Nanoparticulate delivery of potent microtubule inhibitor for metastatic melanoma treatment.
J Control Release. 2019 Jul 19;:
Authors: Bariwal J, Kumar V, Chen H, Bhattarai R, Yang P, Li W, Mahato RI
Melanoma is the most aggressive type of skin cancer, which readily metastasizes through lymph nodes to the lungs, liver, and brain. Since the repeated administration of most chemotherapeutic drugs develops chemoresistance and severe systemic toxicities, herein we synthesized 2-(4-hydroxy-1H-indol-3-yl)-1H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) methanone (abbreviated as QW-296), a novel tubulin destabilizing agent with little susceptible to transporter-mediated drug resistance. QW-296 disturbed the microtubule dynamics at the nanomolar concentration in A375 and B16F10 melanoma cells. QW-296 binding to colchicine-binding site on tubulin protein was confirmed by molecular modeling and tubulin polymerization assay. QW-296 significantly inhibited A375 and B16F10 cell proliferation, induced G2/M cell cycle arrest and led to apoptosis and cell death. To improve its aqueous solubility, QW-296 was encapsulated into methoxy poly(ethyleneglycol)-b-poly(carbonate-co-lactide) [mPEG-b-P(CB-co-LA)] polymeric nanoparticles by solvent evaporation, with the mean particle size of 122.0 ± 2.28 nm and drug loading of 3.70% (w/w). Systemic administration of QW-296 loaded nanoparticles into C57/BL6 albino mice bearing lung metastatic melanoma at the dose of 20 mg/kg 4 times a week for 1.5 weeks resulted in significant tumor regression and prolonged mouse median survival without significant change in mouse body weight. In conclusion, QW-296 loaded nanoparticles have the potential to treat metastatic melanoma.
PMID: 31330213 [PubMed - as supplied by publisher]
Corrigendum: Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month followup of negative test results and utility data from a large US registry study.
Dermatol Online J. 2019 Jun 06;25(6):
Authors: Ferris LK, Rigel DS, Siegel DM, Skelsey MK, Peck GL, Hren C, Gorman C, Frumento T, Jansen B, Yao Z, Rock J, Knezevich SR, Cockerell CJ
The revised version of the article corrected Figure 2. This change appears in the revised online PDF copy of this article.
PMID: 31329399 [PubMed - in process]
Neoadjuvant BRAF-targeted therapy in regionally advanced and oligometastatic melanoma.
Pigment Cell Melanoma Res. 2019 Jul 22;:
Authors: Eroglu Z, Eatrides J, Naqvi SMH, Kim Y, Rich J, Babacan NA, Brohl AS, Markowitz J, Sarnaik A, Zager J, Khushalani NI, Sondak VK, Messina J
BACKGROUND: Current management of locoregional and oligometastatic melanoma is typically with surgery; however, some patients are unable to undergo resection due to location/size of their tumors and/or the anticipated morbidity of the surgery. While there are currently no established guidelines for neoadjuvant therapy in melanoma, neoadjuvant BRAF-targeted therapy may make resection more feasible.
METHODS: A retrospective analysis was conducted of 23 patients with BRAFV600-mutant, stage III/IV melanoma treated with BRAF-targeted therapy prior to surgery, with no adjuvant treatment. Surgical specimens, preoperative imaging and clinical outcomes were evaluated.
RESULTS: Ten of 23 patients (44%) attained a pathologic complete response (pCR), with no correlation between RECIST-response based on preoperative imaging and pathologic response. After a median of 43 months follow-up, only 1 patient (10%) with a pCR recurred; while 8 of 13 (62%) patients without a pCR recurred. Patients with a pCR had significantly improved relapse-free (RFS) and overall survival (OS) compared to patients with residual tumor.
CONCLUSION: Neoadjuvant BRAF-targeted therapy is associated with a high pCR rate in patients with stage III-IV melanoma, which may correlate with improved RFS and OS. This article is protected by copyright. All rights reserved.
PMID: 31329344 [PubMed - as supplied by publisher]
The increasing use of shave biopsy for diagnosing invasive melanoma in Australia.
Med J Aust. 2019 Jul 22;:
Authors: de Menezes SL, Kelly JW, Wolfe R, Farrugia H, Mar VJ
OBJECTIVE: To assess changes in the choice of skin biopsy technique for assessing invasive melanoma in Victoria, and to examine the impact of partial biopsy technique on the accuracy of tumour microstaging.
DESIGN: Retrospective cross-sectional review of Victorian Cancer Registry data on invasive melanoma histologically diagnosed in Victoria during 2005, 2010, and 2015.
SETTING, PARTICIPANTS: 400 patients randomly selected from each of the three years, stratified by final tumour thickness: 200 patients with thin melanoma (< 1.0 mm), 100 each with intermediate (1.0-4.0 mm) and thick melanoma (> 4.0 mm).
MAIN OUTCOME MEASURES: Partial and excisional biopsies, as proportions of all skin biopsies; rates of tumour base transection and T-upstaging, and mean tumour thickness underestimation following partial biopsy.
RESULTS: 833 excisional and 337 partial diagnostic biopsies were undertaken. The proportion of partial biopsies increased from 20% of patients in 2005 to 36% in 2015 (P < 0.001); the proportion of shave biopsies increased from 9% in 2005 to 20% in 2015 (P < 0.001), with increasing rates among dermatologists and general practitioners. Ninety-four of 175 shave biopsies (54%) transected the tumour base; wide local excision subsequently identified residual melanoma in 65 of these cases (69%). Twenty-one tumours diagnosed by shave biopsy (12%) were T-upstaged. With base-transected shave biopsies, tumour thickness was underestimated by a mean 2.36 mm for thick, 0.48 mm for intermediate, and 0.07 mm for thin melanomas.
CONCLUSION: Partial biopsy, particularly shave biopsy, was increasingly used for diagnosing invasive melanoma between 2005 and 2015. Shave biopsy has a high rate of base transection, reducing the accuracy of tumour staging, which is crucial for planning appropriate therapy, including definitive surgery and adjuvant therapy.
PMID: 31328802 [PubMed - as supplied by publisher]
Nickel oxide nanoparticles exert selective toxicity on skin mitochondria and lysosomes isolated from the mouse model of melanoma.
J Biochem Mol Toxicol. 2019 Jul 21;:e22376
Authors: Rahimi S, Naserzadeh P, Mousavi Z, Ashtari K, Seydi E, Pourahmad J
Nickel oxide nanoparticles (NiO-NPs) are progressively used for an immense number of new applications in modern industries sectors. Nevertheless, the toxic impact of NiO-NPs has not been clearly elucidated on human melanoma cell lines at the cellular and molecular level. Hence, this study was designed to examine the in vitro cytotoxicity potentials of NiO-NPs on malignant cutaneous melanoma (MCM) mitochondria. Results revealed that NiO-NPs significantly increased reactive oxygen species level, lipid peroxidation, and mitochondrial membrane potential and decreased succinate dehydrogenase activity, glutathione level, and ATP content on skin mitochondria isolated from the mouse model of melanoma compared with the non-cancerous mouse skin mitochondria. Our results revealed that NiO-NPs induced lysosomal membrane labialization on mentioned mitochondria. The current study showed that NiO-NPs could significantly induce selective cytotoxicity on MCM mitochondria. Therefore, this compound may be considered as a promising candidate for further in vivo and clinical studies to reach a new anti-MCM drug.
PMID: 31328346 [PubMed - as supplied by publisher]