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Danijela Maksimović-Ivanić, Mirna Bulatović, David Edeler, Christian Bensing, Igor Golić, Aleksandra Korać, Goran N Kaluđerović, Sanja Mijatović
Extraordinary progress in medicinal inorganic chemistry in the past few years led to the rational design of novel platinum compounds, as well as nonplatinum metal-based antitumor agents, including organotin compounds, whose activity is not based on unrepairable interaction with DNA. To overcome poor solubility and toxicity problems that limited the application of these compounds numerous delivering systems were used (Lila et al. in Biol Pharm Bull 37:206-211, 2014; Yue and Cao in Curr Cancer Drug Targets 16:480-488, 2016; Duan et al...
February 13, 2019: Journal of Biological Inorganic Chemistry: JBIC
Saleh Rachidi, Maneet Kaur, Tim Lautenschlaeger, Zihai Li
Cancer is a chronic inflammatory state which is often associated with increased platelet counts. Cancer cells induce thrombopoiesis and activate platelets, which in turn facilitate cancer invasion and metastasis. In this study, we investigate the correlation between platelet counts with each of stage and overall survival in melanoma. This is a retrospective cohort study of 642 melanoma patients diagnosed or treated at a tertiary medical center between 2000 and 2016. Multivariable analysis adjusted for age, sex, stage, and treatment modality...
February 13, 2019: Platelets
Ashley M Hopkins, Madele Van Dyk, Andrew Rowland, Michael J Sorich
This study aimed to evaluate the impact of early adverse events on overall survival (OS), progression-free survival (PFS) and objective response within a pooled secondary analysis of participants treated with first-line vemurafenib or vemurafenib plus cobimetinib in the clinical trials BRIM3 and coBRIM. The study included 583 participants who received vemurafenib monotherapy and 247 who received vemurafenib plus cobimetinib. Adverse events requiring vemurafenib/cobimetinib dose adjustment within the first 28 days of therapy were significantly associated with OS (Hazard Ratio (HR) [95%CI]: Dose reduced/interrupted = 0...
February 13, 2019: Pigment Cell & Melanoma Research
Junji Kato, Tokimasa Hida, Masanori Someya, Sayuri Sato, Masahide Sawada, Kohei Horimoto, Mao Fujioka, Tomoyuki Minowa, Yoshiyuki Matsui, Takaaki Tsuchiya, Mio Kitagawa, Kensei Nakata, Koh-Ichi Sakata, Toshihiko Torigoe, Hisashi Uhara
Some studies showed that clinical response to immune check point inhibitors is lower in acral and mucosal melanoma than in cutaneous melanoma. Although the synergistic effect of radiotherapy (RT) and ipilimumab has been reported in patients with brain metastasis, the efficacy of combined RT and anti-programmed death 1 (PD-1) therapy for acral and mucosal melanoma is unclear. The present study aimed to evaluate the efficacy of combined RT and anti-PD-1 therapy for acral and mucosal melanoma. We retrospectively analyzed patients with acral or mucosal melanoma who were treated with anti-PD-1 and RT at Sapporo Medical University Hospital...
February 13, 2019: Journal of Dermatology
Markus Wortmann, Xianghui Xiao, Guido Wabnitz, Yvonne Samstag, Maani Hakimi, Dittmar Böckler, Susanne Dihlmann
OBJECTIVE AND DESIGN: Abdominal aortic aneurysm (AAA) is heavily infiltrated with leukocytes, expressing the DNA sensor absent in melanoma 2 (AIM2) and other inflammasome components. METHODS: Using multicolour flow cytometry, we here compared the expression of the inflammasome components AIM2, NLRP3, and ASC in different peripheral immune cells derived from AAA patients with those from non-AAA patients in a case-control study. In parallel, peripheral blood mononuclear cells (PBMC) of AAA patients and controls were stimulated in vitro with poly-dA:dT or lipopolysaccharide (LPS) to analyze inflammasome activation...
February 13, 2019: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Melissa Danesh, Beverly Faulkner-Jones, Anupam Desai, Caroline C Kim
No abstract text is available yet for this article.
February 13, 2019: JAMA Dermatology
Karen L Connolly, Kishwer S Nehal, Erica H Lee
No abstract text is available yet for this article.
February 13, 2019: JAMA Dermatology
John F Thompson, Serigne Lo, Richard A Scolyer
No abstract text is available yet for this article.
February 13, 2019: JAMA Dermatology
Robin Reschke, Jan-Christoph Simon, Mirjana Ziemer
Rechallenge of targeted therapy in patients with BRAFV600 -mutated melanoma plays an important role, because of the prolonged overall survival of melanoma patients. Patients may be rechallenged after a drug-free interval following adverse drug reactions, after radiation therapy or surgery, following disease progression on subsequent immunotherapy or chemotherapy, or after disease progression without interim therapeutic intervention. To date, only few data has been published on treatment outcomes associated with rechallenge...
February 13, 2019: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Peter Sarich, Karen Canfell, Emily Banks, Ellie Paige, Sam Egger, Grace Joshy, Rosemary Korda, Marianne Weber
BACKGROUND: Evidence suggests that people who develop serious health conditions are likely to cease drinking alcohol (sometimes known as 'sick-quitters'). We quantified the likelihood of quitting drinking in relation to the onset of a variety of health conditions. METHODS: Odds ratios (OR) and 95% confidence intervals (CI) of ceasing alcohol consumption after diagnosis of 28 health conditions and four general indicators of health were derived from logistic regression among 97,852 drinkers aged ≥45 years between baseline (2006-2009) and median 5...
February 13, 2019: Alcoholism, Clinical and Experimental Research
Arnaud de la Fouchardière, Claire Caillot, Julien Jacquemus, Emeline Durieux, Aurélie Houlier, Véronique Haddad, Daniel Pissaloux
Recent advances in genomics have improved the molecular classification of cutaneous melanocytic tumors. Among them, deep penetrating nevi (DPN) and plexiform nevi have been linked to joint activation of the MAP kinase and dysregulation of the β-catenin pathways. Immunohistochemical studies have confirmed cytoplasmic and nuclear expression of β-catenin and its downstream effector cyclin D1 in these tumors. We assessed nuclear β-catenin immunohistochemical expression in a large group of DPN as well as in the four most frequent differential diagnoses of DPN: "blue" melanocytic tumors, Spitz tumors, nevoid and SSM melanomas, and pigmented epithelioid melanocytomas (PEM)...
February 12, 2019: Virchows Archiv: An International Journal of Pathology
Miao Qiu, Keqing Huang, Yanzhuo Liu, Yuqing Yang, Honglin Tang, Xiaoxiao Liu, Chenlong Wang, Honglei Chen, Yu Xiong, Jing Zhang, Jing Yang
High-fat diet (HFD) promotes lung pre-metastatic niche formation and metastasis. Thus, there is an urgent need to identify the underlying mechanisms and develop strategies to overcome them. Here we demonstrate that glycyrrhizic acid (GA) prevents HFD-enhanced pre-metastatic niche formation and metastasis through gut microbiota. GA reduced HFD-enhanced myeloid-derived suppressor cell recruitment, pro-metastatic protein S100A8/A9 expression and metastasis burden of 4T1 breast cancer and B16F10 melanoma, accompanied by gut microbiota alteration and colonic macrophage polarization far away the M1-like phenotype...
February 12, 2019: Mucosal Immunology
Hui-Wen Tseng, Sung-Chou Li, Kuo-Wang Tsai
Melanoma is a highly aggressive cancer with high mortality in advanced stages.Metformin is an oral biguanide drug used for diabetes and has demonstrated positive effects oncancer prevention and treatment. Herein, we found that metformin significantly suppressedmelanoma cancer cell motility and growth through inducing cell cycle arrest at the G2/M phase andpromoting cell apoptosis. Using the next-generation sequencing approach, we identified threeupregulated microRNAs (miRNA; miR-192-5p, miR-584-3p, and miR-1246) in melanoma cellstreated with metformin...
February 11, 2019: Cancers
Tuba N Gide, Camelia Quek, Alexander M Menzies, Annie T Tasker, Ping Shang, Jeff Holst, Jason Madore, Su Yin Lim, Rebecca Velickovic, Matthew Wongchenko, Yibing Yan, Serigne Lo, Matteo S Carlino, Alexander Guminski, Robyn P M Saw, Angel Pang, Helen M McGuire, Umaimainthan Palendira, John F Thompson, Helen Rizos, Ines Pires da Silva, Marcel Batten, Richard A Scolyer, Georgina V Long, James S Wilmott
Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57). These data identified activated T cell signatures and T cell populations in responders to both treatments...
February 11, 2019: Cancer Cell
Yoshiyuki Nakamura, Ryota Tanaka, Hiroshi Maruyama, Yosuke Ishitsuka, Naoko Okiyama, Rei Watanabe, Manabu Fujimoto, Yasuhiro Fujisawa
Background: Anti-programmed cell death protein 1 monoclonal antibodies (αPD-1mAbs) have been shown to be effective for advanced malignant melanoma. Treatment with αPD-1mAbs can also cause immune-related adverse events (irAEs). However, clinical predictive factors for treatment responses or irAE risk remain unclear. Objective: To identify useful blood biomarkers for response and occurrence of irAEs with αPD-1mAbs treatment. Methods: We retrospectively collected data from patients with melanoma treated with αPD-1mAbs at the University of Tsukuba Hospital...
February 12, 2019: Japanese Journal of Clinical Oncology
Kelly G Paulson, Miranda Lahman, Aude G Chapuis, Isaac Brownell
Among all tumor types, skin cancers are profoundly sensitive to immunotherapy. Indeed, the recently reported response rates for anti-PD-1 (anti-programmed-death 1) therapy for cutaneous malignant melanomas (MM), Merkel cell carcinomas, basal cell carcinomas, cutaneous squamous cell carcinomas and Kaposi sarcomas are all above 40%. This unique immunogenicity renders skin cancers as a paradigm for tumor-immune interactions and is driven by high mutational burdens, overexpressed tumor antigens and/or viral antigens...
February 8, 2019: International Immunology
Ruth E Farmer, Deborah Ford, Rohini Mathur, Nish Chaturvedi, Rick Kaplan, Liam Smeeth, Krishnan Bhaskaran
Background: Previous studies provide conflicting evidence on whether metformin is protective against cancer. When studying time-varying exposure to metformin, covariates such as body mass index (BMI) and glycated haemoglobin (HbA1c) may act as both confounders and causal pathway variables, and so cannot be handled adequately by standard regression methods. Marginal structural models (MSMs) with inverse probability of treatment weights (IPTW) can correctly adjust for such confounders. Using this approach, the main objective of this study was to estimate the effect of metformin on cancer risk compared with risk in patients with T2DM taking no medication...
February 6, 2019: International Journal of Epidemiology
N C Støer, E Botteri, R Ghiasvand, M Busund, S Vangen, E Lund, M B Veierød, E Weiderpass
BACKGROUND: The association between reproductive factors and risk of cutaneous melanoma (CM) is unclear. We investigated this issue in the Norwegian Women and Cancer (NOWAC) cohort study. OBJECTIVES: To examine the association between the reproductive factors age at menarche, menstrual cycle length, parity, age at first and last birth, menopausal status, breastfeeding duration and length of ovulatory life and CM risk, overall and by histological subtypes and anatomical site METHODS: We followed 165,712 women aged 30-75 at inclusion from 1991-2007 to the end of 2015...
February 12, 2019: British Journal of Dermatology
Margaret Ottaviano, Sabino De Placido, Paolo Antonio Ascierto
AbstractSeveral researches have been carried over the last few decades to understand of how cancer evades the immune system and thus to identify therapies that could directly act on patient's immune system in the way of restore or induce a response to cancer. As a consequence, "cancer immunotherapy" is conquering predominantly the modern scenario of the fight against cancer. The recent clinical success of immune checkpoint inhibitors (ICIs) has created an entire new class of anti-cancer drugs and restored interest in the field of immuno-oncology, leading to regulatory approvals of several agents for the treatment of a variety of malignancies...
February 12, 2019: Virchows Archiv: An International Journal of Pathology
Linh T Nguyen, Samuel D Saibil, Valentin Sotov, Michael X Le, Leila Khoja, Danny Ghazarian, Luisa Bonilla, Habeeb Majeed, David Hogg, Anthony M Joshua, Michael Crump, Norman Franke, Anna Spreafico, Aaron Hansen, Ayman Al-Habeeb, Wey Leong, Alexandra Easson, Michael Reedijk, David P Goldstein, David McCready, Kazuhiro Yasufuku, Thomas Waddell, Marcelo Cypel, Andrew Pierre, Bianzheng Zhang, Sarah Boross-Harmer, Jane Cipollone, Megan Nelles, Elizabeth Scheid, Michael Fyrsta, Charlotte S Lo, Jessica Nie, Jennifer Y Yam, Pei Hua Yen, Diana Gray, Vinicius Motta, Alisha R Elford, Stephanie DeLuca, Lisa Wang, Stephanie Effendi, Ragitha Ellenchery, Naoto Hirano, Pamela S Ohashi, Marcus O Butler
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Secondary endpoints were safety and assessment of immune correlates following TIL infusion...
February 11, 2019: Cancer Immunology, Immunotherapy: CII
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