N323 - Week 5 (Oncology Physiology - Cancer Physiology)

**Risk Factors of Cancer (3)

Ultraviolet Radiation

Alcohol Consumption

Infection, Sexual & Reproductive Behavior

**Ultraviolet Radiation (5)

causes basal cell carcinoma, squamous cell carcinoma, and melanoma (increased incidence)

-principal source is sunlight (UVA & UVB)

-Released TNF-A in epidermis

-Promotes ROS (Reactive oxygen species)

-promotes skin inflammation & release of free radicals

*Basal cell carcinoma (BCC)

cancer on outer layer of skin, lower layer of epidermis

*Squamous Cell Carcinoma

cancer in flat cells, surface of the skin

*melanoma

cancer in melanocytes (pigment cells)

*3 Types of UV light

UVA (weaker but penetrates deeper)

UVB (affects our outer skin more

UVC (not worried)

*TNF-A in Epidermis

exposure to UV light causes it to activate & cluster

TNF-A activates pathways in skin cells (disrupts them) -> CANCER!

*Reactive Oxygen Species (ROS)

causes protein & DNA damage w/in our skin cell, disrupts pathways, promotes more inflammation at these sites & increases release of free radicals -> CANCER!

**Alcohol Consumption (3)

Risk factor for oral cavity, pharynx, larynx, esophagus, liver, colorectum, and breast cancers

-Genetic factors involved

-No "safe limit" of intake

**Infection, sexual & reproductive behavior

Top cancer-causing infections

EX: -Human papillomavirus (HPV)

-Helicobacter pylori (75%-89% of all stomach cancers)

-Hepatitis B (HBV)

-Hepatitis C (HCV)

*Human Papillomavirus (HPV)

an STI that causes cervical dysplasia (abnormal cell growth, precursor to cancer)

-can be detected w/ pap smears

*Hepatitis B and C (HBV & HBC)

infection of the liver, caused by bacteria (food borne, blood borne or sexually transmitted infections)

**HBV and HCV account for large majority of liver cancers

**Benign Tumors (6)

grow slowly

-well-defined capsule

-not invasive

-well differentiated

-low mitotic index

-do not metastasize

**Malignant Tumor (6)

grow rapidly

-NOT encapsulated

-invasive

-poorly differentiated (all similar looking, similar to dysplasia)

-high mitotic index (lots of cells go through mitosis)

-can spread distantly (metastasis)

**Classification & Nomenclature of Benign Tumors (4)

Adenoma (from epithelial tissue)

Fibroma (from fibrous or connective tissue)

Hemangiomas (from blood vessels)

Lipomas (from fat tissue)

**Classification & Nomenclature of Malignant Tumors (5)

carcinoma (from epithelial tissue)

adenocarcinoma (from ductal or glandular tissue)

sarcoma (from mesenchymal tissue (connective tissue: bone, muscle..))

lymphoma (from lymphatic tissue)

leukemia (from blood-forming cells)

Cancer

Predominantly a disease of aging (BUT environment & behavior can act as a risk)

Clonal Proliferation or expansion of Cancer (2)

as a result of mutation, a cell acquires characteristics that allow it to have selective advantage over its neighbor

-leading to increased growth rate or decreased apoptosis

Transformation of Normal Cells to Cancer Cells (4)

-decreased need for growth factors to multiply

-lack contact inhibition

-anchorage independence

-immortality

Telomeres

protected ends (caps) of chromosomes, signal end of chromosome (protected & maintained by telomerase in germ cells, stem cells)

-as telomeres get shorter -> signals end of cell life span (apoptosis)

Telomeres of cancer cells

have a lot of telomerase that prevents their telomeres from shortening as they duplicate -> keeps them alive & immortal

**telomerase activity is not found in most normal cells (only rapidly dividing cells)

Tumor-Associated Macrophage (TAM) (4)

key cells that promote tumor survival

-presence frequently correlates w/ a worse prognosis

-block T-cytotoxic cell & cell fxn -> diminished cytotoxic response

-produces cytokines that help tumor growth & spread

**Carcinoma in SITU (CIS)

Preinvasive epithelial malignant tumors of glandular or epithelial origin that have not broken through the basement membrane or invaded the surrounding stroma

- (early stage cancer, stay in epithelial cells)

Invasion of cancer cells

cellular multiplication (mitotic rate > cellular death rate)

-release of lytic enzymes (damages surrounding tissue)

-decreased cell-to-cell adhesion

-increased motility

Local Spread of Cancer Cells

Direct invasion of continuous organs

Metastasis of cancer cells (3)

spread of cancer from a primary site of origin to a distant site

-metastases to distant organs (through lymphatics & blood)

-requires great efficiency, usually occurs late

Clinical Manifestations of Cancer (Signs of Cancer)

1. Syndrome of Cachexia

2. Anemia

3. Leukopenia & thrombocytopenia

4. Infection

Syndrome of Cachexia

most severe from of malnutrition

(includes anorexia, early satiety, weight loss, anemia, asthenia (lack of energy), taste alterations and altered protein, lipid, & carb metabolism)

Anemia

a decrease of hemoglobin in the blood

mechanisms of anemia (4)

Chronic bleeding resulting in iron deficiency

Severe malnutrition

Medical therapies

Malignancy in blood-forming organs

Leukopenia and thrombocytopenia

is caused by direct tumor invasion to the bone marrow (decrease of WBCs & platelets)

-chemotherapy drugs are toxic to the bone marrow

infection

risk increases when the absolute neutrophil & lymphocyte counts fall

Cancer Stages based on Metastasis (4)

Stage 1: No metastasis

Stage 2: Local invasion

Stage 3: Spread to Regional Structures

Stage 4: Distant Metastasis

**TNM System (WHO)

T- tumor spread

N- node involvement

M- presence of distant metastasis

Tumor Cell Markers (biologic markers)

substances produced by cancer cells or that are found on or in tumor cells, in the blood, CSF, or urine

-EX: PSA & PAP used for prostate cancer

Tumor markers are used to: (4)

screen & identify individuals at high risk for cancer

-diagnose specific types of tumors

-observe clinical course of cancer

-problem: false positives & negatives

Histology of Cancer

tumors are classified based on immunohistochemical analysis of protein expression for improved treatment

-enhanced molecular characterization subdivides into smaller groups

What cancers is finding the histology most useful for? (3)

adenocarcinoma

-breast cancers

-non small cell lung cancer

Examples of Cancer Treatment

surgery & radiation

Sugery

to prevent cancer (colon polyps)

-biopsy for diagnosis & staging

-lymph node sampling

-palliative surgery (for comfort of pt, to decrease pain)

Radiation (3)

try to eradicate cancer w/o excessive toxicity

-avoid damage to normal structures

-damages the cancer cell's DNA

Leukemia & lymphoma

cancer of blood & lymph cells

-(stages are different b/c it is alrdy spread throughout ur body)

Lymphatic system

important part of immune system, part of circulatory system

-pathway that maintains fluid balance

-allows disease to spread more easily

Liver & spleen

help maintain lymph nodes & involved in blood systems

Malignant Lymphomas (4)

1. primary lymphoid tissue (thymus, bone marrow)

2. secondary lymphoid tissue (lymph nodes, spleen, tonsils, intestinal)

3. Hodgkin lymphoma (related to Epstein Barr Virus (EBV))

4. Non-Hodgkin lymphoma

Hodgkin Lymphoma

marked by reed-Sternberg cells in lymph nodes

Reed-Sternberg cells

derived from malignant B cells that usually become binucleate

-release cytokines

Stages I-IV of Hodgkin's Lymphoma

Stage I: Enlargened single lymph node

- Stage II: 2 lymph nodes Enlargened (same side of diaphragm).. whole lymph node structure

- Stage III: both sides of diaphragm

- Stage IV: diffuse or disseminated through the whole body (most lymph nodes & system)

Clinical Manifestations of Hodgkin Lymphoma (4)

enlarged painless neck lymph nodes

-lymphadenopathy causing pressure or obstruction

-mediastinal mass (in the body)

-fever, weight loss, night sweats, pruritus (itching), fatigue

Tests used to detect Hodgkin's Lymphoma (3)

chest X-rays, lymphangiography & biopsy (most indicative -> look for red Sternberg cells)

Non-Hodgkin Lymphoma

includes B cell, T cell & Natural Killer (NK) neoplasms

-generic term for diverse group of lymphomas

-linked to chromosome translocations

-NO reed Sternberg cells, NO stages

clinical manifestations of non-hodgkin lymphoma (4)

-Localized or generalized painless lymphadenopathy

-Nodal enlargement and transformation over months or years

-Retroperitoneal and abdominal masses with symptoms of abdominal fullness and back pain

-Ascites (fluid in the peritoneal cavity) and leg swelling

Test used for Non-hodgkin lymphoma

biopsy (primary means of diagnosis)

Types of Leukemia (4)

1. acute myeloid leukemia (AML)

2. acute lymphoblastic leukemia (ALL)

3. chronic myeloid leukemia (CML)

4. chronic lymphocytic leukemia (CLL)

Acute leukemias (AML and ALL) (4)

undifferentiated cells

-abrupt onset, rapid progression

-short survival time

-get disease -> get diagnosed very quickly

AML vs ALL

AML: rapid growth of myeloblast

ALL: rapid growth of lymphoblasts

Chronic Leukemia (CML & CLL)

more differentiated

-does not fxn normally

-slow progression

-can have for a long before diagnosis

CML v CLL

CML: increase in myeloblast over time

CLL: increase in lymph cells overtime ->affects humoral immunity, may present as painless lymphadenopathy

Pathophysiological Symptoms of Leukemia (6)

anemia

-bleeding

-unintended weight loss

-bone pain

-liver and/or spleen enlargement

-increased uric acid level