Methylene blue photodynamic therapy in malignant melanoma decreases expression of proliferating cell nuclear antigen and heparanases

Wagner, Mariana Fatima Muaccad Gama; Suarez, Eloah Rabello; Theodoro, Therésè Rachell; Filho, Carlos D' Apparecida Santos Machado; Gama, M. F. M.; Tardivo, João Paulo; Paschoal, Francisco Macedo; Pinhal, Maria Aparecida Silva

doi:10.1111/j.1365-2230.2011.04291.x

Cited by 50 publications

(36 citation statements)

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“…HPA-1 has been reported to degrade the extracellular matrix and facilitate the process of the invasion and metastasis of carcinoma (Liu et al, 2008;Yingying et al, 2009;Wagner et al, 2012). A predominant correlation was observed between HPA-1 expression and tumor invasion and lymphatic metastasis in gastric carcinoma (Endo et al, 2001;Takaoka et al, 2003), and this finding is consistent with the results of our study.…”

Section: Discussionsupporting

confidence: 83%

Increased Levels of β-catenin, LEF-1, and HPA-1 Correlate with Poor Prognosis for Acral Melanoma with Negative BRAF and NRAS Mutation in BRAF Exons 11 and 15 and NRAS Exons 1 and 2

Yang

Zhang

et al. 2015

DNA and Cell Biology

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To determine the expression of b-catenin, lymphoid enhancer-binding protein-1 (LEF-1), and heparanase-1 (HPA-1) and to evaluate these proteins' potential prognostic values in malignant acral melanoma without mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2, specimens from 90 patients with wild-type BRAF and NRAS were assessed and analyzed by immunohistochemistry and western blotting. The positive expression of b-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was observed in 36 (72%), 31 (62%), and 32 (64%) of the detected acral melanomas, respectively. The expression of b-catenin, lymphoid enhancerbinding protein-1, and heparanase-1 was not correlated with gender, age, or diseased body parts ( p > 0.05), but was significantly positively correlated with the tumor node metastasis (TNM) stage and metastasis (correlation = 0.406 and 0.716, 0.397 and 0.582, 0.353 and 0.579; p = 0.040 and 0.0001, 0.0040 and 0.0001, 0.0120 and 0.0001, respectively). We also observed that the increased expression of b-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was significantly correlated with decreased survival and poor prognosis ( p = 0.001, 0.010, and 0.023, respectively). A multifactorial analysis using Cox's regression model revealed that b-catenin, lymphoid enhancer-binding protein-1, heparanase-1, and the TNM stage were all independent factors in malignant melanoma (risk ratios were 7.294, 5.550, 5.622, and 4.794; p-values were 0.007, 0.018, 0.018, and 0.029, respectively). This study may provide the basis for the use of b-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 as novel targets in the treatment of malignant invasion and metastasis in acral melanoma cancer. The expression of b-catenin, LEF-1, and HPA-1 was assessed and compared in malignant melanoma with that of peritumoral tissue and benign nevus in the patients with negative mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2. The study may provide the basis for b-catenin, LEF-1, and HPA-1 as new targets in the treatment of malignant invasion and metastasis in melanoma cancer.

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Section: Discussionsupporting

confidence: 83%

Increased Levels of β-catenin, LEF-1, and HPA-1 Correlate with Poor Prognosis for Acral Melanoma with Negative BRAF and NRAS Mutation in BRAF Exons 11 and 15 and NRAS Exons 1 and 2

Yang

Zhang

et al. 2015

DNA and Cell Biology

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“…These facts suggest that MB could be used either as chemotherapeutic or as photosensitizer. However, it is noteworthy that no treatment condition with MB-PDT achieved complete remission of tumors [51].…”

Section: Preclinical Studies On Skin Melanomamentioning

confidence: 97%

“…We agree with this affirmation in regard to the current research about photodynamic intervention on skin melanoma. Our comparative analysis revealed a disconnect between several hypotheses generated by in vitro therapeutic studies and in vivo assays, which could probably be explained by the ability of mouse models to preserve crucial features of tumor biology [49][50][51]53].…”

Section: Organotypic Human Skin ----mentioning

confidence: 99%

Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment

et al. 2015

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Melanoma is among the most aggressive and treatment-resistant human skin cancer. Photodynamic therapy (PDT), a minimally invasive therapeutic modality, is a promising approach to treating melanoma. It combines a non-toxic photoactivatable drug called photosensitizer with harmless visible light to generate reactive oxygen species which mediate the antitumor effects. The aim of this review was to compile the available data about PDT on melanoma. Our comparative analysis revealed a disconnection between several hypotheses generated by in vitro therapeutic studies and in vivo and clinical assays. This fact led us to highlight new preclinical experimental platforms that mimic the complexity of tumor biology. The tumor and its stromal microenvironment have a dynamic and reciprocal interaction that plays a critical role in tumor resistance, and these interactions can be exploited for novel therapeutic targets. In this sense, we review two strategies used by photodynamic researchers: (a) developing 3D culture systems which mimic tumor architecture and (b) heterotypic cultures that resemble tumor microenvironment to favor therapeutic regimen design. After this comprehensive review of the literature, we suggest that new complementary preclinical models are required to better optimize the clinical outcome of PDT on skin melanoma.

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“…Several approaches have also been developed using phenothiazinium derivatives, such as methylene blue (MB), as a new treatment strategy, leading to a PDT protocol which is efficient and also inexpensive [21–25]. In addition to the low cost and commercial availability, the use of MB is also interesting because it has been safely used for decades in other clinical applications [21, 22, 26, 27]. …”

Section: Introductionmentioning

confidence: 99%

Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells

et al. 2017

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BackgroundBreast cancer is the main cause of mortality among women. The disease presents high recurrence mainly due to incomplete efficacy of primary treatment in killing all cancer cells. Photodynamic therapy (PDT), an approach that causes tissue destruction by visible light in the presence of a photosensitizer (Ps) and oxygen, appears as a promising alternative therapy that could be used adjunct to chemotherapy and surgery for curing cancer. However, the efficacy of PDT to treat breast tumours as well as the molecular mechanisms that lead to cell death remain unclear.MethodsIn this study, we assessed the cell-killing potential of PDT using methylene blue (MB-PDT) in three breast epithelial cell lines that represent non-malignant conditions and different molecular subtypes of breast tumours. Cells were incubated in the absence or presence of MB and irradiated or not at 640 nm with 4.5 J/cm2. We used a combination of imaging and biochemistry approaches to assess the involvement of classical autophagic and apoptotic pathways in mediating the cell-deletion induced by MB-PDT. The role of these pathways was investigated using specific inhibitors, activators and gene silencing.ResultsWe observed that MB-PDT differentially induces massive cell death of tumour cells. Non-malignant cells were significantly more resistant to the therapy compared to malignant cells. Morphological and biochemical analysis of dying cells pointed to alternative mechanisms rather than classical apoptosis. MB-PDT-induced autophagy modulated cell viability depending on the cell model used. However, impairment of one of these pathways did not prevent the fatal destination of MB-PDT treated cells. Additionally, when using a physiological 3D culture model that recapitulates relevant features of normal and tumorous breast tissue morphology, we found that MB-PDT differential action in killing tumour cells was even higher than what was detected in 2D cultures.ConclusionsFinally, our observations underscore the potential of MB-PDT as a highly efficient strategy which could use as a powerful adjunct therapy to surgery of breast tumours, and possibly other types of tumours, to safely increase the eradication rate of microscopic residual disease and thus minimizing the chance of both local and metastatic recurrence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3179-7) contains supplementary material, which is available to authorized users.

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Methylene blue photodynamic therapy in malignant melanoma decreases expression of proliferating cell nuclear antigen and heparanases

Abstract: MB-PDT is a cheap and efficient method of decreasing MM volume and thus disease progression. This reduction is mediated by downregulation of PCNA and heparanases.

Cited by 50 publications

References 25 publications

Increased Levels of β-catenin, LEF-1, and HPA-1 Correlate with Poor Prognosis for Acral Melanoma with Negative BRAF and NRAS Mutation in BRAF Exons 11 and 15 and NRAS Exons 1 and 2

Increased Levels of β-catenin, LEF-1, and HPA-1 Correlate with Poor Prognosis for Acral Melanoma with Negative BRAF and NRAS Mutation in BRAF Exons 11 and 15 and NRAS Exons 1 and 2

Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment

Methylene blue photodynamic therapy induces selective and massive cell death in human breast cancer cells

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