Figure 4 - uploaded by Mary Beth Steck
Content may be subject to copyright.
MC1R gene location on chromosome 16p24.3. Retrieved from http://ghr.nlm.nih.gov/dynamicImages/chromomap/MC1R.jpeg
Source publication
Cutaneous malignant melanoma (CMM) is an epidemic cancer in the United States. Survival rates for invasive CMM have not increased in past decades despite numerous clinical trials and the effective use of various combinations of chemotherapy agents to treat other cancers. Recent research has investigated the role of melanocortin 1 receptor (MC1R), a...
Context in source publication
Context 1
... is one of a family of five melanocortin receptors, is located on the positive strand of chromosome 16p24.3, and has a genomic size of 3,099 base pairs with the genomic sequence chromosome 16:88,511,788-88,514,886 (see Figure 4; Ibrahim & Haluska, 2009; University of California, Santa Cruz, Genome Browser, 2013). The gene has been referred to using sev- eral terms in bioinformatics databases, including melanocyte- stimulating hormone receptor, melanocortin receptor, or melanocortin receptor 1. ...
Citations
... The third stage, known as the radial growth phase is characterized by a cancerous histological phenotype, rapid growth across the epidermis with only minor incursions across the basement membrane, and constitutive activation of ERK signaling to drive rapid clonal cell proliferation (Haass and Herlyn 2005;Miller and Mihm 2006;Shain and Bastian 2016). Explanted cells from lesions in the radial growth phase, or any earlier phase, are typically unable to produce colonies in soft agar, as they are typically reliant on exogenous growth factors (Miller and Mihm 2006;Steck 2014). Since the cells are largely unable to penetrate deeper than the basement membrane, surgical excision up to this stage remains highly effective (Steck 2014). ...
... Explanted cells from lesions in the radial growth phase, or any earlier phase, are typically unable to produce colonies in soft agar, as they are typically reliant on exogenous growth factors (Miller and Mihm 2006;Steck 2014). Since the cells are largely unable to penetrate deeper than the basement membrane, surgical excision up to this stage remains highly effective (Steck 2014). ...
... It has been theorized that this newfound ability to communicate and attach to fibroblasts might be instrumental in facilitating the transition from the radial growth phase to the vertical growth phase (Haass and Herlyn 2005). At this point the tumor is fully competent to invade and metastasize to distant organs, though continuing accumulation of mutations may speed this process (Steck 2014). Once metastasis to distant organs has occurred, the tumor has entered its final stage is now termed metastatic melanoma. ...
Melanoma metastasis is fatal. Melanoma cells are often characterized by an activated extracellular signal-regulated kinase (ERK) pathway downstream of mutations in BRAF. Therapies targeting these BRAF mutations are useful for a while; however, patients ultimately develop resistance to these therapies. Recent evidence suggests that this resistance occurs when tumor cells leave their microenvironment and migrate on a stiff, activated tumor stroma; that is, this resistance is linked to the presence of an extracellular matrix reminiscent of a fibrotic micronvironment. These data suggest that agents targeting fibrosis might be used to treat melanoma. We therefore discuss what is known about the tumor stroma in melanoma. An emergent target, CCN2 (CTGF), that is required for fibrosis, may also be a good target for drug-resistant melanoma. Intriguingly, anti-CCN2 antibodies are currently under clinical development.
Background:
Elucidation of key biomarkers, as indicators and drivers of the pathologic processes in cutaneous melanoma (CM), has led to the development of effective targeted therapies.
Objectives:
This article provides an overview of key concepts in advanced CM, particularly the essential role of biomarkers and biomarker testing to guide treatment.
Methods:
A comprehensive literature search was conducted in CINAHL® and PubMed® using the following search terms.
Findings:
Targeted BRAF/MEK inhibitors, as well as immune checkpoint inhibitors, have vastly improved long-term outcomes in advanced CM. Deepening understanding of the biologic and genomic features of CM and their interactions with the host immune system is critical for predicting treatment and survival outcomes and developing new therapies.
As we gain a greater understanding of acne pathogenesis, both new agents as well as new uses for established drugs are being considered for the treatment of acne vulgaris. Multiple clinical trials assessing new formulations or combinations of established acne treatments have been conducted, and novel uses of antimicrobials such as modified diallyl disulfide oxide and nitric oxide are being assessed in clinical trials. There are also a multitude of new therapies currently being studied that target the inflammatory cascade of acne pathogenesis, including sebosuppressive and anti-inflammatory phytochemicals, and small molecule inhibitors targeting sebaceous glands and enzymes, among others. Laser and light therapy is also being modified for the treatment of acne through combination methods with metal nanoshells and vacuum assistance. Probiotics have gained popularity in medicine as greater knowledge of the microbiome and its effects on multiple organ systems is being elucidated. Studies describing the positive effects of certain ammonia-oxidizing bacterial strains in the regulation of the skin's inflammatory response are ongoing. Therapies for acne are constantly evolving and current gold-standard acne therapy may be supplemented with novel treatment modalities in the near future.
Metastatic melanoma represents the most aggressive form of skin cancer with a median survival around 13 months. The low efficacy of actual chemotherapy is explained by important resistance phenomenon. The objective of this work consists in developing a new alternative strategy based on siRNA (small interfering RNA) encapsulated into lipid nanocapsules (LNCs) for intravenous injection. Firstly, the experiments were focused on development and optimization of formulation process for the encapsulation of siRNA into LNCs. The result demonstrated an encapsulation efficiency evaluated at 35% by spectrophotometer analysis, an important stability at 4°C (for at less 3 month) and an efficient gene inhibition in melanoma cells. The second part of this work studied the melanoma targeting potential of surface modified LNCs after systemic injection. In this way, pegylation with different polymers and Affitin grafting (affinity peptide) was performed on siRNA LNCs. The biodistribution on healthy animals and subcutaneous melanoma tumor bearing mice revealed the distinct behavior of various modified LNCs. All pegylated LNCs showed a preferential accumulation in tumor site in comparison with non-modified or Affitins LNCs. In a third part, the anti-cancer efficacy was tested with siRNA targeting Bcl-2, an anti-apoptotic member, or Alpha 1 subunit of Na/K ATPase. A reduction of tumoral volume evaluated at 25% was observed for Bcl-2 siRNA LNC. Moreover, the association with new promising anticancerous drug, ferrocifens, and Bcl-2 siRNA co-encapsulated into LNCs evidenced promising effects. This work demonstrated the capacity of LNC to deliver siRNA into melanoma cells and tumor after systemic administration thank to new targeting strategies in melanoma
