Clinical Science Week 10 (Unit 2)

What is a cancer?

uncontrolled cell proliferation and spread of abnormal cells

What does neoplasia mean?

The process of new growth of abnormal tissue

(act of new growth)

What is a neoplasm?

A new growth of abnormal tissue; a tumor

(The result of neoplasia)

What is the process of cell division called?

Mitosis

What does the typical mitosis process yield?

2 genetically identical daughter cells

There are 2 types of genes coded into chromosomes that are impacted by neoplasia. What are these 2 genes and their role in cell growth?

Proto-oncogenes: pro-growth

Tumor Suppressor genes: (anti-growth)

Describe the "schedule" for cell division. (4 stages)

1) G1 - cell growth 1; prepare for DNA replication

2) S - Synthesis; DNA replication occurs

3) G2 - Cell Growth 2; prepare for Mitosis

4) M - Mitosis occurs

What 2 genes impact the cell growth cycle?

proto-oncogenes (pro-growth)

tumor suppressor genes (anti-growth)

What are the 4 mechanisms that regulate cell division?

1. internal mechanisms (proto-oncogenes and tumor suppressor genes)

2. environmental cues

3. chemical cues

4. hormonal cues

How do proto-oncogenes and tumor suppressor genes contribute to carcinogenesis?

Increased proto-oncogene expression leads to increased cell growth (too much acceleration)

Decreased tumor suppressor gene expression leads to decreased growth suppression (too little braking)

Malignancy alters which cellular process? What type of cell does this result in?

alters cellular differentiation.

Results in anaplastic cells (cells unrelated to the parent cell)

What is Dysplasia? Is it reversible?

Dysplasia = altered size, shape, and organization of cells. This is reversible (metaplasia + hyperplasia + disorganization)

Describe metaplasia. Is it reversible?

abnormal change from 1 cell type to another. This is reversible

Ex. in the respiratory tract, columnar epithelium begin to differentiate into squamous epithelium.

What is hyperplasia?

increase in number of cells in tissue

What is the common name for a neoplasm?

tumor

What does malignant mean?

invasive; spread to nearby tissue and may metastasize

what does carcinoma in situ mean?

"cancer in its place"

cancer has not left its original tissue

(pre-invasive, premalignant)

What is the difference between a benign tumor and malignant tumor?

Benign tumors = non-invasive, slow growing, encapsulated, and well-differentiated.

Malignant tumors = invasive/metastatic, fast growing, non-encapsulated, poorly differentiated

How does the name (suffix) of a tumor change is it is benign vs malignant

benign = tissue + oma

ex. fibrOMA, melanOMA

malignant = tissue + carcinoma or sarcoma

ex. osteoSARCOMA, angioSARCOMA

What is the difference between a primary tumor and secondary tumor?

Primary = arises from cells local in given structure

Secondary = Arises from cells that have metastasized from another part of the body

What is metastasis?

movement of cells from one part of the body to another. This identifies a neoplasm as malignant

How does a cancer metastasize?

-Cancer begins in situ (in original tissue)

-invades the tumor border

-enters lymphatics

-enters circulatory system

-spreads to other tissues and invades

What is somatic mutation theory? Oncogenesis theory? Stem Cell Theory?

Somatic Mutation Theory: tumor begins via acquired genetic/chromosome change

Oncogenesis Theory: Oncogenes are activated via carcinogens or virus (either upregulation of proto-oncogenes or downregulation of tumor suppressor genes)

Stem Cell Theory: There is a "cancer STEM cell" that can differentiate into cancer cells. Believed because there are recurrent cancers.

What are the 3 modes of travel for metastasis? What are the 5 most common sites for metastasis?

modes of travel:

-blood

-lymphatics

-direct extension

most common sites:

-lymph nodes

-liver

-lung

-bone

-brain

Describe the metastatic cascade. (6 steps)

1. tumor grows (neoplasia)

2. tumor angiogenesis occurs (tumor develops capillary network for nutrients, O2, hormones, and waste elimination)

3. Cells break away from the primary tumor and travel through blood and lymphatics (break tumor border into

4. Become trapped in capillaries of organs

5. infiltrate organ tissue

6. Form new tumor

What is immunosurveillance?

continuous searching and destroying of cancerous cells

What is the immune response to neoplasm in situ?

-lymphocytes proliferate

-lymphocytes and macrophages infiltrate tumors

how is immunosurveillance able to identify a cancerous cell from normal cells? (2 ways)

1) Via tumor-specific antigens that are presented on MHC's.

-CD8 cytotoxic T cells bind to the MHC-I complex and identify the peptide on the end. If it is normal they move on. If it is a tumor specific antigen, they kill it.

2) Via tumor-associated antigens

Could be:

-The products of upregulation of oncogene or downregulation of tumor suppressor genes ("You're doing too much or too little")

-Mutated "self-protein" ("you look different")

-Increased expression of "self-proteins" ("you're acting weird")

-oncogenic virus ("You are sick")

What cell from the innate immune system can attack tumor cells?

Macrophages

What cells from the Adaptive immune system can fight off tumor cells?

CD8 & CD4 T-cells

What are some of the strategies that cancer implements to stay alive and combat the immune system and cancer treatments?

- overwhelming rate of proliferation

-Decreased regulation of MHC-I

-Mutation/modulation of antigens that decreases their loading onto MHC-I (suppresses/internalizes tumor-specific antigens)

-Induced immune suppression via anti-inflammatory cytokines

What does immunotherapy do to combat cancer?

Boost the immune response against cancer

-use immunomodulatory factors (cytokines, monoclonal antibodies)

How does Chimeric antigen receptor T-Cells (CAR-T therapy) fight cancer?

T cells are taken from the patient's blood and modified in a lab to fight the antigen for the tumor and then reinfused into the body

(Take, modify, return)

What is the suffix of a cancer impacting epithelial tissue? connective tissue and muscle? nerve tissues? lymphoid tissue? hematopoietics?

-Epithelial: carcinomas (ex. adenocarcinoma)

-Connective tissue/muscle: sarcomas (ex. osteosarcoma)

-Nerve tissue: named for type of cell involved (ex. astrocytoma)

-Lymphoid: lymphoma (ex. Hodgkin's lymphoma)

-Hematopoietic: Leukemias, multiple myeloma (myel = myeloid lineage + oma = cancer [myeloid cancer])

What are the 5 stages of cancer based on? Describe the 5 stages.

Based on:

-rate of growth

-extent

-prognosis

-Stage 0: carcinoma in situ; premalignant or preinvasive

-Stage I: Early stage, usually localized to primary organ

-Stage II: Increased risk of regional spread because of tumor size and grade

-Stage III: Cancer spread regionally but may not be disseminated to distant organs

-Stage IV: Cancer has spread and disseminated to distant site(s)

What is TNM staging for cancer? Clinical stage? Pathologic Stage?

TNM is referencing the tumor, nodes, and metastases of the of the canacer

Clinical stage means the cancer was evaluated with an exam in clinic. Denoted as a "c"

Pathologic stage means the cancer was evaluated via a tissue study in a lab. Denoted as a "p"

What is the T in TMN for? What are the different ratings you can have for the "T?" (7 of them)

T is for Tumor; referring to size of primary tumor

TX = primary tumor cannot be assessed

Tis = carcinoma in situ (pre-invasive)

T0 = no evidence of primary tumor (undetectable)

T1,2,3, or 4 = progressive increase in tumor size and involvement

What is the N in TMN for? What are the different ratings you can have for the "N?" (5 of them)

N is for Nodes; regional lymph node involvement in the cancer

NX = nodes cannot be assessed

N0 = No metastasis to regional lymph nodes

N1,2 or 3 = Increasing degrees of involvement of regional lymph nodes

What is the M in TMN for? What are the different ratings you can have for the "M?" (3)

M is for Metastases

MX = Presence of distant metastases not assessed

M0 = no metastases

M1 = distant metastases

In the Ann Arbor Staging for Lymphoma cancer, what are the 4 letters and what do they mean?

A: absence of constitutional symptoms

B: Presence of constitutional symptoms

E: Extranodal

X: mass >10cm of mediastinum (or 1/3 of chest on radiograph)

What does a lower score for a neoplasm indicate? What does a higher score indicate?

Lower = more differentiation of tissue with tumor (potential better outcome)

Higher = poor cellular differentiation

(keep in mind there are grading systems specific to different tumor types)

What are the most common newly diagnosed cancers? (4)

Breast, prostate, lung, and colorectal

What are the 3 most common cancers in men?

1) Prostate

2) Lung

3) Colorectal

What are the 3 most common cancers in women?

1) breast

2) lung

3) colorectal

At what age does the risk of cancer increase significantly?

50 and older

Cancer related deaths are second to only _________ disease?

heart disease

Survival rates for cancer went from

69%

(Just know its about 3/5 people survive now)

What is the lifetime probability of developing cancer at any site for males in the US? Females?

males = 1 in 2

females = 1 in 3

What is the common trend in interracial cancer survivability rates? Why is it thought this is?

White individuals have a higher survivability rate than other races.

Variance explained: social determinants of health

How have survivability rates for the most common forms of cancer changed in the last 40 years amongst all races?

increased

What are the 3 leading sites for new cancer deaths in men? women?

Men:

1) lung & bronchus

2) prostate

3) colorectal

Female:

1) lung & bronchus

2) breast

3) pancreas

What are the 4 endogenous (internal) risk factors for cancer? 5 Exogenous (external)?

Endogenous:

-Genetics (BRCA1 & BRCA2 genes)

-Hormones (ex. prolonged estrogen exposure)

-Immunosuppression/immunodeficiency

-Age (increased exposure to carcinogens)

Exogenous

-Lifestyle (tobacco or alcohol use)

-Viral Exposure (HIV, HPV, or EBV)

-Chemicals (environmental or pharmacological)

-Radiation exposure (UV)

-Diet/Nutrition (immune response, hormones, obesity)

Name 4 modifiable risk factors of cancer.

-lifestyle behaviors (smoking / alcohol)

-Pollution

-Household fuels

-Contaminated injections (vaccines)

-obesity

-sexual behavior

-physical inactivity

Name 4 unmodifiable risk factors of cancer.

-Age

-Exposure to viruses

-Exposure to hormones

-Biologic sex

-Ethnicity

-Socioeconomic status

-Heredity

-Stress

What is both the leading cause of preventable death and preventable cause of cancer in the U.S.?

smoking

(increases risk of developing over 12 types of cancer)

In 1965, 42% of individuals smoked cigarettes. What % smoke now?

10%

How does combined alcohol and tobacco use impact the rusk of developing cancer?

Exponential increase in cancer risk

What type of pain may a patient describe to you that is a red flag for cancer? (2)

Deep, boring pain

Pain that is worse at night or at rest

What are 2 general clinical manifestations of cancer that visibly be seen?

-thickening or lump

-sore that does not heal (abnormal bleeding)

Name 5 systemic signs of cancer that would be red flags for a PT?

-unexplained weight loss (cancer cachexia)

-change in bowel or bladder habits

-nagging cough or hoarseness

-fatigue

-malaise

-weakness

-fever (caused by pyrogens)

What are paraneoplastic syndromes?

Rare disorders caused by an immune or hormonal response to an underlying cancer

What are the clinical manifestations of lung cancer? (2)

-persistent, dry, non-productive cough

-exertional dyspnea (shortness of breath)

What is the primary clinical manifestation of prostate cancer?

-urinary changes (difficulty initiating and/or emptying)

What is the primary clinical manifestation of breast cancer?

Lump/thickening of breast (not useful for a PT)

What is the primary clinical manifestation of colon cancer?

Change in bowel function (color or shape [shaped like ribbons])

What are the primary clinical manifestations of bladder cancer? (2)

blood in urine

dysuria (pain when peeing)

What are the primary clinical manifestations of esophageal cancer? (2)

-pain/difficulty with swallowing

-indigestion/heartburn

What are the primary clinical manifestations of leukemia/lymphoma cancer?

-Unexplained fevers

-Night sweats

What is the primary clinical manifestation of osteosarcoma cancer?

-unexplained pain in long bones of teenagers (often discounted as growing pains)

What are the 5 most common sites of "seeding" during metastasis.

lymph nodes

liver

lung

bone

brain

the lungs are the most common metastatic site for which 3 cancers?

Bone

Breast

prostate

The liver (poor prognosis) is the most common metastatic site for which 3 cancers?

stomach

colon

pancreas

What are the manifestations of liver cancer? Name 4.

-abdominal or R upper quadrant pain (referred pain)

-malaise

-fatigue

-weight loss

-early satiety

- low-grade fever

-anorexia

The bones are the primary metastasis site for which 3 types of cancer? What are bone cancer's (osteosarcoma's) clinical manifestations?

primary metastatic site for lung, breast, and prostate cancer

Manifestations:

-deep pain

-instability

-osteolytic metastases (leading to fracture)

-Osteoblastic metastases (leading to dense scarring)

What is the significance of a metastases impacting the CNS? Name 3 of the clinical manifestations that occur when metastases impact the CNS?

Significance = life threatening and disabling

Manifestations:

-Increases intracranial pressure

-Obstruction of cerebrospinal fluid flow

-cognitive changes

-neuromuscular changes

-sensory and motor dysfunction

-progressive central or radicular back pain

-bowel/bladder changes

-gradual distal weakness/sensory disturbances

A patient comes into the clinic with a previous history of cancer. If they are experiencing MSK pain, what could be a potential differential diagnosis? What about if they are experiencing nervous system changes? What about a persistent, non-productive cough with shortness of breath with exercise?

MSK pain may = bone metastases

Nervous system changes may = brain metastases

Cough and shortness of breath may = lung metastases

Should cancer patients exercise? If so, what should this look like for cancer patients?

Yes, they can exercise as this is thought to help with treatments, fatigue, and overall wellbeing.

Should have an individualized approach with an overall decrease in activity levels