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https://www.readbyqxmd.com/read/29348439/dual-suppression-of-inner-and-outer-mitochondrial-membrane-functions-augments-apoptotic-responses-to-oncogenic-mapk-inhibition
#1
Madhavika N Serasinghe, Jesse D Gelles, Kent Li, Lauren Zhao, Franco Abbate, Marie Syku, Jarvier N Mohammed, Brateil Badal, Cuahutlehuanitzin A Rangel, Kyle L Hoehn, Julide Tok Celebi, Jerry Edward Chipuk
Mitogen-activated protein kinase (MAPK) pathway inhibitors show promise in treating melanoma, but are unsuccessful in achieving long-term remission. Concordant with clinical data, BRAFV600E melanoma cells eliminate glycolysis upon inhibition of BRAFV600E or MEK with the targeted therapies Vemurafenib or Trametinib, respectively. Consequently, exposure to these therapies reprograms cellular metabolism to increase mitochondrial respiration and restrain cell death commitment. As the inner mitochondrial membrane (IMM) is sub-organellar site of oxidative phosphorylation (OXPHOS), and the outer mitochondrial membrane (OMM) is the major site of anti-apoptotic BCL-2 protein function, we hypothesized that suppressing these critical mitochondrial membrane functions would be a rational approach to maximize the pro-apoptotic effect of MAPK inhibition...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29344481/choroidal-melanoma-mimicker-a-case-of-metastatic-clear-cell-renal-cell-carcinoma
#2
Chris B Komanski, Shaina M Rubino, Jacob C Meyer, Craig M Greven
Choroidal melanoma is the most common primary intraocular malignancy, yet metastatic disease remains the most common malignancy of the eye. Differentiating these entities is essential as treatment, systemic associations, and prognosis vary dramatically between the two. Established diagnostic criteria are accurate for the diagnosis of uveal melanoma. Yet, metastatic disease may be misdiagnosed as a uveal melanoma in rare cases. We report a case of metastatic clear-cell renal cell carcinoma masquerading as uveal melanoma...
November 2017: Ocular Oncology and Pathology
https://www.readbyqxmd.com/read/29331749/paediatric-dysgerminoma-results-of-three-consecutive-french-germ-cell-tumours-clinical-studies-tgm-85-90-95-with-late-effects-study
#3
Gwénaëlle Duhil de Bénazé, Hélène Pacquement, Cécile Faure-Conter, Catherine Patte, Daniel Orbach, Nadège Corradini, Claire Berger, Hélène Sudour-Bonnange, Cécile Vérité, Hélène Martelli, Brice Fresneau
METHODS: French patients (≤18years) treated for dysgerminoma between 1985 and 2005 in TGM-85, 90, 95 protocols were included. Treatment was based on primary unilateral oophorectomy followed by prophylactic lymph node irradiation (1985-1998) or a wait-and-see strategy (1998-2005) for localised completely resected tumours (pS1) or by platinum-based chemotherapy for advanced diseases. RESULTS: Forty-eight patients (median age 12.8 years) were included. Six patients had gonadal dysgenesis...
January 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29283791/durable-complete-response-after-discontinuation-of-pembrolizumab-in-patients-with-metastatic-melanoma
#4
Caroline Robert, Antoni Ribas, Omid Hamid, Adil Daud, Jedd D Wolchok, Anthony M Joshua, Wen-Jen Hwu, Jeffrey S Weber, Tara C Gangadhar, Richard W Joseph, Roxana Dronca, Amita Patnaik, Hassane Zarour, Richard Kefford, Peter Hersey, Jin Zhang, James Anderson, Scott J Diede, Scot Ebbinghaus, F Stephen Hodi
Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( ClinicalTrials.gov identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab...
December 28, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29277453/sarcoidosis-post-anti-pd-1-therapy-mimicking-relapse-of-metastatic-melanoma-in-a-patient-undergoing-complete-remission
#5
N Yatim, C Mateus, P Charles
Novel treatments of metastatic melanoma include the usage of checkpoint inhibitors such as anti-cytotoxic-T-lymphocyte-associated antigen (CTLA-4) or anti-programmed death-1 (PD-1) antibodies, which are immunomodulatory antibodies that enhance the immune response against tumors. While they have substantially improved the prognosis for patients, these therapies are associated with a large spectrum of immune-related adverse effects (irAEs). We report a patient developing pulmonary and cutaneous sarcoidosis after pembrolizumab therapy while complete regression of stage IV melanoma was perceived...
December 22, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29260113/successful-long-term-treatment-of-paraneoplastic-optic-neuropathy-with-mycophenolate-mofetil-prednisone-and-plasmapheresis
#6
Alia Durrani, Rohan J Shah, Stephen J Kim
Purpose: To report long-term follow-up of a case of paraneoplastic optic neuropathy (PON) successfully treated with combination therapy. Observations: We present a confirmed case of PON from cutaneous melanoma with nearly six years of meticulous follow-up in which vision was preserved and disease remission was successfully induced with combination mycophenolate mofetil, prednisone, and plasmapheresis therapy. Conclusions and importance: Treatment of PON and long-term follow-up are not well described in the literature...
December 2017: American Journal of Ophthalmology Case Reports
https://www.readbyqxmd.com/read/29230811/whole-exome-sequencing-of-oral-mucosal-melanoma-reveals-mutational-profile-and-therapeutic-targets
#7
Jiong Lyu, Zhijian Song, Jianhua Chen, Matthew J Shepard, Hao Song, Guoxin Ren, Zhiqiang Li, Wei Guo, Zhengping Zhuang, Yongyong Shi
Oral mucosal melanoma (OMM) is rare and aggressive subtype of melanoma with little known about its pathogenesis carcinogenesis. We therefore performed whole-exome sequencing (WES) on 19 matched OMM tumor/normal pairs in order to gain insight on potential genetic drivers of tumor formation. For the first time we describe the comprehensive mutational profile of OMM. Our data suggests that the genetic background of OMM differs from those of other melanoma subtypes. We identified recurrent mutations involving KIT, POLE,PTPRD, PTCHD2 and DMXL2...
December 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29225988/effective-administration-of-rituximab-in-anti-mda5-antibody-positive-dermatomyositis-with-rapidly-progressive-interstitial-lung-disease-and-refractory-cutaneous-involvement-a-case-report-and-literature-review
#8
Yuka Ogawa, Dai Kishida, Yasuhiro Shimojima, Koichi Hayashi, Yoshiki Sekijima
We describe the case of a 48-year-old man with dermatomyositis (DM) who demonstrated rapidly progressive interstitial lung disease (RP-ILD) and refractory cutaneous involvement together with high levels of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5-Ab). Even after combination immunosuppressive therapy including a corticosteroid, cyclosporine A, and intravenous cyclophosphamide, his respiratory insufficiency and cutaneous involvement progressively worsened. However, the administration of rituximab (RTX) resulted in clinical remission as well as a visible reduction in anti-MDA5-Ab levels, suggesting that RTX could be a useful remedy in cases refractory to conventional immunosuppressive agents, especially those of RP-ILD related to anti-MDA5-Ab-positive DM...
2017: Case Reports in Rheumatology
https://www.readbyqxmd.com/read/29207115/current-status-and-future-prospects-of-the-strategy-of-combining-car%C3%A2-t-with-pd%C3%A2-1-blockade-for-antitumor-therapy-review
#9
Jinjing Xu, Qing Zhang, Kang Tian, Haiyu Wang, Hong Yin, Junnian Zheng
The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor‑modified T‑cell immunotherapy (CAR‑T) and programmed cell death protein-1 blockade (PD‑1 blockade). CAR‑T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients...
February 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29177265/metastatic-melanoma-response-to-combination-therapy-with-ipilimumab-and-vemurafenib
#10
Christos Sachpekidis, Jessica C Hassel, Antonia Dimitrakopoulou-Strauss
Combination therapies for the treatment of metastatic melanoma are a matter of debate nowadays. We report on a stage IV metastatic melanoma patient with the BRAF V600 mutation and a large tumor burden initially treated with two cycles of ipilimumab. Due to dramatic disease progression, demonstrated on interim 18F-FDG PET/CT, vemurafenib was added in the patient's therapeutical scheme. After completion of the concurrent ipilimumab and vemurafenib administration, a third 18F-FDG PET/CT showed an impressive metabolic remission of the metastatic disease, reflecting the potential role of the modality in treatment response evaluation of melanoma patients receiving combination therapies...
November 27, 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29145317/complete-remission-and-long-term-survival-of-a-patient-with-melanoma-metastases-treated-with-high-dose-fever-inducing-viscum-album-extract-a-case-report
#11
Paul G Werthmann, Alexander Hintze, Gunver S Kienle
INTRODUCTION: Metastatic malignant cutaneous melanoma (MCM)-a highly immunogenic cancer-typically has a poor prognosis. Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects. CASE PRESENTATION: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment. VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and intralesionally...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29138980/cd28-neg-t-lymphocytes-of-a-melanoma-patient-harbor-tumor-immunity-and-a-high-frequency-of-germline-encoded-and-public-tcrs
#12
Hisayoshi Hashimoto, Marco Sterk, Karin Schilbach
Increased numbers of CD8(+)CD28(neg.) T cells have been detected in the peripheral blood of patients with several types of malignancies. However, the role of these cells in anticancer immunity are not yet clear and CD8(+)CD28(neg.) T cells are a controversially discussed subpopulation reported both as immunosuppressive and cytotoxic. In this study, we examined the T cell receptor (TCR) repertoire and complementarity-determining region 3 sequences of CD28(neg.) T cells in a melanoma patient with recurrent disease who achieved long-term disease-free status...
November 14, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29124281/absolute-number-of-new-lesions-on-18-f-fdg-pet-ct-is-more-predictive-of-clinical-response-than-suv-changes-in-metastatic-melanoma-patients-receiving-ipilimumab
#13
Hoda Anwar, Christos Sachpekidis, Julia Winkler, Annette Kopp-Schneider, Uwe Haberkorn, Jessica C Hassel, Antonia Dimitrakopoulou-Strauss
PURPOSE: Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of (18)F-FDG PET/CT, using the patients' clinical response as reference. METHODS: The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent (18)F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged (18)F-FDG-avid lesions, as well as on the SUV changes after therapy...
November 10, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29114741/factors-associated-with-clinical-remission-of-skin-disease-in-dermatomyositis
#14
Paige W Wolstencroft, Lorinda Chung, Shufeng Li, Livia Casciola-Rosen, David F Fiorentino
Importance: Cutaneous disease represents a significant burden for patients with dermatomyositis. However, quantitative estimates of the probability of skin disease remission and clinical factors associated with skin outcomes are lacking. Objective: To characterize cutaneous disease course in adult patients with dermatomyositis. Design, Setting, and Participants: Prospective cohort study conducted at a dermatology clinic at a tertiary academic referral center...
November 7, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/29114389/adoptive-cell-therapy-with-cd4-t-helper-1-cells-and-cd8-cytotoxic-t-cells-enhances-complete-rejection-of-an-established-tumour-leading-to-generation-of-endogenous-memory-responses-to-non-targeted-tumour-epitopes
#15
Kunyu Li, Braeden Donaldson, Vivienne Young, Vernon Ward, Christopher Jackson, Margaret Baird, Sarah Young
The results of adoptive T-cell therapies (ACTs) are very encouraging and show clinical evidence that ACT can provide a cure for patients with metastatic disease. However, various response rates and long-term cancer remission have been observed in different ACT trials. The types of T cells, prior treatment with chemotherapy and co-administration of other immune-target therapies have been found to influence the efficacy of ACT. In this study, we investigate the ability of ACT using CD4(+) T helper 1 (Th1) cells and CD8(+) cytotoxic T lymphocytes (CTLs) to reject the growth of established B16-ovalbumin (OVA) melanoma...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29110637/constitutional-mutation-in-cdkn2a-is-associated-with-long-term-survivorship-in-multiple-myeloma-a-case-report
#16
Vallari Shah, Kevin D Boyd, Richard S Houlston, Martin F Kaiser
BACKGROUND: Multiple Myeloma is a cancer of plasma cells associated with significantly reduced survival. Long term survivorship from myeloma is very rare and despite advances in its treatment the disease is generally considered incurable. We report a patient diagnosed with myeloma carrying a germline mutation of a tumour suppressor gene who has effectively been cured. CASE PRESENTATION: A 36-year-old woman was diagnosed with IgG lambda myeloma in 1985. She was treated with melphalan chemotherapy followed by high-dose melphalan and autologous stem cell rescue and since remained in complete remission despite not having received any additional therapy...
November 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29094091/ipilimumab-in-pretreated-patients-with-advanced-malignant-melanoma-results-of-the-south-african-expanded-access-program
#17
Bernardo L Rapoport, Daniel A Vorobiof, Lydia M Dreosti, Adam Nosworthy, Georgina McAdam, Johan P Jordaan, Helen Miller-Jansön, Margreet de Necker, Janetta C de Beer, Hennie Duvenhage
Purpose: The primary objective of this study was to evaluate 1- and 2-year survival rates and durable remissions in pretreated patients with advanced (unresectable or metastatic) malignant melanoma treated with ipilimumab in a South African expanded-access program (SA-EAP). Patients and Methods: This multicenter, retrospective study obtained data from pretreated patients with advanced malignant melanoma who were eligible for the ipilimumab SA-EAP. Ipilimumab was administered at a dose of 3 mg/kg intravenously every 3 weeks for four cycles to adults with advanced melanoma for whom at least one line of treatment for metastatic disease had failed...
October 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/29052782/clinical-and-immunologic-evaluation-of-three-metastatic-melanoma-patients-treated-with-autologous-melanoma-reactive-tcr-transduced-t-cells
#18
Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29041990/piceatannol-induced-apoptosis-through-up-regulation-of-microrna-181a-in-melanoma-cells
#19
Maotao Du, Zhong Zhang, Tao Gao
BACKGROUND: Melanoma took top position among the lethal cancers and, despite there have been some great attempts made to increase the natural life of patients with metastatic disease, long-lasting and complete remissions are few. Piceatannol, owns the similar function as resveratrol, has been defined as an anti-cancer agent playing important role in inhibition of proliferation, migration and metastasis in various cancer. Thus, we aim to investigate the anti-cancer effect and mechanisms of piceatannol in melanoma cells...
October 17, 2017: Biological Research
https://www.readbyqxmd.com/read/29033936/coinhibitory-receptor-expression-and-immune-checkpoint-blockade-maintaining-a-balance-in-cd8-t-cell-responses-to-chronic-viral-infections-and-cancer
#20
REVIEW
Isobel S Okoye, Michael Houghton, Lorne Tyrrell, Khaled Barakat, Shokrollah Elahi
In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called "immune checkpoints" by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer...
2017: Frontiers in Immunology
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