nonthermal plasma;
tirapazamine;
medical device;
melanoma;
skin cancer;
gap junctions;
porcine skin;
VEMURAFENIB;
MECHANISMS;
CYTOTOXICITY;
COBIMETINIB;
CELLS;
TUMOR;
SKIN;
D O I:
10.3390/cells12162113
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
Although melanoma accounts for only 5.3% of skin cancer, it results in >75% of skin-cancer-related deaths. To avoid disfiguring surgeries on the head and neck associated with surgical excision, there is a clear unmet need for other strategies to selectively remove cutaneous melanoma lesions. Mohs surgery is the current treatment for cutaneous melanoma lesions and squamous and basal cell carcinoma. While Mohs surgery is an effective way to remove melanomas in situ, normal tissue is also excised to achieve histologically negative margins. This paper describes a novel combination therapy of nonthermal plasma (NTP) which emits a multitude of reactive oxygen species (ROS) and the injection of a pharmaceutical agent. We have shown that the effects of NTP are augmented by the DNA-damaging prodrug, tirapazamine (TPZ), which becomes a free radical only in conditions of hypoxemia, which is often enhanced in the tumor microenvironment. In this study, we demonstrate the efficacy of the combination therapy through experiments with B16-F10 and 1205 Lu metastatic melanoma cells both in vitro and in vivo. We also show the safety parameters of the therapy with no significant effects of the therapy when applied to porcine skin. We show the need for the intratumor delivery of TPZ in combination with the surface treatment of NTP and present a model of a medical device to deliver this combination therapy. The importance of functional gap junctions is indicated as a mechanism to promote the therapeutic effect. Collectively, the data support a novel therapeutic combination to treat melanoma and the development of a medical device to deliver the treatment in situ.
机构:
Donghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R China
Shanghai Inst Pollut Control & Ecol Secur, Shanghai 200092, Peoples R ChinaDonghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R China
Zhang, Ai
Jiang, Xinyuan
论文数: 0引用数: 0
h-index: 0
机构:
Donghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R ChinaDonghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R China
Jiang, Xinyuan
Ding, Yongqiang
论文数: 0引用数: 0
h-index: 0
机构:
Donghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R ChinaDonghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R China
Ding, Yongqiang
Jiang, Nan
论文数: 0引用数: 0
h-index: 0
机构:
Donghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R ChinaDonghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R China
Jiang, Nan
Ping, Qian
论文数: 0引用数: 0
h-index: 0
机构:
Shanghai Inst Pollut Control & Ecol Secur, Shanghai 200092, Peoples R China
Tongji Univ, Coll Environm Sci & Engn, State Key Lab Pollut Control & Resource Reuse, Kay Lab Yangtze River Water Environm, Shanghai 200092, Peoples R China
Tongji Univ, Coll Environm Sci & Engn, Shanghai 200092, Peoples R ChinaDonghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R China
Ping, Qian
Wang, Lin
论文数: 0引用数: 0
h-index: 0
机构:
Shanghai Inst Pollut Control & Ecol Secur, Shanghai 200092, Peoples R China
Tongji Univ, Coll Environm Sci & Engn, State Key Lab Pollut Control & Resource Reuse, Kay Lab Yangtze River Water Environm, Shanghai 200092, Peoples R China
Tongji Univ, Coll Environm Sci & Engn, Shanghai 200092, Peoples R ChinaDonghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R China
Wang, Lin
Liu, Yanan
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h-index: 0
机构:
Donghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R China
Shanghai Inst Pollut Control & Ecol Secur, Shanghai 200092, Peoples R ChinaDonghua Univ, Coll Environm Sci & Engn, Shanghai 201620, Peoples R China
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Lelliott, Emily J.
论文数: 引用数:
h-index:
机构:
Cullinane, Carleen
Martin, Claire A.
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Martin, Claire A.
Walker, Rachael
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Walker, Rachael
Ramsbottom, Kelly M.
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Ramsbottom, Kelly M.
Souza-Fonseca-Guimaraes, Fernando
论文数: 0引用数: 0
h-index: 0
机构:
Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia
Walter Eliza Hall Inst Med Res, Div Mol Immunol, Parkville, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Souza-Fonseca-Guimaraes, Fernando
Abuhammad, Shatha
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Abuhammad, Shatha
Michie, Jessica
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Michie, Jessica
Kirby, Laura
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Kirby, Laura
Young, Richard J.
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Young, Richard J.
Slater, Alison
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Slater, Alison
Lau, Peter
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Lau, Peter
Meeth, Katrina
论文数: 0引用数: 0
h-index: 0
机构:
Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USAPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Meeth, Katrina
Oliaro, Jane
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Oliaro, Jane
Haynes, Nicole
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
Univ Melbourne, Dept Pathol, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Haynes, Nicole
McArthur, Grant A.
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
McArthur, Grant A.
Sheppard, Karen E.
论文数: 0引用数: 0
h-index: 0
机构:
Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia
Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia
Univ Melbourne, Dept Biochem & Mol Biol, Melbourne, Vic, AustraliaPeter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia