The Development of Nonthermal Plasma and Tirapazamine as a Novel Combination Therapy to Treat Melanoma In Situ

被引:3
|
作者
Yehl, Matthew [1 ]
Kucharski, Dominik [1 ]
Eubank, Michelle [1 ]
Gulledge, Brandon [1 ]
Rayan, Gamal [1 ]
Uddin, Md Gias [1 ]
Remmers, Genevieve [2 ]
Kandel, Eugene S. [3 ]
Dufaux, Douglas P. [4 ]
Hutcherson, Timothy C. [1 ]
Sexton, Sandra [3 ]
Zucker, Shoshanna N. [1 ]
机构
[1] DYouville Univ, Sch Pharm, 320 Porter Ave, Buffalo, NY 14201 USA
[2] IDEXX Labs, 1 IDEXX Dr, Westbrook, ME 04092 USA
[3] Roswell Park Comprehens Canc Ctr, 665 Elm St, Buffalo, NY 14203 USA
[4] Alfie Technol Corp, 227 Thorn Ave, Orchard Pk, NY 14127 USA
关键词
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.
引用
收藏
页数:15
相关论文
共 50 条
  • [21] A NOVEL COMBINATION THERAPY USING SUBEROYLANILIDE HYDROXAMIC ACID AND RITONAVIR TO TREAT PROSTATE CANCER
    Sato, Akinori
    Asano, Takako
    Horiguchi, Akio
    Ito, Keiichi
    Sumitomo, Makoto
    Asano, Tomohiko
    JOURNAL OF UROLOGY, 2009, 181 (04): : 52 - 52
  • [22] Development of Novel Gene Therapy Paradigms to Treat a Form of Hereditary Blindness
    Surace, Enrico Maria
    Maritato, Rosa
    MOLECULAR THERAPY, 2020, 28 (04) : 318 - 319
  • [23] Cold plasma - A novel approach to treat therapy-resistant corneal infections
    Fuchsluger, Thomas
    ACTA OPHTHALMOLOGICA, 2019, 97
  • [24] Development of a Novel Multiplex Cancer Vaccine for the Therapy of Patients With Melanoma
    Maida, Anthony E.
    Enstrom, Amanda
    Lam, Kit S.
    Ye, Jianhua
    Castro, Miguel
    JOURNAL OF IMMUNOTHERAPY, 2008, 31 (09) : 944 - 945
  • [25] Cold plasma - a novel approach to treat therapy- resistant corneal infections
    Fuchsluger, T.
    ACTA OPHTHALMOLOGICA, 2018, 96 : 40 - 41
  • [26] Development of combination therapy to delay resistance in BRAF-inhibitor treated melanoma
    Seretis, A.
    Cappellano, G.
    Bellmann, L.
    Hornsteiner, F.
    Tripp, C. H.
    Ortner-Tobider, D.
    Mullins, D. W.
    Amon, L.
    Lehmann, C.
    Dudziak, D.
    Stoitzner, P.
    EXPERIMENTAL DERMATOLOGY, 2021, 30 (03) : E63 - E63
  • [27] Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma
    Onuchic, Ana Claudia
    Machado, Camila M. L.
    Saito, Renata F.
    Rios, Francisco J.
    Jancar, Sonia
    Chammas, Roger
    MEDIATORS OF INFLAMMATION, 2012, 2012
  • [28] A novel combination of suicide gene therapy and histone deacetylase inhibitor for treatment of malignant melanoma
    Yamamoto, S
    Yamano, T
    Tanaka, M
    Hoon, DSB
    Takao, S
    Morishita, R
    Aikou, T
    Kaneda, Y
    CANCER GENE THERAPY, 2003, 10 (03) : 179 - 186
  • [29] A novel combination of suicide gene therapy and histone deacetylase inhibitor for treatment of malignant melanoma
    Seiji Yamamoto
    Tomoki Yamano
    Maki Tanaka
    Dave S B Hoon
    Sonshin Takao
    Ryuichi Morishita
    Takashi Aikou
    Yasufumi Kaneda
    Cancer Gene Therapy, 2003, 10 : 179 - 186
  • [30] Combination of convalescent plasma therapy and repurposed drugs to treat severe COVID-19 patient with multimorbidity
    Das, Santa Kumar
    Ranabhat, Kamal
    Bhattarai, Suraj
    Karki, Khem Bahadur
    Gyanwali, Pradip
    Paneru, Hem Raj
    Nepal, Bipin
    Dumre, Shyam Prakash
    Acharya, Subhash Prasad
    CLINICAL CASE REPORTS, 2021, 9 (04): : 2132 - 2137