1. Neoplasia (4&5 of 6) Ali Al Khader, M.D. Faculty of Medicine
Al-Balqa’ Applied University

2. Carcinogenic agents
3 major classes:
-Chemicals
-Radiation
-Microbes

3. Chemicals Direct-Acting or Indirect-Acting
Chimney sweeps and chronic exposure to soot
Direct-Acting or
Indirect-Acting

4. Direct-Acting chemical carcinogens
No metabolic conversion is needed
Some are cancer chemotherapy drugs!!! …alkylating agents
…used for Hodgkin lymphoma & others, & mainly causes leukemia
…Such agents may be used for non-neoplastic conditions

5. Indirect-Acting chemical carcinogens
Require metabolic conversion to an ultimate carcinogen
…polycyclic hydrocarbons, present in fossil fuels
benzo[a]pyrene and other carcinogens in cigarette smoking…lung cancer
also in animal fat and smoked meat/fish
epoxides are the active products…bind to nucleic acids and proteins

6. Indirect-Acting chemical carcinogens, cont’d
…aromatic amines and azo dyes
…β-naphthylamine and bladder cancer
The cytochrome P-450–dependent monooxygenases are especially involved…polymorphism between people
Some strains of Aspergillus, a mold that grows on improperly stored grains and nuts…Aflatoxin B1
aniline dye and rubber industries

7. Radiation carcinogenesis
Hiroshima and Nagasaki:
-Leukemia
-Thyroid
-Breast
-Colon
-Lung
…etc.

8. Radiation carcinogenesis, cont’d
Therapeutic irradiation of the head and neck…papillary thyroid carcinoma
Double stranded DNA breaks seem to be the most important form of DNA damage caused by radiation
Natural UV radiation derived from the sun
…skin cancers (melanomas, squamous cell carcinomas, and basal cell
carcinomas)
…at greatest risk are fair-skinned people who live in locales such as
Australia and New Zealand that receive a great deal of sunlight

9. Radiation carcinogenesis, cont’d
Non-melanoma skin cancers…total cumulative exposure to UV radiation
Melanoma…intense intermittent exposure—as occurs with sunbathing
UV light…pyrimidine dimers
Patients with the inherited
disease xeroderma pigmentosum
have a defect in the nucleotide
excision repair pathway
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10. Viral & microbial oncogenesis
HTLV-1…CD4+ T cells
EBV
HPV
HBV & HCV

11. HPV Cervix, anogenital & oropharyngeal (esp., tonsils)
E6 & E7 gene products
-binds RB and release E2F from it
-also inactivates p21 & p27 (CDKIs)
degrades p53

12. EBV B cell lymphoma Hodgkin lymphoma Nasopharyngeal carcinoma
T cell lymphoma
Gastric carcinoma
NK cell lymphoma
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13. HBV & HCV
HBV & HCV
Helicobacter pylori

14. Clinical aspects Can benign tumors cause death?
Complications: -mass effect
-bleeding and infection…by ulceration of surfaces
-rupture
-secretion of hormones…etc.
-cachexia

15. Cancer cachexia not starvation but due to mediators -TNF
= progressive loss of body fat and lean body mass, accompanied by profound weakness, anorexia, and anemia
not starvation but due to mediators
-TNF
-proteolysis-inducing factor
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16. Paraneoplastic syndromes
= symptom complexes that cannot be readily explained by local or distant spread of the tumor or by the elaboration of hormones not indigenous to the tissue of origin of the tumor
10-15% of cancers
Hypercalcemia, Cushing syndrome, and nonbacterial thrombotic endocarditis…of the most common ones
…mainly lung, breast and hematologic malignancies

17. Paraneoplastic syndromes, cont’d
Hypercalcemia resulting from skeletal metastases is not a paraneoplastic syndrome
Bronchogenic carcinomas:
Can secrete products identical to or having the effects of ACTH, antidiuretic hormone, parathyroid hormone, serotonin, human chorionic gonadotropin, and other bioactive substances
Hypercoagulability: -venous thrombosis
-nonbacterial thrombotic endocarditis
Clubbing of the fingers and hypertrophic osteoarthropathy in patients with lung carcinomas
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18. Grading and staging What is the difference?
What is TNM staging system?

19. Thank You