A Bayesian Sequential Learning Framework to Parameterise Continuum Models of Melanoma Invasion into Human Skin.
Bull Math Biol. 2018 Nov 15;:
Authors: Browning AP, Haridas P, Simpson MJ
We present a novel framework to parameterise a mathematical model of cell invasion that describes how a population of melanoma cells invades into human skin tissue. Using simple experimental data extracted from complex experimental images, we estimate three model parameters: (i) the melanoma cell proliferation rate, [Formula: see text]; (ii) the melanoma cell diffusivity, D; and (iii) [Formula: see text], a constant that determines the rate that melanoma cells degrade the skin tissue. The Bayesian sequential learning framework involves a sequence of increasingly sophisticated experimental data from: (i) a spatially uniform cell proliferation assay; (ii) a two-dimensional circular barrier assay; and (iii) a three-dimensional invasion assay. The Bayesian sequential learning approach leads to well-defined parameter estimates. In contrast, taking a naive approach that attempts to estimate all parameters from a single set of images from the same experiment fails to produce meaningful results. Overall, our approach to inference is simple-to-implement, computationally efficient, and well suited for many cell biology phenomena that can be described by low-dimensional continuum models using ordinary differential equations and partial differential equations. We anticipate that this Bayesian sequential learning framework will be relevant in other biological contexts where it is challenging to extract detailed, quantitative biological measurements from experimental images and so we must rely on using relatively simple measurements from complex images.
PMID: 30443704 [PubMed - as supplied by publisher]
Microneedle-Assisted Topical Delivery of Photodynamically Active Mesoporous Formulation for Combination Therapy of Deep-Seated Melanoma.
ACS Nano. 2018 Nov 16;:
Authors: Tham HP, Xu K, Lim WQ, Chen H, Zheng M, Thng TGS, Venkatraman SS, Xu C, Zhao Y
Topical treatment using photodynamic therapy (PDT) for many types of skin cancers has largely been limited by the inability of existing photosensitizers to penetrate into the deep skin tissue. To overcome these problems, we developed a mesoporous nanovehicle with dual loading of photosensitizers and clinically relevant drugs for combination therapy, while utilizing microneedle technology to facilitate their penetration into deep skin tissue. Sub-50 nm photodynamically active mesoporous organosilica nanoparticles were synthesized with photosensitizers covalently bonded to the silica matrix, which dramatically increased the quantum yield and photostability of these photosensitizers. The mesopores of the nanoparticles were further loaded with small-molecule inhibitors, i. e., dabrafenib and trametinib, that target the hyperactive mitogen-activated protein kinase (MAPK) pathway for melanoma treatment. As-prepared empty nanovehicle was cytocompatible with normal skin cells in the dark, while NIR-irradiated drug-loaded nanovehicle showed a synergistic killing effect on skin cancer cells mainly through reactive oxygen species and caspase-activated apoptosis. The nanovehicle could significantly inhibit the proliferation of tumor cells in a 3D spheroid model in vitro. Porcine skin fluorescence imaging demonstrated that microneedles could facilitate the penetration of nanovehicle across the epidermis layer of skin to reach deep-seated melanoma sites. Tumor regression studies in a xenografted melanoma mouse model confirmed superior therapeutic efficacy of the nanovehicle through combinational PDT and targeted therapy.
PMID: 30444343 [PubMed - as supplied by publisher]
Neurocutaneous Melanosis with Leptomeningeal Melanoma Involving Supratentorium and Infratentorium.
Cureus. 2018 Sep 10;10(9):e3275
Authors: Thomas S, Patel B, Varghese SS, Backianathan S
Neurocutaneous melanoma is a rare congenital syndrome associated with congenital melanocytic nevi with meningeal melanosis or melanoma. The disease is aggressive and has a high propensity for leptomeningeal metastases. We present the case history of a man with neurocutaneous melanoma managed with radical excision followed by hypofractionated adjuvant radiotherapy. One year, eight months later, he had a recurrence of the condition with leptomeningeal spread and was managed with re-excision of the recurrent lesion. Although our patient was disease-free for 20 months after the initial surgery, he survived only approximately five months after the second surgery, which reflects the associated poor prognosis of the disease.
PMID: 30443446 [PubMed]
Cytoplasmic Pin1 expression is increased in human cutaneous melanoma and predicts poor prognosis.
Sci Rep. 2018 Nov 15;8(1):16867
Authors: Chen X, Liu X, Deng B, Martinka M, Zhou Y, Lan X, Cheng Y
The prolyl isomerase Pin1 is widely over-expressed or over-activated in cancers and promotes tumorigenesis. The authors investigated the expression level of Pin1 and analyzed the prognostic value of Pin1 expression using a large-scale melanoma tissue microarray study. Two independent sets of tissue microarrays were employed, including 114 melanoma cases in the discovery set and 424 in the validation set (538 cases in total), 32 normal nevi and 86 dysplastic nevi 118 cases of nevi. The subcellular Pin1 expression in different stages of melanocytic lesions and its prognostic significance were studied. High expression (IRS 0-8) of cytoplasmic Pin1 was observed in 3.13%, 8.33%, 16.49% and 22.76% of the biopsies in normal nevi, dysplastic nevi, primary melanoma and metastatic melanoma, respectively. Significant differences for cytoplasmic Pin1 staining were observed between normal nevi and metastatic melanoma (P = 0.011, χ2 test), between dysplastic nevi and primary melanoma (P = 0.046, χ2 test) and between dysplastic nevi and metastatic melanoma (P = 0.016, χ2 test). Kaplan-Meier survival analysis showed that increased cytoplasmic Pin1 expression was associated with a worse 5-year melanoma-specific survival of melanoma (P < 0.001) and metastatic melanoma patients (P = 0.004). Multivariate Cox regression analysis showed that cytoplasmic Pin1 expression is an independent prognostic factor in melanoma. Our data indicate that cytoplasmic Pin1 plays an important role in melanoma pathogenesis and progression, and serve as a potential prognostic marker for melanoma.
PMID: 30442923 [PubMed - in process]
Identification of Primary and Metastatic Melanoma based on Copy Number Variation.
Conf Proc IEEE Eng Med Biol Soc. 2018 Jul;2018:1319-1322
Authors: Seo H, Cho DH
The development of new sequencing technology has stimulated the cancer-related genome analysis. Copy number variation is one of the most important features that represents the structural variation. In this paper, we suggest the metastasis identification method of melanoma using copy number variations. The identification marker is defined in consideration of the presence and the type of copy number variations in primary and metastatic tumors. The optimization of marker is also provided and classification performances of developed markers are compared using the linear classifier.
PMID: 30440634 [PubMed - in process]