Clinical Aspects of Neoplasia

Host defense against Tumors (tumor immunity)

Host defense is by certain antigens in normal healthy cells. In tumor cells, alterations take place or antibodies attack, resulting in tumor cells.

Anti-tumor mechanisms

1. Expression of tumor antigens

• Tumor specific antigen
• Tumor associated antigen
• HCA-1 molecules expression

2. Production of antibodies against tumor cell antigens
3. Cytotoxic T lymphocytes (CD8+) protect against viruses associated tumors
4. First basic defense is by natural killer cells
5. Macrophages

• Activated T lymphocytes and natural killer cells by INF-gamma
• Kill tumor cells by phagocytic activity.

Escape from immune mechanisms

• Outgrowth of antigen negative tumor cells
• Reduced expression of HLA-1 antigen
• Masking of cell surface antigen by mucopolysaccharides
• Certain tumor products are potent immunosuppressants e.g. TGF-beta
• Some tumor cells express fas ligand (fas L) and kill FaS expressing T lymphocytes that come in contact with them

Clinical Implications

Local effects

1.      Compression of nearby structures

Example includes pancreatic carcinoma on bile duct leading to obstruction

2.      Ulceration/bleeding

• Colon
• Gastric
• Renal cell carcinoma

3.      Infection (often due to obstruction)

• Pneumonia
• Urinary infection

4.      Rupture or infarction

• Ovarian
• Bladder
• Colon

Clinical Significance

May be the earliest manifestations.

Cancer Cachexia

• Progressive weakness, loss of apetite, anemia and profound weight loss (>20%), often correlate with tumor mass and spread.
• Probably related to macrophage production of TNF-gamma.

Treatment of Cancer

• Most anti-cancer treatment is directed towards killing actively dividing cells.
• Newer drugs target tumor cells by immune mechanisms or hormones.

Further details are available at

• Cancer Chemotherapy -An Introduction
• Alkylating Agents
• Methotrexate, 5-Fluorouracil, Purine Antagonists and Antibiotics Used in Cancer Chemotherapy
• Vinca Alkaloids, Taxanes, Epipodophyllotoxins, Camptothecins, Hormones, Anti-hormones, Asparaginase, Monoclonal Antibodies and Cytokines

Complications

1. Minor aplasia
2. Alopecia
3. Sterility
4. GIT damage
5. Lung damage
6. Kidney damage

Treatment approaches

1. Surgical therapy –early stage/debulk
2. Chemotherapy
3. Radiotherapy
4. Neoadjuvant therapy –therapy in which radiotherapy is applied first to reduce mass of cells, once cells shrink it becomes easy to remove them by surgical procedure.

Combination type of therapy is generally applied.