week 2 lec 3 Flashcards
skin cancer
high prevalence, rarely lethal
from step-wise mutations
oncogene
induce cancer when turned on (from photo-oncogenes mutation which usually regulate cell proliferation and apoptosis)
tumor suppressor gene
when turned off lead to cancer (usually cause apoptosis and regulate cell proliferation)
alleles affected for oncogene and tumor suppressor genes
oncogene- one allele
tumor suppressor genes- both alleles
which UV ray damages DNA and causes mutation
UVA
then creates ROS and suppress immune function
what causes basal cell carcinoma
ionizing radiation
types of skin cancer
sqamous cell carcinoma (cumulative exposure)
basal cell carcinoma (intermittent exposure early in life)
melanoma (intermittent exposure)
signature UV mutations
C>T cytosine to thymine in tumour suppressor genes (esp. TP53) and oncogenes
what protects the skin from UVR
melanin (darker skin)
Fitzpatrick scale
for susceptibility to UV radiation
i.e.
I- always burns, never tans
VI- burns only with very high UVR doses, tans
people with dark skin and skin cancer?
still at risk and great mortality
risk factors for skin cancer
outdoor work, age, ozone damage, diet,
most common cancer in humans
basal cell carcinoma
what is basal cell carcinoma from
basal keratinocytes and adnexal structures; not mucosal tissue
basal cell carcinoma caused by
UVB mostly (ultraviolet light)
where is basal cell carcinoma present
head and neck
Locally destructive; rarely metastatic
pathogenesis of basal cell carcinoma
UVB –> mutations in tumor suppressor genes p53 and PTCH1
malfunction (genes) of sonic hedgehog signalling pathway (for cell differentiation and replication)
mutation in basal cell carcinoma
p53 and PTCH1 (tumor suppressor genes)
and sonic hedgehog signalling
sonic hedgehog pathway normal vs mutation
normal: PTCH1 inhibits SMO; no signals reach nucleus for transcription
mutation of PTCH1: hedgehog ligands bind, SMO not inhibited, promotes transcription of target genes
squamous cell carcinoma comes from
basal keratinocytes
who is squamous cell carcinoma most common in
darker skin ppl and immunosuppressed
2nd most common in whites
whats likely to metastasize
sqaumoous cell carcinoma
risk factors for squamous cell carcinoma
UV, genes, skin damage, immunosuppression (HIV viral, iatrogenic), carcinogens, immune system,
Genotype
Phenotype
Environmental (UVR exposure, viral infection, chemical, ionizing radiation, photosensitizing or immunosuppressive drugs, immunosuppression, chronic skin inflammation)
viral carcinogens causing cancer
HPV does what
turn off tumor suppressor genes (TP53)
chemical carcinogens (environmental, occupational, iatrogenic)
damage DNA, immunosuppression
immunosuppression increases risk of all cancer especially
squamous cell carcinoma
immunosuppression exams
immunosuppressant medication (organ transplant, rheumatoid disease), HIV diagnosis (SCC and Kaposi’s sarcoma)
critical anti-cancer mechanism
immunocompetence- recognize and destroy atypical cells
how does immune system fight cancer cells
recognize as foreign peptide –> activate innate and adaptive immune (cytotoxic T cells)
chronic inflammation is commonly from
chronic ulcers, mostly due to burns
and inflammatory skin/ mucosal conditions (i.e. lichen sclerosis, discoid lupus)
what will cause squamous cell carcinoma to be very aggressive
chronic inflammation
prolonged inflammation promotes
tumorigenesis (mediated by growth factors, increased proliferation, production of reactive oxygen species )
multiple alterations to get squamous cell carcinoma
insult to epidermis -> premalignant changes –> hyperkeratosis and ulceration –> in situ carcinoma –> invade through basement membrane
malignant melanoma in
malignancy of melatocytes
where does maligngnt melanoma occur
any mucocutaneous tissue
agressive and high mortality rate
malignant melanoma
most common malignant melanoma in people with dark skin
Acral lentiginous melanoma: most common form in people with dark skin; commonly appears on the soles of the feet and under the nails
risk factors for malignant melanoma
genes (CDKN2A, CDK4, POT1, TERT)
UV exposure
melanocytic nevi
history of changing mole
atypical nevus syndrome
family hc
tanning bed
immunosuppression
stages to get to metastatic melanoma
nevus crosses basement membrane of dermis eventually (diagram slide 27)
which nevi has greater risk of malignancy
large congenital nevi and atypical moles (ABCDE)
overall nevi have very low risk
hair follicle spends 90% of time in
anagen phase
phases of hair follicle cycle
anagen (growth) 90% (2-8 years)
catagen (involution)
telogen (rest) ~9%
exogen (shedding 1%
most common cause of hair loss
androgenetic alopecia
what is androgenetic alopecia
Nonscarring progressive miniaturization of the hair follicle and shortening of
anagen phase
risks for androgenetic alopecia
genetics (post puberty)
having testicles
male pattern androgenetic alopecia
Recession of the frontal hairline in a triangular pattern; followed by vertex thinning with progression until the top of the scalp is completely bald
Occipital area and sides of the scalp are spared
female pattern androgenetic alopecia
diffuse centroparietal thinning with maintenance of the frontal hair line
or Christmas treat pattern; diffuse centroparietal thinning with a breaching of the frontal hair line
ethology of androgenetic alopecia
genes, androgens (i.e. dihydrotestosterone), elevated inflammatory cytokines
female pattern: estrogenic, hormonal dysregulation
telogen effluvium more in men or women
women
telogen effluvium
diffuse hair loss (>25% of scalp hairs must be lost to be clinically detectable)
Early termination of anagen and increase of % of hairs in telogen phase
increase hair shedding
what hairs are shed in telogen effluvium
club hairs (ie. late stage of telogen; lacking an enclosing sac and pigmentation)
causes of telogen effluvium
psychophysiologic stressors
timeline of telogen effluvium
usually resovles in 3-6 months when remove trigger
acute or chronic
subtypes of telogen effluvium
acute telogen effluvium
chronic diffuse telogen hair loss
chronic telogen effluvium
acute telogen effluvium
timeline and causes
shedding for 2-4 months after trigger, variable hair loss per day
effluvium of the newborn, surgery, crash diet weight loss, febrile illness, drugs
diffuse telogen hair loss timeline and causes
> 6 months
thyroid, malnutrition, aging, systemic illness, psychological stress, iron and zinc deficiency, STI (HIV and syphilis)
chronic telogen effluvium timeline and cause
4th and 6th decade. long this hair.
abrupt and excessive with bitemporal recession
idiopathic (shortening of anagen)
anagen phase in telogen effluvium
premature termination of anagen: physiologic stress, interferons, heparin
prolonged anagen with abrupt termination; post-partum
short anagen phase, immediate telogen release; drugs
alopecia areata
non scarring autoimmune hair loss
well demarcated patches of hair loss
most common hair loss in kids
alopecia areata
alopecea areata pathogenesis
autoimmune, genes, emotional stress trigger
CD8 cytototoxic T cells target hair follicles, ROS
shrink follicles, increase catagen and telogen, inflammatory infiltrate surrounds follicular bulb
50% of nail diseases
onychomycosis
onychomycosis
fungal infection of nail predisposed by adjacent skin infection (mostly dermatophyte and immunosuppression)
where does onychomycosis effect most
toes >fingers
distal and distal-lateral > proximal subungual
distal-lateral onychomycosis
fungus invades under nail plate
hyperkeratosis and infam
seperate nail plate from nail bed
thickening and crumbling
psoriasis
itchy, scaly skin; autoimmune
what is psoriasis associated with 90% of the time
nail changes
aberrant immune response to biomechanical stressing and microtraumas of the nail– joint apparatus
psoriatic nail changes
hyptrkeratotiss in nail plate = leukonychia
nail plate shedding and pitting
nail separation via hyperplasia and sebum (oil or salmon spot)
vulnerable to fungal infection
