Current concepts in Pathogenesis
of cancer

INDIAN DENTAL ACADEMY
Leader in continuing dental education

www.indiandentala...


History : Egypt 3000 to 1500 B.C



Head and neck cancer : sixth most common cancer worldwide.



Increased incidence...
Contents:
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






The cell cycle check point.
Oncogenes.
Tumor suppressor genes.
Apoptosis.
Metastasis.
Viral oncog...
classification


Familial / sporadic

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Cell type



Tissue of origin

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Benign / malignant

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Degree of differentiat...
Charateristic features
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Local increase in cell number

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Loss of normal arrangements of cell



Variation of cell size...
Cancer is a gentic disorder at the cellular level

www.indiandentalacademy.com
Benign and Malignant cell

www.indiandentalacademy.com
Aetiology.






Principal carcinogens
 Smoking.
 Alcohol.
Site specific
 Nickel & chromate dust
 Nitrosamines
 Ha...
EVIDENCE



>7 cigrattes / day – 2.4 relative risk .
>25 cigrattes / day – 16.4
Cessation - 70% reduction after 10 years....


DIET.


Henderson; Ross; Pike;-1991. Cancer science.
Towards the primary prevention of
cancer.primary prevention of ca...
Initiators & promoter


1.Single exposure to alter cell



Irreversible process



High doses carcinogenic



2.contac...
Principle of carcinogenesis

www.indiandentalacademy.com
Evidence


Study by berenblum



In skin cancer



Initiator: methylcholanthrene



Promoter: croton oil



It applie...
PATHOPHYSIOLOGY : The cell cycle

www.indiandentalacademy.com
The check points

www.indiandentalacademy.com
The cyclins.


G1- cdk



G1/ S-cdk



S- cdk
M- cdk
Enzyme complex







SCF
APC

www.indiandentalacademy.com
THE CELL CYCLE CONTROL SYSTEM

www.indiandentalacademy.com
CELL CYCLE PROTEINS



Protein kinases: CAK, Wee1 kinase, cdc25



Cdk inhibitory proteins: sic1, p27, p21, p16



Ubiq...


Cancer- 2005;104;2709 – 2716.



Cyclin D1 gene aberration is a predictive marker for
occult cervical lymph node metas...
Result


Sensitivity 71%



Specificity 89%



Result – increased aberration of CCND 1 – Elective neck
dissection.

www...
Oncogene

TSR Gene
www.indiandentalacademy.com
P53 Gene :Apoptosis


Guardian of the genome



Tumor suppressor gene



G1 – G0.



Inactivated by Mdm 2



Suicidal...
Newer therapy


Monoclonal antibody therapy.



Activates death receptors in tumor cells.



Chemo + apoptotic drugs - ...
Telomere shortenning – repetitive cell senescence

www.indiandentalacademy.com
Viral oncogenes

www.indiandentalacademy.com
Radiation and cancer

www.indiandentalacademy.com
metastasis

www.indiandentalacademy.com
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www.indiandentalacademy.com
www.indiandentalacademy.com
www.indiandentalacademy.com
www.indiandentalacademy.com
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www.indiandentalacademy.com
www.indiandentalacademy.com
www.indiandentalacademy.com
www.indiandentalacademy.com
www.indiandentalacademy.com
Recent advances in tumor angiogenesis




On June 20, 2006, the FDA granted approval for a
labeling extension for bevaci...
Recent advances in cancer biology


The New England Journal of Medicine, Feb. 9, 2006



Cetuximab (Erbitux®) Plus Radia...









Journal of Clinical Oncology, Nov. 20, 2005
Oxaliplatin (Eloxatin®) Plus Radiation Superior in
Advanced Naso...
Proteomics & Cancer


Refers to the study of the proteins. Because proteins are
involved in almost all biological activit...
Biology therapy / Immunotherapy


Biological therapies use the body’s immune system to fight
cancer or to lessen the side...
Nutrition and Cancer













The journal Mechanisms of Ageing and Development
Arthur B. Robinson, Oregon Inst...
The CARET study trial






The Beta Carotene and Retinol Efficacy Trial
The purpose of the study was to test whether ...
Conclusion

MEDBIOWORLD.COM
CANCER.GOV

www.indiandentalacademy.com
Thank you

www.indiandentalacademy.com
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Current concepts in the pathogenesis of cancer /certified fixed orthodontic courses by Indian dental academy

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Current concepts in the pathogenesis of cancer /certified fixed orthodontic courses by Indian dental academy

  1. 1. Current concepts in Pathogenesis of cancer INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com www.indiandentalacademy.com
  2. 2.  History : Egypt 3000 to 1500 B.C  Head and neck cancer : sixth most common cancer worldwide.  Increased incidence in developing countries.  “ There is tremendous literature on cancer ,but what we know for sure about it can be printed on a calling card” -August Bier www.indiandentalacademy.com
  3. 3. Contents:        The cell cycle check point. Oncogenes. Tumor suppressor genes. Apoptosis. Metastasis. Viral oncogenes. Molecular therapies.  Biological therapy.  Gene therapy. Tailored medical therapy  www.indiandentalacademy.com
  4. 4. classification  Familial / sporadic  Cell type  Tissue of origin  Benign / malignant  Degree of differentiation  Anatomic site  function www.indiandentalacademy.com
  5. 5. Charateristic features  Local increase in cell number  Loss of normal arrangements of cell  Variation of cell size and shape  Increase in nuclear size and density  Increase in mitotic activity  Abnormal mitosis  Decreased interaction between cells  Invasion and metstasis www.indiandentalacademy.com
  6. 6. Cancer is a gentic disorder at the cellular level www.indiandentalacademy.com
  7. 7. Benign and Malignant cell www.indiandentalacademy.com
  8. 8. Aetiology.    Principal carcinogens  Smoking.  Alcohol. Site specific  Nickel & chromate dust  Nitrosamines  Hard wood dust. Viral  HPV  EBV www.indiandentalacademy.com
  9. 9. EVIDENCE  >7 cigrattes / day – 2.4 relative risk . >25 cigrattes / day – 16.4 Cessation - 70% reduction after 10 years. Mutation  Smoking – 33%  Smoking +alcohol – 58%  Neither – 17%  Alcohol : 13 YRS STUDY IN 28180 PTS.      Beer / spirits – RR 3.0 With wine – RR 0.5 www.indiandentalacademy.com
  10. 10.  DIET.  Henderson; Ross; Pike;-1991. Cancer science. Towards the primary prevention of cancer.primary prevention of cancer. 254, 1131 – 1137.  “High consumption of dietary fat is linked with breast , prostate, ovarian cancer”.  “Diet low in fiber is associated with colon cancer”.  “Vitamin C and E exert a protective effect by decreasing the formation of carcinogenic nitrosamines”. www.indiandentalacademy.com
  11. 11. Initiators & promoter  1.Single exposure to alter cell  Irreversible process  High doses carcinogenic  2.contact after initiator  Reversible in early stages  Needs prolonged exposure  No metabolic conversion www.indiandentalacademy.com
  12. 12. Principle of carcinogenesis www.indiandentalacademy.com
  13. 13. Evidence  Study by berenblum  In skin cancer  Initiator: methylcholanthrene  Promoter: croton oil  It applies only to chemicals  Egs. of promoter benzopyrene radiation,virus,hormones. www.indiandentalacademy.com
  14. 14. PATHOPHYSIOLOGY : The cell cycle www.indiandentalacademy.com
  15. 15. The check points www.indiandentalacademy.com
  16. 16. The cyclins.  G1- cdk  G1/ S-cdk  S- cdk M- cdk Enzyme complex     SCF APC www.indiandentalacademy.com
  17. 17. THE CELL CYCLE CONTROL SYSTEM www.indiandentalacademy.com
  18. 18. CELL CYCLE PROTEINS  Protein kinases: CAK, Wee1 kinase, cdc25  Cdk inhibitory proteins: sic1, p27, p21, p16  Ubiquitin ligases: scf, apc, cdc20, hct1  Gene regulatory proteins: E2F ,P53 www.indiandentalacademy.com
  19. 19.  Cancer- 2005;104;2709 – 2716.  Cyclin D1 gene aberration is a predictive marker for occult cervical lymph node metastasismin stage I and 2 OSCC  Myo ; yuki ; sonoda in Tokyo.  FISH and FNAC.  Chromosome 11q13 – CCND1 gene - encodes for cyclin D1 protein  Total no. of pts – 45.  Stage 1 – 29 ; Stage 2 – 16 . Follow up 2.5 yrs.  Late Metastasis – 17 ; nil – 28. www.indiandentalacademy.com
  20. 20. Result  Sensitivity 71%  Specificity 89%  Result – increased aberration of CCND 1 – Elective neck dissection. www.indiandentalacademy.com
  21. 21. Oncogene TSR Gene www.indiandentalacademy.com
  22. 22. P53 Gene :Apoptosis  Guardian of the genome  Tumor suppressor gene  G1 – G0.  Inactivated by Mdm 2  Suicidal decision  Depends on both int. and external cell signals..  activation of caspases www.indiandentalacademy.com
  23. 23. Newer therapy  Monoclonal antibody therapy.  Activates death receptors in tumor cells.  Chemo + apoptotic drugs - synergistic  Drugs Trastuzumab and rituximab are under clinical trails.  Draw back : drug resistance  COX 2 levels are elevated in certain cancers  Clinical data: pts under cox inhibitors have decreased colon cancer www.indiandentalacademy.com
  24. 24. Telomere shortenning – repetitive cell senescence www.indiandentalacademy.com
  25. 25. Viral oncogenes www.indiandentalacademy.com
  26. 26. Radiation and cancer www.indiandentalacademy.com
  27. 27. metastasis www.indiandentalacademy.com
  28. 28. www.indiandentalacademy.com
  29. 29. www.indiandentalacademy.com
  30. 30. www.indiandentalacademy.com
  31. 31. www.indiandentalacademy.com
  32. 32. www.indiandentalacademy.com
  33. 33. www.indiandentalacademy.com
  34. 34. www.indiandentalacademy.com
  35. 35. www.indiandentalacademy.com
  36. 36. www.indiandentalacademy.com
  37. 37. www.indiandentalacademy.com
  38. 38. www.indiandentalacademy.com
  39. 39. Recent advances in tumor angiogenesis   On June 20, 2006, the FDA granted approval for a labeling extension for bevacizumab (Avastin®) administered in combination with intravenous 5fluorouracil-based chemotherapy, for the secondline treatment of metastatic carcinoma of the colon or rectum. Patients treated with the Avastin combination were reported by investigator assessment to have significantly longer progression-free survival and higher overall response rate. www.indiandentalacademy.com
  40. 40. Recent advances in cancer biology  The New England Journal of Medicine, Feb. 9, 2006  Cetuximab (Erbitux®) Plus Radiation Beneficial for Patients with Head and Neck Cancer  Between 1999 and 2002, a total of 424 patients with stage III or IV head and neck cancer  The median duration of locoregional control was 24.4 months with the combined therapy and 14.9 months for radiation alone.  patients on the combined therapy saw their risk of death cut by 26 percent compared to the radiation-only group www.indiandentalacademy.com
  41. 41.      Journal of Clinical Oncology, Nov. 20, 2005 Oxaliplatin (Eloxatin®) Plus Radiation Superior in Advanced Nasopharyngeal Cancer Oxaliplatin is a newer platinum-based drug that has fewer side effects than cisplatin Patients who were treated with radiation plus oxaliplatin did significantly better than those receiving radiation alone. None of the patients getting chemoradiotherapy had died after two years, compared to a survival rate of 77 percent for those getting radiation alone Relapse rate:  chemo + Rad – 17%  Only Rad – 4% www.indiandentalacademy.com
  42. 42. Proteomics & Cancer  Refers to the study of the proteins. Because proteins are involved in almost all biological activities, the proteome is a rich source of biological information.  Age – 12 yrs.  A $104 million program.  5,00,000 cellular proteins  Future: Bio markers - Nanotechnology – A.I www.indiandentalacademy.com
  43. 43. Biology therapy / Immunotherapy  Biological therapies use the body’s immune system to fight cancer or to lessen the side effects that may be caused by some cancer treatments  Biological response modifiers  The U.S. Food and Drug Administration (FDA) has approved the use of interferon alpha for the treatment of certain types of cancer.  MOA’s; hybridomas.  Tailor made treatment – heterogenicity. www.indiandentalacademy.com
  44. 44. Nutrition and Cancer         The journal Mechanisms of Ageing and Development Arthur B. Robinson, Oregon Institute of Science and Medicine, December 1999 Excellent nutrition strengthens the immune system and other defense mechanisms But,once cancer has established itself, excellent nutrition leads to its accelerated growth. Linus Pauling Institute of Science and Medicine. vitamin C in ordinary doses accelerated the growth rate of squamous cell carcinoma in mice. 1-5gms / 100 gms Ann Wigmore's establishment for diet www.indiandentalacademy.com
  45. 45. The CARET study trial     The Beta Carotene and Retinol Efficacy Trial The purpose of the study was to test whether a beta carotene supplement reduced the risk of cancer A 12 year study In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial, 18 percent more lung cancers were diagnosed and 8 percent more overall deaths occurred in study participants taking beta carotene. www.indiandentalacademy.com
  46. 46. Conclusion MEDBIOWORLD.COM CANCER.GOV www.indiandentalacademy.com
  47. 47. Thank you www.indiandentalacademy.com

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