2nd
For all ages, cancer is the ____ most common case of death in the U.S.
66%
The overall 5-year survival rate for cancer is now ____%.
Contact Inhibition
Normal cells respect boundaries of surrounding cells and tissues and stay out of other territories, thus inhibiting growth of surrounding tissues unlike themselves (occurs thru barrier of physical contact); this is particularly evident during wound healin
Apoptosis
Programmed cell death: occurs when cell becomes mutated or damaged.
* Body's safety mechanism: normal!
* Greek for "shedding of leaves from tree"
Something inside or outside cell triggers "cell suicide" genes to produce damaging enzymes: cell shrinks & pu
2 adverse effects of cancer cells
Cancer cells lose contact inhibition and grow on top of one another or on top of/between normal cells; Cancer cells respond differently to body's regulating mechanisms: divide indiscriminately; proliferate despite mutations; etc.
Pyramid effect
Proliferation of cancer cells is continuous and indiscriminate: tumor grows b/c cells continue to multiply: 1x2x4x8x16
Protooncogenes
Normal cellular genes: regulate ordinary cell processes; "Genetic Locks" that keep cell in mature functioning state; PROMOTE growth
Tumor Suppressor genes
SUPPRESS growth; regulate ordinary cell growth
* BRCA1 & BRCA2 (alterations cause breast & ovarian cancer
* APC gene (alterations lead to colorectal cancer)
* p53 (alterations cause bladder, breast, colorectal, esophageal, liver, lung, ovarian cancers)
Oncogenes
Tumor-inducing genes: mutation of protooncogenes; cell becomes malignant and may produce proteins or hormones from fetal/embryonic periods that shouldn't be created.
How might protooncogenes be altered?
May be "unlocked" by: carcinogen exposure (chemical, radiation), oncogenic viruses, genetic alterations
Characteristics of benign neoplasms
Well-differentiated, encapsulated, expansive mode of growth, characteristics similar to parent cell (fairly normal), slight vascularity
Characteristics of malignant neoplasms
Poorly differentiated, metastatic capacity, moderate to marked vascularity, possible recurrence, mode of growth is infiltrative & expansive, rarely encapsulated, cells abnormal (unlike parent cells)
3 stages of cancer development
Initiation, promotion, progression
Initiation
1st stage of cancer development: IRREVERSIBLE mutation of genetic structure; may develop into clone of neoplastic cells; set off by chemical, viral, genetic, radiation factors
Example of chemical carcinogens
pesticides, asbestos, radon, chemotherapy drugs, immunosuppressants, cigarette tar, diet coke
Promotion
2nd stage of cancer development: REVERSIBLE proliferation of altered cells: increase in altered cells causes an increase in mutations
Promoting Agents
Dietary fat, obesity, cigarette smoking, alcohol consumption: lifestyle behaviors that are modifiable
half
Approximately ____ of cancer-related deaths in the U.S. are related to tobacco use, physical inactivity, obesity, and unhealthy diet.
Complete carcinogen & example
This is both an initiator and a promoter: ex: cigarette smoke
Latent period
May be between 1-40 years; between initial cellular alterations and clinical evidence of cancer (critical mass: 1 cm tumor w/ 1 billion cancer cells); length of period varies with mitotic rate of tissue of origin & other environmental factors
Progression
Final stage of cancer development: increased growth rate of tumor, including invasiveness & metastasis; Metastasis begins with rapid development of a primary tumor
Progression
In what stage of cancer development, does a tumor develop its own blood supply (to survive) & penetrate walls of lymph or vascular vessels allowing it to metastasize elsewhere?
Role of immune system in cancer & loopholes of this function
To reject or destroy cancer cells if perceived as non-self: may be inadequate if cancer cells arise from the body's own normal cells
Immunologic surveillance
The response of the immune system to antigens, such as tumor-associated antigens (TAAs), of the malignant cells; occurs continuously
Lymphocytes
These cells involved in immune response monitor cell surface antigens and detect and destroy abnormal cells
Functions of cytotoxic T cells in battling cancer:
Kill tumors (dominant role); produce cytokines, such as interferon and interleukin, which stimulate T cells, NK cells, B cells, and macrophages to get busy and fight!
Functions of NK cells in fighting cancer:
Lyse tumor cells indiscriminately; with stimulation from T cells' cytokines, cytotoxic activity increases
Functions of monocytes/macrophages in fighting cancer:
When activated by interferon, lyse tumor cells; also secrete interleukin, tumor necrosis factor (cause hemorragic necrosis of tumors), and colony-stimulating factors (regulate BC production & stimulate fxn of WBCs)
Functions of B cells in fighting cancer:
Produce specific antibodies that bind to tumor cells and kill them by complement fixation & lysis
Immunologic Escape
When cancer cells evade the immune system: occurs when cancer cells may have weak surface antigens, immune system tolerance to tumor antigens, suppression of T cell stimulating factors, antibodies binding TAAs (thus preventing recognition by T cells)
Oncofetal antigens
antigens that are normal during fetal development, but appear in the presence of certain cancers; theory about reappearance of fetal antigens: may occur as a result of cell regaining capacity to differentiate into multiple cell types
Examples of oncofetal antigens
Carcinoembryonic antigens (CEA) and Alpha-fetoprotein (AFP)
Carcinoembryonic antigen (CEA)
Produced during fetal development, normally disappears during last 3 months of fetal life (production stops after birth); fetal protein increases in various cancers
CEA as tumor marker
Used to monitor effect of therapy and indicate tumor recurrence; elevated CEA titers after surgery indicates tumor was not completely removed; rise in CEA after chemo/radiation indicates recurrence or metastasis
Alpha-fetoprotein (AFP)
Produced by fetal or malignant liver cells; found in developing fetus, newborns, pregnant women
AFP as tumor marker
AFP levels found to be elevated in testicular carcinoma, viral hepatitis, nonmalignant liver disorders; AFP Dx value in hepatocellular cancer, & produced when mets liver growth occurs
3 ways tumors can be classified
Anatomic site, histology (grading), extent of disease (staging)
anatomic site classification
In this classification of cancer, tumors are identified by the tissue of origin, location of the body, and behavior of the tumor (benign or malignant)
Benign epithelial tissue tumors (surface epithelium/granular epithelium)
Papilloma and adenoma are examples of benign/malignant epithelial/connective/nervous/hematopoietic tissue tumors?
Malignant epithelial tissue tumors
Carcinoma and adenocarcinoma are examples of benign/malignant epithelial/connective/nervous/hematopoietic tissue tumors?
Benign connective tissue tumors (fibrous tissue, cartilage, striated muscle, bone)
Fibroma, chondroma, rhabdomyoma, osteoma are examples of benign/malignant epithelial/connective/nervous/hematopoietic tissue tumors?
Malignant connective tissue tumors (fibrous tissue, cartilage, striated muscle, bone)
Fibrosarcoma, chondrosarcoma, rhabdomyosarcoma, osteosarcoma are examples of benign/malignant epithelial/connective/nervous/hematopoietic tissue tumors?
Benign nervous tissue tumors (meninges, nerve cells)
Meningioma, ganglioneuroma are examples of benign or malignant epithelial/connective/nervous/hematopoietic tissue tumors?
Malignant nervous tissue tumors (meninges, nerve cells)
Meningeal sarcoma and neuroblastoma are examples of benign or malignant epithelial/connective/nervous/hematopoietic tissue tumors?
Malignant hematopoietic tissue tumors (lymphoid tissue, plasma cells, bone marrow)
Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, lymphocytic & myelogenous leukemia are examples of benign or malignant epithelial/connective/nervous/hematopoietic tissue tumors?
Benign
There are no benign/malignant hematopoietic tissue tumors.
Histologic Grading
In this type of cancer classification, four grades are used to evaluate abnormal cells based on their resemblance to tissue of origin & degree of differentiation from tissue of origin. (The more they resemble the original tissue, the better the prognosis.
Grade I (Histologic Classification of Cancer)
Mild dysplagia (cells differ slightly from normal cells); well differentiated (look most like tissue of origin): Low grade
Grade II (Histologic Classification of Cancer)
Moderate dysplasia (cells abnormal); moderately differentiated: intermediate grade
Grade III (Histologic Classification of Cancer)
Severe dysplasia (cells are very abnormal); poorly differentiated: high grade
Grade IV (Histologic Classification of Cancer)
Anaplasia (cells are immature & primitive); undifferentiated; cell of origin is difficult to determine: high grade
Grade X (Histologic Classification of Cancer)
Grade cannot be assessed
Staging
Term for classifying the extent and spread of disease, based on anatomic extent rather than appearance of cells: clinical staging, TNM classification system
Stage 0 (Clinical staging)
Cancer in situ
Stage I (Clinical staging)
Tumor limited to tissue of origin; localized tumor growth
Stage II (Clinical staging)
Limited local spread of tumor
Stage III (Clinical staging)
Extensive local and regional spread of tumor
Stage IV (Clinical staging)
Metastasis of tumor
TNM Classification System
This system is used to determine the ANATOMIC EXTENT of disease according to tumor size and invasiveness, presence or absence of regional spread to lymph nodes, and metastasis to distant organs.
T of TNM
extent of primary tumor
N of TNM
absence or presence & extent of regional lymph node involvement
M of TNM
absence or presence of distant metastases
Risk Factors for Cancer
Family Hx of CA, dietary habits (alcohol, high fat, high carbs, etc), radiation exposure, viral exposure, carcinogenic exposure
Primary prevention & detection of cancer: What can patients be educated about?
Reduce/avoid exposure to known carcinogens (cigarettes, alcohol, asbestos)
Balanced diet
Exercise regularly
Adequate rest
Regular check-ups
Reduce/eliminate/decrease stressors
Teach CAUTION (seven warning signs of CA)
Self-exams
Seek care promptly if CA s
Seven (late) warning signs of cancer
C: Change in bowel/bladder habits
A: A sore that does not heal
U: Unusual bleeding/discharge from body orifice or mole/freckle
T: Thickening of tissue/lump in breast or elsewhere
I: Indigestion or difficulty swallowing
O: Obvious in a wart or mole
N: Nagg
Secondary Prevention & Possible/Positive Dx of Cancer: Points to remember
Patient may experience fear & anxiety
Clear & repeated explanations possible/necessary
Diagnostic plan: health hx (emphasis on risk factors), physical exam, specific lab/diagnostic studies
Diagnostic Tests for CA
Cytology studies (Pap smear), Chest Xray, CBC, Guaiac for occult blood (w/ sigmoid/colonoscopy), Liver fxn test, Radiologic exam (mammogram), Radioisotope scan (bone/liver/lung/brain), CT, MRI, Oncofetal agent check: CEA/AFP, Bone marrow exam, Biopsy
Biopsy
Removal of a tissue sample (by needle, incision, or excision) for pathological analysis; may be percutaneous, endoscopic, surgical; provides a definite Dx of CA; determines degree of differentiation
Frozen section
Biopsy of a small amount of tissue, thinly sliced, quickly frozen, & stained for immediate evaluation
Curative therapy
A goal for CA Tx: may involve surgery or extended periods of systemic therapy (chemo) to provide a cure
Control treatment plan
A goal for CA Tx: initial course & maintenance therapy (for recurrence): when cancer is incurable, but possible to live with for a time
Palliation
A goal for CA Tx: relief or control of symptoms; maintenance of quality of life (may need to stop all therapies to feel better before imminent death)
Factors that determine treatment modality:
Cell type, Location/size of tumor, Extent of disease, Physiologic status, Psychological status; Finances
General purposes of surgical therapy
Prevention, Cure & control, Supportive & palliative care, Rehabilitative care
Uses for surgical therapy
Used for diagnosis (biopsy)
Used to determine diagnostic & treatment plan
Used to cure or control disease process of cancer (remove site where CA typically spreads): mastectomy, i.e.
Examples of prophylactic surgical therapy procedures:
mastectomy, pneumonectomy, thyroidectomy, bowel resection
Examples of supportive care (surgical therapy) procedures:
GT, colostomy, suprapubic cystostomy
Examples of palliation (surgical therapy) procedures:
colostomy to relieve bowel obstruction; laminectomy to relieve spinal cord compression
Examples of rehabilitative (surgical therapy) procedures:
breast reconstruction post mastectomy
Goals of radiation therapy
Cure, control, and palliation
How are cancer cells different? (3 factors)
* APC (tumor-suppressor) gene is lost
* Mutant RAS gene, an oncogene, keeps pumping new genes (the combination of the 2 above create cancer cell growth)
* Immortality (Telomerase from embryonic cells is normally turned off, but is reactivated by cancer ce
p53
Which tumor suppressor gene is activated by some cancer treatments and begins to work with the therapy to fight the disease?