Cancer: Part 1

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?