Murray A Cotter

Publications (7)41.76 Total impact

• Article: Use of oral N-acetylcysteine for protection of melanocytic nevi against UV-induced oxidative stress: towards a novel paradigm for melanoma chemoprevention.

  Agnessa Gadeliya Goodson, Murray A Cotter, Pamela Cassidy, Mark Wade, Scott R Florell, Tong Liu, Kenneth M Boucher, Douglas Grossman
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  ABSTRACT: Induction of oxidative stress has been implicated in UV-induced melanoma. We sought to determine whether the antioxidant N-acetylcysteine (NAC) could be safely administered to protect melanocytic nevi from the oxidative stress resulting from acute UV exposure. Patients at increased risk for melanoma were recruited from a screening clinic. Induction and detection of oxidative stress (reactive oxygen species and glutathione depletion) was optimized in nevi following ex vivo UV irradiation. Nevi were removed from patients before, and following, oral ingestion of a single (1,200 mg) dose of NAC, and then these nevi were UV irradiated (4,000 J/m(2)). Oxidative stress was induced in nevi 24 to 48 hours following ex vivo UV irradiation. A single oral dose of NAC was well tolerated in all patients (n = 72). Basal levels of reduced glutathione and the NAC metabolite cysteine were well correlated between similar-appearing nevi from the same patient and were significantly increased in nevi removed 3 hours after NAC ingestion compared with nevi removed before drug ingestion. In approximately half (9 of 19) of patients tested, UV-induced glutathione depletion was attenuated in the postdrug (compared with predrug) nevus. NAC can be safely administered to patients for the purpose of modulating UV-induced oxidative stress in nevi. This study suggests the feasibility of patients taking NAC prophylactically before acute UV exposure, to prevent pro-oncogenic oxidative stress in nevi and ultimately reduce long-term melanoma risk.
  Clinical Cancer Research 11/2009; 15(23):7434-40. · 7.74 Impact Factor
• Article: Response to Gray-Schopfer et al. and Michaloglou et al.

  Murray A Cotter, Scott R Florell, Sancy A Leachman, Douglas Grossman
  Journal of Investigative Dermatology 05/2008; 128(6):1583-1584. · 6.31 Impact Factor
• Article: Treatment of lentigo maligna with imiquimod before staged excision.

  Murray A Cotter, Jeffrey K McKenna, Glen M Bowen
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  ABSTRACT: Imiquimod 5% cream has demonstrated effectiveness in the treatment of lentigo maligna (LM) in several small studies. None of the studies to date have included posttreatment surgical removal to confirm negative histologic margins. The aim of this retrospective analysis was to assess the efficacy of topical imiquimod in LM by circumferentially examining vertically oriented sections from a geometrically designed "picture frame" margin as well as bread-loafed sections of the central portion after staged excisions of imiquimod-treated lesions of LM. Forty patients with biopsy-confirmed LM were treated five times a week for 3 months with 5% imiquimod cream before staged excision. Tazarotene 0.1% gel was added when no clinical signs of erythema developed with imiquimod alone after 1 month (10 patients). After the course of topical therapy, patients were assessed for clinical and complete histologic clearance after staged excision. A total of 33 of 40 patients had a complete clinical response as determined by the absence of remaining clinical lesion on physical examination. Upon histologic review, 30 of 40 patients had no evidence of LM whereas 10 of 40 harbored residual disease. One patient was found to have histologic evidence of invasion after completing the topical protocol. After a mean follow-up of 18 months (range, 12-34 months) and after complete surgical excision of the treatment site, none of the imiquimod-treated patients had evidence of recurrence. Imiquimod appears to be an effective adjunctive treatment for LM but does not qualify as a replacement therapy for surgery.
  Dermatologic Surgery 03/2008; 34(2):147-51. · 1.80 Impact Factor
• Article: Absence of senescence-associated beta-galactosidase activity in human melanocytic nevi in vivo.

  Murray A Cotter, Scott R Florell, Sancy A Leachman, Douglas Grossman
  Journal of Investigative Dermatology 11/2007; 127(10):2469-71. · 6.31 Impact Factor
• Article: N-acetylcysteine protects melanocytes against oxidative stress/damage and delays onset of ultraviolet-induced melanoma in mice.

  Murray A Cotter, Joshua Thomas, Pamela Cassidy, Kyle Robinette, Noah Jenkins, Scott R Florell, Sancy Leachman, Wolfram E Samlowski, Douglas Grossman
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  ABSTRACT: UV radiation is the major environmental risk factor for melanoma and a potent inducer of oxidative stress, which is implicated in the pathogenesis of several malignancies. We evaluated whether the thiol antioxidant N-acetylcysteine (NAC) could protect melanocytes from UV-induced oxidative stress/damage in vitro and from UV-induced melanoma in vivo. In vitro experiments used the mouse melanocyte line melan-a. For in vivo experiments, mice transgenic for hepatocyte growth factor and survivin, shown previously to develop melanoma following a single neonatal dose of UV irradiation, were given NAC (7 mg/mL; mother's drinking water) transplacentally and through nursing until 2 weeks after birth. NAC (1-10 mmol/L) protected melan-a cells from several UV-induced oxidative sequelae, including production of intracellular peroxide, formation of the signature oxidative DNA lesion 8-oxoguanine, and depletion of free reduced thiols (primarily glutathione). Delivery of NAC reduced thiol depletion and blocked formation of 8-oxoguanine in mouse skin following neonatal UV treatment. Mean onset of UV-induced melanocytic tumors was significantly delayed in NAC-treated compared with control mice (21 versus 14 weeks; P = 0.0003). Our data highlight the potential importance of oxidative stress in the pathogenesis of melanoma and suggest that NAC may be useful as a chemopreventive agent.
  Clinical Cancer Research 11/2007; 13(19):5952-8. · 7.74 Impact Factor
• Article: Melanocyte expression of survivin promotes development and metastasis of UV-induced melanoma in HGF-transgenic mice.

  Joshua Thomas, Tong Liu, Murray A Cotter, Scott R Florell, Kyle Robinette, Adrianne N Hanks, Douglas Grossman
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  ABSTRACT: We previously found the apoptosis inhibitor Survivin to be expressed in melanocytic nevi and melanoma but not in normal melanocytes. To investigate the role of Survivin in melanoma development and progression, we examined the consequences of forced Survivin expression in melanocytes in vivo. Transgenic (Tg) mouse lines (Dct-Survivin) were generated with melanocyte-specific expression of Survivin, and melanocytes grown from Dct-Survivin mice expressed Survivin. Dct-Survivin melanocytes exhibited decreased susceptibility to UV-induced apoptosis but no difference in proliferative capacity compared with melanocytes derived from non-Tg littermates. Induction of nevi in Dct-Survivin and non-Tg mice by topical application of 7,12-dimethylbenz(a)anthracene did not reveal significant differences in lesion onset (median, 10 weeks) or density (4 lesions per mouse after 15 weeks). Dct-Survivin mice were bred with melanoma-prone MH19/HGF-B6 Tg mice, and all progeny expressing either individual, neither, or both (Survivin/HGF) transgenes were UV-treated as neonates and then monitored for 43 weeks. Melanocytes in neonatal Survivin+/HGF+ mouse skin were less susceptible to UV-induced apoptosis than those from Survivin-/HGF+ mice. Onset of melanocytic tumors was earlier (median, 18 versus 24 weeks; P = 0.01, log-rank test), and overall tumor density was greater (7.7 versus 5.2 tumors per mouse; P = 0.04) in Survivin+/HGF+ compared with Survivin-/HGF+ mice. Strikingly, melanomas arising in Survivin+/HGF+ mice showed a greater tendency for lymph node (35% versus 0%; P = 0.04) and lung (53% versus 22%) metastasis and lower rates of spontaneous apoptosis than those in Survivin-/HGF+ mice. These studies show a role for Survivin in promoting both early and late events of UV-induced melanoma development in vivo.
  Cancer Research 07/2007; 67(11):5172-8. · 7.86 Impact Factor
• Article: Unsuitability of organ donation from a patient with a history of melanoma?

  Murray A Cotter, Payam Tristani-Firouzi
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  ABSTRACT: A 52-year-old man with a history of melanoma presented to the emergency department with a massive intracranial hemorrhage. The patient deteriorated rapidly and was being considered as a potential organ donor. Three years before presentation, the patient had undergone wide excision of a 3.75-mm melanoma from his back with sentinel lymph node biopsy, which yielded negative findings. He had been well until the day of presentation. Although there are no specific guidelines for candidacy of organ donation from patients with a history of melanoma, there are several reports of donor-derived melanoma in organ transplant recipients, most with grave consequences. The literature relevant to this case is reviewed and discussed.
  Journal of the American Academy of Dermatology 07/2006; 54(6):1096-8. · 3.99 Impact Factor