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melanoma Stage 3

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https://www.readbyqxmd.com/read/28430130/timp1-promotes-cell-survival-by-activating-the-pdk1-signaling-pathway-in-melanoma
#1
Mariana Toricelli, Fabiana H M Melo, Aline Hunger, Daniela Zanatta, Bryan E Strauss, Miriam G Jasiulionis
High TIMP1 expression is associated with poor prognosis in melanoma, where it can bind to CD63 and β1 integrin, inducing PI3-kinase pathway and cell survival. Phosphatidylinositol (3,4,5)-trisphosphate (PIP3), generated under phosphatidylinositol-3-kinase (PI3K) activation, enables the recruitment and activation of protein kinase B (PKB/AKT) and phosphoinositide-dependent kinase 1 (PDK1) at the membrane, resulting in the phosphorylation of a host of other proteins. Using a melanoma progression model, we evaluated the impact of Timp1 and AKT silencing, as well as PI3K, PDK1, and protein kinase C (PKC) inhibitors on aggressiveness characteristics...
April 21, 2017: Cancers
https://www.readbyqxmd.com/read/28417343/adjuvant-therapy-for-melanoma
#2
REVIEW
Aya Agha, Ahmad A Tarhini
Systemic adjuvant therapy for surgically resected cutaneous melanoma that is at high risk for disease recurrence and death targets residual micrometastatic disease which is the source of future local or distant relapse. Interferon-alfa (IFNα) has been the most extensively studied in regimens that varied by dosage, route of administration, formulation, and duration of therapy. Most regimens have demonstrated improvements in relapse-free survival (RFS), while the regimen administered at high dosage (HDI) showed improvements in overall survival (OS) in two out of three RCTs...
May 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28396670/grass-carp-laboratory-of-genetics-and-physiology-2-serves-as-a-negative-regulator-in-retinoic-acid-inducible-gene-i-and-melanoma-differentiation-associated-gene-5-mediated-antiviral-signaling-in-resting-state-and-early-stage-of-grass-carp-reovirus-infection
#3
Youliang Rao, Quanyuan Wan, Chunrong Yang, Jianguo Su
Laboratory of genetics and physiology 2 (LGP2) is a key component of RIG-I-like receptors (RLRs). However, the lack of the caspase recruitment domains (CARDs) results in its controversial functional performance as a negative or positive regulator in antiviral responses. Especially, no sufficient evidence uncovers the functional mechanisms of LGP2 in RLR signaling pathways in teleost. Here, negative regulation mechanism of LGP2 in certain situations in retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5)-mediated antiviral responses was identified in Ctenopharyngodon idella kidney cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28396509/clinical-features-of-acquired-resistance-to-anti-pd-1-therapy-in-advanced-melanoma
#4
Daniel Y Wang, Zeynep Eroglu, Alpaslan Ozgun, Paul D Leger, Shilin Zhao, Fei Ye, Jason J Luke, Richard W Joseph, Rizwan Haq, Patrick A Ott, F Stephen Hodi, Jeffrey A Sosman, Douglas B Johnson, Elizabeth I Buchbinder
Anti-PD-1 therapy has improved clinical outcomes in advanced melanoma, but most patients experience intrinsic resistance. Responding patients can develop acquired resistance to anti-PD-1. We retrospectively reviewed 488 patients treated with anti-PD-1 from three academic centers and identified 36 patients with acquired resistance, defined as disease progression following objective response. The incidence, timing, disease sites, post-progression survival (PPS), and outcomes were evaluated descriptively. The acquired resistance cohort consisted of 67% with more than 1 feature of poor prognosis (stage M1c, elevated LDH, or brain metastasis), and 67% had previously received ipilimumab...
April 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28395880/treatment-of-metastatic-uveal-melanoma-with-adoptive-transfer-of-tumour-infiltrating-lymphocytes-a-single-centre-two-stage-single-arm-phase-2-study
#5
Smita S Chandran, Robert P T Somerville, James C Yang, Richard M Sherry, Christopher A Klebanoff, Stephanie L Goff, John R Wunderlich, David N Danforth, Daniel Zlott, Biman C Paria, Arvind C Sabesan, Abhishek K Srivastava, Liqiang Xi, Trinh H Pham, Mark Raffeld, Donald E White, Mary Ann Toomey, Steven A Rosenberg, Udai S Kammula
BACKGROUND: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma...
April 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28387914/dacarbazine-inhibits-proliferation-of-melanoma-femx-1-cells-by-up-regulating-expression-of-mirna-200
#6
Y-N Chen
OBJECTIVE: Melanoma is a highly aggressive tumour, and treatment efficacy depends on the stage of the tumour. Early stage cutaneous melanoma is efficiently treated by surgical excision. In contrast, late-stage melanoma requires chemotherapy with dacarbazine (DTIC). Unfortunately, advanced melanoma can often be resistant to DTIC. The mechanisms of anti-melanoma effects of DTIC are still poorly understood, which hinders development of more potent therapies. In this study, we examined the effects of DTIC on growth inhibition of FEMX-1 melanoma cell line, expression of apoptosis-related proteins, and expression of micro (mi)RNA-200 (miRNA-200a, miRNA-200b, miRNA-200c, and miRNA-141)...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28375785/conditional-survival-an-assessment-of-the-prognosis-of-patients-at-time-points-after-initial-diagnosis-and-treatment-of-locoregional-melanoma-metastasis
#7
Lauren E Haydu, Richard A Scolyer, Serigne Lo, Michael J Quinn, Robyn P M Saw, Kerwin F Shannon, Andrew J Spillane, Jonathan R Stretch, William H McCarthy, John F Thompson
Purpose Standard cancer staging and prognostic estimates are determined at the time of the patient's initial disease presentation. Conditional survival is an alternative, dynamic assessment from follow-up time points after the initial disease diagnosis and is based on the condition of survivorship. Estimates of conditional survival can provide critical prognostic information for patients and clinicians, guide subsequent cancer follow-up schedules, and influence decisions regarding treatments. The current study presents conditional survival estimates developed from a cohort of 4,540 patients diagnosed with stage III melanoma treated at a single institution...
April 4, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28370956/use-of-support-services-in-a-sample-of-patients-with-high-risk-primary-melanomas-in-urban-regional-and-rural-queensland
#8
Lena A von Schuckmann, Bernhard M Smithers, Kiarash Khosrotehrani, Vanessa L Beesley, Jolieke C van der Pols, Maria B Hughes, Adele C Green
OBJECTIVE: To characterise use of support services in patients diagnosed with high-risk primary melanoma by their location of residence. METHODS: In a cross-sectional study of 787 patients with histologically-confirmed clinical stage 1B-2 melanoma, we estimated odds ratios (ORs) using regression models to assess the association of support service use with residence in rural, regional or urban areas. We also evaluated demographic and clinical correlates of support service use...
March 28, 2017: Australian and New Zealand Journal of Public Health
https://www.readbyqxmd.com/read/28369774/temporal-trends-in-healthcare-utilization-following-primary-melanoma-diagnosis-among-medicare-beneficiaries
#9
J P Lott, Q Wang, L J Titus, T Onega, H D Nelson, M A Weinstock, J G Elmore, A N A Tosteson
BACKGROUND: Despite increasing melanoma incidence in the United States, little is known about the impact of primary melanoma diagnosis on healthcare utilization and changes in utilization over time. OBJECTIVE: To evaluate population-based temporal trends in healthcare utilization following primary melanoma diagnosis. METHODS: We conducted a before-after multiple time series study of Medicare beneficiaries ages ≥66 years with primary melanoma diagnoses between 2000 and 2009 using the Surveillance, Epidemiology, and End Results-Medicare database...
March 30, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28359784/ipilimumab-10-mg-kg-versus-ipilimumab-3-mg-kg-in-patients-with-unresectable-or-metastatic-melanoma-a-randomised-double-blind-multicentre-phase-3-trial
#10
Paolo A Ascierto, Michele Del Vecchio, Caroline Robert, Andrzej Mackiewicz, Vanna Chiarion-Sileni, Ana Arance, Céleste Lebbé, Lars Bastholt, Omid Hamid, Piotr Rutkowski, Catriona McNeil, Claus Garbe, Carmen Loquai, Brigitte Dreno, Luc Thomas, Jean-Jacques Grob, Gabriella Liszkay, Marta Nyakas, Ralf Gutzmer, Joanna Pikiel, Florent Grange, Christoph Hoeller, Virginia Ferraresi, Michael Smylie, Dirk Schadendorf, Laurent Mortier, Inge Marie Svane, Delphine Hennicken, Anila Qureshi, Michele Maio
BACKGROUND: A phase 2 trial suggested increased overall survival and increased incidence of treatment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma. We report a phase 3 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg. METHODS: This randomised, double-blind, multicentre, phase 3 trial was done in 87 centres in 21 countries worldwide. Patients with untreated or previously treated unresectable stage III or IV melanoma, without previous treatment with BRAF inhibitors or immune checkpoint inhibitors, were randomly assigned (1:1) with an interactive voice response system by the permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intravenous infusion for 90 min every 3 weeks for four doses...
March 27, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28356222/neutrophil-to-lymphocyte-ratio-is-associated-with-outcome-during-ipilimumab-treatment
#11
Michael R Cassidy, Rachel E Wolchok, Junting Zheng, Katherine S Panageas, Jedd D Wolchok, Daniel Coit, Michael A Postow, Charlotte Ariyan
BACKGROUND: Ipilimumab (IPI) and BRAF inhibitors (BRAFi) improve survival in melanoma, but not all patients will benefit and toxicity can be significant. Pretreatment neutrophil to lymphocyte ratio (NLR) has been associated with outcome in IPI-treated patients, but has not been studied during treatment or in BRAFi-treated patients. METHODS: Using a prospectively maintained database, patients with unresectable stage III or IV melanoma treated with IPI or a BRAFi (vemurafenib or dabrafenib as monotherapy) from 2006 to 2011 were identified...
March 24, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28351318/cytotoxicity-of-citral-against-melanoma-cells-the-involvement-of-oxidative-stress-generation-and-cell-growth-protein-reduction
#12
Larissa Juliani Sanches, Poliana Camila Marinello, Carolina Panis, Tatiane Renata Fagundes, José Andrés Morgado-Díaz, Julio Cesar Madureira de-Freitas-Junior, Rubens Cecchini, Alessandra Lourenço Cecchini, Rodrigo Cabral Luiz
Citral is a natural compound that has shown cytotoxic and antiproliferative effects on breast and hematopoietic cancer cells; however, there are few studies on melanoma cells. Oxidative stress is known to be involved in all stages of melanoma development and is able to modulate intracellular pathways related to cellular proliferation and death. In this study, we hypothesize that citral exerts its cytotoxic effect on melanoma cells by the modulation of cellular oxidative status and/or intracellular signaling...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28346662/intravenous-immunoglobulin-contributes-to-control-anti-melanoma-differentiation-associated-protein-5-mda5-antibody-associated-dermatomyositis-with-palmar-violaceous-macules-papules
#13
H Koguchi-Yoshioka, N Okiyama, K Iwamoto, Y Matsumura, T Ogawa, S Inoue, R Watanabe, M Fujimot
Autoantibodies to melanoma differentiation-associated protein 5 (MDA5) are associated with a subset of dermatomyositis (DM) patients who have rapidly progressive interstitial lung disease (RP-ILD) with poor prognosis. Intensive immunosuppressive therapy is initiated before irreversible lung damage can occur; however, there are few lines of evidence for the treatment of RP-ILD. Here, we report 3 cases of anti-MDA5 antibody-associated DM with RP-ILD in which the patients were treated with combined modality therapy including high-dose prednisolone, tacrolimus, intravenous cyclophosphamide, and immunoglobulins (IVIG)...
March 27, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28346283/nonvisualized-sentinel-lymph-nodes-on-lymphoscintigraphy-in-melanoma-predictive-factors-and-surgical-outcomes
#14
Darryl Schuitevoerder, Lisa Grinlington, Jeffrey Stevens, Robert Nance, Jeanine Fortino, John T Vetto
PURPOSE: Preoperative lymphoscintigraphy is the standard for the identification of sentinel lymph nodes (SLNs) in melanoma. The impact of negative scintigraphy [nonvisualization (NV) of the SLN] on surgical outcomes is inadequately reported in the literature. The objectives of this study were to determine the incidence, predictive factors, and surgical outcomes of NV in clinically node-negative melanoma patients. PATIENTS AND METHODS: A retrospective review of a prospective, Institutional Review Board approved, melanoma sentinel node database from January 2005 to August 2015 was performed...
May 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28345826/value-of-sentinel-lymph-node-sln-mapping-and-biopsy-using-combined-intracervical-radiotracers-and-blue-dye-injections-for-endometrial-cancer
#15
Farah Farzaneh, Atefeh Moridi, Zahra Azizmohammadi, Mojtaba Ansari J, Maryam Sadat Hosseini, Maliheh Arab, Tahereh Ashrafganjoei, Mina Mazaheri
Background: Lymphadenectomy, as part of the initial surgical staging of patients with endometrial carcinoma, remains a controversial topic in gynecologic oncology. Sentinel lymph node (SLN) mapping has become a well-accepted procedure for melanomas and breast cancer; a number of investigators have begun to explore the utility and accuracy of this technique with regard to endometrial cancer. Aim: This study was conducted to evaluate SLN mapping of early stage endometrial cancer with blue dye in conjunction with a radioactive tracer...
February 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28344807/ipilimumab-induced-thrombotic-thrombocytopenic-purpura-ttp
#16
Jeanelle King, Javier de la Cruz, Jose Lutzky
BACKGROUND: CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4) was the first immune checkpoint receptor clinically targeted for use in cancer treatment. It is expressed exclusively on T-cells where its primary role is to regulate the amplitude of the early stages of T-cell activation.1 Ipilimumab, a CTLA-4 blocking antibody, has been widely used for the treatment of patients with high risk and metastatic melanoma. Given its mechanism of action and consequent immune activation, the side effect profile of this drug greatly differs from that of standard cytotoxic chemotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28342215/efficacy-and-safety-of-nivolumab-in-japanese-patients-with-previously-untreated-advanced-melanoma-a-phase-ii-study
#17
Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami
Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation via overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has demonstrated promising anti-cancer activity in various cancers. We conducted a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28335082/reporting-of-mitotic-rate-in-cutaneous-melanoma-a-study-using-the-national-cancer-data-base
#18
Patrick D Lorimer, Emily C Benham, Kendall Walsh, Yimei Han, Meghan R Forster, Terry Sarantou, Richard L White, Joshua S Hill
BACKGROUND: The seventh edition of the American Joint Commission on Cancer staging manual (AJCC7, published 2009), updated thin cutaneous melanoma staging protocols with the incorporation of mitotic rate (MR). In these patients, higher MR is associated with decreased survival. This study utilizes the National Cancer Data Base (NCDB) to evaluate MR reporting since AJCC7. METHODS: The NCDB was queried for patients with primary cutaneous melanoma from 1998 to 2013...
March 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28334439/a-phase-2-trial-of-dasatinib-in-patients-with-locally-advanced-or-stage-iv-mucosal-acral-or-vulvovaginal-melanoma-a-trial-of-the-ecog-acrin-cancer-research-group-e2607
#19
Kevin Kalinsky, Sandra Lee, Krista M Rubin, Donald P Lawrence, Anthony J Iafrarte, Darell R Borger, Kim A Margolin, Mario M Leitao, Ahmad A Tarhini, Henry B Koon, Andrew L Pecora, Anthony J Jaslowski, Gary I Cohen, Timothy M Kuzel, Christopher D Lao, John M Kirkwood
BACKGROUND: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11(L576P) . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes. METHODS: Patients received 70 mg of oral dasatinib twice daily...
March 23, 2017: Cancer
https://www.readbyqxmd.com/read/28315947/impact-of-18-f-fdg-pet-ct-on-surgical-management-in-patients-with-advanced-melanoma-an-outcome-based-analysis
#20
Andrea Forschner, Susann-Cathrin Olthof, Brigitte Gückel, Peter Martus, Werner Vach, Christian la Fougère, Konstantin Nikolaou, Ulrike Keim, Thomas Kurt Eigentler, Claus Garbe, Christina Pfannenberg
PURPOSE: To evaluate the influence of (18)F-FDG-PET/CT on clinical decision making and outcome in advanced melanoma patients planned for radical metastasectomy. METHODS AND MATERIALS: A cohort of 333 patients with mainly stage III/IV melanoma having a PET/CT for clinical reasons was prospectively enrolled in our oncologic PET/CT registry between 2013 and 2015. Referring physicians completed questionnaires regarding their intended management for each patient before and after PET/CT...
March 18, 2017: European Journal of Nuclear Medicine and Molecular Imaging
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