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https://www.readbyqxmd.com/read/29673969/rgd-cadherins-and-%C3%AE-2%C3%AE-1-integrin-in-cancer-metastasis-a-dangerous-liaison
#1
REVIEW
J Ignacio Casal, Rubén A Bartolomé
We propose a new cadherin family classification comprising epithelial cadherins (cadherin 17 [CDH17], cadherin 16, VE-cadherin, cadherin 6 and cadherin 20) containing RGD motifs within their sequences. Expression of some RGD cadherins is associated with aggressive forms of cancer during the late stages of metastasis, and CDH17 and VE-cadherin have emerged as critical actors in cancer metastasis. After binding to α2β1 integrin, these cadherins promote integrin β1 activation, and thereby cell adhesion, invasion and proliferation, in liver and lung metastasis...
April 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29662054/characterising-the-phenotypic-evolution-of-circulating-tumour-cells-during-treatment
#2
Simon Chang-Hao Tsao, Jing Wang, Yuling Wang, Andreas Behren, Jonathan Cebon, Matt Trau
Real-time monitoring of cancer cells' phenotypic evolution during therapy can provide vital tumour biology information for treatment management. Circulating tumour cell (CTC) analysis has emerged as a useful monitoring tool, but its routine usage is restricted by either limited multiplexing capability or sensitivity. Here, we demonstrate the use of antibody-conjugated and Raman reporter-coated gold nanoparticles for simultaneous labelling and monitoring of multiple CTC surface markers (named as "cell signature"), without the need for isolating individual CTCs...
April 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29648671/effect-of-age-on-melanoma-risk-prognosis-and-treatment-response
#3
Simone Ribero, Luigia Stefania Stucci, Elena Marra, Riccardo Marconcini, Francesco Spagnolo, Laura Orgiano, Virginia Picasso, Paola Queirolo, Guiseppe Palmieri, Pietro Quaglino, Veronique Bataille
As for all types of cancer, the incidence of melanoma increases with age. However, naevus counts (the principal risk factor for melanoma) decrease with age; hence the relationship between ageing and melanoma is complex. Subjects who maintain a high naevus count after the age of 50 years are more likely to be affected by melanoma, as their lesions do not senesce. Longer telomere length, which is strongly related to age, is linked to high naevus counts/melanoma risk; thus melanoma biology is influenced by factors that slow down ageing...
April 12, 2018: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29615812/structure-function-analysis-and-therapeutic-efficacy-of-antibodies-to-fungal-melanin-for-melanoma-radioimmunotherapy
#4
J D Nosanchuk, A Jeyakumar, A Ray, E Revskaya, Z Jiang, R A Bryan, K J H Allen, R Jiao, M E Malo, B L Gómez, A Morgenstern, F Bruchertseifer, D Rickles, G B Thornton, A Bowen, A Casadevall, E Dadachova
Metastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with188 Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29600445/tumor-lysate-based-vaccines-on-the-road-to-immunotherapy-for-gallbladder-cancer
#5
REVIEW
Daniel Rojas-Sepúlveda, Andrés Tittarelli, María Alejandra Gleisner, Ignacio Ávalos, Cristián Pereda, Iván Gallegos, Fermín Eduardo González, Mercedes Natalia López, Jean Michel Butte, Juan Carlos Roa, Paula Fluxá, Flavio Salazar-Onfray
Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials...
March 29, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29595366/dabrafenib-in-combination-with-trametinib-in-the-treatment-of-patients-with-braf-v600-positive-advanced-or-metastatic-non-small-cell-lung-cancer-clinical-evidence-and-experience
#6
Arjun Khunger, Monica Khunger, Vamsidhar Velcheti
Mutations in the BRAF oncogene are found in 2-4% of all non-small cell lung cancer (NSCLC) patients. The most common activating mutation present within the BRAF oncogene is associated with valine substitution for glutamate at position 600 (V600E) within the BRAF kinase. BRAF-targeted therapies are effective in patients with melanoma and NSCLC harboring BRAF V600E mutation. In both melanoma and NSCLC, dual inhibition of both BRAF and the downstream mitogen-activated protein kinase (MEK) improves response rates compared with BRAF inhibition alone...
January 2018: Therapeutic Advances in Respiratory Disease
https://www.readbyqxmd.com/read/29581915/four-year-survival-and-counting-after-stereotactic-radiosurgery-to-nearly-100-brain-metastases-a-case-report
#7
Robin Saiki, Amanda Brill, Robert E Breeze
Brain metastases are a relatively common consequence of Stage IV melanoma. Historically, patients with brain metastases fare poorly, with median survival of only weeks to months. Patients with multiple metastases in the brain have often been overlooked in the literature, with the focus being placed more on patients with only a small number of metastases. The authors present a case of a 42-year-old man with a total of 98 brain metastases treated over several Gamma Knife sessions. He is nearly five years out from his initial treatment...
January 23, 2018: Curēus
https://www.readbyqxmd.com/read/29580859/stage-iv-melanoma-of-unknown-primary-a-population-based-study-in-the-united-states-from-1973-to-2014
#8
Jeffrey F Scott, Ruzica Z Conic, Cheryl L Thompson, Meg R Gerstenblith, Jeremy S Bordeaux
BACKGROUND: Melanoma of unknown primary (MUP) is incompletely described on a population level. OBJECTIVE: We sought to characterize stage IV MUP in a population-based cancer registry. METHODS: We developed a novel search algorithm to identify cases of stage IV MUP in the Surveillance, Epidemiology, and End Results (SEER)-18 registries from 1973 to 2014. Stage IV melanoma of known primary (MKP) served as a comparison group. Age-standardized incidence rates, demographic characteristics, adjusted disease-specific survival (DSS), and Cox proportional hazard models were calculated for MUP and MKP...
March 23, 2018: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29573941/encorafenib-plus-binimetinib-versus-vemurafenib-or-encorafenib-in-patients-with-braf-mutant-melanoma-columbus-a-multicentre-open-label-randomised-phase-3-trial
#9
Reinhard Dummer, Paolo A Ascierto, Helen J Gogas, Ana Arance, Mario Mandala, Gabriella Liszkay, Claus Garbe, Dirk Schadendorf, Ivana Krajsova, Ralf Gutzmer, Vanna Chiarion-Sileni, Caroline Dutriaux, Jan Willem B de Groot, Naoya Yamazaki, Carmen Loquai, Laure A Moutouh-de Parseval, Michael D Pickard, Victor Sandor, Caroline Robert, Keith T Flaherty
BACKGROUND: Combined BRAF-MEK inhibitor therapy is the standard of care for BRAFV600 -mutant advanced melanoma. We investigated encorafenib, a BRAF inhibitor with unique target-binding properties, alone or in combination with the MEK inhibitor binimetinib, versus vemurafenib in patients with advanced BRAFV600 -mutant melanoma. METHODS: COLUMBUS was conducted as a two-part, randomised, open-label phase 3 study at 162 hospitals in 28 countries. Eligible patients were aged 18 years or older and had histologically confirmed locally advanced (American Joint Committee on Cancer [AJCC] stage IIIB, IIIC, or IV), unresectable or metastatic cutaneous melanoma, or unknown primary melanoma; a BRAFV600E or BRAFV600K mutation; an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; and were treatment naive or had progressed on or after previous first-line immunotherapy...
March 21, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29552543/cutaneous-angiosarcoma-the-possibility-of-new-treatment-options-especially-for-patients-with-large-primary-tumor
#10
REVIEW
Yasuhiro Fujisawa, Koji Yoshino, Taku Fujimura, Yoshiyuki Nakamura, Naoko Okiyama, Yosuke Ishitsuka, Rei Watanabe, Manabu Fujimoto
The most widely accepted treatment for cutaneous angiosarcoma (CAS) is wide local excision and postoperative radiation to decrease the risk of recurrence. Positive surgical margins and large tumors (T2, >5 cm) are known to be associated with poor prognosis. Moreover, T2 tumors are known to be associated with positive surgical margins. According to previous reports, the majority of CAS patients in Japan had T2 tumors, whereas less than half of the patients in the studies from western countries did so. Consequently, the reported 5-year overall survival of Japanese CAS patients without distant metastasis was only 9%, lower than that for stage-IV melanoma...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29552014/autoantibodies-may-predict-immune-related-toxicity-results-from-a-phase-i-study-of-intralesional-bacillus-calmette-gu%C3%A3-rin-followed-by-ipilimumab-in-patients-with-advanced-metastatic-melanoma
#11
Jessica Da Gama Duarte, Sagun Parakh, Miles C Andrews, Katherine Woods, Anupama Pasam, Candani Tutuka, Simone Ostrouska, Jonathan M Blackburn, Andreas Behren, Jonathan Cebon
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced melanoma. The first ICI to demonstrate clinical benefit, ipilimumab, targets cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4); however, the long-term overall survival is just 22%. More than 40 years ago intralesional (IL) bacillus Calmette-Guérin (BCG), a living attenuated strain of Mycobacterium bovis , was found to induce tumor regression by stimulating cell-mediated immunity following a localized and self-limiting infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29541385/targeting-the-cyclin-dependent-kinase-and-retinoblastoma-axis-overcomes-standard-of-care-resistance-in-braf-v600e-mutant-melanoma
#12
Antoneicka L Harris, Samantha E Lee, Louis K Dawson, Laura A Marlow, Brandy H Edenfield, William F Durham, Thomas J Flotte, Michael Thompson, Daniel L Small, Aidan J Synnott, Svetomir N Markovic, John A Copland
Patient-derived tumor xenograft (PDTX) mouse models were used to discover new therapies for naïve and drug resistant BRAF V600E -mutant melanoma. Tumor histology, oncogenic protein expression, and antitumor activity were comparable between patient and PDTX-matched models thereby validating PDTXs as predictive preclinical models of therapeutic response in patients. PDTX models responsive and non-responsive to BRAF/MEK standard of care (SOC) therapy were used to identify efficacious combination therapies. One such combination includes a CDK4/6 inhibitor that blocks cell cycle progression...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29531842/contemporary-outcomes-from-the-use-of-regular-imaging-to-detect-relapse-in-high-risk-cutaneous-melanoma
#13
Kok Haw Jonathan Lim, Lavinia Spain, Claire Barker, Alexandros Georgiou, Gerard Walls, Martin Gore, Samra Turajlic, Ruth Board, James M Larkin, Paul Lorigan
Background: Agreement on the utility of imaging follow-up in patients with high-risk melanoma is lacking. A UK consensus statement recommends a surveillance schedule of CT or positron-emission tomography-CT and MRI brain (every 6 months for 3 years, then annually in years 4 and 5) as well as clinical examination for high-risk resected Stages II and III cutaneous melanoma. Our aim was to assess patterns of relapse and whether imaging surveillance could be of clinical benefit. Patients and methods: A retrospective study of patients enrolled between July 2013 and June 2015 from three UK tertiary cancer centres followed-up according to this protocol was undertaken...
2018: ESMO Open
https://www.readbyqxmd.com/read/29511905/the-value-of-metastasectomy-in-stage-iv-cutaneous-melanoma
#14
REVIEW
Uwe Wollina, Piotr Brzezinski
Cutaneous melanoma is an aggressive neoplasia of melanocytes. Prognosis is dependent on tumor stage. Stage IV melanoma is characterized by the occurrence of distant metastases. Response of metastases to classical chemotherapy is limited and toxicity of treatment is high. In recent years, new developments in immunotherapy and targeted therapies improved prognosis of stage IV melanoma patients with better tolerability of treatment. There is no dispute about surgical treatment of primary melanoma. But what is the value of metastasectomy in the era of new systemic treatments? This review aims to discuss available data for surgical removal of distant metastases for several organs and tissues...
March 6, 2018: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29485532/stat5-expression-correlates-with-recurrence-and-survival-in-melanoma-patients-treated-with-interferon-%C3%AE
#15
Devayani Machiraju, Iris Moll, Christoffer Gebhardt, Antje Sucker, Kristina Buder-Bakhaya, Dirk Schadendorf, Jessica C Hassel
Interferons (IFN) have a direct growth-inhibiting effect on tumor cells through Janus kinase-dependent activation of the transcription factor signal transducer and activator of transcription (STAT1). In vitro, signaling through STAT5 has been demonstrated to counteract this effect and lead to IFN resistance of melanoma cell lines. In 32 patients treated with IFN-α in an adjuvant setting, we investigated paraffin-embedded tumor tissue from primary melanomas and melanoma metastases for expression of STAT3 and STAT5, by immunohistochemistry, and for expression of phosphorylated signaling transduction activating transcription factor (pSTAT)3 and pSTAT5, by immunofluorescence...
February 26, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29485531/sarcoid-like-reactions-in-patients-receiving-modern-melanoma-treatment
#16
Florentia Dimitriou, Anna L Frauchiger, Mirjana Urosevic-Maiwald, Mirjam C Naegeli, Simone M Goldinger, Marjam Barysch, Daniel Franzen, Jivko Kamarachev, Ralph Braun, Reinhard Dummer, Joanna Mangana
The development of cancer immunotherapy and targeted therapy has reached an important inflection point in the history of melanoma. Immune checkpoint inhibitors and kinase inhibitors are today's standard of care treatments in advanced melanoma patients. Treatment-related toxicities can be very intriguing and quite challenging. Sarcoidosis is a multisystemic granulomatous disease characterized by an aberrant immune response to unknown antigens, whereas sarcoid-like reactions (SLRs) refer to localized clinical features...
February 26, 2018: Melanoma Research
https://www.readbyqxmd.com/read/29483107/liquid-profiling-of-circulating-tumor-dna-in-plasma-of-melanoma-patients-for-companion-diagnostics-and-monitoring-of-braf-inhibitor-therapy
#17
Verena Haselmann, Christoffer Gebhardt, Ingrid Brechtel, Angelika Duda, Claudia Czerwinski, Antje Sucker, Tim Holland-Letz, Jochen Utikal, Dirk Schadendorf, Michael Neumaier
BACKGROUND: The current standard for determining eligibility of patients with metastatic melanoma for BRAF -targeted therapy is tissue-based testing of BRAF mutations. As patients are rarely rebiopsied, detection in blood might be advantageous by enabling a comprehensive assessment of tumor mutational status in real time and thereby representing a noninvasive biomarker for monitoring BRAF therapy. METHODS: In all, 634 stage I to IV melanoma patients were enrolled at 2 centers, and 1406 plasma samples were prospectively collected...
February 26, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29470692/validation-of-the-chowdhury-overall-survival-score-in-patients-with-melanoma-brain-metastasis-treated-with-gamma-knife-radiosurgery
#18
R J Rodenburg, P E Hanssens, V K Y Ho, L V Beerepoot
Melanoma brain metastases (MBM) are common in patients with stage IV disease. For Gamma Knife radiosurgery (GKRS) on MBM, risk scores such as RPA and melanoma-GPA aid to identify prognostic subgroups. This study aimed to validate the overall survival (OS) risk score developed by Chowdhury et al. in our center's patient cohort. A total of 104 MBM patients were treated with GKRS between 1/1/2002 and 31/12/2014 in our institution. Patients were categorized according to RPA, melanoma-GPA and Chowdhury OS score...
February 22, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29462228/impact-of-gene-expression-profiling-on-decision-making-in-clinically-node-negative-melanoma-patients-after-surgical-staging
#19
Darryl Schuitevoerder, Michael Heath, Robert W Cook, Kyle R Covington, Jeanine Fortino, Sancy Leachman, John T Vetto
INTRODUCTION: The surgeon's role in the follow-up of pathologic stage I and II melanoma patients has traditionally been minimal. Melanoma genetic expression profile (GEP) testing provides binary risk assessment (Class 1-low risk, Class 2-high risk), which can assist in predicting metastasis and formulating appropriate follow up. We sought to determine the impact of GEP results on the management of clinically node negative cutaneous melanoma patients staged with sentinel lymph node biopsy (SLNB)...
February 1, 2018: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29456865/a-real-world-example-of-coverage-with-evidence-development-in-australia-ipilimumab-for-the-treatment-of-metastatic-melanoma
#20
Hansoo Kim, Samantha Comey, Karl Hausler, Greg Cook
Background: Australian Government subsidisation of ipilimumab for the treatment of patients with metastatic melanoma was conditional on the sponsor entering a 'managed entry scheme' to assess the 2-year overall survival rate in metastatic melanoma patients who received ipilimumab in the first year of Pharmaceutical Benefits Scheme listing. Methods: All unresectable stage IIIc / IV metastatic melanoma patients treated with at least one dose of ipilimumab therapy in Australia from the PBS listing date to a time point 12 months later (i...
2018: Journal of Pharmaceutical Policy and Practice
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