Toxicology and development summary (minor biomedical topics in healthcare)
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Course
Toxicology and development (AB_1026)
Institution
Vrije Universiteit Amsterdam (VU)
ENGLISH: This is a summary of all lectures of toxicology and development (in English). It contains all important information, with pictures for clarification.
ENGLISH: This is a summary of all toxicology and development lectures (in English). It contains all the important information, with pictu...
Oncology and Public Health Summary Lectures
Lecture 1: Introduction into the course
In NL we have national screening programmes for breast cancer, colon cancer and cervix
cancer. In total there are 260 cancer types, but the big five are: breast cancer, squamous
cell carcinoma (skin), lung cancer, prostate cancer and colon cancer. Over time, the five
year survival rate has risen, mainly in common cancers. In NL, cancer is the leading cause
of death, and around ⅓ of cancer deaths is due to behavior.
Public health and health
Public health: the science and art of preventing diseases, prolonging life and promoting
health through the organized efforts of society.
Health: a state of complete physical, mental and social well-being and not merely the
absence of disease or infirmity.
Oncology and public health
The focus relies on prevention, increasing health care capacity, efficient organizations in
health care, digitalization, supporting needs of patients and survivors and increasing the
quality of life and quality of end-of-life.
Lecture 2: Introduction into public health
Public health is preventing diseases, prolonging life and promoting health in society. The
focus is on groups rather than individuals, and it refers to collective actions to improve
population health.
Application of public health
There are three important fields in public health research: epidemiology/community
diagnosis, collective prevention/health promotion and health care organization/performance.
- Based on population, disease prevention, health promotion and interventions
(environment, behavior) rather than the individual, diagnosis, treatment and
intervention (medical care).
Public health functions
WHO: assessment and monitoring health communities/population to identify health
problems, formulation of public policies to solve local and national health problems and
assure that all have access to appropriate and cost-effective care.
Major public health achievements
Since 1900: vaccination, safer workplaces and control of infectious diseases
Since 1920: safer/healthier foods, healthier mothers and babies (less mortality) and family
planning
Since 1965: fluoridation of drinking water, motor-vehicle safety, recognition of tobacco as a
health hazard and decline in deaths from CVD and stroke.
→ Biggest success (1840): improving sewage disposal and clean water supply
Current public health challenges
Infectious diseases, chronic diseases, overweight/obesity, mental health, environmental
quality and social issues (violence, drugs, teenage pregnancy).
1
,Global burden of cancer
Cancer is the leading cause of death: ⅛ deaths worldwide. It is expected that this number
only will rise, because of an increasing global population, increasing age, more screening
(detecting) and increases of risk factors (smoke, obesity, inactivity and diet).
- There are geographic variations in cancer: not everywhere the burden of cancer is
the same (some countries have a higher prevalence of specific cancers than others)
Prevention of cancer (RIVM)
1. Primary prevention (preventing occurrence of disease)
- encourage healthy lifestyle, vaccination (e.g. HPV), etc
2. Secondary prevention (detect and treat the disease early, before symptoms occur)
- screening for cancers
3. Tertiary prevention (prevent damage and pain from the disease, slow down the
disease and prevent the disease from causing more problems)
- Survivorship care, improve HRQoL, prevention of recurrence
Factors influencing cancer risk
By living healthy, the risk of cancer can be reduced by 30%. In the Netherlands a lot of
people get cancer due to their lifestyle (smoking, not enough fruit/veggies, too much red
meat, obesity, alcohol, not enough physical activity, and UV).
WCRF recommendations
The World Cancer Research Fund wants: international funding for cancer research,
How do we study cancer risks
By studying epidemiology. E.g. with observational studies and prospective cohort studies.
For rare cancers we use case control studies (overestimates a little bit).
- Risks can be increased or decreased because of behaviors/environment
Recommendations
Do not smoke, have a healthy weight, move more, avoid high calorie foods and sugary
drinks, eat more grains, veggies, fruits and beans, limit red/processed meat, do not drink
alcohol, eat less salt, do not rely on supplements, breastfeed your baby (if possible). Cancer
survivors should follow these recommendations where possible.
Why public health policy?
Policy is needed to enable people to achieve and maintain a healthy weight by influencing
food environment, food system, built environment and behavioral change communication
e.g. Because there are a lot of factors individuals have no influence on: environment,
economic and social factors, policies are needed.
Lecture 3: Introduction into oncology
Our body consists of around 30 trillion cells. Groups of cells work together in forming tissues
and organs. Organs work together so we can live. Cancer can arise in any of those cells.
What is cancer?
Cancer comprises a large group of disease characterized by abnormal cells which:
1. Continue to proliferate
2
, 2. Invade in local tissues
3. Can spread to other organs
Metastasis: spreading of cancer cells from the primary place to other places in the body
Tumor: abnormal accumulation or growth of cells that divide uncontrollably
Benign and malignant tumors
Benign: ‘good’ tumor, respects your borders, will not metastasize, and will never kill you
Malignant: ‘bad’ tumor, lots or necrosis, irregular shape, and can metastasize.
- There are a billion cells needed to form a tumor as bit as a grape. A patient usually
had cancer for several years before it is detected or causes symptoms.
Types of cancer
Carcinoma (85% of all cancers)
- Arises from tissues that line or cover internal organs, the thoracic and abdominal
cavity.
+ Adenocarcinoma: glandular tissue (epithelial cells breast, colon, prostate)
+ Squamous cell carcinoma (epithelial cells skin, lung)
+ Translation cell carcinoma (urothelial cells bladder, uterus, kidneys)
Sarcoma (1% of all cancers)
- Originates in bones and soft tissue
+ Soft tissue carcinoma (fat, muscle, nerves, lymph vessels), osteosarcoma
(bone) and angiosarcoma (blood vessels)
Glioma
- Originates in glial cells of the CNS (brain tumor)
Melanoma
- Originates in the melanocytes of the skin
Leukemia
- Originates in the blood-forming tissues of the bone marrow
Lymphoma and myeloma
- Originates in cells of the immune system
How does cancer arise?
Normally cells grow and multiply: DNA exposed, replicated, two exact copies, cells divide,
each cell contains the same DNA. However this process is vulnerable to damage by toxins
(direct or indirect; increasing cell replication) or random errors (there are mechanisms to fix
errors, but there could be a problem). Normally mistakes in the DNA can be repaired or cells
undergo apoptosis. Some cells will survive with abnormal changes: genomic alterations.
Types of genomic alterations
1. Point mutation (changes in the amino acid sequence of proteins)
3
, 2. Deletion/duplication (leading to loss of function or more function)
3. Insertion (extra amino acid)
4. Translocation (DNA of two chromosomes is being exchanged)
→ Consequences: type and location of the genomic alteration are important. It
could lead to problems in the tumor suppressor genes (brake) and proto-
oncogenes (accelerator).
Proto-oncogenes
When a proto-oncogene mutates it can become an oncogene. A normal proto-oncogene
stimulates cell division, inhibits cell differentiation and prevents cell death (it is a positive cell
cycle regulator). If there is a mutation this could lead to over activation (oncogenes).
- Oncogenes: HER2 in breast cancer, B-RAF and MEK in melanoma.
Tumor suppressor genes
A normal tumor suppressor gene blocks cell cycle progression (e.g. p53). If there is a
mutation, the block is gone (e.g. a non functional p53, which we can not target yet) and
could lead to too much cell cycle progression.
- Tumor suppressor genes: BRCA ½ in breast cancer
Hallmarks of cancer (a multi-hit model)
Due to (coincidence of ) specific genomic alterations, cancer cells can:
1. stimulate their own growth (self-sufficiency in growth signals)
2. resist inhibitory signals that might otherwise stop their growth (insensitivity to anti-
growth signals)
3. resist their programmed cell death (evading apoptosis)
4. multiply indefinitely (limitless replicative potential)
5. stimulate the growth of (new) blood vessels to supply nutrients to the tumor
(sustained angiogenesis)
6. invade local tissues and spread to distant sites (tissue invasion and metastasis)
7. exploit abnormal metabolic pathways allowing them to survive
8. evade the immune system (creating an immunosuppressive environment)
→recognized by the immune system in a very early stage (due to the
expression of tumor-antigens), most newly formed cancer cells are
destroyed in early phase, but some produce signals and cytokines to
inhibit the immune system and will survive→immunotherapy is based on
this (release the brakes on the immune system→kill the cancer cells)
9. show genome instability (which will result in accumulation of genomic
alterations→ some a disadvantage and some an advantage to cancer cells)
and mutation
10. show tumor promoting inflammation
4
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