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Drug screening immune response cancer

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https://www.readbyqxmd.com/read/30016071/nanocarrier-mediated-chemo-immunotherapy-arrested-cancer-progression-and-induced-tumor-dormancy-in-desmoplastic-melanoma
#1
Qi Liu, Fengqian Chen, Lin Hou, Limei Shen, Xueqiong Zhang, Degeng Wang, Leaf Huang
In desmoplastic melanoma, tumor cells and tumor-associated fibroblasts are the major dominators playing a critical role in the fibrosis morphology as well as the immunosuppressive tumor microenvironment (TME), compromising the efficacy of therapeutic options. To overcome this therapeutic hurdle, we developed an innovative chemo-immunostrategy based on targeted delivery of mitoxantrone (MIT) and celastrol (CEL), two potent medicines screened and selected with the best anticancer and antifibrosis potentials. Importantly, CEL worked in synergy with MIT to induce immunogenic tumor cell death...
July 23, 2018: ACS Nano
https://www.readbyqxmd.com/read/29989092/ccl2-sqstm1-positive-feedback-loop-suppresses-autophagy-to-promote-chemoresistance-in-gastric-cancer
#2
Wenxia Xu, Qi Wei, Mengjiao Han, Bingluo Zhou, Hanying Wang, Jianbing Zhang, Qiang Wang, Jie Sun, Lifeng Feng, Shouyu Wang, Yang Ye, Xian Wang, Jianwei Zhou, Hongchuan Jin
Chemotherapy is one of the most important approaches for the treatment of various cancers. However, tumor cells often develop resistance to chemotherapeutic drugs. The tumor microenvironment reconstituted by various cytokines secreted from immune cells was recently found to play important roles in affecting therapeutic response of tumor cells. Herein, we reported that tumor cells can secrete autocrine cytokines to confer chemoresistance by inactivating proapoptotic autophagy. Through cytokine screening, we found that drug resistant cancer cells secreted more CCL2 than drug sensitive cells...
2018: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29867975/zoledronate-triggers-v%C3%AE-2-t-cells-to-destroy-and-kill-spheroids-of-colon-carcinoma-quantitative-image-analysis-of-three-dimensional-cultures
#3
Serena Varesano, Maria Raffaella Zocchi, Alessandro Poggi
New successful anti-cancer strategies are based on the stimulation of immune reaction against tumors: however, preclinical testing of such treatments is still a challenge. To improve the screening of anti-cancer drugs, three-dimensional (3D) culture systems, including spheroids, have been validated as preclinical models. We propose the spheroid 3D system to test anti-tumor drug-induced immune responses. We show that colorectal carcinoma (CRC) spheroids, generated with the epithelial growth factor (EGF), can be co-cultured with Vδ2 T cells to evaluate the anti-tumor activity of these effector lymphocytes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29761297/severe-neurologic-complications-of-immune-checkpoint-inhibitors-a-single-center-review
#4
Sarah Mancone, Thomas Lycan, Tamjeed Ahmed, Umit Topaloglu, Andrew Dothard, William J Petty, Roy E Strowd
BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising class of anticancer drugs associated with immune-related adverse events (IRAEs). In registration studies of selected cancer populations, neurologic IRAEs were rare. Post-marketing experience describing their prevalence in clinical practice continues to be reported. METHODS: A retrospective cohort of patients treated at our institution with ICIs from 2005 to 2017 was identified. Patients with new neurologic ICD codes documented during or after ICI treatment were enrolled...
May 14, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29719628/novel-water-soluble-lignin-derivative-bp-cx-1-identification-of-components-and-screening-of-potential-targets-in-silico-and-in-vitro
#5
Elena I Fedoros, Alexey A Orlov, Alexander Zherebker, Ekaterina A Gubareva, Mikhail A Maydin, Andrey I Konstantinov, Konstantin A Krasnov, Ruben N Karapetian, Ekaterina I Izotova, Sergey E Pigarev, Andrey V Panchenko, Margarita L Tyndyk, Dmitry I Osolodkin, Evgeny N Nikolaev, Irina V Perminova, Vladimir N Anisimov
Identification of molecular targets and mechanism of action is always a challenge, in particular - for natural compounds due to inherent chemical complexity. BP-Cx-1 is a water-soluble modification of hydrolyzed lignin used as the platform for a portfolio of innovative pharmacological products aimed for therapy and supportive care of oncological patients. The present study describes a new approach, which combines in vitro screening of potential molecular targets for BP-Cx-1 using Diversity Profile - P9 panel by Eurofins Cerep (France) with a search of possible active components in silico in ChEMBL - manually curated chemical database of bioactive molecules with drug-like properties...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29699936/il-6-family-cytokines-key-inflammatory-mediators-as-biomarkers-and-potential-therapeutic-targets
#6
REVIEW
Nese Unver, Florencia McAllister
IL-6 is a critical cytokine in acute phase response and involved in the pathogenesis of several chronic inflammatory diseases including cancer. Studies have highlighted that levels of IL-6 and its family members can be useful for diagnosis, prognosis of relapse-free survival and recurrence. IL-6 family cytokines have been identified as cancer biomarkers through screening of inflammatory mediators in different fluids including saliva, serum, and bronchoalveolar lavage fluid (BALF). IL-6 can be modulated by chemopreventive drugs, small molecules, monoclonal antibodies and immune checkpoint inhibitors...
June 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29698433/isolation-and-molecular-characterization-of-novel-glucarpidases-enzymes-to-improve-the-antibody-directed-enzyme-pro-drug-therapy-for-cancer-treatment
#7
Fatma B Rashidi, Alanod D AlQhatani, Sara S Bashraheel, Shabnam Shaabani, Matthew R Groves, Alexander Dömling, Sayed K Goda
Repeated cycles of antibody-directed enzyme pro-drug therapy (ADEPT) and the use of glucarpidase in the detoxification of cytotoxic methotrexate (MTX) are highly desirable during cancer therapy but are hampered by the induced human antibody response to glucarpidase. Novel variants of glucarpidase (formal name: carboxypeptidase G2, CPG2) with epitopes not recognized by the immune system are likely to allow repeated cycles of ADEPT for effective cancer therapy. Towards this aim, over two thousand soil samples were collected and screened for folate hydrolyzing bacteria using folate as the sole carbon source...
2018: PloS One
https://www.readbyqxmd.com/read/29665849/an-innovative-immunotherapeutic-strategy-for-ovarian-cancer-clec10a-and-glycomimetic-peptides
#8
Laura L Eggink, Katherine F Roby, Robert Cote, J Kenneth Hoober
BACKGROUND: Receptors specific for the sugar N-acetylgalactosamine (GalNAc) include the human type II, C-type lectin receptor macrophage galactose-type lectin/C-type lectin receptor family member 10A (MGL/CLEC10A/CD301) that is expressed prominently by human peripheral immature dendritic cells, dendritic cells in the skin, alternatively-activated (M2a) macrophages, and to lesser extents by several other types of tissues. CLEC10A is an endocytic receptor on antigen-presenting cells and has been proposed to play an important role in maturation of dendritic cells and initiation of an immune response...
April 17, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29514083/pi3k-akt-cooperates-with-oncogenic-notch-by-inducing-nitric-oxide-dependent-inflammation
#9
Santiago Nahuel Villegas, Rita Gombos, Lucia García-López, Irene Gutiérrez-Pérez, Jesús García-Castillo, Diana Marcela Vallejo, Vanina Gabriela Da Ros, Esther Ballesta-Illán, József Mihály, Maria Dominguez
The PI3K/Akt signaling pathway, Notch, and other oncogenes cooperate in the induction of aggressive cancers. Elucidating how the PI3K/Akt pathway facilitates tumorigenesis by other oncogenes may offer opportunities to develop drugs with fewer side effects than those currently available. Here, using an unbiased in vivo chemical genetic screen in Drosophila, we identified compounds that inhibit the activity of proinflammatory enzymes nitric oxide synthase (NOS) and lipoxygenase (LOX) as selective suppressors of Notch-PI3K/Akt cooperative oncogenesis...
March 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29510739/measuring-multiple-parameters-of-cd8-tumor-infiltrating-lymphocytes-in-human-cancers-by-image-analysis
#10
Keith E Steele, Tze Heng Tan, René Korn, Karma Dacosta, Charles Brown, Michael Kuziora, Johannes Zimmermann, Brian Laffin, Moritz Widmaier, Lorenz Rognoni, Ruben Cardenes, Katrin Schneider, Anmarie Boutrin, Philip Martin, Jiping Zha, Tobias Wiestler
BACKGROUND: Immuno-oncology and cancer immunotherapies are areas of intense research. The numbers and locations of CD8+ tumor-infiltrating lymphocytes (TILs) are important measures of the immune response to cancer with prognostic, pharmacodynamic, and predictive potential. We describe the development, validation, and application of advanced image analysis methods to characterize multiple immunohistochemistry-derived CD8 parameters in clinical and nonclinical tumor tissues. METHODS: Commercial resection tumors from nine cancer types, and paired screening/on-drug biopsies of non-small-cell lung carcinoma (NSCLC) patients enrolled in a phase 1/2 clinical trial investigating the PD-L1 antibody therapy durvalumab (NCT01693562), were immunostained for CD8...
March 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29498669/using-pdx-for-preclinical-cancer-drug-discovery-the-evolving-field
#11
REVIEW
Juliet A Williams
The ability to create patient derived xenografts (PDXs) has evolved considerably from the breakthrough of the development of immune compromised mice. How researchers in drug discovery have utilized PDX of certain cancer types has also changed from traditionally selecting a few models to profile a drug, to opting to assess inter-tumor response heterogeneity by screening across a broad range of tumor models, and subsequently to enable clinical stratification strategies. As with all models and methodologies, imperfections with this approach are apparent, and our understanding of the fidelity of these models continues to expand...
March 2, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29477100/diversity-of-brain-metastases-screening-and-management-in-non-small-cell-lung-cancer-in-europe-results-of-the-european-organisation-for-research-and-treatment-of-cancer-lung-cancer-group-survey
#12
Antonin Levy, Corinne Faivre-Finn, Baktiar Hasan, Eleonora De Maio, Anna S Berghoff, Nicolas Girard, Laurent Greillier, Sylvie Lantuéjoul, Mary O'Brien, Martin Reck, Anne-Marie C Dingemans, Silvia Novello, Thierry Berghmans, Benjamin Besse, Lizza Hendriks
BACKGROUND: Brain metastases (BM) are frequent in non-small cell lung cancer (NSCLC) patients, but there is a lack of evidence-based management of this patient group. We aimed to capture a snapshot of routine BM management in Europe to identify relevant research questions for future clinical trials. METHODS: An EORTC Lung Cancer Group (LCG) online survey containing questions on NSCLC BM screening and treatment was distributed between 16/02/17 and 15/06/17 to worldwide EORTC LCG members, and through several European scientific societies in the thoracic oncology field...
April 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29466296/sarcoma-spheroids-and-organoids-promising-tools-in-the-era-of-personalized-medicine
#13
REVIEW
Gianluca Colella, Flavio Fazioli, Michele Gallo, Annarosaria De Chiara, Gaetano Apice, Carlo Ruosi, Amelia Cimmino, Filomena de Nigris
Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and help determine the most promising individual treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may have a multitude of genomic aberrations that give rise to more than 70 different histopathological subtypes...
February 21, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29443026/a-paired-bead-and-magnet-array-for-molding-microwells-with-variable-concave-geometries
#14
Gi-Hun Lee, Youngjoon Suh, Joong Yull Park
A spheroid culture is a useful tool for understanding cellular behavior in that it provides an in vivo-like three-dimensional environment. Various spheroid production methods such as non-adhesive surfaces, spinner flasks, hanging drops, and microwells have been used in studies of cell-to-cell interaction, immune-activation, drug screening, stem cell differentiation, and organoid generation. Among these methods, microwells with a three-dimensional concave geometry have gained the attention of scientists and engineers, given their advantages of uniform-sized spheroid generation and the ease with which the responses of individual spheroids can be monitored...
January 28, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29421594/dna-damaging-potential-of-ganoderma-lucidum-extracts
#15
María Soledad Vela Gurovic, Fátima R Viceconte, Marcelo T Pereyra, Maximiliano A Bidegain, María Amelia Cubitto
ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Lingzhi or Reishi) is a medicinal mushroom historically used in Asian countries to treat a wide variety of diseases and prolong life. In the last years, G. lucidum has been internationally recognized as an effective adjuvant in cancer treatment. Among active components, the most recent research indicates that polysaccharides modulate the immune response favoring the recovery from toxicity of chemo and radiotherapy while triterpenes are cytotoxic to tumoral cells mainly by altering gene expression...
May 10, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29367376/new-drugs-and-new-toxicities-pembrolizumab-induced-myocarditis
#16
Faisal Inayat, Muhammad Masab, Sorab Gupta, Waqas Ullah
Pembrolizumab is an immune checkpoint inhibitor that significantly improves clinical outcomes in numerous solid organ malignancies. Despite successful therapeutic responses, this new drug comes with a constellation of adverse reactions. Herein, we chronicle the case of a patient with metastatic non-small-cell lung cancer treated with pembrolizumab. After two cycles, he developed new-onset dyspnoea on exertion. Electrocardiogram showed idioventricular rhythm with diffuse ST-segment elevations. Echocardiography revealed severe biventricular cardiac dysfunction...
January 23, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29285415/preclinical-cancer-models-and-biomarkers-for-drug-development-new-technologies-and-emerging-tools
#17
Muthu Dhandapani, Aaron Goldman
Background and purpose: Predicting the efficacy of anticancer therapy is the holy grail of drug development and treatment selection in the clinic. To achieve this goal, scientists require pre-clinical models that can reliably screen anticancer agents with robust clinical correlation. However, there is increasing challenge to develop models that can accurately capture the diversity of the tumor ecosystem, and therefore reliably predict how tumors respond or resistant to treatment. Indeed, tumors are made up of a heterogeneous landscape comprising malignant cells, normal and abnormal stroma, immune cells, and dynamic microenvironment containing chemokines, cytokines and growth factors...
September 2017: Journal of Molecular Biomarkers & Diagnosis
https://www.readbyqxmd.com/read/29215634/expansion-of-patient-derived-circulating-tumor-cells-from-liquid-biopsies-using-a-ctc-microfluidic-culture-device
#18
Bee Luan Khoo, Gianluca Grenci, Ying Bena Lim, Soo Chin Lee, Jongyoon Han, Chwee Teck Lim
The development of personalized cancer therapy depends on a robust system to monitor the patient's individual response to anticancer treatment. Anticancer drug efficacy has been tested on circulating tumor cells (CTCs) derived from patient blood samples after ex vivo expansion into CTC clusters. Current attempts to culture these primary cancer cells focus on long-term maintenance under growth factor supplements into cell lines, which usually takes >6 months and results in a CTC expansion efficiency of <20%...
January 2018: Nature Protocols
https://www.readbyqxmd.com/read/29170055/immune-drug-discovery-from-venoms
#19
REVIEW
Rocio Jimenez, Maria P Ikonomopoulou, J Alejandro Lopez, John J Miles
This review catalogues recent advances in knowledge on venoms as standalone therapeutic agents or as blueprints for drug design, with an emphasis on venom-derived compounds that affects the immune system. We discuss venoms and venom-derived compounds that affect total immune cell numbers, immune cell proliferation, immune cell migration, immune cell phenotype and cytokine secretion. Identifying novel compounds that 'tune' the system, up-regulating the immune response during infectious disease and cancer and down-regulating the immune response during autoimmunity, will greatly expand the tool kit of human immunotherapeutics...
January 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28768924/a-novel-high-throughput-virtual-screening-protocol-to-discover-new-indoleamine-2-3-dioxygenase-1-ido1-inhibitors
#20
Haojie Xu, Yunlong Song, Qing Yang
Indoleamine 2,3-dioxygenase 1 (IDO1) plays an important role in the immune escape of tumors and has emerged as a promising target for cancer immunotherapy. Despite its potential in immuno-oncology, very few chemotypes have been reported to date. Here, we disigned a novel high throughput virtual screening (HTVS) cascade protocol, combining both pharmacophore modeling and molecular docking and it was employed to query commercially available compounds to identify novel inhibitors. Among the 23 compounds selected for the in vitro IDO1 inhibitory activity assay, five compounds exhibit greater than 20% inhibition at a test concentration of 10 µM, with two compounds having an IC50 value of 23...
2017: Chemical & Pharmaceutical Bulletin
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