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Anti cancer peptide

Robert P Carty, Bo Lin, Daniel Fridman, Matthew R Pincus
We have computed the low energy conformations of the negative regulatory domain of p53, residues 374-388 using Empirical Conformational Energies of Peptides Program including solvation and computed the statistical weights of distinct conformational states. We find that there are two high probability conformations, one an α-helix from Lys 374-Lys 381, followed by another helical structure involving Lys 382-Glu 388 (statistical weight of 0.48) and an all-α-helix for the entire sequence (statistical weight of 0...
October 17, 2018: Protein Journal
Loredana Cappellacci, Diego R Perinelli, Filippo Maggi, Mario Grifantini, Riccardo Petrelli
Histone deacetylase (HDAC) inhibitors are a relatively new class of anti-cancer agents that play important roles in epigenetic or non-epigenetic regulation, inducing death, apoptosis, and cell cycle arrest in cancer cells. Recently, their use has been clinically validated in cancer patients resulting in the approval by the FDA of four HDAC inhibitors, vorinostat, romidepsin, belinostat and panobinostat, used for the treatment of cutaneous/peripheral T-cell lymphoma and multiple myeloma. Many more HDAC inhibitors are in different stages of clinical development for the treatment of hematological malignancies as well as solid tumors...
October 16, 2018: Current Medicinal Chemistry
Philipp Probst, Marco Stringhini, Danilo Ritz, Tim Fugmann, Dario Neri
PURPOSE: There is a growing interest in the use of tumor antigens for therapeutic vaccination strategies. Unfortunately, in most cases, the use of peptide vaccines in patients does not mediate shrinkage of solid tumor masses. EXPERIMENTAL DESIGN: Here, we studied the opportunity to boost peptide vaccination with F8-TNF, an antibody fusion protein that selectively delivers TNF to the tumor extracellular matrix. AH1, a model antigen to investigate CD8+ T cell immunity in BALB/c mice, was used as vaccine...
October 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Bahareh Moazen, Amir Zarrinhaghighi, Foroogh Nejatollahi
Background: CD90, a membrane-associated glycoprotein is a marker used to identify mesenchymal stem cells (MSCs). Recent studies have introduced CD90, which induces tumorigenic activity, as a cancer stem cell (CSC) marker in various malignancies. Blocking CD90 activity with anti-CD90 monoclonal antibodies enhanced anti-tumor effects. To date, highly specific antibody single-chain variable fragments (scFvs) have been isolated against various targets and showed promising results in cancer immunotherapy...
October 2018: Reports of Biochemistry & Molecular Biology
Jane Harper, Katherine J Adams, Giovanna Bossi, Debbie E Wright, Andrea R Stacey, Nicole Bedke, Ruth Martinez-Hague, Dan Blat, Laure Humbert, Hazel Buchanan, Gabrielle S Le Provost, Zoe Donnellan, Ricardo J Carreira, Samantha J Paston, Luise U Weigand, Martina Canestraro, Joseph P Sanderson, Sophie Botta Gordon-Smith, Kate L Lowe, Karolina A Rygiel, Alex S Powlesland, Annelise Vuidepot, Namir J Hassan, Brian J Cameron, Bent K Jakobsen, Joseph Dukes
Robust preclinical testing is essential to predict clinical safety and efficacy and provide data to determine safe dose for first-in-man studies. There are a growing number of examples where the preclinical development of drugs failed to adequately predict clinical adverse events in part due to their assessment with inappropriate preclinical models. Preclinical investigations of T cell receptor (TCR)-based immunotherapies prove particularly challenging as these biologics are human-specific and thus the conventional testing in animal models is inadequate...
2018: PloS One
Yuki Fujiwara, Yi Sun, Robert J Torphy, Jiadai He, Katsuhiko Yanaga, Barish H Edil, Richard D Schulick, Yuwen Zhu
Thalidomide-like drugs have been approved for the treatment of human multiple myeloma (MM), with their direct antitumor effects and immunomodulatory functions well documented. However, the exact molecular mechanisms that govern these effects remain unclear. Here we demonstrate that pomalidomide (POM) promotes immune response by inhibiting expression of PD-L1. POM inhibited PD-L1 expression on tumor cells to promote cytotoxic T lymphocyte (CTL) activity in vitro and suppressed PD-L1 upregulation on antigen-presenting cells (APC) to prevent peptide-induced T cell tolerance...
October 12, 2018: Cancer Research
Shan Tang, Na Zhang, Yue Zhou, Wilian A Cortopassi, Matthew P Jacobson, Li-Jiao Zhao, Ru-Gang Zhong
Protein kinase CK2 is considered as an emerging target in cancer therapy, and recent efforts have been made to develop its ATP-competitive inhibitors, but achieving selectivity with respect to related kinases remains challenging because of the highly conserved ATP-binding pocket of kinases. Non-ATP competitive inhibitors might solve this challenge; one such strategy is to identify compounds that target the CK2α/CK2β interface as CK2 holoenzyme antagonists. Here we improved the binding affinity to CK2α and cell-based anti-cancer activity of a CK2β-derived cyclic peptide (Pc) by combining structure-based computational design with experimental evaluation...
October 11, 2018: Molecular Informatics
O Montvida, J B Green, J Atherton, S K Paul
AIMS: In people with metformin-treated diabetes, to evaluate the risk of acute pancreatitis, pancreatic cancer and other diseases of the pancreas post second-line anti-hyperglycaemic agent initiation. METHODS: People with Type 2 diabetes diagnosed after 2004 who received metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i, n = 50 095), glucagon-like peptide-1 receptor agonist (GLP-1RA, n = 12 654), sulfonylurea (n = 110 747), thiazolidinedione (n = 17 597) or insulin (n = 34 805) for at least 3 months were identified in the US Centricity Electronic Medical Records...
October 10, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Huifang Zhao, Yanqiu Li, Jie Wang, Miao Cheng, Zheng Zhao, Huinian Zhang, Congwei Wang, Junying Wang, Yan Qiao, Junzhong Wang
It is challenging to realize a dual-ion mode of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for detecting small molecules. Herein, graphene coated by porous amorphous carbon with P-O surface group and codoped by phosphorus and nitrogen (O-P,N-C/G) was synthesized from an aerogel formed by phytic acid, polyaniline, and electrochemically exfoliated graphene. The carbon material synthesized has the feature of large surface area (583 m2 /g), good electrical conductivity, strong UV absorption, heteroatom doping, and surface functional groups suitable for laser- induced desorption/ionization...
October 17, 2018: ACS Applied Materials & Interfaces
Francesco Carrozza, Matteo Santoni, Francesco Piva, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Rodolfo Montironi, Nicola Battelli, Stefano Tamberi
Telomerase activity and telomere length are essential for the pathogenesis of several human diseases, including genitourinary tumors. Telomerase constitutes a complex system that includes human telomerase reverse transcriptase (hTERT), human telomerase RNA component (hTR) and telomerase associated protein 1 (TEP1), which are overexpressed in tumor cells compared to normal cells and are involved in the carcinogenesis and progression of renal cell carcinoma (RCC), bladder (BC) and prostate cancer (PCa). In addition, telomerase degraded peptide fragments expressed on the surface of tumor cells lead to their recognition by immune cells...
November 2018: Critical Reviews in Oncology/hematology
Huanli Sun, Yangyang Dong, Jan Feijen, Zhiyuan Zhong
The advancement of tissue and cell-specific drug delivery systems is a key to precision cancer therapy. Peptides, with easy synthesis, low immunogenicity and biological functions closely mimicking or surpassing natural proteins, have been actively engineered and explored to provide nanomedicines with the ability to overcome various extracellular and intracellular delivery barriers ranging from phagocytic clearance in the circulation, low tumor penetration, poor cancer cell selectivity, inferior cell penetration, to endosomal entrapment as well as poor blood brain barrier permeation for brain cancer therapy...
October 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Oussema Khamessi, Hazem Ben Mabrouk, Houcemeddine Othman, Rym ElFessi-Magouri, Michel De Waard, Mejdoub Hafedh, Naziha Marrakchi, Najet Srairi-Abid, Riadh Kharrat
Scorpion peptides are well known for their pharmaceutical potential on different targets. These include mainly the ion channels which were found to be highly expressed in many diseases, including cancer, auto-immune pathologies and Alzheimer. So far, however, the disintegrin activity had only been characterized for snake venom molecules. Herein, we present the first short peptide, purified from the venom of Buthus occitanus tunetanus, (termed RK) able to inhibit the cell adhesion of Glioblastoma, Melanoma and Rat pheochromocytoma to different extracellular matrix (ECM) receptors...
October 1, 2018: International Journal of Biological Macromolecules
T G Moreira, L S Horta, A C Gomes-Santos, R P Oliveira, N M G P Queiroz, D Mangani, B Daniel, A T Vieira, S Liu, A M Rodrigues, D A Gomes, G Gabriely, E Ferreira, H L Weiner, R M Rezende, L Nagy, A M C Faria
Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages...
October 2, 2018: Mucosal Immunology
Can Liu, Huiqing Xie, Jingang Yu, Xiaoqing Chen, Shijie Tang, Lichun Sun, Xiang Chen, Defei Peng, Xiangyan Zhang, Jianda Zhou
Background: Nowadays, the combination of microRNA (miR) is attracting increased attention in clinical cancer trials. However, the clinical use of miR is highly limited because of certain properties such as instability, low-specificity distribution, and metabolic toxicity. Methods: In order to improve the anti-tumor efficacy and reduce the side effects of miR in treating melanoma, a combination of graphene oxide (GO), chitosan (CS), and a cellular penetrating peptide, MPG, was prepared with solid dispersion method in this research...
2018: Drug Design, Development and Therapy
Patrick J Kennedy, Flavia Sousa, Daniel Ferreira, Carla Pereira, Marika Nestor, Carla Oliveira, Pedro L Granja, Bruno Sarmento
Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs displayed spherical morphology around 300 nm and were negatively charged...
September 27, 2018: Acta Biomaterialia
Erminia Massarelli, William William, Faye Johnson, Merrill Kies, Renata Ferrarotto, Ming Guo, Lei Feng, J Jack Lee, Hai Tran, Young Uk Kim, Cara Haymaker, Chantale Bernatchez, Michael Curran, Tomas Zecchini Barrese, Jaime Rodriguez Canales, Ignacio Wistuba, Lerong Li, Jing Wang, Sjoerd H van der Burg, Cornelis J Melief, Bonnie Glisson
Importance: In recurrent human papilloma virus (HPV)-driven cancer, immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies produces tumor regression in only a minority of patients. Therapeutic HPV vaccines have produced strong immune responses to HPV-16, but vaccination alone has been ineffective for invasive cancer. Objective: To determine whether the efficacy of nivolumab, an anti-PD-1 immune checkpoint antibody, is amplified through treatment with ISA 101, a synthetic long-peptide HPV-16 vaccine inducing HPV-specific T cells, in patients with incurable HPV-16-positive cancer...
September 27, 2018: JAMA Oncology
Peng Lyu, Lilin Ge, Rui Ma, Ran Wei, Cian M McCrudden, Tianbao Chen, Chris Shaw, Hang Fai Kwok
Amphibian venom-derived peptides have high potential in the field of anticancer drug discovery. We have isolated a novel Bowman-Birk proteinase inhibitor (BBI)-type peptide from the skin secretion of Pelophylax esculentus (PE) named PE-BBI, and evaluated its bio-functions and anti-cancer activity in vitro. PE-BBI is a heptadecapeptide with C-terminal amidation. The mRNA sequence and primary structure of PE-BBI were identified using RT-PCR and LC/MS, respectively. A trypsin inhibitory assay was used to characterize the serine proteinase inhibitory activity of synthetic PE-BBI...
September 28, 2018: Scientific Reports
Rachel M Guerra, Gregory H Bird, Edward P Harvey, Neekesh V Dharia, Kyle J Korshavn, Michelle S Prew, Kimberly Stegmaier, Loren D Walensky
Cancer cells overexpress a diversity of anti-apoptotic BCL-2 family proteins, such as BCL-2, MCL-1, and BFL-1/A1, to enforce cellular immortality. Thus, intensive drug development efforts have focused on targeting this class of oncogenic proteins to overcome treatment resistance. Whereas a selective BCL-2 inhibitor has been FDA approved and several small molecule inhibitors of MCL-1 have recently entered phase I clinical testing, BFL-1/A1 remains undrugged. Here, we developed a series of stapled peptide design principles to engineer a functionally selective and cell-permeable BFL-1/A1 inhibitor that is specifically cytotoxic to BFL-1/A1-dependent human cancer cells...
September 25, 2018: Cell Reports
Lin Gong, Ying Zheng, Shanling Liu, Zhilan Peng
Objective: To investigate the regulatory role of fibronectin (FN) in the formation of multicellular aggregate (MCA) in ovarian cancer SKOV3 and OVCAR-3 cells and integrin expression. Methods: The dynamic formation of MCA in SKOV3 and OVCAR-3 was determined using the liquid overlay technique in the presence or absence of FN, anti-FN, RGD peptide, control RGE. The expression of α3β1, α4β1 and α5β1 integrin in monolayer cells, MCA and FN-treated MCA were determined by flow cytometry and quantitative RT-PCR...
September 26, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Geyan Wu, Libing Song, Jinrong Zhu, Yameng Hu, Lixue Cao, Zhanyao Tan, Shuxia Zhang, Ziwen Li, Jun Li
Blocking genotoxic stress-induced NF-κB activation would substantially enhance the anti-cancer efficiency of genotoxic chemotherapy. Unlike the well-established classical NF-κB pathway, the genotoxic agents-induced 'nuclear-to-cytoplasmic' NF-κB pathway is initiated from the nucleus and transferred to the cytoplasm. However, the mechanism linking nuclear DNA damage signalling to cytoplasmic IKK activation remains unclear. Here we report that TRIM37, a novel E3 ligase, plays a vital role in genotoxic activation of NF-κB via monoubiquitination of NEMO at K309 in the nucleus, consequently resulting in nuclear export of NEMO and IKK/NF-κB activation...
September 25, 2018: Cancer Research
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