Degenerative Disease the Biology of Skin Cancer

5/24/2018 Degenerative Disease the Biology of Skin Cancer

1/40

Degenerative Disease:

The Biology of Skin Cancer

Oleh:Rini Agustin (20613011)Biologi-SITH-ITB


2/40

Degenerative disease1. Alzheimer's disease

2. Parkinson's Disease3. Friedreich's ataxia

4. Multiple system atrophy

5. Multiple sclerosis

6. Muscular dystrophy (MD)

7. Progressive supranuclear palsy

8. Cancer

9. Niemann Pick disease

10. Atherosclerosis

11. Essential tremor

12. Tay-Sachs Disease

13. Diabetes

14. Heart Disease

15. Keratoconus

16. Osteoporosis

17. Rheumatoid Arthritis

18. Huntington's Disease

19. Marfan's Syndrome

20. Amyotrophic Lateral Sclerosis (ALS), a.k.a., Lou Gehrig's Disease

known medically as a malignant neoplasm, is a broad

group of diseases involving unregulated cell growth.


3/40

Introduction to Cancer

Cancer is one of the biggest killer.

Cancer is a multistep process thatbegins when genetic mutations togrow uncontrollably.

Our genes are a major factor that

determine whether we will developcancer, but environmental factors canincrease our chances of developingcancer.

Cancer is a collection of diseases andone cancer may behave verydifferently from another.

Cancers

Terminology = karkinoma = crab

Tumor?

nonlife-threatening (benign)

life-threatening (malignant)


4/40

Biology of Cancer

metastases

carcinogen

malignancy and neoplasm


5/40

The Hallmarks of Cancer

Have the ability to grow indefinitelythey have

limitless replicative potential.

Are able to ignore the anti-cell-growth signals that

tell cells to stop dividing. Are able to evade the signals that tell them to

undergo apoptosis (self-destruction).

Have the ability to make self-sustaining factors to

promote their own growth.

Are able to recruit other cells to make a network of

new blood vessels to sustain themselves thisprocess is known as angiogenesis.

Can invade other tissues and cause new tumor

growth.


6/40

Who Gets Cancer?

Anyone can develop cancer, since we all have cells that are constantlyundergoing cellular processes such as proliferation and apoptosis to replaceold, damaged, and dying cells, and DNA to repair or fix genetic informationthat have been damaged by environmental factors.

If there is a malfunction in any of these processes, cancer can occur.

Some people are more likely to develop cancer than others because theirgenetic makeup makes them more susceptible.


7/40

Genetics of Cancer Susceptibility

Inherited Cancer

Sporadic Cancer

The Influence of Behavior and

Environment on Cancer

Oncogenes and Tumor Suppressor

Genes


8/40


9/40

The Skin

The skin is an organ withmany specializedfunctions.

It consists of three majorlayersthe epidermis,

dermis, and hypodermis. The epidermis is a

stratified epitheliumwith layers of specializedcell types.

The skin contains stemcells, which give the skinits high regenerativeproperties.


10/40

The skin is also a highly

versatile organ with various functions:

1. Barrier protection against environmental elements

2. Immunological protection against harmful environmental

pathogens3. Providing a water-impermeable barrier

4. Thermoregulation

5. Metabolism of vital nutrients for the body. The skin is avaluable source of vitamin D3 (cholecalciferol)

6. Neurosensory functions


11/40

Ageing Skin

Skin cancer?

1:3

one million new cases skin

cancer are diagnosed in the

United States every year

Before the 1970s skin cancer

mainly affect older people

approximately 40 to 50

percent of 65 year olds in the

United States develop skin

cancer

In recent years, increase in

the number of younger

people developing skin cancer


12/40

Are tan skin cool?

Behavior and attitude


13/40

What about tanning beds?

There is no evidence that tanning in a bed is any safer than tanning in thesun -- in fact, some tanning beds release much stronger UV light than thesun does.

There is a 75% increase in risk for melanoma among those who first usetanning beds in their teens and early twenties.


14/40

Ozone depletion


15/40

Ultraviolet Rays are the Main Cause of Skin Cancer


16/40


17/40

The effects of UV

exposure-ageing of

skin


18/40

Pathogenesis

Ultraviolet radiation can damage DNA directly in epidermal cells.

Thep53 gene is a major protector against DNA damage and is switched on whenUVR causes DNA breakage.

Thep53 gene itself is often mutated by UVR in skin cells. This probably increasesthe chance of a person developing skin cancer.

Ultraviolet radiation can also suppress the immune function of skin.


19/40

Skin cancer

Melanoma

Non-melanoma

skin cancer (NMSC)

Melanoma is a cancer of the pigment-producing cells, the

melanocytes.

Rare (4% of all skin cancers), it is the most aggressive and

deadliest form of skin cancer, making up 80 percent of

deaths due to skin cancer.

Basal cell carcinoma (BCC)

Squamous cell carcinoma (SCC)

BCC is the most common form of any

cancer and affects approximately 800,000

Americans each year, accounting for about

80% of all skin cancers.

SCC makes up approximately 16%

of all skin cancers.

Tipe of

It has been suggested that UVB causes BCC

and SCC, while UVA is thought to causemelanoma.


20/40


21/40

Other factors can increase a persons

susceptibility to skin cancer

a) exposure to ionizing radiation, such as X rays

b) exposure to arsenic (a naturally occurring element found in rocks andsoil). Arsenic is commonly used as a commercial agricultural insecticideand poison; when combined with other elements and high doses it cancause skin cancer

c) heredity, such as when a genetic mutation inherited from a parentincreases the chance that a person will develop skin cancer

d) organ transplantationorgan transplant recipients, who takeimunosuppressive drugs to prevent organ rejection, are at a high risk of

developing nonmelanoma skin cancer

e) viruses, such as the human papillomavirus (HPV), which is known tocause cervical cancer as well as a variety of skin lesions, including wartsand SCC. HPV is thought to interact with carcinogens, such as ultravioletradiation, to interrupt the skins normal defenses against cellular

damage, resulting in skin diseases.


22/40

Risk Factor for Skin Cancer

Ethnicity (Race) and PhysicalCharacteristics

Genetic

Youth

Physical Location

People who live close to theequator are at a higher risk ofdeveloping skin cancer due tothe higher ultraviolet radiationlevels at this location.

Indigenous human

populations that live at theequator generally have darkskin, which provides goodprotection.

Personal habit


23/40

Basal Cell Carcinoma

Basal cell carcinoma is the most common human cancer.

It is an epithelial cancer that is thought to develop from the basal keratinocyte cells

in the epidermis. It is slow growing and rarely metastasizes.

Ultraviolet radiation and race are the main risk factors for developing basal cellcarcinoma.

The inherited form of basal cell carcinoma is known as basal cell

nevus syndrome, which is caused by a genetic mutation in the gene PATCHED1.

Basal cell carcinoma is highly treatable.


24/40

Hedgehog (HH) signaling pathway The PATCHED1 gene normally makes a protein that normally prevents the

activation of a cellular and biochemical pathway

In this pathway, the Hedgehog protein is at the top of its cell signalingnetwork: In the absence of HH, the HH pathway is repressed by PATCHEDprotein. When Hedgehog protein is present, however, it prevents PATCHEDfunction, which then turns on a cascade of cellular and biochemicalprocesses, which results in the activation of specific genes that are

essential for normal development.

HH also active in regulating stem cell populations, such as in the hair follicle.


25/40

Pathogenesis

In addition, mutations have been found in genes such asSMOOTHENED (SMO) that normally code forproteins that activatethe HH pathway. These mutations change the code from makingnormal protein to making abnormal super-active proteins thatcannot be switched off by the normal cellular regulators. In otherwords, these mutant proteins are constitutively active and alwayskeep the HH pathway switched on, allowing cancer to develop.Their function is opposite to PATCHED1 function.

BCNS (Basal Cel Nevu Syndrome) is an inherited condition in whichafflicted individuals develop tens to hundreds of BCC tumors during

their lives, starting in their early teens.


26/40

Various forms of basal cell carcinoma

Various forms of basal cell carcinoma: a) nodular BCC, b) pigmented BCC, c)

superficial BCC.

Early nodular BCC H&E

basophilic nodular

BCC tumor island withprominent clefting

Superficial

multifocal BCCH&E


27/40

Squamous Cell Carcinoma

Squamous cell carcinoma of the skin (SCC) is the second mostcommon cancer.

Squamous cell carcinoma develops from squamous cells in thespinous layer of the epidermis.

Unlike BCC, SCC can arise from a noncancerous precursor growth.

SCC has the potential to metastasize; however, most SCCs do not.

Treatments for SCCs that have not metastasized are similar to thosefor BCC.

Treatments for metastatic SCCs are similar to those for othermetastatic cancers.


28/40

Various forms of squamous cell carcinoma

Various forms of squamous cell carcinoma (SCC): a) actinic keratoses, b) Bowens disease, c)

metastatic SCC.


29/40

Precursor SCC

Unlike BCC, some SCC tumors develop from precursor lesions,which may develop into SCC if not treated. These usually developon skin with extensive sun damage.

Actinic keratosis (AK) is a precancerous lesion that is thought to bethe earliest form of SCC. It appears as a rough, scaly, slightly raised

growth, ranging in color from brown to red and growing up to oneinch (2.5 cm) in diameter. As with all other skin cancers, people withfair skin who sunburn easily and tan poorly, as well as those whoseoccupations or hobbies lead to excessive sun exposure, are most atrisk of developing AK. It is suggested that between 1 percent and 20percent of all AKs develop into SCC and that 60 percent of

predisposed people over the age of 40 have at least one AK. Actinicchelitis (AC) is a type of AK that occurs on the lips (chelitis indicatesthat lesion on the lip). AC causes the lips to become dry, cracked,scaly, and pale or white. It mainly affects the lower lip, whichtypically receives more sun exposure than the upper lip.


30/40

Bowens disease is considered a superficial SCC that hasnot yet spreada SCC in situ. It is slow-growing andappears as a persistent, red-brown, scaly patch that mayresemble psoriasis or eczema. It can appear anywhere onthe skin but is most common on the head, the neck and the

lower leg. If untreated, a Bowens disease lesion mayinvade deeper structures and form a malignant SCC.

Any abnormal skin growth should be referred promptly to adermatologist for examination. If the diagnosis suggests anAK, early treatment will prevent it from developing intoSCC. If the growth is AK or SCC in situ, the treatments arepretty much the same as for treating BCCs.


31/40

Melanoma

Melanoma is the deadliest skin cancer. More than 85 percent of skin cancer deaths

are due to melanoma, although it makes up less than 5 percent of skin cancers.

Melanomas arise from moles, which are clusters of melanin-containing

melanocytes. Excessive sunburn during childhood is linked to developing

melanoma.

Early stage melanoma (Stage I melanoma) has a 100 percent survival rate.

Advanced stage melanoma (Stage IV melanoma) has a 9 to 15 percent survival rate.

The genetic damage caused by UVR is cumulativethat is, continuous chronic

exposure to UVB (ie sunburns) from early childhood results in the accumulation of

many damaging genetic mutations that eventually lead to melanoma


32/40

Various forms of Melanoma

Various forms of Melanoma. Melanomas in situ are often pigmentedand have an irregular

border (ac). Malignant melanoma (d)


33/40

Familial Melanoma/Dysplastic Nevus

Syndrome Familial melanoma (FM), or dysplastic nevus syndrome (DNS), is an

inherited disease in which individuals have a high risk of developingmelanoma.

These people make up 5 to 10 percent of patients diagnosed withmelanoma, and they often have at least one family member who

also has melanoma. These people develop atypical (abnormal) nevithat show histological features of a benign but possiblyprecancerous condition (dysplasia).

FM/DNS has been linked to a gene on chromosome 9, calledp16(also known as CDKN2A, CDKN2, MTS1, and INK4A). As animportantregulator of cell division, p16 protein acts as a brake on

cell cycle progression. It inhibits proteins called cyclin dependent kinases (CDK4 and

CDK6), which promote cell proliferation. If p16 is not workingproperly in a melanocyte, the latter will proliferate uncontrollably.


34/40


35/40

Melanoma Staging


36/40


37/40

Treatment


38/40

How to Detect a Potential Melanoma


39/40

Prevention


40/40

Terima Kasih

Degenerative Disease the Biology of Skin Cancer

Documents

Transcript of Degenerative Disease the Biology of Skin Cancer