scholarly journals Aberrant trafficking of human melanocortin 1 receptor variants associated with red hair and skin cancer: Steady-state retention of mutant forms in the proximal golgi

2009 ◽  
Vol 220 (3) ◽  
pp. 640-654 ◽  
Author(s):  
Berta L. Sánchez-Laorden ◽  
Cecilia Herraiz ◽  
Julio C. Valencia ◽  
Vincent J. Hearing ◽  
Celia Jiménez-Cervantes ◽  
...  
Keyword(s):  
Steady State ◽  
Skin Cancer ◽  
Melanocortin 1 Receptor ◽  
Red Hair ◽  
Mutant Forms

scholarly journals Melanocortin-1 Receptor Gene Variants Determine the Risk of Nonmelanoma Skin Cancer Independently of Fair Skin and Red Hair

2001 ◽  
Vol 68 (4) ◽  
pp. 884-894 ◽  
Author(s):  
Maarten T. Bastiaens ◽  
Jeannet A. C. ter Huurne ◽  
Christine Kielich ◽  
Nelleke A. Gruis ◽  
Rudi G.J. Westendorp ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Receptor Gene ◽  
Nonmelanoma Skin Cancer ◽  
Gene Variants ◽  
Melanocortin 1 Receptor ◽  
Red Hair ◽  
Fair Skin

scholarly journals Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1560
Author(s):  
Amr Gamal ◽  
Haitham Saeed ◽  
Fatma I. Abo El-Ela ◽  
Heba F. Salem
Keyword(s):  
Steady State ◽  
Skin Cancer ◽  
Entrapment Efficiency ◽  
The United States ◽  
Relative Bioavailability ◽  
Passive Targeting ◽  
Therapeutic Benefits ◽  
Steady State Flux

Throughout the United States and the world, skin cancer is the most frequent form of cancer. Sonidegib (SNG) is a hedgehog inhibitor that has been used for skin cancer treatment. However, SNG has low bioavailability and is associated with resistance. The focus of this work is to enhance bioavailability, anti-tumor efficacy and targeting of SNG via developing ethosome gel as a potential treatment for skin cancer. SNG-loaded ethosomes formulation was prepared and characterized in vitro by %entrapment efficiency (%EE), vesicle size, morphology, %release and steady-state flux. The results showed that the prepared formulation was spherical nanovesicles with a %EE of 85.4 ± 0.57%, a particle size of 199.53 ± 4.51 nm and a steady-state flux of 5.58 ± 0.08 µg/cm2/h. In addition, SNG-loaded ethosomes formulation was incorporated into carbopol gel to study the anti-tumor efficacy, localization and bioavailability in vivo. Compared with oral SNG, the formulation showed 3.18 times higher relative bioavailability and consequently significant anti-tumor activity. In addition, this formulation showed a higher rate of SNG penetration in the skin’s deep layers and passive targeting in tumor cells. Briefly, SNG-loaded ethosome gel can produce desirable therapeutic benefits for treatment of skin cancer.

scholarly journals Susceptibility to Cutaneous Squamous Cell Carcinoma in Renal Transplant Recipients Associates with Genes Regulating Melanogenesis Independent of their Role in Pigmentation

2013 ◽  
Vol 5 ◽  
pp. BIC.S12754 ◽  
Author(s):  
Per A. Andresen ◽  
Dag A. Nymoen ◽  
Kristina Kjærheim ◽  
Torbjørn Leivestad ◽  
Per Helsing
Keyword(s):  
Squamous Cell Carcinoma ◽  
Renal Transplant ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Hair Color ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Melanocortin 1 Receptor ◽  
Red Hair

The highly polymorphic melanocortin 1 receptor ( MC1R) gene plays a crucial role in pigmentation. Variants of the gene have been implicated in risk of cutaneous squamous cell carcinoma (SCC) in the general population. In renal transplant (RT) recipients these cancers are more aggressive and very common. To evaluate the risk of SCC relative to MC1R and the pigmentation-associated genes ASIP, TYR, and TYRP1, a group of 217 RT recipients with and without SCC was genotyped. Associations with SCC risk were indicated in carriers of the red hair color associated MC1R variant p.Arg151Cys (OR= 1.99; 1.05–-3.75), and in carriers of two of any of the MC1R variants disclosed (OR = 2.36; 1.08–5.15). These associations appeared independent of traditionally protective phenotypes, also supported by the stratifications from skin phototype and hair color. A tendency towards an increased SCC risk was observed for a specific ASIP haplotype (OR = 1.87; 0.91–3.83), while no such associations were observed for the TYR and TYRP1 variants. Thus, the risk of developing SCC in RT patients is modulated by MC1R variation irrespective of phenotypes considered to be protective. Heterozygous combinations of MC1R variants appear to be more relevant in assessing SCC risk than the effects of variants individually.

Pain sensitivity and experimentally induced sensitisation in red haired females

2011 ◽  
Vol 2 (1) ◽  
pp. 3-6 ◽  
Author(s):  
Trine Andresen ◽  
Dagmar Lunden ◽  
Asbjørn M. Drewes ◽  
Lars Arendt-Nielsen
Keyword(s):  
Pain Sensitivity ◽  
Clinical Importance ◽  
Pain Tolerance ◽  
Melanocortin 1 Receptor ◽  
Red Hair ◽  
Dark Hair ◽  
The Difference ◽  
Topical Capsaicin ◽  
Healthy Females ◽  
Experimentally Induced

AbstractIntroduction and aimPain sensitivity has been linked to the melanocortin-1 receptor (MC1R) gene. A mutation in MC1R can result in pale skin and red hair in humans and may modulate pain responses in general. Human studies have shown that women with non-functional MC1R’s were sensitive to experimental induced cold and heat pain. A study demonstrated that females with red hair required higher dose of anesthesia than females with dark hair to experience analgesia to electrical stimulation. Moreover, women expressing non-functional MC1Rs display greater analgesia from opioid analgesia. If redheads in general respond differently to pain and analgesics, this is of clinical importance. The aim of this study was therefore to investigate pain sensitivity and experimentally induced sensitisation in red haired females.MethodTwenty healthy females with pale skin and red hair (mean age 32 years, range 20–55) and 20 healthy females with blond/dark hair (mean age 31 years, range 20–51) participated in this study. The pain tolerance thresholds to heat and pressure stimulation were determined. Hyperalgesia was induced experimentally by applying 0.075% topical capsaicin cream for 30 min. The secondary pin-prick hyperalgesic area was estimated with a calibrated filament (von Frey hair, 15 g) and the area of allodynia by a soft brush. This was done 0, 30, 60, and 90 min after cream removal.ResultsNeither heat nor pressure pain tolerance thresholds were changed in the two groups. The secondary pin-prick hyperalgesic areas were significantly smaller for red haired females than blond/dark haired females (P = 0.014). There were no significant differences in the allodynic areas.DiscussionAs the secondary hyperalgesic response evoked by topical capsaicin is a central phenomenon, the observed smaller pin-prick hyperalgesic area in the red haired females could indicate a central role of MCRs in development or maintenance of hyperalgesia. Central involvement of MC1Rs or dysfunction of peripheral MC1Rs activating central MC4Rs has been suggested to influence pain sensitivity. The difference observed between red haired and non-red haired females may have implications for pain management regimens as compounds interacting with sensitisation such as NMDA-antagonists or alpha-2-delta-ligands may exert different types of action in people with MC1R mutation.ConclusionThe present study showed that red haired females were less sensitive to topical capsaicin induced pin-prick hyperalgesia compared with blond/dark haired females.ImplicationsThe smaller hyperalgesic area in redheads could be a manifestation of central anti-hyperalgesic involvement of MCRs and could have an influence on the treatment of pain as well as in studies investigating anti-hyperalgesic drugs.

Association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and statins and the risk of cutaneous melanoma (CM): A case-control study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8500-8500 ◽  
Author(s):  
C. Curiel ◽  
M. L. Gomez ◽  
M. B. Atkins ◽  
T. Nijsten ◽  
R. S. Stern
Keyword(s):  
Risk Factors ◽  
Skin Cancer ◽  
Protective Effect ◽  
Case Control Study ◽  
Case Control ◽  
Red Hair ◽  
Frequency Of Use ◽  
History Of ◽  
Control Study ◽  
Statin Use

8500 Background: CM accounts for more than 77% of skin cancer deaths. Chemoprevention strategies have been hampered by the lack of supporting epidemiological data. Methods: A case control study examined the association between statins and NSAIDs use and CM in people over 40 years of age. A total of 400 histologically confirmed CM cases were recruited within 3 months from diagnosis between 3/04 and 12/06. Controls included 600 individuals without history of CM matched for age, gender and neighborhood in a ratio of 1:1.5. All completed a standardized telephone questionnaire that captured demographic characteristics, CM risk factors, and drug exposure history (length and frequency of use). Odds ratios were calculated with testing for statistical significance based on Chi square analysis. Results: To date, all 400 CM cases and 547 controls have been recruited. Interview results out of 387 cases (192 F/195 M) and 505 controls (254 F/251 M) were included for data analysis. Mean age was 58.4 and 58.5 years. The most significant CM risk factors included: red hair phenotype OR: 2.29, history of non-CM skin cancer OR: 2.28, family history of CM OR: 1.76, light complexion OR: 2.7, and history of more than 4 sunburns in childhood OR: 4.06. 100 cases vs. 190 of the controls had been exposed to statins OR 0.58 (CI:0.43–0.78); no greater protective effect was detected with increased duration of statin use (p=0.87 for heterogeneity of ORs for =5 vs. <5 yrs). 238 cases vs. 397 controls reported the use of NSAIDs, OR 0.44 (CI 0.32–0.59). 43 cases reported the use of aspirin-ASA for = 5 years vs. 92 controls OR: 0.37 (CI: 0.20–0.68). Similar results were observed with exposure to other NSAIDs with 38 cases reporting the use for = 5 years vs.109 controls, OR: 0.35 (CI: 0.24- 0.50). Conclusions: This study suggests that extended use of NSAIDs decreases the risk of CM development. Although any statin use demonstrated a decreased risk, the lack of an association between duration of use and protective effect raises questions about a true causal relation. Further analysis with respect to the CM subtype and specific exposure (by dose, and frequency of use) to these groups of drugs may lead to the design of CM chemopreventive clinical trials. Final analysis will be presented at ASCO. No significant financial relationships to disclose.

scholarly journals Mammalian pigmentation is regulated by a distinct cAMP-dependent mechanism that controls melanosome pH

2018 ◽  
Vol 11 (555) ◽  
pp. eaau7987 ◽  
Author(s):  
Dalee Zhou ◽  
Koji Ota ◽  
Charlee Nardin ◽  
Michelle Feldman ◽  
Adam Widman ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Skin Color ◽  
Skin Pigmentation ◽  
Melanin Production ◽  
Melanocortin 1 Receptor ◽  
New Class ◽  
Camp Pathway ◽  
Human Melanocytes ◽  
Rate Limiting

The production of melanin increases skin pigmentation and reduces the risk of skin cancer. Melanin production depends on the pH of melanosomes, which are more acidic in lighter-skinned than in darker-skinned people. We showed that inhibition of soluble adenylyl cyclase (sAC) controlled pigmentation by increasing the pH of melanosomes both in cells and in vivo. Distinct from the canonical melanocortin 1 receptor (MC1R)–dependent cAMP pathway that controls pigmentation by altering gene expression, we found that inhibition of sAC increased pigmentation by increasing the activity of tyrosinase, the rate-limiting enzyme in melanin synthesis, which is more active at basic pH. We demonstrated that the effect of sAC activity on pH and melanin production in human melanocytes depended on the skin color of the donor. Last, we identified sAC inhibitors as a new class of drugs that increase melanosome pH and pigmentation in vivo, suggesting that pharmacologic inhibition of this pathway may affect skin cancer risk or pigmentation conditions.

Melanocortin-1-receptor gene and sun sensitivity in individuals without red hair

The Lancet ◽  
2000 ◽  
Vol 355 (9209) ◽  
pp. 1072-1073 ◽  
Author(s):  
Eugene Healy ◽  
Niamh Flannagan ◽  
Amanda Ray ◽  
Carole Todd ◽  
Ian J Jackson ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Melanocortin 1 Receptor ◽  
Red Hair ◽  
Sun Sensitivity

scholarly journals The Role of Melanocortin 1 Receptor in Cutaneous Malignant Melanoma

2014 ◽  
Vol 16 (4) ◽  
pp. 421-428 ◽  
Author(s):  
Mary Beth Steck
Keyword(s):  
Malignant Melanoma ◽  
Mapk Pathway ◽  
The United States ◽  
Cutaneous Malignant Melanoma ◽  
Mitogen Activated Protein Kinase ◽  
Genomic Research ◽  
Melanocortin 1 Receptor ◽  
Red Hair ◽  
Increased Risk

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 gene associated with red-hair phenotype in White individuals and with increased risk for developing CMM, in the mitogen-activated protein kinase (MAPK) pathway. This limited narrative review discusses the incidence, history, and risk factors for CMM. It explores familial CMM and provides a brief review of melanocyte development and melanogenesis. Histology of CMM and cytogenetic techniques used to identify CMM mutations is also discussed. The structure and function of MC1R is described, with particular attention to MC1R’s role in the MAPK pathway. Finally, the review touches on individualized therapy for CMM using genetic biomarkers and explores the promise of genomic research for finding effective treatments.

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