Dibyajyoti Saha1*, Ankit Tamrakar1, Mayukh Jana2
and Supradip Mandal2
1School of
Pharmacy, Chouksey Engineering College. Lal Khadan, Masturi
Road, Bilaspur-495004, C.G.
2Bharat Technology,
Banitabla, Uluberia,
Howrah-711316
ABSTRACT:
Protection against sun-induced damage
leading to photo carcinogenesis in skin is a highly desirable goal.
Epidemiological and experimental studies provide evidence that some naturally
occurring chemical agents in the human diet can diminish cancer risk. Extensive
documentation has validated the role of UV irradiation as a tumor initiator and
promoter, inducing both squamous and basal cell
carcinomas. Development of skin cancer has been frequently observed in patients
with XP. This disease is characterized by deleterious mutations in the genes
involved in the DNA damage repair system, with a marked reduction in the
ability of its cells to repair potentially carcinogenic mutations mainly those
caused by UV, thus making these patients highly photosensitive and predisposed
to skin cancer. The article highlights important factors, types of skin cancer with
its mechanisms and prevention strategy.
KEYWORDS: Skin cancer, Carcinoma, Melanoma, Papilloma
virus, Tumor.
INTRODUCTION:
Skin cancer is a disease in which skin cells
lose the ability to grow normally. Abnormal cells grow out of control and form
a mass or ‘tumor’. When abnormal originate in the skin, the mass is called a
skin tumor1.
Skin cancer is classified as melanoma skin
cancer or nonmelanoma skin cancer on the cell of
origin. The second consists of basal cell and squamous
cell carcinomas are a most common malignancy. Squamous
cell carcinomas derived from most superficial keratinocytes,
and have greater risk for metastatic spread and higher mortality. Solar
ultraviolet radiation is the major modifiable risk factors and exposures of
greater consequence are thought to occur in childhood and adolescence2.
TYPES
OF SKIN CANCER3
1. Basal cell carcinoma.
2. Squamous cell carcinoma.
3. Malignant melanoma.
4. Cutaneous T-cell lymphoma.
5. Kaposi’s Carcinoma.
6. Merkel cell carcinoma
7. Sebaceous carcinoma.
8. Atypical fibroxanthoma.
9. Micocystic adnexal carcinoma
10. Sarcoma
CAUSES
OF SKIN CANCER4:
1. Ultraviolet radiation i.e. UVA and UVB.
2. A family history of skin cancer.
3. Skin which has a lot of moles (more than
50).
4. Red or fair hair.
5. Blue eyes.
6. Freckles.
7. Bad sunburn as child.
8. Using a sunbed.
9. Increasing age.
10. Reduced immunity.
11. Chemical pollution.
12. Arsenic
13. A large no. of X-rays.
14. Cigar and pipe smoking causes lip cancer.
15. Fair skins.
SIGNS
AND SYMPTOMS OF SKIN CANCER5
1. Basal cell carcinoma: Usually looks like a
raised, smooth, pearly bump on the sun exposed skin of the head,
neck/shoulders. Sometimes, small blood vessels can be seen within the tumor.
Crusting and bleeding in the centre of the tumor frequently develops.
2. Squamous cell carcinoma: It is commonly a red,
scaling, thickened patch on sun exposed skin. Ulceration and bleeding may
occur, also form large mass.
3. An open sore that bleeds oozes or crusts and
remains open for a few weeks. A persistent, non-healing sore is a very common
sign of an early basal cell carcinoma.
4. A reddish patch or irritated area,
frequently occurring on the chest, shoulders, arms or legs. Sometimes the patch
crusts. It may also itch or hurt. At the other times, it persists with no
noticeable discomfort.
5. A shiny bump or nodule that is pearly or
translucent and is often pink, red or white. The bump can also be tan, black or
brown, especially in dark-haired people, and can be confused with a mole.
6. A pink growth with a slightly elevated
rolled border and a crusted indentation in the center. As the growth slowly
enlarges, tiny blood vessels may develop on the surface.
FEATURES
OF SKIN CANCER:6
1. Asymmetry: One half of the abnormal skin
area is different than the other half.
2. Borders
: Irregular borders.
3. Colors
: Varies from one area to another with shades of tan, brown/black (sometimes
white, red or blue).
4. Diameter
: Usually (but not always) larger than 6mm in size (diameter of a pencil
eraser).
The skin cancer divided into two stages:
1. Localized skin cancer.
2. Metastatic cancer.
SKIN
CARCINOGENESIS AND CANCER PREVENTION DEPENDING FACTORS:
1. Photo carcinogenesis.
2. UV radiation.
3. Immunosurveillance.
4. Photoprotection.
5. Limit of Photoprotection.
6. Enhancement of DNA repair.
7. Chemical carcinogens.
8. AIDS.
9. Papilloma virus infraction.
10. Basal cell nerves syndrome.
11. Radio dermatitis.
12. Impaired and chronic immune
function/suppression.
TREATMENT
OF SKIN CANCER:
1. Surgery:
a. Cryosurgery
b. Micrographic surgery.
c. Laser surgery.
d. Cryosurgery for a small tumor.
2. Chemotherapy.
3. Radiation therapy.
4. Photo dynamic therapy.
5. Biological therapy.
6. Immune therapy.
7. Clinical trials.
8. Mohr’s chemo surgery.
Actually treatment depends upon:
a. Type of skin cancer
b. Its stage and location.
c. The individual’s age and overall health.
PREVENTION
OF SKIN CANCER:
1. Avoiding sunburns.
2. Reducing exposure to UV radiation,
especially in early years.
3. Do not use sunbeds.
4. Monthly skin check up.
5. Wearing protective clothing when outdoors.
6. Use SPF valve 50 sunblock
lotion.
7. Reapply sunblock
every two hours after swimming.
8. Avoiding sun exposure.
9. Use a broad spectrum sunscreen that blocks
both UVA and UVB radiation.
10. Nutritional protection.
11. Use green tea (antioxidants).
12. Also use vitamin C, E and carotenoids.
ROLE
OF HUMAN PAPILLOMA VIRUS IN SKIN CANCER:
Like the mutations, the HPV of protein p53
in human skin cancers, a fact that has recently been the object of an
extensive review. Out of more than 100 HPV subtypes identified, only a small
subgroup named high-risk mucotropic HPV (HPV types
16, 18, 31, 33, 35 and 58), has been responsible for the development of
cervical cancer7. As in cervix carcinomas, HPV DNA is often detected
in skin carcinomas, where over 40 subtypes were identified, but they are not
high risk. It was suggested that mechanisms different from those occurring in
genital cancer might be involved in the malignant neoplastic
transformation of the skin.
Recently, HPV-38 was detected in 50% of skin
carcinomas and in 10% of healthy skin samples, and it may be responsible for
the immortalization of human keratinocytes in
culture. Another study demonstrated that HPV-38 DNA was present in 43% of AK,
as well as in 13% and 16% SCC and BCC, respectively. It is furthermore believed
that several HPV types are involved in verruciform epidermodysplasia.
MOLECULAR
MECHANISM OF ACTION FOR SKIN CANCER:
a. DNA Damage: Ultraviolet radiation is known
to cause distinct mutation in keratinocytes that
ultimately contribute to the development of non-melanoma skin cancers, which induced
basal cell carcinoma and squamous cell carcinoma8.
b. DNA repair: The type of DNA damage caused by
UV radiation is repaired via the nucleotide excision repair pathways. The
importance of this pathway is protecting against skin cancer by considering individual
with the hereditary disorder xeroderma pigmentosum (XP)9.
c. Gene Damaged by UV Radiation:
·
Tumor
Suppressor Gene p53:
Targets of DNA damage caused by UV radiation
exposure include both proto-oncogenes and tumor
suppressor genes. However, mutations in the tumor suppressor gene p53 are throught to play a critical role in the development of
precancerous lesions and have been implicated in all types of skin cancer7,10.
·
Ras Proto-Oncogenes:
The ras family of
proto-oncogenes has also been implicated as a target
for UV-B radiation damage. The ras proto oncogenes encode G proteins that hydrolyze guanosine 5’-triphosphate and mediate cell signaling for
many growth factor receptors. When damaged by UV radiation, a ras proto oncogene becomes an oncogene, which produces a mutant protein that no longer
hydrolyzes guanosine 5’-triphosphate and cell growth
is now allowed in the absence of growth factors11.
·
PTCH
Tumor Suppressor Gene:
PTCH is the second tumor suppressor gene
implicated in BCC. It has also implicated in sporadic BCC’s.
·
Other
Genes:
A number of other genes have implicated in
the development of melanoma. Some of these include the CMM1 gene on chromosome
1p36, tumor suppressor gene p16, on chromosome 9p21, the cyclin
dependent kinase gene CDK4 on chromosome 12q14, as
well as, a number of genes associated with the p53-related pathways12.
CONLUSION:
Chemical carcinogens can be induce skin
tumor. A significant proportion of various tumors i.e. fibrosarcomas,
sarcomas, papillomas, carcinomas, squamous
cell carcinomas etc. exhibit over expression. Perhaps the most widely studied
etiologic agent in animals of skin cancer in ultraviolet radiation. Solar UVB
radiation (280-320nm) has been implicated in the induction of human skin tumors13, 14.
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Received on 23.02.2011 Accepted on 11.05.2011
© Asian Pharma
Press All Right Reserved
Asian J. Pharm.
Res. 1(2): April-June 2011;
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