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Drug resistance in melanoma

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https://www.readbyqxmd.com/read/27917404/the-emerging-role-of-cdk5-in-cancer
#1
Karine Pozo, James A Bibb
Cdk5 is an atypical cyclin-dependent kinase that is well characterized for its role in the central nervous system rather than in the cell cycle. However Cdk5 has been recently implicated in the development and progression of a variety of cancers including breast, lung, colon, pancreatic, melanoma, thyroid and brain tumors. This broad pro-tumorigenic role makes Cdk5 a promising drug target for the development of new cancer therapies. Here we review the contribution of Cdk5 to molecular mechanisms that confer upon tumors the ability to grow, proliferate and disseminate to secondary organs, as well as resistance to chemotherapies...
October 2016: Trends in Cancer
https://www.readbyqxmd.com/read/27903184/microinvasive-tumor-endoresection-in-combination-with-ocular-stereotactic-radiosurgery
#2
Oleg A Sinyavskiy, Roman L Troyanovsky, Pavel I Ivanov, Alexandr S Golovin, Andrey V Tibilov, Svetlana N Solonina, Anna M Astapenko, Irina S Zubatkina
OBJECTIVE The use of Gamma Knife radiosurgery (GKRS) as monotherapy in the treatment of uveal melanoma (UM) allows clinicians to achieve high local tumor control with low recurrence but does not prevent secondary enucleation due to glaucoma in cases of large tumors. The authors analyzed indications for tumor endoresection (ER), the time interval between irradiation and surgery, and the features and results of performing ER for UM after GKRS. METHODS Thirty-seven patients between 28 and 78 years of age (16 male and 11 female patients) with UM underwent GKRS with a dose of 70 to 80 Gy that was applied to the center of the tumor with complete immobilization of the eye during the procedure...
December 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27895032/molecular-pathways-receptor-ectodomain-shedding-in-treatment-resistance-and-monitoring-of-cancer
#3
Miles A Miller, Ryan J Sullivan, Douglas A Lauffenburger
Proteases known as sheddases cleave the extracellular domains of their substrates from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17 are among the most prominent sheddases, being widely expressed in many tissues, frequently over-expressed in cancer, and promiscuously cleaving diverse substrates. It is increasingly clear that the proteolytic shedding of transmembrane receptors impacts pathophysiology and drug response. Receptor substrates of sheddases include the cytokine receptors TNFR1 and IL-6R; the Notch receptors; type-I and -III TGF-β receptors; receptor tyrosine kinases (RTKs) such as HER2, HER4, and VEGFR2; and in particular, MET and TAM-family RTKs AXL and Mer (MerTK)...
November 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27889630/1-2-3-triazolyl-ester-of-ketorolac-a-click-chemistry-based-highly-potent-pak1-blocking-cancer-killer
#4
Binh Cao Quan Nguyen, Hideaki Takahashi, Yoshihiro Uto, M D Shahinozzaman, Shinkichi Tawata, Hiroshi Maruta
An old anti-inflammatory/analgesic drug called Toradol is a racemic form of Ketorolac (50% R-form and 50% S-form) that blocks the oncogenic RAC-PAK1-COX-2 (cyclooxygenase-2) signaling, through the direct inhibition of RAC by the R-form and of COX-2 by the S-form, eventually down-regulating the production of prostaglandins. However, due to its COOH moiety which is clearly repulsive to negatively-charged phospholipid-based plasma membrane, its cell-permeability is rather poor (the IC50 against the growth of human cancer cells such as A549 is around 13 μM)...
November 20, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27881234/denspm-overcame-bcl-2-mediated-resistance-against-paclitaxel-treatment-in-mcf-7-breast-cancer-cells-via-activating-polyamine-catabolic-machinery
#5
Zeynep Akyol, Ajda Çoker-Gürkan, Elif Damla Arisan, Pınar Obakan-Yerlikaya, Narçin Palavan-Ünsal
PURPOSE: The Bcl-2 mediated resistance is one of the most critical obstacle in cancer therapy. Conventional chemotherapeutics such as Paclitaxel, a commonly used in the treatment of metastatic breast cancer, is not sufficient to overcome Bcl-2 mediated drug resistance mechanism. Thus, combinational drug regimes are favored by researchers to overcome resistance phenotype against drugs. N1,N11-diethylnorspermine (DENSpm), a polyamine analogue, which is a promising drug candidate induced-cell cycle arrest and apoptosis in various cancer cells such as prostate, melanoma, colon and breast cancer cells via activated polyamine catabolism and reactive oxygen generation...
November 20, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27864056/lactoferrin-nanoparticle-mediated-targeted-delivery-of-5-fluorouracil-for-enhanced-therapeutic-efficacy
#6
Sonali Kumari, Anand K Kondapi
Malignant melanoma is an aggressive form of skin cancer with high mortality rates. Common treatments for malignant melanoma involve a combination of radiotherapy and chemotherapy with fluorouracil (5-FU). A major challenge with melanoma treatment is active resistance to chemotherapeutic drugs. Superior treatment outcome lies on balance involving optimum therapeutic doses and the side effects associated with dose escalation. The study aimed to efficiently entrap 5-FU in lactoferrin nanoparticles (LfNPs) in an attempt to enhance its therapeutic efficacy...
November 15, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27863726/-met-receptor-inhibition-hope-against-resistance-to-targeted-therapies
#7
REVIEW
Audrey Hochart, Pierre Leblond, Xuefen Le Bourhis, Samuel Meignan, David Tulasne
Overcoming the drug resistance remains a crucial issue in cancer treatment. For refractory patients, the use of MET receptor tyrosine kinase inhibitors seems to be hopeful. Indeed, important mechanisms underlying drug resistance argue for association of MET inhibitors with targeted therapies, both on first-line to prevent a primary resistance and on the second line to overcoming acquired resistance. Indeed, met gene amplification is the second most common alteration involved in acquired resistance to anti-epidermal growth factor receptor (EGFR) therapies in non-small cells lung cancer (NSCLC)...
November 15, 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27863476/is-immunohistochemistry-of-braf-v600e-useful-as-a-screening-tool-and-during-progression-disease-of-melanoma-patients
#8
Laura Schirosi, Sabino Strippoli, Francesca Gaudio, Giusi Graziano, Ondina Popescu, Michele Guida, Giovanni Simone, Anita Mangia
BACKGROUND: In clinical practice the gold standard method to assess BRAF status in patients with metastatic melanoma is based on molecular assays. Recently, a mutation-specific monoclonal antibody (VE1), which detects the BRAF V600E mutated protein, has been developed. With this study we aimed to confirm the clinical value of the VE1 Ventana® antibody, as today a univocal validated and accredited immunohistochemical procedure does not exist, to preliminary detect BRAF status in our routine diagnostic procedures...
November 18, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27852006/a-combination-of-photodynamic-therapy-and-chemotherapy-displays-a-differential-cytotoxic-effect-on-human-metastatic-melanoma-cells
#9
Fa Nsole Biteghe, L M Davids
BACKGROUND: Cutaneous melanoma represents the most lethal form of skin cancer and remains refractory to current therapies. Failure of treatment has been attributed to the over-expression of ABC transporters which efflux the drugs, below their cytotoxic threshold within cells. Therefore, this study set to investigate; the efficacy of a combinatorial approach comprising chemotherapy (Dacarbazine) and photodynamic therapy (PDT) to overcome resistance in pigmented and unpigmented metastatic melanoma and potentially identify resistant mechanisms...
November 8, 2016: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/27846884/future-perspectives-in-melanoma-research-meeting-report-from-the-melanoma-bridge-napoli-december-1st-4th-2015
#10
Paolo A Ascierto, Sanjiv Agarwala, Gerardo Botti, Alessandra Cesano, Gennaro Ciliberto, Michael A Davies, Sandra Demaria, Reinhard Dummer, Alexander M Eggermont, Soldano Ferrone, Yang Xin Fu, Thomas F Gajewski, Claus Garbe, Veronica Huber, Samir Khleif, Michael Krauthammer, Roger S Lo, Giuseppe Masucci, Giuseppe Palmieri, Michael Postow, Igor Puzanov, Ann Silk, Stefani Spranger, David F Stroncek, Ahmad Tarhini, Janis M Taube, Alessandro Testori, Ena Wang, Jennifer A Wargo, Cassian Yee, Hassane Zarour, Laurence Zitvogel, Bernard A Fox, Nicola Mozzillo, Francesco M Marincola, Magdalena Thurin
The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's disease...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27835901/mutational-activation-of-braf-confers-sensitivity-to-transforming-growth-factor-beta-inhibitors-in-human-cancer-cells
#11
Lindsay C Spender, G John Ferguson, Sijia Liu, Chao Cui, Maria Romina Girotti, Gary Sibbet, Ellen B Higgs, Morven K Shuttleworth, Tom Hamilton, Paul Lorigan, Michael Weller, David F Vincent, Owen J Sansom, Margaret Frame, Peter Ten Dijke, Richard Marais, Gareth J Inman
Recent data implicate elevated transforming growth factor-β (TGFβ) signalling in BRAF inhibitor drug-resistance mechanisms, but the potential for targeting TGFβ signalling in cases of advanced melanoma has not been investigated. We show that mutant BRAFV600E confers an intrinsic dependence on TGFβ/TGFβ receptor 1 (TGFBR1) signalling for clonogenicity of murine melanocytes. Pharmacological inhibition of the TGFBR1 blocked the clonogenicity of human mutant BRAF melanoma cells through SMAD4-independent inhibition of mitosis, and also inhibited metastasis in xenografted zebrafish...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27823888/novel-gold-i-complexes-with-5-phenyl-1-3-4-oxadiazole-2-thione-and-phosphine-as-potential-anticancer-and-antileishmanial-agents
#12
Joana Darc S Chaves, Luiza Guimarães Tunes, Chris Hebert de J Franco, Thiago Martins Francisco, Charlane Cimini Corrêa, Silvane M F Murta, Rubens Lima Monte-Neto, Heveline Silva, Ana Paula S Fontes, Mauro V de Almeida
The current anticancer and antileishmanial drug arsenal presents several limitations concerning their specificity, efficacy, costs and the emergence of drug-resistant cells lines, which encourages the urgent need to search for new alternatives. Inspired by the fact that gold(I)-based compounds are promising antitumoral and antileishmanial drug candidates, we synthesized novel gold(I) complexes containing phosphine and 5-phenyl-1,3,4-oxadiazole-2-thione and evaluated their anticancer and antileishmanial activities...
October 24, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27822406/pd-1-inhibition-and-treatment-of-advanced-melanoma-role-of-pembrolizumab
#13
REVIEW
Ali R Jazirehi, Alexandra Lim, Tam Dinh
Remarkable clinical responses have been seen in patients with metastatic melanoma with targeted therapy (BRAFi vemurafenib, MEKi) and with modern immune cell-based approaches such as TCR engineered adoptive cell transfer (ACT) and earlier experiences with high-dose IL-2. The proximal mediators of these immune therapies are tumor-reactive CTL. Various mechanisms of resistance to immune-mediated apoptotic signals have been described, including phenotypic changes, effector cell exhaustion, functional tolerance, deficiencies in Ag processing and presentation, and mutation or down-regulation of antigenic epitopes...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27801548/%C3%AE-c-in-%C3%AE-c-out-that-s-what-it-s-all-about
#14
Edward J Hartsough, Michael J Vido
No abstract text is available yet for this article.
November 1, 2016: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/27797970/molecular-pathways-maintaining-mapk-inhibitor-sensitivity-by-targeting-nonmutational-tolerance
#15
Michael P Smith, Claudia Wellbrock
Targeting hyperactive MAPK signaling has proven to be an effective treatment for a variety of different cancers. Responses to the BRAF inhibitors vemurafenib and dabrafenib and the MEK inhibitors trametinib and cobimetinib are, however, transient, and complete remission is rarely observed; rather, outgrowth of resistant clones within progressed tumors appears inevitable. These resistant tumors display great heterogeneity, which poses a major challenge to any salvage therapy. Recent focus has, therefore, been on the early dynamics of inhibitor response during tumor regression...
October 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27793895/vanillin-analogues-o-vanillin-and-2-4-6-trihydroxybenzaldehyde-inhibit-nf%C3%A4-b-activation-and-suppress-growth-of-a375-human-melanoma
#16
Annamária Marton, Erzsébet Kúsz, Csongor Kolozsi, Vilmos Tubak, Giuseppe Zagotto, Krisztina Buzás, Luigi Quintieri, Csaba Vizler
BACKGROUND/AIM: Constitutive activation of nuclear factor kappa-B (NFĸB) is a hallmark of various cancer types, including melanoma. Chemotherapy may further increase tumour NFĸB activity, a phenomenon that, in turn, exacerbates drug resistance. This study aimed at preliminary screening of a panel of aromatic aldehydes, including vanillin, for cytotoxicity and suppression of tumour cell NFĸB activity. MATERIALS AND METHODS: The cytotoxic and NFĸB-inhibitory effects of 10 aromatic aldehydes, including vanillin, were investigated in cultured A375 human melanoma cells...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27793883/immune-blockade-inhibition-in-breast-cancer
#17
REVIEW
Ioannis A Voutsadakis
Besides limited success in treatment of melanoma and renal cell carcinoma, immune treatments of cancer (cancer immunotherapy) had not until recently met the great expectations associated with them over the years. This failure appears now to be reversed with the introduction of checkpoint (immune blockade) inhibitors. Two receptor-ligand checkpoint inhibition pairs, the one based on the inhibition of inhibitory receptor cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and the other based on the inhibition of the programmed death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pair have entered the clinical arena...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27792834/biphasic-effects-of-propranolol-on-tumour-growth-in-b16f10-melanoma-bearing-mice
#18
Sonia Maccari, Maria Buoncervello, Andrea Rampin, Massimo Spada, Daniele Macchia, Luciana Giordani, Tonino Stati, Claudia Bearzi, Liviana Catalano, Roberto Rizzi, Lucia Gabriele, Giuseppe Marano
BACKGROUND AND PURPOSE: Propranolol is a vasoactive drug that shows antiangiogenic and antitumour activities in melanoma. However, it is unknown whether these activities are dose-dependent and whether there is a relationship between systemic vascular effects of propranolol and anti-melanoma activity. EXPERIMENTAL APPROACH: Effects of increasing doses of propranolol (10, 20, 30 and 40 mg·kg(-1) ·day(-1) ) on tumour growth were studied in B16F10 melanoma-bearing mice...
October 28, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27786591/suppression-of-b-raf-v600e-melanoma-cell-survival-by-targeting-mitochondria-using-triphenyl-phosphonium-conjugated-nitroxide-or-ubiquinone
#19
Seung-Keun Hong, Dmytro Starenki, Pui-Kei Wu, Jong-In Park
Most BRAF-mutated melanomas initially responsive to the FDA-approved inhibitors preferentially targeting B-Raf mutated in Val600 residue eventually relapse, requiring additional therapeutic modalities. Recent studies report the significance of metabolic reprograming in mitochondria for maintenance of BRAF-mutated melanomas and for development of their drug resistance to B-Raf inhibitors, providing a rationale for targeting mitochondria as a potential therapeutic strategy for melanoma. We therefore determined whether mitochondria-targeted metabolism-interfering agents can effectively suppress human B-Raf(V600E) melanoma cell lines and their dabrafenib/PLX4032-resistant progenies using mitochondria-targeted carboxy-proxyl (Mito-CP) and ubiquinone (Mito-Q)...
October 27, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27786239/simultaneous-delivery-of-paclitaxel-and-bcl-2-sirna-via-ph-sensitive-liposomal-nanocarrier-for-the-synergistic-treatment-of-melanoma
#20
Teegala Lakshminarayan Reddy, Koteswara Rao Garikapati, S Gopal Reddy, B V Subba Reddy, J S Yadav, Utpal Bhadra, Manika Pal Bhadra
pH-sensitive drug carriers that are sensitive to the acidic (pH = ~6.5) microenvironments of tumor tissues have been primarily used as effective drug/gene/siRNA/microRNA carriers for releasing their payloads to tumor cells/tissues. Resistance to various drugs has become a big hurdle in systemic chemotherapy in cancer. Therefore delivery of chemotherapeutic agents and siRNA's targeting anti apoptotic genes possess advantages to overcome the efflux pump mediated and anti apoptosis-related drug resistance...
October 27, 2016: Scientific Reports
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