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https://www.readbyqxmd.com/read/28239468/immunotherapy-associated-autoimmune-hemolytic-anemia
#1
Uqba Khan, Farman Ali, Muhammad Siddique Khurram, Awais Zaka, Tarik Hadid
BACKGROUND: Immunotherapy has been widely used in the treatment of several solid and hematologic malignancies. Checkpoint inhibitors have been the forefront of cancer immunotherapy in recent years. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) pathway are the prototypic checkpoint targets for immunotherapy. When combined, CTLA-4 and PD-1 checkpoint inhibitors work synergistically, but with increased probability of toxicity. The following case represents an unusual adverse effect of combined treatment with ipilimumab and nivolumab used for treatment of metastatic melanoma...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28239466/nivolumab-induced-myxedema-crisis
#2
Uqba Khan, Humaira Rizvi, Dahlia Sano, Jane Chiu, Tarik Hadid
BACKGROUND: Nivolumab is an anti-programmed cell death (anti-PD-1) monoclonal antibody that is approved by Food and Drug Administration for treatment of metastatic non-small cell lung cancer, metastatic melanoma, relapsed Hodgkin lymphoma and advanced renal cell cancer. We report a rare case of myxedema crisis induced by nivolumab in a patient with metastatic squamous cell carcinoma of lung. CASE PRESENTATION: Fifty three-year old woman with metastatic squamous cell carcinoma currently on treatment with nivolumab presented with diffuse facial and tongue swelling, slurred speech, depressed mentation, fatigue and weakness...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28238718/towards-therapeutic-advances-in-melanoma-management-an-overview
#3
REVIEW
Swarnendra Singh, Atif Zafar, Saman Khan, Imrana Naseem
Melanoma is one of the most aggressive types of skin cancer with rapidly increasing incidence rate. The disease is largely considered incurable and the patients diagnosed with metastatic melanoma have a survival of not more than five years. Despite of the recent advances in anti-melanoma chemo- and immunotherapies, the available drugs are relatively toxic and responsive to only a limited subset of lesions. Currently, topical pharmacotherapy is demonstrated as an effective approach for the treatment of various skin cancers...
February 23, 2017: Life Sciences
https://www.readbyqxmd.com/read/28238683/endothelial-notch1-activity-facilitates-metastasis
#4
Elfriede Wieland, Juan Rodriguez-Vita, Sven S Liebler, Carolin Mogler, Iris Moll, Stefanie E Herberich, Elisa Espinet, Esther Herpel, Amitai Menuchin, Jenny Chang-Claude, Michael Hoffmeister, Christoffer Gebhardt, Hermann Brenner, Andreas Trumpp, Christian W Siebel, Markus Hecker, Jochen Utikal, David Sprinzak, Andreas Fischer
Endothelial cells (ECs) provide angiocrine factors orchestrating tumor progression. Here, we show that activated Notch1 receptors (N1ICD) are frequently observed in ECs of human carcinomas and melanoma, and in ECs of the pre-metastatic niche in mice. EC N1ICD expression in melanoma correlated with shorter progression-free survival. Sustained N1ICD activity induced EC senescence, expression of chemokines and the adhesion molecule VCAM1. This promoted neutrophil infiltration, tumor cell (TC) adhesion to the endothelium, intravasation, lung colonization, and postsurgical metastasis...
February 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28238077/immunotolerance-as-a-mechanism-of-resistance-to-targeted-therapies-in-melanoma
#5
Mario Mandalà, Daniela Massi
The therapy of metastatic melanoma (MM) was radically changed by the introduction of inhibitors of BRAF, an oncogene mutated in ≈40-50% of patients. Oncogenic BRAF promotes an immune-compromised tumour microenvironment (TME). Inhibition of MAPK pathway signaling with BRAF (BRAFi) and MEK inhibitors (MEKi) attenuates immune escape and increases the melanoma immunogenicity through multiple mechanisms, including elevation of melanoma antigen expression and improved T cell infiltration and function. These changes sustain the TME for response to immunotherapy...
February 26, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28235882/fda-approval-summary-accelerated-approval-of-pembrolizumab-for-second-line-treatment-of-metastatic-melanoma
#6
Meredith K Chuk, Jennie T Chang, Marc R Theoret, Emmanuel Sampene, Kun He, Shawna L Weis, Whitney S Helms, Runyan Jin, Hongshan Li, Jingyu Yu, Hong Zhao, Liang Zhao, Mark Paciga, Deborah Schmiel, Rashmi Rawat, Patricia Keegan, Richard Pazdur
On September 4, 2014, FDA approved pembrolizumab (KEYTRUDA, Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating Phase 1 trial...
February 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28230715/a-multireferral-centre-retrospective-cohort-analysis-on-the-experience-in-treatment-of-metastatic-uveal-melanoma-and-utilization-of-sequential-liver-directed-treatment-and-immunotherapy
#7
Malinda Itchins, Paolo A Ascierto, Alexander M Menzies, Meredith Oatley, Serigne Lo, Dariush Douraghi-Zadeh, Timmothy Harrington, Richard Maher, Antonio M Grimaldi, Alexander Guminski
Metastatic uveal melanoma is a rare malignancy with a poor prognosis. To date, systemic therapy has been ineffective; however, there are few data on the benefits of anti-CTLA4 or anti-PD-1 antibodies in sequence with liver-directed therapy. A retrospective cohort analysis was carried out on 37 consecutive patients managed in a tertiary referral centre examining the safety and efficacy of treatment; patterns of care; and impact on survival. The sequential treatment with transarterial chemotherapy (TAC), systemic immunotherapy (IT) and systemic chemotherapy was reviewed...
February 22, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28230241/results-of-a-phase-ii-open-label-non-comparative-study-of-intralesional-pv-10-followed-by-radiotherapy-for-the-treatment-of-in-transit-or-metastatic-melanoma
#8
Matthew Foote, Tavis Read, Janine Thomas, Michael Wagels, Bryan Burmeister, B Mark Smithers
BACKGROUND: In-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction. METHODS: An open-label, single-arm phase II study was performed to assess the efficacy and safety of PV-10 followed by hypofractionated radiotherapy...
February 23, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28225857/malignant-melanoma-with-synchronous-thyroid-metastases-case-report-and-literature-review
#9
Maria Manuel Costa, Sandra Belo, João Capela-Costa, Jennifer Costa, Davide Carvalho
Thyroid metastases are rare in clinical practice. We describe the case of an 85-year-old woman who was referred to our department due to a multinodular goiter with compressive symptoms and subclinical hyperthyroidism. The patient was also undergoing evaluation for a polyp in her left nasal cavity, which was then diagnosed as a malignant melanoma of the nasal mucosa. A thoracoabdominal magnetic resonance imaging obtained for cancer staging revealed a > 50% tracheal obstruction caused by the goiter. The patient underwent simultaneous total thyroidectomy and melanoma excision...
February 16, 2017: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28225791/characterization-of-long-noncoding-rna-and-messenger-rna-signatures-in-melanoma-tumorigenesis-and-metastasis
#10
Siqi Wang, Wenliang Fan, Bing Wan, Mengqi Tu, Feng Jin, Fang Liu, Haibo Xu, Ping Han
The incidence of melanoma, the most aggressive and life-threatening form of skin cancer, has significantly risen over recent decades. Therefore, it is essential to identify the mechanisms that underlie melanoma tumorigenesis and metastasis and to explore novel and effective melanoma treatment strategies. Accumulating evidence s uggests that aberrantly expressed long noncoding RNAs (lncRNAs) have vital functions in multiple cancers. However, lncRNA functions in melanoma tumorigenesis and metastasis remain unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28224623/outcome-and-prognostic-factors-following-curative-intent-surgery-for-oral-tumours-in-dogs-234-cases-2004-to-2014
#11
B N Sarowitz, G J Davis, S Kim
OBJECTIVES: To describe the long-term outcomes and prognostic factors associated with curative-intent surgery for oral tumours in a large series of dogs. METHODS: Retrospective review of records for dogs with oral tumours treated with curative-intent surgery. Data collected included signalment, weight, surgical procedure, lymph node staging results, computed tomography results, tumour size, histopathology results including margin evaluation, complications, adjunctive therapies, local recurrence or metastasis, date and cause of death and owner satisfaction...
February 22, 2017: Journal of Small Animal Practice
https://www.readbyqxmd.com/read/28224364/the-impact-of-smoking-on-sentinel-node-metastasis-of-primary-cutaneous-melanoma
#12
Maris S Jones, Peter C Jones, Stacey L Stern, David Elashoff, Dave S B Hoon, John Thompson, Nicola Mozzillo, Omgo E Nieweg, Dirk Noyes, Harald J Hoekstra, Jonathan S Zager, Daniel F Roses, Alessandro Testori, Brendon J Coventry, Mark B Smithers, Robert Andtbacka, Doreen Agnese, Erwin Schultz, Eddy C Hsueh, Mark Kelley, Schlomo Schneebaum, Lisa Jacobs, Tawnya Bowles, Mohammed Kashani-Sabet, Douglas Johnson, Mark B Faries
BACKGROUND: Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy. METHODS: Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis...
February 21, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28224120/oncolytic-virotherapy-including-rigvir-and-standard-therapies-in-malignant-melanoma
#13
REVIEW
Hani M Babiker, Irbaz Bin Riaz, Muhammad Husnain, Mitesh J Borad
The treatment of metastatic melanoma has evolved from an era where interferon and chemotherapy were the mainstay of treatments to an era where immunotherapy has become the frontline. Ipilimumab (IgG1 CTLA-4 inhibitor), nivolumab (IgG4 PD-1 inhibitor), pembrolizumab (IgG4 PD-1 inhibitor) and nivolumab combined with ipilimumab have become first-line therapies in patients with metastatic melanoma. In addition, the high prevalence of BRAF mutations in melanoma has led to the discovery and approval of targeted molecules, such as vemurafenib (BRAF kinase inhibitor) and trametinib (MEK inhibitor), as they yielded improved responses and survival in malignant melanoma patients...
2017: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/28223438/dysregulated-gpcr-signaling-and-therapeutic-options-in-uveal-melanoma
#14
Vivian Chua, Dominic Lapadula, Clinita Randolph, Jeffrey L Benovic, Philip Wedegaertner, Andrew E Aplin
: Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage UM. In order to provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease...
February 21, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28222231/two-cases-of-anti-programmed-cell-death-1-associated-bullous-pemphigoid-like-disease-and-eruptive-keratoacanthomas-featuring-combined-histopathology
#15
Justin P Bandino, David M Perry, Christina E Clarke, Richard M Marchell, Dirk M Elston
Programmed cell death protein 1 (PD-1) inhibitors (pembrolizumab, nivolumab) are novel immunotherapies revolutionizing the management of advanced malignancy with an improved adverse effect profile, yet the immune-related side effects are still being characterized.(1,2) We report the unique concurrence of bullous pemphigoid-like disease (BP) with keratoacanthomas and squamous cell carcinomas in two patients receiving anti-PD-1 immunotherapy for metastatic melanoma. This article is protected by copyright. All rights reserved...
February 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28221865/cost-effectiveness-of-immune-checkpoint-inhibition-in-braf-wild-type-advanced-melanoma
#16
Christine G Kohn, Simon B Zeichner, Qiushi Chen, Alberto J Montero, Daniel A Goldstein, Christopher R Flowers
Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration-approved immune checkpoint inhibitors-pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)-demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma...
February 21, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28221211/a-rare-case-of-ck20-ck7-double-negative-merkel-cell-carcinoma
#17
Mary D Le, Luke H OʼSteen, David S Cassarino
The authors present a case of Merkel cell carcinoma (MCC) with unique immunohistochemical staining characteristics. A 57-year-old woman presented with a firm 0.3 cm tan papule on her left nasal-labial fold that was reportedly increasing in size and bleeding. She had a history of multiple head and neck actinic keratoses, papillary thyroid carcinoma, and a family history of an uncle with melanoma. The clinical differential diagnosis was "non-melanoma skin cancer." Histological examination showed a markedly atypical-appearing basaloid neoplasm, present mostly in the dermis, with focal pagetoid spread into the epidermis...
March 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28221189/a-retrospective-analysis-of-the-efficacy-of-pembrolizumab-in-melanoma-patients-with-brain-metastasis
#18
Ibiayi Dagogo-Jack, Michael Lanfranchi, Justin F Gainor, Anita Giobbie-Hurder, Donald P Lawrence, Alice T Shaw, Ryan J Sullivan
A total of 50% of patients with melanoma will develop brain metastasis (BM). Pembrolizumab was approved for treatment of metastatic melanoma on the basis of significant systemic antitumor activity. Because of low enrollment of patients with BM in pembrolizumab trials, efficacy against melanoma BM remains unknown. We reviewed records of 89 consecutive patients with melanoma treated with pembrolizumab at our institution between May 1, 2014 and October 31, 2015 to determine the time to progression. Thirty-six (40%) patients had BM before pembrolizumab...
February 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28218738/adipogenic-niches-for-melanoma-cell-colonization-and-growth-in-bone-marrow
#19
Juan Wang, Guang-Liang Chen, Shan Cao, Ming-Chun Zhao, Yong-Qing Liu, Xiao-Xiang Chen, Cheng Qian
Bone marrow (BM) adipocytes are abundant in BM and may be involved in the process of bone metastasis. However, their behaviors in metastatic BM niches during bone metastasis have not been fully explored. In this study, intracardiac transplantation of B16-F10 melanoma cells into immunocompetent C57BL/6 mice was performed. Tibial marrow sections were stained with hematoxylin and eosin, Masson's trichrome, tartrate-resistant acid phosphatase, and fatty acid-binding protein 4 (FABP4) and analyzed using a histomorphometric system...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28217853/use-of-cytological-samples-of-metastatic-melanoma-for-ancillary-studies
#20
H M Ko, M A Saieg, G da Cunha Santos, S Kamel-Reid, S L Boerner, W R Geddie
OBJECTIVE: Fine needle aspiration (FNA) is widely used in the diagnosis of metastatic melanoma, both at initial presentation and in the setting of recurrent disease. The purpose of this study was to evaluate the performance of confirmatory immunohistochemistry (IHC) and molecular analysis of the BRAF mutation in cytological preparations of metastatic melanoma. METHODS: A 2-year retrospective review of pathology reports was performed on cytological samples of metastatic melanoma at the University Health Network (Toronto, Canada) and the Santa Casa Medical School (Sao Paulo, Brazil)...
February 20, 2017: Cytopathology: Official Journal of the British Society for Clinical Cytology
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