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Patho Test 3 Ch 12 Cancer Biology

Terms in this set (56)

Complications of Cancer and Cancer Therapies: (See box 12-2 Page 396)
1. Para-neoplastic syndromes (See table 12-11 page 395)
Some tumors release hormones, acting as ectopic sources. They do not respond to
negative feedback controls. Hence hyper secretion syndromes. E.g Serotonin, flushing,
diarrhea, and wheezing.
2. Pain initially little or no pain, but is present in 60-80% of terminally ill cancer
patients
Cause: a. Pressure
b. Bowel or blood flow obstruction (ischemia)
c. Stretching of viscera (abdominal)
d. Tissue destruction. (Bone)

e. Inflammation and Kinin & cytokine release.
3. Fatigue Most frequently reported symptom of cancer and cancer treatment. Described
as a lack of energy, lethargy, depression, inability to concentrate
Causes: a. Sleep disturbances
b. Biochemical changes, cytokines, 9 neurotransmitter .
c. Nutritional status Muscle loss
d. Anemia
4. Cachexia (See fig 11-27 page 390)
wasting away of lean body mass, may have to do with the stress response.
Increase sympathetic stimulation and cortisol.
Causes: multiple:1. Anorexia— pain, depression, chemotherapy, alterations in taste.
High blood glucose & blood fat levels, trigger
satiation
2. Poor use of glucose
3. Decrease insulin secretion, (epi ->â?)
4. Increased catabolism of proteins, increased blood AA's Cortisol?
5. Decreased peristalsis. (epi ->â?)
6. Increased triglyceride hydrolysis (epi ->â?)
7. Aversion to red meat
5. Anemia Three general mechanisms that cause anemia in cancer.

1. Chronic bleeding due to tissue disruption.
2. Medical therapies, e.g. chemotherapy.
3. Malignancy in hemopoietic tissues.
4. Malnutrition
6. Leukopenia and Thrombocytopenia Loss of WBC's and platelets.
Causes: 1. Chemotherapy.
2. Malignancy in hemopoietic tissues.
7. Infection 1. Reduction of immune system components
2. Loss of Gut barrier, -> invasion by normal flora,
Due to a. GI tumor
b. Chemotherapy
8. GI complications 1. Loss of Gut barrier due to decrease cell replacement (Chemo),
2. Loss of absorption surface area ...Mal-absorption.
3. Diarrhea,
4. Sepsis from loss of Gut barrier.
9. Alopecia, (hair loss) Usually temporary.
Cell surface changes in cancer cells and their functional importance:
1. Decrease in Glycosphingolipids:
Normal effect: Decreases cell responsiveness
to grow factors.
Cancer: Decrease Glycosphingolipids,
possibly increase the cells
responsiveness to growth
factors.
2. Changes in Glycoproteins and glycolipids:
Decreased communication between cells.
May increase immune response to the
cancer cells.
3. Loss of Fibronectin:
With collagen and elastin, Fibronectin is a cell-surface protein that
mediates cellular adhesive interactions., adhesiveness. Protein that form
Cadherins and integrins. Which form the adhesion junctions between
cells and between the cell and surrounding CT.
4. Secrete Protease:
e.g. activates Plasminogen, disrupts extracellular matrix.
Decrease adhesiveness. Allows the cancer cells to escape the capsule
5. Decreased Anchorage Proteins:
Desmosomes, Adherens, junctions. Normal cells need to
be anchored to undergo mitosis, Cancer cells undergo
anchorage independent mitosis. This also allows them to
metastasize. This is linked to changes in Fibronectin
6. Decreased gap junctions:
Thought to play a mayor role in cancer development.
Many tumors promote, alter or block gap junction function
or formation. Blocks Cell-cell communication.
Gap junction are either blocked or down-regulated in
cancer cells.This implies that there is reduced or absent cellcell
communication and decreased contact inhibition by
neighboring cells. Gap Junctions can be down regulated by
known carcinogenic agents.

Note: All of above changes alter the cell's ability to communication with the community of cells it
should be apart of. This leads to Destiny independent growth in transformed cells

Note: Normal cells prevent the development of blood vessels by secreting Thrombospondin. Tumor cells may not secrete thrombospondin.
Successful tumors are capable of manipulating the inflammatory and immune responses to Phenotypes associated with healing and growth factors rather than destructive .
Chemotherapy: 1. Kills cells that are active in mitosis or are capable of mitosis.
Hopefully the chemo eradicates enough cells that the body can kill
the rest. E.g Methotrexate, L-asparaginase, cyclophosphamide,
anthracyclines
2. Combinations of different types of chemical agents have been the
most successful. Each drug attacks the tumor cells at a specific
weakness. 75 - 80% long term remission or cure rates.
3. Some cells in Tumor mass may be resistant

Surgery: Objective: 1. Remove the whole tumor before it metastasizes.
2. Preventative Surgery, e.g Mastectomy
2. Remove the pressure to:
A. alleviate pain., not intent to cure.
B. Debulk prior to chemotherapy
C. Determine Staging, Nodal involvement
indicating spread

Radiation: Focuses on only the tumor and hopefully doesn't damage too severely the
tissue around it. Damages or destroys large macromolecules like DNA.

Immunotherapy:
Advantage: 1. Selectively Kill tumor cells, while sparing normal cells.
2. Memory cells for prevention of emergence of primary tumor
BCG Bacterial wall extracts are injected into tumor,
Activates macrophages and NK cells
Some success with Urogenital and Lung CA
DNCB Dinitrochlorobenzene
Body first sensitized, then DNCB is painted on Skin tumor,
Causes Hypersensitivity response e.g (Type IV) similar to poison Ivy
LAK (Lymphokine Activated Killer) cell therapy
Cultured Tc cells in IL-2 activated against TSA (Tumor specific Antigens)
LAK cells reinserted into patient, cause lysis of tumor cells
Used successfully against melanoma and Renal cell carcinoma
Monoclonal Antibodies: 1. Used to diagnose and monitor treatment results
2. Goal: to mediate tumor rejection,
3. Has been most successful against hematologic and
Lymphatic cancers
4. Conjugated Antibodies, attach radioactive isotopes or
toxins, when antibodies bind to tumor cells, they kill
target selectively as with radioactive iodine with Thyroid
cancer
Alternative Therapies: "Rarely is there evidence that they are medically effective"!