SENSITIVITY OF HUMAN METASTATIC MELANOMA CELLS TO THE ESTER ANALOG OF RAPAMYCIN, CCI-779

2004 ◽  
Vol 78 ◽  
pp. 729
Author(s):  
E Maellaro ◽  
M A. Valentini ◽  
B Del Bello ◽  
M Carmellini
2013 ◽  
Vol 1 (Suppl. 1) ◽  
pp. A3.7
Author(s):  
Stefan Salzmann

2020 ◽  
pp. 107728
Author(s):  
Julita Kulbacka ◽  
Grzegorz Chodaczek ◽  
Joanna Rossowska ◽  
Anna Szewczyk ◽  
Jolanta Saczko ◽  
...  

Gene ◽  
2021 ◽  
pp. 145552
Author(s):  
Yasunori Hino ◽  
Md Mahfuzur Rahman ◽  
Yu-Chang Lai ◽  
Al Asmaul Husna ◽  
Hui-wen Chen ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2284
Author(s):  
Serena Stamatakos ◽  
Giovanni Luca Beretta ◽  
Elisabetta Vergani ◽  
Matteo Dugo ◽  
Cristina Corno ◽  
...  

Metabolic changes promoting cell survival are involved in metastatic melanoma progression and in the development of drug resistance. In BRAF-inhibitor resistant melanoma cells, we explored the role of FASN, an enzyme involved in lipogenesis overexpressed in metastatic melanoma. Resistant melanoma cells displaying enhanced migratory and pro-invasive abilities increased sensitivity to the BRAF inhibitor PLX4032 upon the molecular targeting of FASN and upon treatment with the FASN inhibitor orlistat. This behavior was associated with a marked apoptosis and caspase 3/7 activation observed for the drug combination. The expression of FASN was found to be inversely associated with drug resistance in BRAF-mutant cell lines, both in a set of six resistant/sensitive matched lines and in the Cancer Cell Line Encyclopedia. A favorable drug interaction in resistant cells was also observed with U18666 A inhibiting DHCR24, which increased upon FASN targeting. The simultaneous combination of the two inhibitors showed a synergistic interaction with PLX4032 in resistant cells. In conclusion, FASN plays a role in BRAF-mutated melanoma progression, thereby creating novel therapeutic opportunities for the treatment of melanoma.


2008 ◽  
Vol 12 (2) ◽  
pp. 64-70 ◽  
Author(s):  
Liren Tang ◽  
Mingwan Su ◽  
Yi Zhang ◽  
Wency Ip ◽  
Magdalena Martinka ◽  
...  

Background: Endothelin-3 (ET-3) is an essential paracrine factor for the proliferation, migration, and survival of embryonic melanocytes during fetal development. Its expression is tightly regulated, being completely turned off in adult skin. Objective: In this study, results are presented that demonstrate abnormal expression of ET-3 by metastatic melanoma cells in both tissue biopsies and cell culture. Further, in vitro experiments showed that metastatic melanoma cells have the capacity to respond to ET-3 stimulation by increasing survival. Conclusion: Therefore, an abnormal autocrine stimulation pathway involving ET-3 is present in metastatic melanoma cells. Blocking this signal transduction pathway may prove useful for the treatment of metastatic melanoma.


2003 ◽  
Vol 21 (17) ◽  
pp. 3343-3350 ◽  
Author(s):  
Robert Soiffer ◽  
F. Stephen Hodi ◽  
Frank Haluska ◽  
Ken Jung ◽  
Silke Gillessen ◽  
...  

Purpose: Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) by retroviral-mediated gene transfer generates potent antitumor immunity in patients with metastatic melanoma. Further clinical development of this immunization scheme requires simplification of vaccine manufacture. We conducted a phase I clinical trial testing the biologic activity of vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer.Patients and Methods: Excised metastases were processed to single cells, transduced with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1 × 106, 4 × 106, or 1 × 107tumor cells, depending on overall yield, and were injected intradermally and subcutaneously at weekly and biweekly intervals.Results: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 745 ng/106cells/24 hours. Toxicities were restricted to grade 1 to 2 local skin reactions. Eight patients were withdrawn early because of rapid disease progression. Vaccination elicited dense dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates at injection sites in 19 of 26 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransduced tumor cells in 17 of 25 patients. Metastatic lesions that were resected after vaccination showed brisk or focal T-lymphocyte and plasma cell infiltrates with tumor necrosis in 10 of 16 patients. One complete, one partial, and one mixed response were noted. Ten patients (29%) are alive, with a minimum follow-up of 36 months; four of these patients have no evidence of disease.Conclusion: Vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma.


Oncotarget ◽  
2019 ◽  
Vol 10 (58) ◽  
pp. 6079-6095 ◽  
Author(s):  
Channay Naidoo ◽  
Cherie Ann Kruger ◽  
Heidi Abrahamse

Oncotarget ◽  
2014 ◽  
Vol 5 (9) ◽  
pp. 2450-2461 ◽  
Author(s):  
Powrnima Joshi ◽  
Barbara Jacobs ◽  
Adeeb Derakhshan ◽  
Lee R. Moore ◽  
Paul Elson ◽  
...  

2014 ◽  
Vol 171 (24) ◽  
pp. 5708-5727 ◽  
Author(s):  
Christine Wasinger ◽  
Martin Künzl ◽  
Christoph Minichsdorfer ◽  
Christoph Höller ◽  
Maria Zellner ◽  
...  

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