Skin cancer: Difference between revisions
Jump to navigation
Jump to search
Sara Mohsin (talk | contribs) |
Sara Mohsin (talk | contribs) |
||
| Line 142: | Line 142: | ||
*[[Skin]] [[Cancer (medicine)|cancer]] is most closely [[Association (statistics)|associated]] with [[chronic inflammation]] of the [[skin]] | *[[Skin]] [[Cancer (medicine)|cancer]] is most closely [[Association (statistics)|associated]] with [[chronic inflammation]] of the [[skin]] | ||
===Normal skin function=== | ===Normal skin function=== | ||
*Skin is the largest organ of body with following functions: | *[[Skin]] is the [[Large-print|largest]] [[Organ (biology)|organ]] of [[Human body|body]] with following [[Function (biology)|functions]]: | ||
**As a physical barrier, it provides protection against: | **As a [[Physical activity|physical]] [[Barrier (pharmaceutical)|barrier]], it provides [[Protecting group|protection]] against: | ||
***Sunlight | ***[[Sunlight]] | ||
***Heat | ***[[Heat]] | ||
***Infection | ***[[Infection]] | ||
***Injury | ***[[Injury]] | ||
**Controls the body temperature (provides insulation to the internal body organs) | **[[Control|Controls]] the [[body temperature]] (provides [[Insulator|insulation]] to the [[internal]] [[Human body|body]] [[organs]]) | ||
**It stores: | **It stores: | ||
***Water | ***[[Water]] | ||
***Vitamin D | ***[[Vitamin D]] | ||
***Fat | ***[[Fat]] | ||
===Normal skin anatomy=== | ===Normal skin anatomy=== | ||
*The two main layers of skin include: | *The two [[Main effect|main]] layers of [[skin]] include: | ||
**Outer layer of epidermis (skin cancer starts in this layer), which has following three different kinds of cells: | **Outer layer of [[Epidermis (skin)|epidermis]] ([[skin]] [[Cancer (disease)|cancer]] starts in this layer), which has following three different kinds of [[Cells (biology)|cells]]: | ||
***Top layer of epidermis is made up of thin, flat squamous cells | ***[[Top7|Top]] layer of [[Epidermis (skin)|epidermis]] is made up of thin, [[Flat affect|flat]] '''[[Squamous cell|squamous cells]]''' | ||
***Round basal cells are present below the layer of squamous cells | ***[[Round face|Round]] [[Basal cell|'''basal cells''']] are [[Presenting symptom|present]] below the layer of [[Squamous cell|squamous cells]] | ||
***Lower epidermal layer has melanin producing cells (melanocytes) which on increased sun exposure lead to more pigment production causing skin darkening | ***Lower [[epidermal]] layer has [[melanin]] [[Product (biology)|producing]] [[Cells (biology)|cells]] ([[melanocytes]]) which on increased [[sun exposure]] [[lead]] to more [[pigment]] [[Product (biology)|production]] [[Causality|causing]] [[skin]] [[Dark matter|darkening]] | ||
**Inner layer of dermis | **[[Inner coat|Inner]] layer of [[dermis]] | ||
{| | {| | ||
| | | | ||
Revision as of 14:52, 25 July 2019
|
Skin cancer Microchapters |
| Skin cancer | |
| ICD-10 | C43-C44 |
|---|---|
| ICD-9 | 172, 173 |
| ICD-O: | 8010-8720 |
| MeSH | D012878 |
For patient information click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4] Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[5]
Overview
Skin cancer is the malignant growth on the skin which is the most common type of malignancy in Caucasians. Skin cancer generally develops in the epidermis (the outermost layer of skin), so a tumor is usually clearly visible. This makes most skin cancers detectable in the early stages. There are three common types of skin cancer, each of which is named after the type of the skin cell from which it arises. Cancers caused by UV exposure may be prevented by avoiding exposure to sunlight or other UV sources, wearing sun-protective clothes, and using a broad-spectrum sunscreen. Skin cancers are the fastest growing type of cancer in the United States. Skin cancer represents the most commonly diagnosed malignancy, surpassing lung, breast, colorectal and prostate cancer. More than 1 million Americans were estimated to be diagnosed with skin cancer in 2007.
Historical Perspective
- In 1988, Bestor first identified DNA methyltransferase 1 (DNMT1), which is the primary target of UV radiations in carcinogenic process of skin cancer[1]
- From 1992 to 1994, free American Academy of Dermatology's National Skin Cancer Early Detection and Screening Program was launched which provided broad skin cancer educational information to general public and enabled almost 750,000 free expert skin cancer examinations which mostly found out thin, localized stage 1 melanomas with high projected 5-year survival rate[2][3]
- From 2001 to 2005, American Academy of Dermatology National Melanoma/Skin Cancer Screening Program was launched which led to the conclusion that HARMM criteria can be used to identify the higher-risk subgroup of skin cancer screening population via assessment of multiple risk factors for MM , which will not only reduce the cost but will also increase the yields for suspected MM in future mass screening initiatives[4]
Classification
- Skin cancer is broadly divided into melanoma and nonmelanoma types as shown in the following table:[5][6][7][8][9]
Pathophysiology
- Skin cancer is most closely associated with chronic inflammation of the skin
Normal skin function
Normal skin anatomy
- The two main layers of skin include:
- Outer layer of epidermis (skin cancer starts in this layer), which has following three different kinds of cells:
- Top layer of epidermis is made up of thin, flat squamous cells
- Round basal cells are present below the layer of squamous cells
- Lower epidermal layer has melanin producing cells (melanocytes) which on increased sun exposure lead to more pigment production causing skin darkening
- Inner layer of dermis
- Outer layer of epidermis (skin cancer starts in this layer), which has following three different kinds of cells:
 |
 |
 |
![[1]](https://commons.wikimedia.org/wiki/Category:Epidermis_(skin)#/media/File:Epidermal_layers.svg){kind=link}
![[3]](https://commons.wikimedia.org/wiki/Category:Epidermis_(skin)#/media/File:Skinlayers.png){kind=link}
Epigenetics
UVA & UVB have both been implicated in causing DNA damage resulting in cancer by any of the following mechanisms:[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]
- UV radiation induces histone 3 methylation changes in the gene promoters of matrix metalloproteinase 1 and MMP3 in primary human dermal fibroblasts leading to the increased expression of MMP1 and MMP3[29]
- UVB irradiation leads to DNA CpG methylation and transcriptomic changes in following genes & cancer related pathways at the different stages of carcinogenesis:
- PTEN
- p53
- Nrf2
- p21(Waf1/Cip1)
- Inflammatory signaling
- Enf2
- Mgst2
- Vegfa
- Cdk4
- UVA irradiation causes an increase in intracellular reactive oxygen species (ROS), prostaglandin E2 (PGE2), and PGE2 receptors, which leads to decreased expression of transcription factor zinc finger E-box binding homeobox 1(ZEB1) which binds to DNA methyltransferase 1 (DNMT1) promoter and regulates its transcription, thus leading to senescence of DNMT1 in human dermal fibroblasts (HDFs). This causes low methylation level of senescence related proteins p53 thus, increasing its expression, eventually resulting in cellular senescence[14][30][31][32][33][34][35][29][36][37][38][39][1][40][41][42][43][44][13][45][46][47][48][49][50][51]
| UVA exposure to the sun-exposed skin | |||||||||||||||||||
| Suppression of the contact hypersensitivity (CHS) response | |||||||||||||||||||
| Increased intracellular ROS, PGE2, and PGE2 receptors in human dermal fibroblasts | |||||||||||||||||||
| Decreased expression of transcription factor zinc finger E-box binding homeobox 1(ZEB1) | |||||||||||||||||||
| Decreased binding of ZEB1 to DNA methyltransferase 1 (DNMT1) promoter | |||||||||||||||||||
| Senescence of DNMT1 (gene silencer) | |||||||||||||||||||
This leads to:
| |||||||||||||||||||
| Cellular senescence | |||||||||||||||||||
- UV radiation leads to overexpression of COX-2 whose end product is prostaglandin E2, involved in skin carcinogenesis[52][53][54][55]
- Overexpression of MiR-211, MiR-217 and miR-377 is associated with suppression of DNMT-1 mediated methylation of p16 and pRb, thus, inducing senescence in human skin fibroblasts[1][56][57]
- MicroRNA-152 and -181a modulate the levels of adhesion proteins and extra-cellular matrix components, such as integrin α5 and collagen XVI hence, in this way lead to senescence of human dermal fibroblasts[58]
- Decreased expression of UHRF1 (ubiquitin-like with PHD and ring finger domains 1) is the main initial event in suppressing DNMT1-mediated DNA methylation which increases WNT5A expression resulting in consequent induction of senescence[59][1]
- MicroRNA‐21 is involved in regulation of ERK/NF‐κB signaling pathway which affects the proliferation, migration, and apoptosis of human melanoma A375 cells by targeting SPRY1, PDCD4, and PTEN
Gross Pathology
- Macroscopically, the tumor is often elevated, fungating, or may be ulcerated with irregular borders
- Malignant melanoma appears as a small lesion having irregular borders & portions with multiple colors such as white, pink, red, blue or blue-black
- Basal cell carcinoma appears as a waxy or a pearly bump, or a brown scar-like or flesh-colored flat lesion, or a scabbing or a bleeding sore that heals and returns
- Squamous cell carcinoma appears as a red, firm nodule or a flat lesion having a crusted, scaly surface
- Bowen's disease appears as a red or brown scaly patch/plaque on the sun-damaged skin
- Merkel cell carcinoma appears as shiny, firm nodules just beneath or on the skin & in hair follicles
- Kaposi's sarcoma appears as purple or red patches on skin or mucous membrane
Microscopic Pathology
- Microscopically, tumor cells destroy the basement membrane and form sheets or compact masses which invade the subjacent connective tissue (dermis)[8]
- In well-differentiated carcinomas, tumor cells are pleomorphic/atypical, but resembling normal keratinocytes from prickle layer (large, polygonal, with abundant eosinophilic (pink) cytoplasm and central nucleus)
- Their disposal tends to be similar to that of normal epidermis: immature/basal cells at the periphery, becoming more mature to the centre of the tumor masses
- Tumor cells transform into keratinized squamous cells and form round nodules with concentric, laminated layers, called "cell nests" or "epithelial/keratinous pearls"
- The surrounding stroma is reduced and contains inflammatory infiltrate (lymphocytes)
- Poorly differentiated squamous carcinomas contain more pleomorphic cells and no keratinization
Causes
- Skin cancer occurs due to mutations in DNA of skin cells causing them to grow out of control leading to formation of a mass of cancer cells
Epidemiology & Demographics
- Skin cancer is a common condition because of the increased exposure to UV radiation (caused by increasing popularity of sun tanning/sun bathing)
- It is the most common malignancy in Caucasian population[60][61][62][63][64][65][66][67][68][69]
- Individuals with lighter-skin are more vulnerable to get it
- One out of every three new cancers arises from skin in United States[70]
- Incidence of both malignant melanoma (MM) and non-melanoma skin cancer (NMSC) is increasing with MM having an annual increase of 0.6% in individuals >50 years[71][72]
- In 2016, the estimated number of new cases of skin melanoma was 76,380 which is 4.5% of all new cancer cases[73]
- Annual incidence of melanoma in situ is 9.5% according to some recent epidemiological studies[73]
- National Cancer Registries has reported an underestimation of the incidence of melanoma in certain countries, hence, its incidence may even be higher than actually documented depending upon population-based varying risk factors and discrepancies in national registration systems[74]
Risk factors
Common risk factors for skin cancer include:[75][76][6]
Screening
According to different studies going on for so many years, following data is available regarding the different methods/tools and their effectiveness for skin cancer screening:
- From 1992 to 1994, free American Academy of Dermatology's National Skin Cancer Early Detection and Screening Program was launched which provided broad skin cancer educational information to general public and enabled almost 750,000 free expert skin cancer examinations which mostly found out thin, localized stage 1 melanomas with high projected 5-year survival rate[2][3]
- From 2001 to 2005, American Academy of Dermatology National Melanoma/Skin Cancer Screening Program was launched which led to the conclusion that HARMM criteria can be used to identify the higher-risk subgroup of skin cancer screening population via assessment of multiple risk factors for MM , which will not only reduce the cost but will also increase the yields for suspected MM in future mass screening initiatives[4]
- Melanoma Genetics Program identifies the genetic causes of skin cancer, and also provides genetic counseling to the individuals having a strong family history of melanoma[77][78][79][2][80][81][82]
- Dermoscopy usage improves the ability of primary care physicians to triage lesions which are suggestive of skin cancer and saves from unnecessary expert consultations[83]
- Combination of dermoscopy and short-term sequential digital dermoscopy imaging (SDDI) in a primary care setting doubles the sensitivity for melanoma diagnosis and also leads to >50% chance of reduction in excision or referral of benign pigmented lesions[84][85][86][87][88]
Diagnosis
The two sentinel features of skin cancer diagnosis are skin examination and subsequent biopsy of the suspected skin lesion. Common history, symptoms, physical examination findings and diagnostic tests are mentioned below:
History and Symptoms
Common sites of involvement
- Primarily involves the sun-exposed areas of skin such as:
- Can also involve the skin areas very rarely exposed to sun such as:
- Underneath fingernails or toenails
- Palm of the hand
- Sole of the foot
- Genital region
Common symptoms
- There are a variety of different skin cancer symptoms including crabs or changes in the skin that do not heal, ulcers in the skin, discoloration, and changes in existing moles
- Malignant melanoma appears as a small lesion having irregular borders & portions with multiple colors such as white, pink, red, blue or blue-black
- Basal cell carcinoma appears as a waxy or a pearly bump, or a brown scar-like or flesh-colored flat lesion, or a scabbing or a bleeding sore that heals and returns
- Squamous cell carcinoma appears as a red, firm nodule or a flat lesion having a crusted, scaly surface
- Bowen's disease appears as a red or brown scaly patch/plaque on the sun-damaged skin
- Merkel cell carcinoma appears as shiny, firm nodules just beneath or on the skin & in hair follicles
- Kaposi's sarcoma appears as purple or red patches on skin or mucous membrane
Physical Examination
- On physical examination, basal cell carcinoma usually looks like a raised, smooth, pearly bump on the sun-exposed skin of the head, neck or shoulders[89]
- Small blood vessels, crusting and bleeding in the center of tumor can be seen sometimes, hence, often mistaken as a non-healing sore
- Squamous cell carcinoma commonly appears as a red, scaling, thickened patch on sun-exposed skin with/without ulceration or bleeding, and can develop into a large mass if left untreated
- Most melanomas appear as brown to black looking lesions
- Signs indicating a malignant melanoma include change in size, shape, color or elevation of a mole
- Appearance of a new mole during adulthood, or new pain, itching, ulceration or bleeding of an existing mole should always be checked as it is suspicious for melanoma
Laboratory Tests
- Dermoscopy usage improves the ability of primary care physicians to triage lesions which are suggestive of skin cancer and saves from unnecessary expert consultations[83]
- Combination of dermoscopy and short-term sequential digital dermoscopy imaging (SDDI) in a primary care setting doubles the sensitivity for melanoma diagnosis and also leads to >50% chance of reduction in excision or referral of benign pigmented lesions[84][85][86][87][88]
Biopsy
- Skin biopsy (i.e. removal of a sample of suspicious skin for testing) is an essential component of skin cancer diagnosis and by histopathological lab analysis, can determine whether it is a skin cancer or not, and if so, what type of skin cancer it is
Other Diagnostic Studies
- In case of a metastatic stage IV skin cancer such as a large SCC, melanoma, & merkel cell carcinoma, lymph nodes become involved, which requires further testing such as:
- Sentinel lymph node biopsy
- Imaging tests for lymph node involvement such as Chest X-ray, CT, MRI, PET scan or ultrasound depending on the site involved
- Eye examination with dilated pupil to look for retina and optic nerve involvement in case of metastasis
Treatment
- Treatment of skin cancer varies depending upon the size, type, depth, location, stage of the tumor, involved body part, and patient’s general health
- Small lesions limited only to the skin surface can easily be cured by simple initial skin biopsy and may not require any further treatment whereas large lesions with metastasis require further treatment options as shown in the table below:[90][91]
Prevention
Although the possibility of skin cancer can't be eliminated completely, but the risk for developing skin cancer can be significantly reduced by acting on the following preventive measures in the first place to decrease the excessive exposure to UV rays:[76][92]
| Preventive method | Details |
|---|---|
| Avoiding sunburns and suntans | |
| Wearing protective clothing | Wear the following while being in the outdoor environment: |
| Wearing SPF sunscreen | |
| Avoiding tanning beds | |
| Being aware of sun-sensitizing medications |
|
| Checking skin regularly and reporting any new or unusual skin changes to the doctor |
|
| Watching dysplastic nevi (abnormal irregular multiple moles) regularly |
|
| Reducing the exposure to ultraviolet (UV) radiation, especially during the early years of life |
|
Effectiveness of sunscreen in prevention of skin cancer
Multiple studies have been carried out to find out the effectiveness of sunscreen in protection against skin cancer[93][94][95][96][97][98][99][100][101]
Skin Cancer Prevention Facial-Aging Mobile App
Related Chapters
References
- ↑ 1.0 1.1 1.2 1.3 Xie HF, Liu YZ, Du R, Wang B, Chen MT, Zhang YY; et al. (2017). "miR-377 induces senescence in human skin fibroblasts by targeting DNA methyltransferase 1". Cell Death Dis. 8 (3): e2663. doi:10.1038/cddis.2017.75. PMC 5386568. PMID 28277545.
- ↑ 2.0 2.1 2.2 "Skin Cancer (Melanoma) Treatment Program - Massachusetts General Hospital, Boston, MA".
- ↑ 3.0 3.1 Koh HK, Norton LA, Geller AC, Sun T, Rigel DS, Miller DR; et al. (1996). "Evaluation of the American Academy of Dermatology's National Skin Cancer Early Detection and Screening Program". J Am Acad Dermatol. 34 (6): 971–8. doi:10.1016/s0190-9622(96)90274-1. PMID 8647990.
- ↑ 4.0 4.1 Goldberg MS, Doucette JT, Lim HW, Spencer J, Carucci JA, Rigel DS (2007). "Risk factors for presumptive melanoma in skin cancer screening: American Academy of Dermatology National Melanoma/Skin Cancer Screening Program experience 2001-2005". J Am Acad Dermatol. 57 (1): 60–6. doi:10.1016/j.jaad.2007.02.010. PMID 17490783.
- ↑ "Nonmelanoma skin cancer - Symptoms and causes - Mayo Clinic".
- ↑ 6.0 6.1 Linares MA, Zakaria A, Nizran P (2015). "Skin Cancer". Prim Care. 42 (4): 645–59. doi:10.1016/j.pop.2015.07.006. PMID 26612377.
- ↑ Lee PK (2004). "Common skin cancers". Minn Med. 87 (3): 44–7. PMID 15080294.
- ↑ 8.0 8.1 Paolino G, Donati M, Didona D, Mercuri SR, Cantisani C (2017). "Histology of Non-Melanoma Skin Cancers: An Update". Biomedicines. 5 (4). doi:10.3390/biomedicines5040071. PMC 5744095. PMID 29261131.
- ↑ Majores M, Bierhoff E (2015). "[Actinic keratosis, Bowen's disease, keratoacanthoma and squamous cell carcinoma of the skin]". Pathologe. 36 (1): 16–29. doi:10.1007/s00292-014-2063-3. PMID 25663185.
- ↑ Neubert T, Lehmann P (2008). "Bowen's disease - a review of newer treatment options". Ther Clin Risk Manag. 4 (5): 1085–95. PMC 2621408. PMID 19209288.
- ↑ Yang Y, Yin R, Wu R, Ramirez CN, Sargsyan D, Li S; et al. (2019). "DNA methylome and transcriptome alterations and cancer prevention by triterpenoid ursolic acid in UVB-induced skin tumor in mice". Mol Carcinog. doi:10.1002/mc.23046. PMID 31237383.
- ↑ Yang Y, Wu R, Sargsyan D, Yin R, Kuo HC, Yang I; et al. (2019). "UVB drives different stages of epigenome alterations during progression of skin cancer". Cancer Lett. 449: 20–30. doi:10.1016/j.canlet.2019.02.010. PMC 6411449. PMID 30771437.
- ↑ 13.0 13.1 Yang AY, Lee JH, Shu L, Zhang C, Su ZY, Lu Y; et al. (2014). "Genome-wide analysis of DNA methylation in UVB- and DMBA/TPA-induced mouse skin cancer models". Life Sci. 113 (1–2): 45–54. doi:10.1016/j.lfs.2014.07.031. PMC 5897904. PMID 25093921.
- ↑ 14.0 14.1 Yi Y, Xie H, Xiao X, Wang B, Du R, Liu Y; et al. (2018). "Ultraviolet A irradiation induces senescence in human dermal fibroblasts by down-regulating DNMT1 via ZEB1". Aging (Albany NY). 10 (2): 212–228. doi:10.18632/aging.101383. PMC 5842848. PMID 29466247.
- ↑ Zhang C, Yuchi H, Sun L, Zhou X, Lin J (2017). "Human amnion-derived mesenchymal stem cells protect against UVA irradiation-induced human dermal fibroblast senescence, in vitro". Mol Med Rep. 16 (2): 2016–2022. doi:10.3892/mmr.2017.6795. PMC 5561982. PMID 28627622.
- ↑ Zhang C, Wen C, Lin J, Shen G (2015). "Protective effect of pyrroloquinoline quinine on ultraviolet A irradiation-induced human dermal fibroblast senescence in vitro proceeds via the anti-apoptotic sirtuin 1/nuclear factor-derived erythroid 2-related factor 2/heme oxygenase 1 pathway". Mol Med Rep. 12 (3): 4382–4388. doi:10.3892/mmr.2015.3990. PMID 26126510.
- ↑ Youn HJ, Kim KB, Han HS, An IS, Ahn KJ (2017). "23-Hydroxytormentic acid protects human dermal fibroblasts by attenuating UVA-induced oxidative stress". Photodermatol Photoimmunol Photomed. 33 (2): 92–100. doi:10.1111/phpp.12294. PMID 28106292.
- ↑ Yang S, Zhou B, Xu W, Xue F, Nisar MF, Bian C; et al. (2017). "Nrf2- and Bach1 May Play a Role in the Modulation of Ultraviolet A-Induced Oxidative Stress by Acetyl-11-Keto-β-Boswellic Acid in Skin Keratinocytes". Skin Pharmacol Physiol. 30 (1): 13–23. doi:10.1159/000452744. PMID 28142143.
- ↑ Hseu YC, Chou CW, Senthil Kumar KJ, Fu KT, Wang HM, Hsu LS; et al. (2012). "Ellagic acid protects human keratinocyte (HaCaT) cells against UVA-induced oxidative stress and apoptosis through the upregulation of the HO-1 and Nrf-2 antioxidant genes". Food Chem Toxicol. 50 (5): 1245–55. doi:10.1016/j.fct.2012.02.020. PMID 22386815.
- ↑ Hseu YC, Lo HW, Korivi M, Tsai YC, Tang MJ, Yang HL (2015). "Dermato-protective properties of ergothioneine through induction of Nrf2/ARE-mediated antioxidant genes in UVA-irradiated Human keratinocytes". Free Radic Biol Med. 86: 102–17. doi:10.1016/j.freeradbiomed.2015.05.026. PMID 26021820.
- ↑ Zhao P, Alam MB, Lee SH (2018). "Protection of UVB-Induced Photoaging by Fuzhuan-Brick Tea Aqueous Extract via MAPKs/Nrf2-Mediated Down-Regulation of MMP-1". Nutrients. 11 (1). doi:10.3390/nu11010060. PMC 6357030. PMID 30597920.
- ↑ Sun Z, Park SY, Hwang E, Zhang M, Seo SA, Lin P; et al. (2017). "Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK/AP-1 and activation of Nrf2-ARE antioxidant system". J Cell Mol Med. 21 (2): 336–348. doi:10.1111/jcmm.12968. PMC 5264136. PMID 27641753.
- ↑ Sun Z, Du J, Hwang E, Yi TH (2018). "Paeonol extracted from Paeonia suffruticosa Andr. ameliorated UVB-induced skin photoaging via DLD/Nrf2/ARE and MAPK/AP-1 pathway". Phytother Res. 32 (9): 1741–1749. doi:10.1002/ptr.6100. PMID 29748977.
- ↑ Al-Matouq J, Holmes TR, Hansen LA (2019). "CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death". Mol Carcinog. doi:10.1002/mc.23075. PMID 31237025.
- ↑ Sehati N, Sadeghie N, Mansoori B, Mohammadi A, Shanehbandi D, Baradaran B (2019). "MicroRNA-330 inhibits growth and migration of melanoma A375 cells: In vitro study". J Cell Biochem. doi:10.1002/jcb.29211. PMID 31237010.
- ↑ Xiong Y, Liu L, Qiu Y, Liu L (2018). "MicroRNA-29a Inhibits Growth, Migration and Invasion of Melanoma A375 Cells in Vitro by Directly Targeting BMI1". Cell Physiol Biochem. 50 (1): 385–397. doi:10.1159/000494015. PMID 30286469.
- ↑ Mao XH, Chen M, Wang Y, Cui PG, Liu SB, Xu ZY (2017). "MicroRNA-21 regulates the ERK/NF-κB signaling pathway to affect the proliferation, migration, and apoptosis of human melanoma A375 cells by targeting SPRY1, PDCD4, and PTEN". Mol Carcinog. 56 (3): 886–894. doi:10.1002/mc.22542. PMID 27533779.
- ↑ Orioli D, Dellambra E (2018). "Epigenetic Regulation of Skin Cells in Natural Aging and Premature Aging Diseases". Cells. 7 (12). doi:10.3390/cells7120268. PMC 6315602. PMID 30545089.
- ↑ 29.0 29.1 Gesumaria L, Matsui MS, Kluz T, Costa M (2015). "Solar-simulated ultraviolet radiation induces histone 3 methylation changes in the gene promoters of matrix metalloproteinases 1 and 3 in primary human dermal fibroblasts". Exp Dermatol. 24 (5): 384–5. doi:10.1111/exd.12675. PMC 4471858. PMID 25707437.
- ↑ Gilchrest BA (2013). "Photoaging". J Invest Dermatol. 133 (E1): E2–6. doi:10.1038/skinbio.2013.176. PMID 23820721.
- ↑ Poon F, Kang S, Chien AL (2015). "Mechanisms and treatments of photoaging". Photodermatol Photoimmunol Photomed. 31 (2): 65–74. doi:10.1111/phpp.12145. PMID 25351668.
- ↑ Xie H, Liu F, Liu L, Dan J, Luo Y, Yi Y; et al. (2013). "Protective role of AQP3 in UVA-induced NHSFs apoptosis via Bcl2 up-regulation". Arch Dermatol Res. 305 (5): 397–406. doi:10.1007/s00403-013-1324-y. PMID 23463292.
- ↑ Battie C, Jitsukawa S, Bernerd F, Del Bino S, Marionnet C, Verschoore M (2014). "New insights in photoaging, UVA induced damage and skin types". Exp Dermatol. 23 Suppl 1: 7–12. doi:10.1111/exd.12388. PMID 25234829.
- ↑ Rando TA, Chang HY (2012). "Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock". Cell. 148 (1–2): 46–57. doi:10.1016/j.cell.2012.01.003. PMC 3336960. PMID 22265401.
- ↑ Bormann F, Rodríguez-Paredes M, Hagemann S, Manchanda H, Kristof B, Gutekunst J; et al. (2016). "Reduced DNA methylation patterning and transcriptional connectivity define human skin aging". Aging Cell. 15 (3): 563–71. doi:10.1111/acel.12470. PMC 4854925. PMID 27004597.
- ↑ Pollack BP, Sapkota B, Boss JM (2009). "Ultraviolet radiation-induced transcription is associated with gene-specific histone acetylation". Photochem Photobiol. 85 (3): 652–62. doi:10.1111/j.1751-1097.2008.00485.x. PMID 19076306.
- ↑ Zheng QH, Ma LW, Zhu WG, Zhang ZY, Tong TJ (2006). "p21Waf1/Cip1 plays a critical role in modulating senescence through changes of DNA methylation". J Cell Biochem. 98 (5): 1230–48. doi:10.1002/jcb.20838. PMID 16514663.
- ↑ So AY, Jung JW, Lee S, Kim HS, Kang KS (2011). "DNA methyltransferase controls stem cell aging by regulating BMI1 and EZH2 through microRNAs". PLoS One. 6 (5): e19503. doi:10.1371/journal.pone.0019503. PMC 3091856. PMID 21572997.
- ↑ Kinney SR, Pradhan S (2011). "Regulation of expression and activity of DNA (cytosine-5) methyltransferases in mammalian cells". Prog Mol Biol Transl Sci. 101: 311–33. doi:10.1016/B978-0-12-387685-0.00009-3. PMID 21507356.
- ↑ Benetti R, Gonzalo S, Jaco I, Muñoz P, Gonzalez S, Schoeftner S; et al. (2008). "A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases". Nat Struct Mol Biol. 15 (3): 268–79. doi:10.1038/nsmb.1399. PMC 2990406. PMID 18311151.
- ↑ Kar S, Deb M, Sengupta D, Shilpi A, Parbin S, Torrisani J; et al. (2012). "An insight into the various regulatory mechanisms modulating human DNA methyltransferase 1 stability and function". Epigenetics. 7 (9): 994–1007. doi:10.4161/epi.21568. PMC 3515020. PMID 22894906.
- ↑ Pal S, Tyler JK (2016). "Epigenetics and aging". Sci Adv. 2 (7): e1600584. doi:10.1126/sciadv.1600584. PMC 4966880. PMID 27482540.
- ↑ Sierra MI, Fernández AF, Fraga MF (2015). "Epigenetics of Aging". Curr Genomics. 16 (6): 435–40. doi:10.2174/1389202916666150817203459. PMC 4765531. PMID 27019618.
- ↑ Jung M, Pfeifer GP (2015). "Aging and DNA methylation". BMC Biol. 13: 7. doi:10.1186/s12915-015-0118-4. PMC 4311512. PMID 25637097.
- ↑ Nandakumar V, Vaid M, Tollefsbol TO, Katiyar SK (2011). "Aberrant DNA hypermethylation patterns lead to transcriptional silencing of tumor suppressor genes in UVB-exposed skin and UVB-induced skin tumors of mice". Carcinogenesis. 32 (4): 597–604. doi:10.1093/carcin/bgq282. PMC 3066413. PMID 21186298.
- ↑ Prasad R, Katiyar SK (2013). "Prostaglandin E2 Promotes UV radiation-induced immune suppression through DNA hypermethylation". Neoplasia. 15 (7): 795–804. doi:10.1593/neo.13424. PMC 3689242. PMID 23814491.
- ↑ López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013). "The hallmarks of aging". Cell. 153 (6): 1194–217. doi:10.1016/j.cell.2013.05.039. PMC 3836174. PMID 23746838.
- ↑ Postigo AA (2003). "Opposing functions of ZEB proteins in the regulation of the TGFbeta/BMP signaling pathway". EMBO J. 22 (10): 2443–52. doi:10.1093/emboj/cdg225. PMC 155983. PMID 12743038.
- ↑ Postigo AA, Depp JL, Taylor JJ, Kroll KL (2003). "Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins". EMBO J. 22 (10): 2453–62. doi:10.1093/emboj/cdg226. PMC 155984. PMID 12743039.
- ↑ Johnson AA, Akman K, Calimport SR, Wuttke D, Stolzing A, de Magalhães JP (2012). "The role of DNA methylation in aging, rejuvenation, and age-related disease". Rejuvenation Res. 15 (5): 483–94. doi:10.1089/rej.2012.1324. PMC 3482848. PMID 23098078.
- ↑ Kim HY, Lee DH, Shin MH, Shin HS, Kim MK, Chung JH (2018). "UV-induced DNA methyltransferase 1 promotes hypermethylation of tissue inhibitor of metalloproteinase 2 in the human skin". J Dermatol Sci. 91 (1): 19–27. doi:10.1016/j.jdermsci.2018.03.009. PMID 29685765.
- ↑ Rundhaug JE, Fischer SM (2008). "Cyclo-oxygenase-2 plays a critical role in UV-induced skin carcinogenesis". Photochem Photobiol. 84 (2): 322–9. doi:10.1111/j.1751-1097.2007.00261.x. PMID 18194346.
- ↑ An KP, Athar M, Tang X, Katiyar SK, Russo J, Beech J; et al. (2002). "Cyclooxygenase-2 expression in murine and human nonmelanoma skin cancers: implications for therapeutic approaches". Photochem Photobiol. 76 (1): 73–80. PMID 12126310.
- ↑ Fischer SM (2002). "Is cyclooxygenase-2 important in skin carcinogenesis?". J Environ Pathol Toxicol Oncol. 21 (2): 183–91. PMID 12086405.
- ↑ Maldve RE, Kim Y, Muga SJ, Fischer SM (2000). "Prostaglandin E(2) regulation of cyclooxygenase expression in keratinocytes is mediated via cyclic nucleotide-linked prostaglandin receptors". J Lipid Res. 41 (6): 873–81. PMID 10828079.
- ↑ Yu H, Yang W (2016). "MiR-211 is epigenetically regulated by DNMT1 mediated methylation and inhibits EMT of melanoma cells by targeting RAB22A". Biochem Biophys Res Commun. 476 (4): 400–405. doi:10.1016/j.bbrc.2016.05.133. PMID 27237979.
- ↑ Mancini M, Lena AM, Saintigny G, Mahé C, Di Daniele N, Melino G; et al. (2014). "MicroRNAs in human skin ageing". Ageing Res Rev. 17: 9–15. doi:10.1016/j.arr.2014.04.003. PMID 24784027.
- ↑ Mancini M, Saintigny G, Mahé C, Annicchiarico-Petruzzelli M, Melino G, Candi E (2012). "MicroRNA-152 and -181a participate in human dermal fibroblasts senescence acting on cell adhesion and remodeling of the extra-cellular matrix". Aging (Albany NY). 4 (11): 843–53. doi:10.18632/aging.100508. PMC 3560438. PMID 23238588.
- ↑ Jung HJ, Byun HO, Jee BA, Min S, Jeoun UW, Lee YK; et al. (2017). "The Ubiquitin-like with PHD and Ring Finger Domains 1 (UHRF1)/DNA Methyltransferase 1 (DNMT1) Axis Is a Primary Regulator of Cell Senescence". J Biol Chem. 292 (9): 3729–3739. doi:10.1074/jbc.M116.750539. PMC 5339756. PMID 28100769.
- ↑ Whiteman DC, Green AC, Olsen CM (2016). "The Growing Burden of Invasive Melanoma: Projections of Incidence Rates and Numbers of New Cases in Six Susceptible Populations through 2031". J Invest Dermatol. 136 (6): 1161–1171. doi:10.1016/j.jid.2016.01.035. PMID 26902923.
- ↑ de Vries E, Coebergh JW (2004). "Cutaneous malignant melanoma in Europe". Eur J Cancer. 40 (16): 2355–66. doi:10.1016/j.ejca.2004.06.003. PMID 15519506.
- ↑ Lasithiotakis K, Krüger-Krasagakis S, Manousaki A, Ioannidou D, Panagiotides I, Tosca A (2006). "The incidence of cutaneous melanoma on Crete, Greece". Int J Dermatol. 45 (4): 397–401. doi:10.1111/j.1365-4632.2006.02492.x. PMID 16650166.
- ↑ Månsson-Brahme E, Johansson H, Larsson O, Rutqvist LE, Ringborg U (2002). "Trends in incidence of cutaneous malignant melanoma in a Swedish population 1976-1994". Acta Oncol. 41 (2): 138–46. PMID 12102157.
- ↑ Stang A, Pukkala E, Sankila R, Söderman B, Hakulinen T (2006). "Time trend analysis of the skin melanoma incidence of Finland from 1953 through 2003 including 16,414 cases". Int J Cancer. 119 (2): 380–4. doi:10.1002/ijc.21836. PMID 16477634.
- ↑ Ulmer MJ, Tonita JM, Hull PR (2003). "Trends in invasive cutaneous melanoma in Saskatchewan 1970-1999". J Cutan Med Surg. 7 (6): 433–42. doi:10.1177/120347540300700601. PMID 15926213.
- ↑ Dennis LK (1999). "Analysis of the melanoma epidemic, both apparent and real: data from the 1973 through 1994 surveillance, epidemiology, and end results program registry". Arch Dermatol. 135 (3): 275–80. PMID 10086448.
- ↑ Geller AC, Miller DR, Annas GD, Demierre MF, Gilchrest BA, Koh HK (2002). "Melanoma incidence and mortality among US whites, 1969-1999". JAMA. 288 (14): 1719–20. doi:10.1001/jama.288.14.1719. PMID 12365954.
- ↑ Hall HI, Miller DR, Rogers JD, Bewerse B (1999). "Update on the incidence and mortality from melanoma in the United States". J Am Acad Dermatol. 40 (1): 35–42. doi:10.1016/s0190-9622(99)70562-1. PMID 9922010.
- ↑ Perera E, Gnaneswaran N, Staines C, Win AK, Sinclair R (2015). "Incidence and prevalence of non-melanoma skin cancer in Australia: A systematic review". Australas J Dermatol. 56 (4): 258–67. doi:10.1111/ajd.12282. PMID 25716064.
- ↑ "Common Cancer Types - National Cancer Institute".
- ↑ "Cancer Facts & Figures 2016 | American Cancer Society".
- ↑ Welch HG, Woloshin S, Schwartz LM (2005). "Skin biopsy rates and incidence of melanoma: population based ecological study". BMJ. 331 (7515): 481. doi:10.1136/bmj.38516.649537.E0. PMC 1199022. PMID 16081427.
- ↑ 73.0 73.1 "Melanoma of the Skin - Cancer Stat Facts".
- ↑ Monshi B, Vujic M, Kivaranovic D, Sesti A, Oberaigner W, Vujic I; et al. (2016). "The burden of malignant melanoma--lessons to be learned from Austria". Eur J Cancer. 56: 45–53. doi:10.1016/j.ejca.2015.11.026. PMID 26802530.
- ↑ Ishdorj G, Beiggi S, Nugent Z, Streu E, Banerji V, Dhaliwal D; et al. (2019). "Risk factors for skin cancer and solid tumors in newly diagnosed patients with chronic lymphocytic leukemia and the impact of skin surveillance on survival". Leuk Lymphoma: 1–10. doi:10.1080/10428194.2019.1620941. PMID 31237469.
- ↑ 76.0 76.1 "Skin cancer - Symptoms and causes - Mayo Clinic".
- ↑ Gauwerky K, Ruzicka T, Berking C (2009). "[Skin cancer screening at the family doctor's office]". MMW Fortschr Med. 151 (25): 38–42, quiz 43. PMID 19739523.
- ↑ Treiber N, Huber MA, Scharffetter-Kochanek K, Schneider LA (2014). "[Early detection of skin cancer]". MMW Fortschr Med. 156 (4): 37–40. PMID 24908774.
- ↑ Mierzwa T, Zegarski W, Placek W, Zegarska B (2004). "[Skin cancer screening program in the population of Bydgoszcz]". Wiad Lek. 57 Suppl 1: 211–4. PMID 15884241.
- ↑ Bajaj S, Wolner ZJ, Dusza SW, Braun RP, Marghoob AA, DeFazio J (2019). "Total Body Skin Examination Practices: A Survey Study Amongst Dermatologists at High-Risk Skin Cancer Clinics". Dermatol Pract Concept. 9 (2): 132–138. doi:10.5826/dpc.0902a09. PMC 6502292 Check
|pmc=value (help). PMID 31106016. - ↑ Argenziano G, Zalaudek I, Hofmann-Wellenhof R, Bakos RM, Bergman W, Blum A; et al. (2012). "Total body skin examination for skin cancer screening in patients with focused symptoms". J Am Acad Dermatol. 66 (2): 212–9. doi:10.1016/j.jaad.2010.12.039. PMID 21757257.
- ↑ "Skin Cancer Screening: MedlinePlus Lab Test Information".
- ↑ 83.0 83.1 Argenziano G, Puig S, Zalaudek I, Sera F, Corona R, Alsina M; et al. (2006). "Dermoscopy improves accuracy of primary care physicians to triage lesions suggestive of skin cancer". J Clin Oncol. 24 (12): 1877–82. doi:10.1200/JCO.2005.05.0864. PMID 16622262.
- ↑ 84.0 84.1 Menzies SW, Emery J, Staples M, Davies S, McAvoy B, Fletcher J; et al. (2009). "Impact of dermoscopy and short-term sequential digital dermoscopy imaging for the management of pigmented lesions in primary care: a sequential intervention trial". Br J Dermatol. 161 (6): 1270–7. doi:10.1111/j.1365-2133.2009.09374.x. PMID 19747359.
- ↑ 85.0 85.1 van der Rhee JI, Bergman W, Kukutsch NA (2010). "The impact of dermoscopy on the management of pigmented lesions in everyday clinical practice of general dermatologists: a prospective study". Br J Dermatol. 162 (3): 563–7. doi:10.1111/j.1365-2133.2009.09551.x. PMID 19832836.
- ↑ 86.0 86.1 Dinnes J, Deeks JJ, Chuchu N, Ferrante di Ruffano L, Matin RN, Thomson DR; et al. (2018). "Dermoscopy, with and without visual inspection, for diagnosing melanoma in adults". Cochrane Database Syst Rev. 12: CD011902. doi:10.1002/14651858.CD011902.pub2. PMC 6517096 Check
|pmc=value (help). PMID 30521682. - ↑ 87.0 87.1 Ferrante di Ruffano L, Takwoingi Y, Dinnes J, Chuchu N, Bayliss SE, Davenport C; et al. (2018). "Computer-assisted diagnosis techniques (dermoscopy and spectroscopy-based) for diagnosing skin cancer in adults". Cochrane Database Syst Rev. 12: CD013186. doi:10.1002/14651858.CD013186. PMC 6517147 Check
|pmc=value (help). PMID 30521691. - ↑ 88.0 88.1 Ferrante di Ruffano L, Dinnes J, Deeks JJ, Chuchu N, Bayliss SE, Davenport C; et al. (2018). "Optical coherence tomography for diagnosing skin cancer in adults". Cochrane Database Syst Rev. 12: CD013189. doi:10.1002/14651858.CD013189. PMID 30521690.
- ↑ Godsell G (2003). "Recognising the signs of skin cancer". Nurs Times. 99 (31): 44–5. PMID 13677122.
- ↑ "Skin cancer - Diagnosis and treatment - Mayo Clinic".
- ↑ "Skin Cancer Treatment (PDQ®)–Patient Version - National Cancer Institute".
- ↑ "Skin Cancer Prevention and Early Detection".
- ↑ Young AR, Claveau J, Rossi AB (2017). "Ultraviolet radiation and the skin: Photobiology and sunscreen photoprotection". J Am Acad Dermatol. 76 (3S1): S100–S109. doi:10.1016/j.jaad.2016.09.038. PMID 28038885.
- ↑ Burnett ME, Hu JY, Wang SQ (2012). "Sunscreens: obtaining adequate photoprotection". Dermatol Ther. 25 (3): 244–51. doi:10.1111/j.1529-8019.2012.01503.x. PMID 22913442.
- ↑ Bissonnette R (2008). "Update on sunscreens". Skin Therapy Lett. 13 (6): 5–7. PMID 18806906.
- ↑ Medeiros VL, Lim HW (2010). "Sunscreens in the management of photodermatoses". Skin Therapy Lett. 15 (6): 1–3. PMID 20532468.
- ↑ Diaz JH, Nesbitt LT (2013). "Sun exposure behavior and protection: recommendations for travelers". J Travel Med. 20 (2): 108–18. doi:10.1111/j.1708-8305.2012.00667.x. PMID 23464719.
- ↑ Andersen PA, Buller DB, Walkosz BJ, Scott MD, Beck L, Liu X; et al. (2017). "A Randomized Trial of an Advanced Sun Safety Intervention for Vacationers at 41 North American Resorts". J Health Commun. 22 (12): 951–963. doi:10.1080/10810730.2017.1382615. PMC 6309206. PMID 29161214.
- ↑ Buller DB, Andersen PA, Walkosz BJ, Scott MD, Beck L, Cutter GR (2017). "Effect of an intervention on observed sun protection by vacationers in a randomized controlled trial at North American resorts". Prev Med. 99: 29–36. doi:10.1016/j.ypmed.2017.01.014. PMC 5432386. PMID 28189810.
- ↑ Buller DB, Andersen PA, Walkosz BJ, Scott MD, Beck L, Cutter GR (2016). "Rationale, design, samples, and baseline sun protection in a randomized trial on a skin cancer prevention intervention in resort environments". Contemp Clin Trials. 46: 67–76. doi:10.1016/j.cct.2015.11.015. PMC 4714565. PMID 26593781.
- ↑ Li, Heidi; Colantonio, Sophia; Dawson, Andrea; Lin, Xing; Beecker, Jennifer (2019). "Sunscreen Application, Safety, and Sun Protection: The Evidence". Journal of Cutaneous Medicine and Surgery: 120347541985661. doi:10.1177/1203475419856611. ISSN 1203-4754.
- ↑ Brinker TJ, Heckl M, Gatzka M, Heppt MV, Resende Rodrigues H, Schneider S; et al. (2018). "A Skin Cancer Prevention Facial-Aging Mobile App for Secondary Schools in Brazil: Appearance-Focused Interventional Study". JMIR Mhealth Uhealth. 6 (3): e60. doi:10.2196/mhealth.9794. PMC 5866300. PMID 29523502.
- ↑ Brinker TJ, Brieske CM, Schaefer CM, Buslaff F, Gatzka M, Petri MP; et al. (2017). "Photoaging Mobile Apps in School-Based Melanoma Prevention: Pilot Study". J Med Internet Res. 19 (9): e319. doi:10.2196/jmir.8661. PMC 5610355. PMID 28887295.
- ↑ Brinker TJ, Schadendorf D, Klode J, Cosgarea I, Rösch A, Jansen P; et al. (2017). "Photoaging Mobile Apps as a Novel Opportunity for Melanoma Prevention: Pilot Study". JMIR Mhealth Uhealth. 5 (7): e101. doi:10.2196/mhealth.8231. PMC 5550737. PMID 28747297.