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https://www.readbyqxmd.com/read/28917578/emerging-biomarkers-for-cancer-immunotherapy-in-melanoma
#1
REVIEW
Margaret L Axelrod, Douglas B Johnson, Justin M Balko
The treatment and prognosis of metastatic melanoma has changed substantially since the advent of novel immune checkpoint inhibitors (ICI), agents that enhance the anti-tumor immune response. Despite the success of these agents, clinically actionable biomarkers to aid patient and regimen selection are lacking. Herein, we summarize and review the evidence for candidate biomarkers of response to ICIs in melanoma. Many of these candidates can be examined as parts of a known molecular pathway of immune response, while others are clinical in nature...
September 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28916919/laparoscopic-liver-resection-for-metastatic-melanoma
#2
Davit L Aghayan, Airazat M Kazaryan, Åsmund Avdem Fretland, Mushegh A Sahakyan, Bård I Røsok, Bjørn Atle Bjørnbeth, Bjørn Edwin
BACKGROUND: Stage IV metastatic melanoma carries a poor prognosis. In the case of melanoma liver metastasis (MLM), surgical resection may improve survival and represents a therapeutic option, with varying levels of success. Laparoscopic liver resection (LLR) for metastatic melanoma is poorly studied. The aim of this study was to analyze the outcomes of LLR in patients with MLM. MATERIALS AND METHODS: Between April 2000 and August 2013, 11 (1 cutaneous, 9 ocular and 1 unknown primary) patients underwent LLR for MLM at Oslo University Hospital-Rikshospitalet and 13 procedures in total were carried out...
September 15, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28916526/monoclonal-antibodies-directed-against-cadherin-rgd-exhibit-therapeutic-activity-against-melanoma-and-colorectal-cancer-metastasis
#3
Ruben A Bartolomé, Carmen Aizpurua, Marta Jaén, Sofia Torres, Eva Calviño, Juan I Imbaud, J Ignacio Casal
PURPOSE: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). EXPERIMENTAL DESIGN: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28916225/stereotactic-radiosurgery-of-early-melanoma-brain-metastases-after-initiation-of-anti-ctl-4-treatment-is-associated-with-improved-intracranial-control
#4
Yi An, Wen Jiang, Betty Y S Kim, Jack M Qian, Chad Tang, Penny Fang, Jennifer Logan, Neil M D'Souza, Lauren E Haydu, Xin A Wang, Kenneth R Hess, Harriet Kluger, Isabella C Glitza, Anita Mahajan, James W Welsh, Steven H Lin, James B Yu, Michael A Davies, Patrick Hwu, Erik P Sulman, Paul D Brown, Veronica L S Chiang, Jing Li
BACKGROUND: Numerous studies suggest that radiation can boost antitumor immune response by stimulating release of tumor-specific antigens. However, the optimal timing between radiotherapy and immune checkpoint blockade to achieve potentially synergistic benefits is unclear. MATERIAL AND METHODS: Multi-institutional retrospective analysis was conducted of ninety-nine metastatic melanoma patients from 2007 to 2014 treated with ipilimumab who later received stereotactic radiosurgery (SRS) for new brain metastases that developed after starting immunotherapy...
September 12, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28915798/vemurafenib-plus-cobimetinib-in-unresectable-stage-iiic-or-stage-iv-melanoma-response-monitoring-and-resistance-prediction-with-positron-emission-tomography-and-tumor-characteristics-reposit-study-protocol-of-a-phase-ii-open-label-multicenter-study
#5
Bernies van der Hiel, John B A G Haanen, Marcel P M Stokkel, Daniel S Peeper, Connie R Jimenez, Jos H Beijnen, Bart A van de Wiel, Ronald Boellaard, Alfons J M van den Eertwegh
BACKGROUND: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with (18)F-Fluorodeoxyglucose ((18)F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of (18)F-FDG uptake within 2 weeks following treatment...
September 15, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28912983/metastatic-melanoma-of-the-gallbladder-in-an-asymptomatic-patient
#6
Asad Khan, Sejal Patel, Daniel J Zaccarini, Mary McGrath
Malignant Melanoma (MM) is among the most dangerous malignancies with some of the least known survival rates. Melanoma most commonly metastasizes to regional lymph nodes, the lungs, and brain. Metastatic disease of the gallbladder (GB) is exceptionally rare making it difficult to diagnose. The fact that typically patients do not present until they are symptomatic-only after widespread metastatic disease has already occurred-is further complicating the diagnosis of MM of the GB. For this reason, MM of the GB is rarely discovered in living patients...
2017: Case Reports in Gastrointestinal Medicine
https://www.readbyqxmd.com/read/28912145/dynamic-18-f-fdg-pet-lymphography-for-in-vivo-identification-of-lymph-node-metastases-in-murine-melanoma
#7
Hannah H Lockau, Volker Neuschmelting, Anuja Ogirala, Antoni Vilaseca, Jan Grimm
Objective: Positron Lymphography using (18)F-FDG followed by Cerenkov guided resection of lymph nodes in healthy mice has previously been introduced by our group. Our aim in this study was to further assess the technique`s potential beyond merely localizing sentinel lymph nodes. We now aimed to evaluate the potential of Positron Lymphography to characterize the nodes with respect to their tumor status on order to identify metastatic lymph nodes. We explored if metastatic nodes could be distinguished from normal nodes via dynamic (18)F-FDG-lymphography, in order to then be resected under Cerenkov imaging guidance...
September 14, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28910160/a-novel-approach-to-the-differentiation-of-intrabulbar-tumors-in-color-doppler-imaging
#8
Monika Modrzejewska, Marta P Wiącek
AIM OF THE STUDY: The similarity of many benign intrabulbar lesions to a malignant tumor requires detailed differential diagnostics. However, none of the known methods can be used as the only one to determine the type of lesions. The aim of this study was to determine color Doppler imaging (CDI) markers characteristic of choroidal melanoma and metastatic intrabulbar tumors, increasing the diagnostic value and giving a new insight into the use of this method. MATERIALS AND METHODS: CDI was performed in 44 patients with malignant tumors and in 49 patients with benign tumors...
September 14, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28904226/tumor-lymphangiogenesis-promotes-t-cell-infiltration-and-potentiates-immunotherapy-in-melanoma
#9
Manuel Fankhauser, Maria A S Broggi, Lambert Potin, Natacha Bordry, Laura Jeanbart, Amanda W Lund, Elodie Da Costa, Sylvie Hauert, Marcela Rincon-Restrepo, Christopher Tremblay, Elena Cabello, Krisztian Homicsko, Olivier Michielin, Douglas Hanahan, Daniel E Speiser, Melody A Swartz
In melanoma, vascular endothelial growth factor-C (VEGF-C) expression and consequent lymphangiogenesis correlate with metastasis and poor prognosis. VEGF-C also promotes tumor immunosuppression, suggesting that lymphangiogenesis inhibitors may be clinically useful in combination with immunotherapy. We addressed this concept in mouse melanoma models with VEGF receptor-3 (VEGFR-3)-blocking antibodies and unexpectedly found that VEGF-C signaling enhanced rather than suppressed the response to immunotherapy. We further found that this effect was mediated by VEGF-C-induced CCL21 and tumor infiltration of naïve T cells before immunotherapy because CCR7 blockade reversed the potentiating effects of VEGF-C...
September 13, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28900082/-inhibition-of-invasive-properties-of-murine-melanoma-by-bovine-pancreatic-dnase-i-in-vitro-and-in-vivo
#10
L A Alexeeva, O A Patutina, A V Sen'kova, M A Zenkova, N L Mironova
After a long pause, the accumulation of data on the involvement of tumor-specific DNA and extracellular DNA in metastasis has again placed enzymes with deoxyribonuclease activity in the focus of the search for antitumor and antimetastatic drugs. In this work, the ability of bovine pancreatic DNase I to reduce the invasive potential of B16 melanoma has been investigated in vitro and in vivo. It was found that DNase I had a cytotoxic effect on B16 melanoma cells (IC50 ≈ 10^(4) U/mL). At the same time, significantly lower doses of DNase I (10^(2)-10^(3) U/mL) inhibited the migratory activity of melanoma cells in vitro, causing a decrease in the distance of cell front migration and in the area of scratch healing 48 h after the enzyme addition, as well as reducing the rate of cell migration...
July 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28898550/rare-yet-relevant-tumor-cells-a-new-twist-to-melanoma-cell-plasticity
#11
Daniel Zingg, Lukas Sommer
Metastatic cancers, including malignant cutaneous melanoma, have remained an incurable disease for most patients. Major advancements in the fields of targeted therapies and immunotherapies have brought some breakthrough to successfully eradicate metastatic melanoma. However, a large fraction of patients suffer from intrinsic or acquired resistances to these therapeutics and eventually display progressing disease (Hugo et al., 2015; Sharma et al., 2017; Sun et al., 2014). This article is protected by copyright...
September 12, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28895944/genome-wide-in-vivo-mouse-screen-data-from-studies-to-assess-host-regulation-of-metastatic-colonisation
#12
Louise van der Weyden, Natasha A Karp, Agnieszka Swiatkowska, David J Adams, Anneliese O Speak
The process of metastasis is a multi-stage cascade with prior studies suggesting that the colonisation of the secondary site is the rate limiting step. This process involves contributions from the tumour cells and also non-tumour intrinsic factors such as the stroma and the haematopoietic system. In this study, we present data from screening 810 genetically-modified mouse lines with the experimental metastasis assay where intravenous delivery of murine metastatic melanoma B16-F10 cells was used to assess the formation of pulmonary metastasic foci...
September 12, 2017: Scientific Data
https://www.readbyqxmd.com/read/28894934/tumor-infiltrating-lymphocytes-in-lymph-node-metastases-of-stage-iii-melanoma-correspond-to-response-and-survival-in-nine-patients-treated-with-ipilimumab-at-the-time-of-stage-iv-disease
#13
Stefan Diem, Omar Hasan Ali, Christoph J Ackermann, David Bomze, Viktor H Koelzer, Wolfram Jochum, Daniel E Speiser, Kirsten D Mertz, Lukas Flatz
Prognosis of metastatic melanoma improved with the development of checkpoint inhibitors. The role of tumor infiltrating lymphocytes (TILs) in lymph node metastases of stage III melanoma remains unclear. We retrospectively characterized TILs in primary melanomas and matched lymph node metastases (stage III melanoma) of patients treated with the checkpoint inhibitor ipilimumab. Tumor infiltrating lymphocytes were characterized for CD3, CD4, and CD8 expressions by immunohistochemistry. 4/9 patients (44%) responded to treatment with ipilimumab (1 complete and 2 partial remissions, 1 stable disease)...
September 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28894827/the-genetic-landscape-of-programmed-death-ligand-1-pd-l1-alterations-in-head-and-neck-cancer
#14
Thomas E Heineman, Adam Widman, Edward C Kuan, Maie St John
OBJECTIVES: Nivolumab has recently been shown in the phase III clinical trial CheckMate-141 to have superior survival rates compared to the current standard of care chemotherapy for recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC). Nivolumab targets the immune inhibitory receptor programmed cell death 1 (PD-1). Programmed cell death ligand 1 (PD-L1) genomics have been poorly characterized in the context of HNSCC, including expression levels of PD-L1 in individual tumors as well as related up or down-regulated genes that might function as co-targets...
June 2017: Laryngoscope Investigative Otolaryngology
https://www.readbyqxmd.com/read/28893027/unusual-skin-carcinomas-induced-by-braf-inhibitor-for-metastatic-melanoma-a-case-report
#15
Stefano Cavalieri, Lorenza Di Guardo, Mara Cossa, Carolina Cimminiello, Michele Del Vecchio
The most frequently reported skin tumours during treatment with targeted therapies for BRAF (B type Rapidly Accelerated Fibrosarcoma kinase) mutated metastatic melanoma are squamous cell carcinomas (SCCs). Basal cell carcinomas (BCCs) have been described in such setting, but no cases of multiple and recurring tumours have been reported so far. A patient with a history of chronic sun exposure and more than 10 BCCs removed since 1998 started treatment with vemurafenib for BRAF mutated metastatic melanoma. Therapy was complicated by sporadic episodes of atrial fibrillation and by the development of recurrent, multiple and diffuse BCCs...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28891408/adjuvant-dabrafenib-plus-trametinib-in-stage-iii-braf-mutated-melanoma
#16
Georgina V Long, Axel Hauschild, Mario Santinami, Victoria Atkinson, Mario Mandalà, Vanna Chiarion-Sileni, James Larkin, Marta Nyakas, Caroline Dutriaux, Andrew Haydon, Caroline Robert, Laurent Mortier, Jacob Schachter, Dirk Schadendorf, Thierry Lesimple, Ruth Plummer, Ran Ji, Pingkuan Zhang, Bijoyesh Mookerjee, Jeff Legos, Richard Kefford, Reinhard Dummer, John M Kirkwood
Background Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations. Methods In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months...
September 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28891339/immunotherapy-in-managing-metastatic-melanoma-which-treatment-when
#17
Teresa Amaral, Francisco Meraz-Torres, Claus Garbe
Ten to fifteen percent of melanoma patients develop distant or unresectable metastasis requiring systemic treatment. Around 45% of the patients diagnosed with metastatic cutaneous melanoma harbor a BRAFV600 mutation and derive benefit from combined targeted therapy with MAPK pathway inhibitors. These offer a rapid response that translates into improvement of symptoms and increased quality of life. However, resistance often develops with subsequent progressive disease. Immunotherapy with checkpoint inhibitors may be offered to BRAF-mutated and wild-type patients and is associated with longer and durable responses that can continue over years...
September 9, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28890854/quantitative-comparison-of-the-spreading-and-invasion-of-radial-growth-phase-and-metastatic-melanoma-cells-in-a-three-dimensional-human-skin-equivalent-model
#18
Parvathi Haridas, Jacqui A McGovern, Sean D L McElwain, Matthew J Simpson
BACKGROUND: Standard two-dimensional (2D) cell migration assays do not provide information about vertical invasion processes, which are critical for melanoma progression. We provide information about three-dimensional (3D) melanoma cell migration, proliferation and invasion in a 3D melanoma skin equivalent (MSE) model. In particular, we pay careful attention to compare the structure of the tissues in the MSE with similarly-prepared 3D human skin equivalent (HSE) models. The HSE model is identically prepared to the MSE model except that melanoma cells are omitted...
2017: PeerJ
https://www.readbyqxmd.com/read/28890195/gk-1-peptide-reduces-tumor-growth-decreases-metastatic-burden-and-increases-survival-in-a-murine-breast-cancer-model
#19
D Torres-García, A Pérez-Torres, K Manoutcharian, U Orbe, R Servín-Blanco, G Fragoso, E Sciutto
GK-1 is a parasite-derived peptide adjuvant of 18 amino acid-length that enhances T-cell function and increases survival in B16-F10 melanoma tumor-bearing mice. This study was designed to evaluate in vivo the antitumor efficacy of GK-1 on 4T1 mouse mammary carcinoma. BALB/c mice with palpable primary tumors were weekly intravenously injected three times with saline solution or three different concentrations (10, 50, or 100μg per mouse) of GK-1. GK-1 significantly increased lifespan (p<0.0001) and reduced the primary tumor weight (p=0...
September 7, 2017: Vaccine
https://www.readbyqxmd.com/read/28888850/ultrasound-based-follow-up-does-not-increase-survival-in-early-stage-melanoma-patients-a-comparative-cohort-study
#20
S Ribero, S Podlipnik, S Osella-Abate, E Sportoletti-Baduel, E Manubens, A Barreiro, V Caliendo, M Chavez-Bourgeois, C Carrera, P Cassoni, J Malvehy, M T Fierro, S Puig
INTRODUCTION: Different protocols have been used to follow up melanoma patients in stage I-II. However, there is no consensus on the complementary tests that should be requested or the appropriate intervals between visits. Our aim is to compare an ultrasound-based follow-up with a clinical follow-up. PATIENTS AND METHODS: Analysis of two prospectively collected cohorts of melanoma patients in stage IB-IIA from two tertiary referral centres in Barcelona (clinical-based follow-up [C-FU]) and Turin (ultrasound-based follow-up [US-FU])...
September 7, 2017: European Journal of Cancer
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