NEOPLASIA
Neoplasia is defined as: “An abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli that evoked the change.”
Neoplasia has genetic and environmental causes. It is important to note that both play parts in causing neoplasia.
Carcinogens/process of carcinogenesis
Chemical carcinogenesis
Initiation
* Results from interaction of chemical with DNA to activate a proto-oncogene or inactivate a tumor suppressor gene by formation of covalent adducts.
* Chemicals that can form adducts (direct acting) are usually electrophiles.
* Many chemical carcinogens require activation by metabolic pathways (pro-carcinogens or indirect acting carcinogens) an example of a metabolic pathway is the p-450 cytochrome mono-oxygenase.
* Initiation alone does not result in tumours.
Promotion
* Promotors are usually irritants or substances that produce cell activation and proliferation.
* Effects of promotors are reversible.
Promotors cannot induce neoplasia: i) alone, ii) if applied before initiator, iii) if applied in too small an amount for effect, or iv) if too much time elapses between applications.
Ultraviolet Light
* Strong epidemiologic relationship to squamous cell, basal cell, and melano-carcinoma in fair skinned people.
The Essay on Fuel Cell Report Chemicals Cells Electricity
Fuel Cells Fuel cells are very important because they offer an alternative environmentally friendly fuel for transportation, which causes a major amount of the damage to or earth and the growing problem of global warming. This issue of course is a factor everywhere on our planet especially in metro areas where cars and transportation are major issues. A fuel cell is an electrochemical energy ...
* Causes formation of pyrimidine dimers in the DNA leading to mutations.
* Activation of T-suppressor cells facilitates emergence of tumor clones.
* Individuals with defects in the enzymes that mediate DNA excision-repair are especially susceptible.
Ionizing Radiation
* Ionizing radiation includes: X-rays, gamma rays, as well as particulate radiation; alpha, beta, positrons, protons, neutrons and primary cosmic radiation. All forms are carcinogenic with special sensitivity in:
* Bone Marrow: Acute leukemia occurs before other radiation-induced neoplasia (Seven year mean latent period in atomic bomb survivors).
* Thyroid: Carcinoma occurs in 9 % of those exposed during infancy or childhood.
* Lung: Increased frequency of lung cancer in miners exposed to Radon gas (an alpha particle emitter).
Figure 1
MECHANISM OF CARCINOGENESIS
Viral Carcinogenesis
* A large number of RNA and DNA viruses have been implicated in the causation of a variety of
cancers in animals and humans some important ones are listed below.
* Human papiloma virus (HPV).
There are more than 70 types of these DNA viruses. HPV types 16, 18
and 31 are associated with precancerous and invasive squamous cancer of the cervix.
* Epstein-Barr Virus (EBV) is a member of the Herpes family. It is associated with 4 types of
human cancers:
1. African Burkitt lymphoma
2. B-cell Lymphoma (particularly in immunosuppressed individuals)
3. Hodgkin lymphoma
4. Nasopharyngeal carcinoma
* Hepatitis B virus is associated with increased risk of developing hepatocellular carcinoma
* RNA viruses like Human T-Cell Leukemia Virus Type 1 (HTLV) is associated with some forms
Of T-Cell leukemia/Lymphoma.
Cancer metastasis
Metastasis is defined as the development of secondary implants discontinuous with the
primary Malignant neoplasm and possibly in remote tissues. Once metastases are detected a
cure becomes difficult if not impossible. Also, patients survival dramatically drops if metastases
The Essay on Lung Cancer 6
Lung cancer is an uncontrolled, extremely deadly division of cells in the lung (World Book, Lung Cancer). The two major types of lung cancer include small and non-small cell. Many different risk factors contribute to lung cancer. There are numerous symptoms that are difficult to detect in the early stages of lung cancer. Doctors use special machines to detect the severity of each stage. Treatments ...
are present.
Cancers spread by three ways:
1. Direct spread into natural cavities. Such as peritoneum, pleura, etc
2. Lymphatic spread (via lymphatic vessels)
3. Haematogenous spread (via veins)
Pathophysiology of metastasis
Metastasis is a multi-step process . A selected clone of cells growing in the primary tumour has to detach from the tumour mass and invade through a thick layer of connective tissue known as the basement membrane (BM).
This process involves the production of a collection of proteolytic enzymes capable of destroying collagen type IV and other proteins and carbohydrate polymers, which are the main constituents of the BM. The metastatic cells then reach blood or lymphatic vessels by which they are transported to distant sites. The tumour cells then extravasate from the vessels to colonize distant organs as micrometastases. Metastasis is therefore a complex process involving multiple steps and requiring the expression of multiple unrelated genes.
Metastasis is an inefficient process. Metastatic tumour cells are typically cleared from the host bi-phasically. The initial phase (6-24 hours), represents an exponential decline of cell numbers due to mechanical trauma, oxygen toxicity and clearance by the immune system. The second more gradual decline phase represents cell death at colonized sites .However, recent evidence from intravital videomicroscopy, have strongly proposed that the major cause of metastasis inefficiency is failure of cells to grow in distant sites post-extravasation .Metastasis is therefore a complex process involving multiple steps and requiring the expression of multiple unrelated genes.
Adhesion to endothelial cells
Tumour cells express E-Selectins
Molecules that bind to
Sialyl-Lewis X on endothelial cells
Direct spread
* Cancer of the Colon invades the peri-colonic fat and breaks free into the peritoneal cavity
* Cancer of the Ovary is another big peritoneal spreader
* Cancer involvement of cavities tends to produce haemorrhagic effusion, adhesions
Lymphatic Spread
* More typical of carcinomas rather than sarcomas (hematogenous)e.g Breast, stomach, Papillary thyroid carcinoma
The Essay on Lung Cancer Cells Spread Stage
There are two different types of lung cancer, non-small cell lung cancer and small cell lung cancer. It is all depending on the size of what the cells look like under a microscope. Both of these types of lung cancer can grow differently which leads to them both being treated differently. Non-small cell lung cancer is the more common of the two and it usually grows fairly slow. There are three main ...
* Cancer cells travel in lymphatics and reach regional lymph nodes. They get arrested, die or grow or travel to other nodes
* Regional Lymph nodes draining the cancer area are first involved
* It is the rationale for lymph node dissection in many Carcinomas. The lymph nodes in the specimen are enlarged and firm.
Hematogenous Spread
* Sarcomas predominate but Carcinomas also use this route.
* Arteries are rarely invaded
* Veins are the route of hematogenous spread
* Liver and Lungs are the usual endpoints of hematogenous spread, but remember that metastases can also metastasise.
* Portal flow to liver and vena caval flow to lungs
* Renal Cell Ca has a propensity to invade the renal vein and hepatocellular cancer has a tendency to penetrate portal and hepatic radicles.
* The distribution of metastases follow the anatomical distribution. Thus, breast cancer in the upper-outer quadrant is likely to metastasise to the axillary lymph nodes, while a upper-inner breast cancer (medial) tends to metastasise to supraclavicular lymphnodes. Colon cancer tends to metastasise to Liver while cancers of the lower rectum tends to metastasise to the lung as described earlier.
* Prostate cancer prefer to metastasise to bone
* Bronchogenic cancer tends to involve adrenals and brain
* Neuroblastoma spread to liver and bones.
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