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Relationship between the agonist activity of synthetic ligands of TRAIL-R2 and their cell surface binding modes.

Relationship between the agonist activity of synthetic ligands of TRAIL-R2 and their cell surface binding modes. Oncotarget. 2018 Mar 20;9(21):15566-15578 Authors: Chekkat N, Lombardo CM, Seguin C, Lechner MC, Dufour F, Nominé Y, De Giorgi M, Frisch B, Micheau O, Guichard G, Altschuh D, Fournel S Abstract Tumor Necrosis Factor Receptor Apoptosis Inducing Ligand (TRAIL) appears as an interesting candidate for targeted cancer therapy as it induces apoptosis in cancer cells without toxicity to normal cells. TRAIL elicits apoptosis through agonist death receptor TRAIL-R1 and TRAIL-R2 engagement. Nevertheless, recombinant soluble TRAIL and monoclonal antibodies against these receptors demonstrated insufficient efficacy in clinical trials. This may be explained by the cell-type dependency of the apoptotic response, itself influenced by the effect on ligand binding mode of factors such as the level of receptor oligomerization or glycosylation. To investigate the relation between binding mode and signaling, we used previously described synthetic divalent and monovalent peptides specific for TRAIL-R2. We measured their pro-apoptotic activity on three cancer cell lines sensitive to rhTRAIL induced-apoptosis and monitored their cell-surface binding kinetics. The two divalent peptides bound with strong affinity to TRAIL-R2 expressed on B lymphoma BJAB cells and induced a high degree of apoptosis. By contrast, the same peptides bound weakly to TRAIL-R2 expresse...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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Suppression of the NF‑κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute. Mol Med Rep. 2018 Feb 16;: Authors: Liu H, Li G, Zhang B, Sun D, Wu J, Chen F, Kong F, Luan Y, Jiang W, Wang R, Xue X Abstract Colorectal cancer (CRC) is a major cause of mortality and morbidity. Chronic inflammation is closely associated with the development, progression and prognosis of the majority of intestinal malignancies. In recent years, targeting the nuclear factor (NF)‑κB signaling pathway for CRC therapy has become an attractive strategy. Riccardin D, a...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Publication date: 25 March 2018 Source:International Journal of Pharmaceutics, Volume 539, Issues 1–2 Author(s): Arivalagan Pugazhendhi, Thomas Nesakumar Jebakumar Immanuel Edison, Indira Karuppusamy, Brindhadevi Kathirvel Cancer is an abnormal condition leading to uncontrolled cell division which causes damage to the body tissues. Around 100 types of cancer are studied so far namely breast cancer, lung cancer, skin cancer, prostate cancer, colon cancer and lymphoma. Major cancer therapies include chemotherapy, surgery and radiations but their major drawbacks are non-specifically distributed antitumor agents, uneven...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research
Immunotherapy is a cut above chemotherapy and radiotherapy: at its best, it is significantly more effective and significantly less harmful to the patient. It has still required years, a great deal of funding, and many failures for those best approaches to arise. Nonetheless, the report here is a cheering example for the sizable fraction of us expected to suffer cancer at some point in the years ahead if the condition is not soon brought under medical control. This immunotherapy appears highly effective, and just importantly, adaptable to many types of cancer. This potential for broad application is the most important aspec...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
BACKGROUNDThe improving efficacy of cancer treatment has resulted in an increasing array of treatment‐related symptoms and associated burdens imposed on individuals undergoing aggressive treatment of their disease. Often, clinical trials compare therapies that have different types, and severities, of adverse effects. Whether rated by clinicians or patients themselves, it can be difficult to know which side effect profile is more disruptive or bothersome to patients. A simple summary index of bother can help to adjudicate the variability in adverse effects across treatments being compared with each other. METHODSAcross 4 ...
Source: Cancer - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research
Authors: Yu H, Xu W, Gong F, Chi B, Chen J, Zhou L Abstract MicroRNA-155 (miR-155) is a well-studied miR and acts as an oncomiR in numerous cancer types. However, the biological functions of miR-155 in colon cancer as well as its target genes have remained to be fully elucidated. In order to investigate the biological functions of miR-155, MTT, colony formation and wound healing assays, cell cycle analysis and detection of apoptosis were performed. The results demonstrated that miR-155 promoted the proliferation of colon cancer cells and enhanced their colony formation capacity, promoted their cell cycle progressio...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
WebMD wasn't a research option when Ivy Brown was diagnosed with Hodgkin's lymphoma in 1974, so her mother looked up her 12-year-old daughter's condition the old-fashioned way, in a hardcover medical volume. "It just said 'fatal,'" Brown explained. Having moved the family to London a month earlier, Brown's parents were still trying to liaise with her pediatrician in the U.S. "My father told me recently that he was sleeping with the phone on his stomach because of the time change," she said. "They were as scared as you can be when you have a child who you think you might lose," Brown explained....
Source: Science - The Huffington Post - Category: Science Source Type: news
A new experimental treatment has achieved what chemotherapy and bone marrow transplants have failed to do: put chronic, relapsing blood cancers into remission. What's more, it uses the body's own natural defense system to attack these cancerous growths.  The treatment involves T cells, a type of immune cell that works as your body's own personal S.W.A.T. team to detect, surround, and destroy foreign invaders like bacteria or viruses. Historically, cancerous cells have grown too fast for T cells to mount an effective defense, and they can also trick T cells into thinking that they’re a healthy part of t...
Source: Science - The Huffington Post - Category: Science Source Type: news
Conclusions: Cellular response to b-AP15 mediated proteasome inhibition is distinct from clinically used bortezomib; therefore b-AP15 has a potential clinical use, in particular for treatment of malignancies resistant to other proteasome inhibitors.Citation Format: Magdalena Mazurkiewicz, Slavica Brnjic, Mårten Fryknäs, Chao Sun, Xiaonan Zhang, Rolf Larsson, Pádraig D'Arcy, Stig Linder. The anticancer activity of the DUB inhibitor b-AP15 is associated with accumulation of proteasome bound ubiquitin and oxidative stress. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association fo...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Experimental and Molecular Therapeutics Source Type: research
Conclusions: Our results demonstrate that treatment with LTX-315 in combination with low-dose CY results in a synergistic antitumor effect in vivo. Thus, local treatment with the immunogenic cell death inducer LTX-315 combined with systemic chemotherapy may represent a promising combination strategy in future cancer therapy.Citation Format: Ketil André Camilio, Liv-Marie Eike, Øystein Rekdal, Baldur Sveinbjornsson. Anticancer effects obtained against A20 lymphomas following treatment with LTX-315 (Oncopore®) in combination with low-dose cyclophosphamide. [abstract]. In: Proceedings of the 106th Annual Mee...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Clinical Research (Excluding Clinical Trials) Source Type: research
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