Melanoma molecular classes and prognosis in the postgenomic era

Tremante, Elisa; Ginebri, Agnese; Monaco, Elisa Lo; Frascione, Pasquale; Filippo, F. Di; Terrenato, Irene; Benevolo, Maria; Mottolese, Marcella; Pescarmona, Edoardo; Visca, P.; Natali, Pier Giorgio; Giacomini, Patrizio

doi:10.1016/s1470-2045(12)70003-7

Cited by 30 publications

(19 citation statements)

References 64 publications

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“…Malignant melanoma is a lethal type of skin cancer, accounting for 80% of skin cancer mortalities (14). The high degree of malignancy and occurrence in a dormant state, in addition to a strong tendency for distant metastasis, invasion and migration, presents a challenge in the provision of a successful clinical treatment.…”

Section: Discussionmentioning

confidence: 99%

Euphorbia fischeriana Steud inhibits malignant melanoma via modulation of the phosphoinositide-3-kinase/Akt signaling pathway

Zhang

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Euphorbia fischeriana Steud, a traditional Chinese medicine, has been shown to inhibit the growth of various cancers by the induction of apoptosis and cell cycle arrest. The purpose of the present study was to investigate the association between the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and the inhibitory effect of Euphorbia fischeriana Steud on the growth and metastasis of melanoma B16 cells in vitro, and the underlying mechanisms. MTT assay results indicated that Euphorbia fischeriana Steud inhibited the growth of B16 cells in a time-and dose-dependent manner. Flow cytometric analysis revealed that Euphorbia fischeriana Steud markedly induced apoptosis of the B16 cells, with arrest at the G0/G1 phase of the cell cycle. In addition, in a Transwell assay Euphorbia fischeriana Steud significantly suppressed the migration of B16 cells. Western blot analysis revealed that the expression levels of phosphatase and tensin homolog (PTEN) were upregulated, and the phosphorylation of Akt was downregulated, which resulted in inhibition of the PI3K/Akt signaling pathway and the eventual suppression of its downstream targets, such as matrix metalloproteinase-2 mRNA, in B16 cells. The results demonstrated that Euphorbia fischeriana Steud inhibited the growth and migration of B16 cells, possibly via modulation of the PI3K/Akt signaling pathway and upregulation of PTEN expression levels, in addition to downregulation of p-Akt expression. The aforementioned findings suggest that Euphorbia fischeriana Steud may have broad therapeutic applications in the treatment of malignant melanoma. IntroductionMalignant melanoma has become a frequently occurring malignancy with an annual increase of ~3% (1). The majority (~90%) of patients with early detected melanoma are curable; however, the efficiency of clinical drugs in the treatment of patients with advanced metastatic melanoma is <20% (2), and the 5-year survival rate is <5%, with a median survival time of only 2-8 months (3,4). Numerous studies have confirmed that the poor prognosis of malignant melanoma is primarily attributable to the high incidence of distant metastasis and a strong capacity for invasion (5-7). Therefore, the development of more effective therapies for the inhibition of metastasis presents a challenge for the treatment of malignant melanoma.Chemotherapy has a significant role in the treatment of cancer. However, the majority of chemotherapy drugs also destroy normal cells, leading to adverse effects (8). Therefore, the identification of natural compounds with a wide range of anticancer activities, high selectivity for the destruction of cancer cells and low toxicity of normal cells is of importance in cancer research. Euphorbia fischeriana Steud (also known as lang-du), a herbaceous plant used in traditional Chinese medicine (TCM), has demonstrated inhibitory effects through its capacity to induce apoptosis, suppress growth and cause cell cycle arrest when assessed within several cancer cell lines, including leukemia a...

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Section: Discussionmentioning

confidence: 99%

Euphorbia fischeriana Steud inhibits malignant melanoma via modulation of the phosphoinositide-3-kinase/Akt signaling pathway

Zhang

Wang

et al. 2016

Experimental and Therapeutic Medicine

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“…Adding to this, only a fraction of new approvals are for agents directed at novel targets, which, in part, has been attributed to the lack of proper in vivo validation (17). Evidently, more reproducible animal models are needed to elucidate the biology of brain metastasis (7,8,13,14), and to functionally validate large-scale genomic and pharmacologic data obtained from human tumor material (19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

“…Such models are required to uncover the enigmatic biology of melanoma brain metastasis (7,8,13,14), to bridge the gap between preclinical and clinical efficacy studies (10,(15)(16)(17)(18), and to functionally validate a vast array of new potential metastasis genes (19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Automated Tracking of Nanoparticle-labeled Melanoma Cells Improves the Predictive Power of a Brain Metastasis Model

et al. 2013

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Biologic and therapeutic advances in melanoma brain metastasis are hampered by the paucity of reproducible and predictive animal models. In this work, we developed a robust model of brain metastasis that empowers quantitative tracking of cellular dissemination and tumor progression. Human melanoma cells labeled with superparamagnetic iron oxide nanoparticles (SPION) were injected into the left cardiac ventricle of mice and visualized by MRI. We showed that SPION exposure did not affect viability, growth, or migration in multiple cell lines across several in vitro assays. Moreover, labeling did not impose changes in cell-cycle distribution or apoptosis. In vivo, several SPION-positive cell lines displayed similar cerebral imaging and histologic features. MRI-based automated quantification of labeled cells in the brain showed a sigmoid association between metastasis frequency and doses of inoculated cells. Validation of this fully automated quantification showed a strong correlation with manual signal registration (r 2 ¼ 0.921, P < 0.001) and incidence of brain metastases (r 2 ¼ 0.708, P < 0.001). Metastasis formation resembled the pattern seen in humans and was unaffected by SPION labeling (histology; tumor count, P ¼ 0.686; survival, P ¼ 0.547). In summary, we present here a highly reproducible animal model that can improve the predictive value of mechanistic and therapeutic studies of melanoma brain metastasis. Cancer Res; 73(8); 2445-56. Ó2013 AACR.

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“…Recently, molecular studies reporting gene expression profiles in melanoma have been reviewed [88]. From more than 100 articles available in the literature, only 14 gene expression studies that identified biomarkers associated with prognosis fulfilled the REMARK criteria [54,[89][90][91][92][93][94][95][96][97][98][99][100]124].…”

Section: Genetic Microarray Signatures: Impact On Prognosis and Technmentioning

confidence: 99%

Tissue prognostic biomarkers in primary cutaneous melanoma

Mandalà

Massi

2014

Virchows Arch

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Cutaneous melanoma (CM) causes the greatest number of skin cancer-related deaths worldwide. Predicting CM prognosis is important to determine the need for further investigation, counseling of patients, to guide appropriate management (particularly the need for postoperative adjuvant therapy), and for assignment of risk status in groups of patients entering clinical trials. Since recurrence rate is largely independent from stages defined by morphological and morphometric criteria, there is a strong need for identification of additional robust prognostic factors to support decisionmaking processes. Most data on prognostic biomarkers in melanoma have been evaluated in tumor tissue samples by conventional morphology and immunohistochemistry (IHC) as well as DNA and RNA analyses. In the present review, we critically summarize main high-quality studies investigating IHC-based protein biomarkers of melanoma outcome according to Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK)-derived criteria. Pathways have been classified and conveyed in the "biologic road" previously described by Hanahan and Weinberg. Data derived from genomic and transcriptomic technologies have been critically reviewed to better understand if any of investigated proteins or gene signatures should be incorporated into clinical practice or still remain a field of melanoma research. Despite a wide body of research, no molecular prognostic biomarker has yet been translated into clinical practice.Conventional tissue biomarkers, such as Breslow thickness, ulceration, mitotic rate and lymph node positivity, remain the backbone prognostic indicators in melanoma.

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Melanoma molecular classes and prognosis in the postgenomic era

Cited by 30 publications

References 64 publications

Euphorbia fischeriana Steud inhibits malignant melanoma via modulation of the phosphoinositide-3-kinase/Akt signaling pathway

Euphorbia fischeriana Steud inhibits malignant melanoma via modulation of the phosphoinositide-3-kinase/Akt signaling pathway

Automated Tracking of Nanoparticle-labeled Melanoma Cells Improves the Predictive Power of a Brain Metastasis Model

Tissue prognostic biomarkers in primary cutaneous melanoma

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