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

Current concepts in Pathogenesis
of cancer

INDIAN DENTAL ACADEMY
Leader in continuing dental education

www.indiandentalacademy.com

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History : Egypt 3000 to 1500 B.C

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Head and neck cancer : sixth most common cancer worldwide.

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Increased incidence in developing countries.

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“ There is tremendous literature on cancer ,but what we know for
sure about it can be printed on a calling card”
-August Bier


Contents:
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The cell cycle check point.
Oncogenes.
Tumor suppressor genes.
Apoptosis.
Metastasis.
Viral oncogenes.
Molecular therapies.
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Biological therapy.

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Gene therapy.
Tailored medical therapy

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classification
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Familial / sporadic

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Cell type

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Tissue of origin

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Benign / malignant

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Degree of differentiation

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Anatomic site

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function

Charateristic features
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Local increase in cell number

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Loss of normal arrangements of cell

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Variation of cell size and shape

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Increase in nuclear size and density

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Increase in mitotic activity

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Abnormal mitosis

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Decreased interaction between cells

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Invasion and metstasis


Cancer is a gentic disorder at the cellular level


Benign and Malignant cell


Aetiology.
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Principal carcinogens
 Smoking.
 Alcohol.
Site specific
 Nickel & chromate dust
 Nitrosamines
 Hard wood dust.
Viral
 HPV
 EBV

EVIDENCE

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>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%

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Alcohol : 13 YRS STUDY IN 28180 PTS.

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Beer / spirits – RR 3.0
With wine – RR 0.5

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DIET.
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Henderson; Ross; Pike;-1991. Cancer science.
Towards the primary prevention of
cancer.primary prevention of cancer. 254, 1131
– 1137.

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“High consumption of dietary fat is linked with
breast , prostate, ovarian cancer”.

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“Diet low in fiber is associated with colon
cancer”.

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“Vitamin C and E exert a protective effect by
decreasing the formation of carcinogenic
nitrosamines”.

Initiators & promoter
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1.Single exposure to alter cell

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Irreversible process

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High doses carcinogenic

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2.contact after initiator

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Reversible in early stages

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Needs prolonged exposure

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No metabolic conversion

Principle of carcinogenesis


Evidence
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Study by berenblum

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In skin cancer

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Initiator: methylcholanthrene

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Promoter: croton oil

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It applies only to chemicals

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Egs. of promoter benzopyrene
radiation,virus,hormones.

PATHOPHYSIOLOGY : The cell cycle


The check points


The cyclins.
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G1- cdk

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G1/ S-cdk

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S- cdk
M- cdk
Enzyme complex

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SCF
APC


THE CELL CYCLE CONTROL SYSTEM


CELL CYCLE PROTEINS

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Protein kinases: CAK, Wee1 kinase, cdc25

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Cdk inhibitory proteins: sic1, p27, p21, p16

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Ubiquitin ligases: scf, apc, cdc20, hct1

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Gene regulatory proteins: E2F ,P53


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Cancer- 2005;104;2709 – 2716.

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Cyclin D1 gene aberration is a predictive marker for
occult cervical lymph node metastasismin stage I and
2 OSCC

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Myo ; yuki ; sonoda in Tokyo.

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FISH and FNAC.

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Chromosome 11q13 – CCND1 gene - encodes for
cyclin D1 protein

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Total no. of pts – 45.

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Stage 1 – 29 ; Stage 2 – 16 . Follow up 2.5 yrs.

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Late Metastasis – 17 ; nil – 28.

Result
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Sensitivity 71%

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Specificity 89%

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


Oncogene

TSR Gene

P53 Gene :Apoptosis
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Guardian of the genome

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Tumor suppressor gene

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G1 – G0.

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Inactivated by Mdm 2

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Suicidal decision

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Depends on both int. and external cell signals..

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activation of caspases

Newer therapy
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Monoclonal antibody therapy.

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Activates death receptors in tumor cells.

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Chemo + apoptotic drugs - synergistic

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Drugs Trastuzumab and rituximab are under
clinical trails.

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Draw back : drug resistance

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COX 2 levels are elevated in certain cancers

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Clinical data: pts under cox inhibitors have
decreased colon cancer

Telomere shortenning – repetitive cell senescence


Viral oncogenes


Radiation and cancer


metastasis


Recent advances in tumor angiogenesis
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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.

Recent advances in cancer biology


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

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Cetuximab (Erbitux®) Plus Radiation Beneficial for Patients
with Head and Neck Cancer

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Between 1999 and 2002, a total of 424 patients with stage III
or IV head and neck cancer

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The median duration of locoregional control was 24.4 months
with the combined therapy and 14.9 months for radiation
alone.

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patients on the combined therapy saw their risk of death cut
by 26 percent compared to the radiation-only group


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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%

Proteomics & Cancer
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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.

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Age – 12 yrs.

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A $104 million program.

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5,00,000 cellular proteins

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Future: Bio markers - Nanotechnology – A.I


Biology therapy / Immunotherapy
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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

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Biological response modifiers

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The U.S. Food and Drug Administration (FDA) has approved
the use of interferon alpha for the treatment of certain types
of cancer.

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MOA’s; hybridomas.

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Tailor made treatment – heterogenicity.

Nutrition and Cancer
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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


The CARET study trial
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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.

Conclusion

MEDBIOWORLD.COM
CANCER.GOV


Thank you


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