liver metastasis associated overall survival (LMOS) was analyzed Results Among 156 patients, 77 patients were initially presented with oligometastasis, 58 patients with non-confluent mass-forming pattern, 14 patients with confluent mass formation, and 7 patients with infiltrative liver metastasis. Patients who showed liver metastasis at initial recurrence or metastasis showed confluent mass-forming (9 patients, 64.3%) or infiltrative liver metastasis (6 patients, 85.7%) as presentation. At patient’s death, initial confluent mass-forming or infiltrative liver metastasis patients showed hepatic dysfunction with CPS 2 or 3. Patients with oligometastasis showed superior LMOS compared to non-confluent mass-forming, confluent mass-forming and infiltrative liver metastasis with worst survival outcome (median LMOS 55.03 months vs. 36.87, 36.93 and 8.8 months, P=0.0021). In luminal B patients, radiologic liver metastasis pattern at patient’s death or last follow-up were associated to cause of patient’s death such as hepatic failure (P=0.044). There were no survival benefit of patients who received local treatment for liver metastasis, compared to patients who only received systemic chemotherapy. Conclusion Initial hepatic metastasis pattern were associated with LMOS, especially infiltrative liver metastasis associated to poor survival outcome. There were no survival benefit of local treatment of liver metastasis during follow-up. Authors are planning on subsequent analysis based on pathologic classification of liver metastasis. Citation Format: Jieun Lee, Moon Hyung Choi, Ahwon Lee, Sung Hak Lee. Pattern of hepatic metastasis as a prognostic index in breast cancer liver metastasis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-54.
Revamped emergency targets set to be phased in from this April
Authors: Gareth Iacobucci
Journal: BMJ (2020)

New NHS waiting time targets for emergency care will be phased in from this April rather than replacing previous standards straight away, a senior NHS official has said.

NHS England’s chief operating officer, Amanda Pritchard, told the Health Service Journal 1 that ongoing testing of proposed changes suggested that the existing four hour target for seeing patients in emergency care—introduced in 2004—did not work well for the current model of clinical practice and service delivery.

In …
High long‐term efficacy of venom immunotherapy after discontinuation
Authors: Matteo Martini, Alice Corsi, Stefano Agolini, Aureliano Marchionni, Leonardo Antonicelli, Maria Beatrice Bilò
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Text messaging and medication adherence - do we have a missed call? [Letter to the Editor]
Authors: Alireza Ahmadvand, Lisa Nissen
Journal: JAMA Internal Medicine (2016)

We read the Original Investigation by Thakkar et al and the Invited Commentary by Nieuwlaat et al in a recent issue of JAMA Internal Medicine with great enthusiasm. Focusing on the second largest unsolved gap in health care and showing promisingly positive effects of short message service (SMS)-based interventions in improving the odds of medication adherence are important aspects of this research...
Feasibility of Computed Tomography Perfusion for Detection of Cardiac Allograft Rejection Following Heart Transplantation
Authors: Anna Oleksiak, Małgorzata Sobieszczańska-Małek, Mariusz Kruk, Tomasz Zieliński, Anna Drohomirecka, Krzysztof Komuda, Małgorzata Karczmarz, Mariusz Kuśmierczyk, Jacek Kądziela, Marcin Demkow, Cezary Kępka
Journal: JACC. Cardiovascular imaging (2020)
Abstract P2-09-10: Genetic variants of CCL5 signaling pathway genes in susceptibility and prognosis of triple negative breast cancers in Arab population
Authors: Salha Bujassoum Al-Bader, Jingxuan Shan, David Bedognetti, Lotfi Chouchane
Journal: Cancer Research (2020)

Abstract Background:Triple-negative breast cancer (TNBC) has a higher rate of early relapse and mortality compared to other types of breast cancer (BC). CCL5 and its signaling pathway have been linked to TNBC. Methods:We characterized variants in CCL5and that of six other CCL5 signaling genes (CCND1, ZMIZ1, CASP8, NOTCH2, MAP3K21 and HS6ST3) among 1,082 unrelated Arab subjects, including 196 TNBC, accessed their association with BC-specific overall survival (OVS) and progression-free survival (PFS), and correlated CCL5 expression with CCL5genotypes. Results: CCND1 rs614367-TTgenotype was highly associated with the TNBC risk (OR = 5.14; P = 0.004) and the rs614367-Tallele was associated with decreased PFS in TNBC. A decreased risk of lymph node metastasis was associated with the MAP3K21rs1294255-C allele, particularly in rs1294255-GC (OR = 0.47; P = 0.001). CCL5variants (rs2107538and rs2280789) were linked to CCL5 serum and mRNA levels. In the TCGA TNBC/Basal-like cohort the MAP3K21rs1294255-G allele was associated with a decreased OVS. High expression of CCL5in breast tumors was significantly associated with an increased OVS in all BC patients, but particularly in TNBC/Basal-like patients. Conclusion:Genetic variation in CCL5 signaling genes may predict not only TNBC risk but also disease aggression. Citation Format: Salha Bujassoum Al-Bader, Jingxuan Shan, David Bedognetti, Lotfi Chouchane. Genetic variants of CCL5 signaling pathway genes in susceptibility and prognosis of triple negative breast cancers in Arab population [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-10.
Acute exacerbation of idiopathic pulmonary fibrosis: international survey and call for harmonisation
Authors: Michael Kreuter, Markus Polke, Simon L.F. Walsh, Johannes Krisam, Harold R. Collard, Nazia Chaudhuri, Sergey Avdeev, Jürgen Behr, Gregory Calligaro, Tamera Corte, Kevin Flaherty, Manuela Funke-Chambour, Martin Kolb, Yasuhiro Kondoh, Toby M. Maher, Maria Molina Molina, Antonio Morais, Catharina C. Moor, Julie Morisset, Carlos Pereira, Silvia Quadrelli, Moises Selman, Argyrios Tzouvelekis, Claudia Valenzuela, Carlo Vancheri, Vanesa Vicens-Zygmunt, Julia Wälscher, Wim Wuyts, Marlies Wijsenbeek, Vincent Cottin, Elisabeth Bendstrup
Journal: European Respiratory Journal (2020)

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is an often deadly complication of IPF. No focussed international guidelines for the management of AE-IPF exist. The aim of this international survey was to assess the global variability in prevention, diagnostic and treatment strategies for AE-IPF. Pulmonologists with ILD expertise were invited to participate in a survey designed by an international expert panel. 509 pulmonologists from 66 countries responded. Significant geographical variability in approaches to manage AE-IPF was found. Common preventive measures included antifibrotic drugs and vaccination. Diagnostic differences were most pronounced regarding use of Krebs von den Lungen-6 and viral testing, while high-resolution computed tomography, brain natriuretic peptide and D-dimer are generally applied. High-dose steroids are widely administered (94%); the use of other immunosuppressant and treatment strategies is highly variable. Very few (4%) responders never use immunosuppression. Antifibrotic treatments are initiated during AE-IPF by 67%. Invasive ventilation or extracorporeal membrane oxygenation are mainly used as a bridge to transplantation. Most physicians educate patients comprehensively on the severity of AE-IPF (82%) and consider palliative care (64%). Approaches to the prevention, diagnosis and treatment of AE-IPF vary worldwide. Global trials and guidelines to improve the prognosis of AE-IPF are needed.
Highly efficient genome editing in primary human bronchial epithelial cells differentiated at air–liquid interface
Authors: Radu Rapiteanu, Tina Karagyozova, Natalie Zimmermann, Kuljit Singh, Gareth Wayne, Matteo Martufi, Nikolai N. Belyaev, Edith M. Hessel, David Michalovich, Ricardo Macarron, Wendy C. Rowan, William J. Cairns, Jan Roger, Joanna Betts, Soren Beinke, Klio Maratou
Journal: European Respiratory Journal (2020)

<b>A single-step, highly efficient CRISPR/Cas9-based genome editing pipeline allows the dissection of the molecular mechanisms underlying primary human bronchial epithelial cell differentiation and function at the air-liquid interface</b>http://bit.ly/2Oymgkw
Combined-therapeutic strategies synergistically potentiate glioblastoma multiforme treatment <i>via</i> nanotechnology
Authors: Jun Yang, Zhuyan Shi, Ruiyuan Liu, Yanyue Wu, Xin Zhang
Journal: Theranostics (2020)

Glioblastoma multiforme (GBM) is a highly aggressive and devastating brain tumor characterized by poor prognosis and high rates of recurrence. Numerous therapeutic strategies and delivery systems are developed to prolong the survival time. They exhibit enhanced therapeutic effects in animal models, whereas few of them is applied in clinical trials. Taking into account the drug-resistance and high recurrence of GBM, combined-therapeutic strategies are exploited to maximize therapeutic efficacy. The combined therapies demonstrate superior results than those of single therapies against GBM. The co-therapeutic agents, the timing of therapeutic strategies and the delivery systems greatly affect the overall outcomes. Herein, the current advances in combined therapies for glioblastoma via systemic administration are exhibited in this review. And we will discuss the pros and cons of these combined-therapeutic strategies via nanotechnology, and provide the guidance for developing rational delivery systems to optimize treatments against GBM and other malignancies in central nervous system.