Chapter 6- Neoplasia PDF

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Chapter 6  Neoplasia

Cancer



2nd leading cause of death in US



Not a single disease; originates in almost any organ o



Comprises changes in any organ

5-year survival rates have improved o

Rates affected by types of cancer, stage at diagnosis, and what/if treatment is available

o

Breast cancer has good rate

o

Pancreatic cancer, not so much

Characteristics of Cancer



Define Is a Disorder of altered cell differentiation and growth o



Results in neoplasia (“new growth”)

Growth is uncoordinated and relatively autonomous. o

Lacks normal regulatory controls over cell growth and division 

o

Grow without regard to cell cycle/division

Tends to increase in size and grow after stimulus ceases or needs of the organism are met 

Cancers cells grow uncoordinated, they are autonomous. It does not have a purpose, and they don’t respond to a normal stimulus. Normally when cells divide a stimulus turns on and they stop dividing but this cancer cells don’t respond and keep on dividing

Components of Tissue Renewal and Repair



Normal tissue renewal and repair involves two components; cell proliferation and differentiation



Cell Proliferation o

Process of cell division

o

Inherent adaptive mechanism for replacing body cells 



Cell Differentiation o

Process of specialization (with each mitotic division)

o

New cells acquire the structure and function of cells they replace

o

Defined the mechanism by which cells become increasingly more specialized with each mitotic division

o

IN CANCER CELLS cancer cells look UNDIFFERENTIATED (not specialized) 





For new cell growth to replace old cells or when additional cells are needed

Allow them to act however they want

Apoptosis o

A form of programmed cell death to eliminate unwanted cells

o

Defined Form of programmed cell death that eliminated senescent cells, cells with deoxyribonucleic acid (DNA) damage, or unwanted shells

o

IN CANCER CELLS No apoptosis of cancer cells

Neoplasia o

Continue to proliferate

o

Undifferentiated

o

No apoptosis

Proliferation and Differentiation



Cell Proliferation o

Process of increasing cell numbers by mitotic cell division

o

In normal tissue; regulated 



Cell differentiation o

Process by which proliferating cells become more specialized

o

Results in fully differentiated adult cells 

o

Stimuli to induce mitosis become more limited as cells become more highly differentiated (Ex. Neurons/Nerve cells)

Textbook process results in fully differentiated, adult cell that has a specific set of structural, functional, and life expectancy characteristics 

2

Number of cells actively dividing equals number of cells dying

Cells of one organ differ from those of another organ due to specific genes that are expressed and the particular pattern of gene expression



Stem cells o

Remains incompletely differentiated throughout life

o

Are reserve cells that remain dormant until there is a need for cell replacement 

They divide to produce other stem cells and cells that can carry out functions of the differentiated cells

The Cell Cycle



Definition o

An orderly sequence of events that occur as a cell duplicates its contents and divides 

o

Cancers don’t obey the rules of neoplasia and they just keep dividing

Genetic information is duplicated



Checkpoints in cell cycle provide opportunities for monitoring the accuracy of deoxyribonucleic acid (DNA) replication



Neoplasia have disorders in proliferation, differentiation, apoptosis o

Neoplasia doesn’t obey cycle 

They continue to actively divide

Proliferation and Differentiation



Well differentiated cells o

o 

Limited in division and reproduction (rarely divide and reproduce) 

Well-differentiated neurons



Cells of skeletal and cardiac muscle

Highly specialized

Parent or progenitor cells o

Cells that continue to divide and reproduce 

o 

Have potential for active proliferation

Stem cells o

Undifferentiated 

o

3

Blood cells, skin cells, liver cells

Don’t have to obey the cell growth mechanism, that’s why cancer cells want to be undifferentiated

Can be triggered to enter cell cycle and produce large numbers of progenitor cells when needed

o

No limits

o

Some implicated in cancer

Potency of Stem Cells



Pluripotent  o



can differentiate into the three germ layers of the embryo

Multipotent  give rise to only a few cell types

o 

Unipotent  o

give rise to one type of differentiated cell, but retain the property of self-renewal 

Cancer stem cells have been identified in breast, prostate and other cancers



Continue to divide and produce daughter cells 

Do so via expression of cell cycle inhibitors

Question





Which of the following cell types is more likely to have arisen from a stem cell in an adult? o

A. Muscle

o

B. Bone

o

C. Epithelial

o

D. Neural

Rationale: Epithelial cells such as skin, organ lining, and vessel lining cells are constantly being replaced.

Neoplastic Growth



4

Neoplasm  large growth o

Neoplasia unregulated cell differentiation and growth

o

Oncogenes cancer promoting genes

o

Neoplasm abnormal mass of tissue in which the growth exceeds and is uncoordinated with that of the normal tissues

Tumors



Body organs composed of two types of tissue o

o

Parenchymal Tissue 

functional components of an organ



In a tumor, these cells determine its behavior and are the component for which a tumor is named

Supporting tissue (or Stromal) 

includes the extracellular matrix and connective tissue that surrounds the parenchymal cell 

lymphatic's, blood vessels o



Tumor o



provide nourishment and support for the parenchymal cells

A mass of cells that arises because of overgrowth

Neoplasm o

Classified as benign or malignant 

Benign 

Well differentiated cells that are clustered together in a single mass o

More specialized

o

Looks a lot like the cells it came from

o

Slow rate of growth 



Are not cancer but they could always keep on growing and start pressing on organs.



Benign cells are usually capsulated, Let’s say there is a benign tumor compressing on the brain, should that tumor be removed? o



Yes, because eventually is will grow big enough that it will not have enough space.

Malignant 

Less well differentiated and have the ability to break loose, enter the circulatory or lymphatic system and form secondary malignant tumors at other sites o

Does not look like the cells it came from

o

It’s not specialized

o

They are able to be metastasized (go to different sites) 



5

Anaplasia

Grow by expansion and remain localized to their site of origin

To feed, get nutrients from other sources

o 

Used to describe the loss of cell differentiation in cancerous tissue

Dysplasia (adaptation, deranged growth) o

Can lead to cancer, but not always

Characteristics of Benign and Malignant Neoplasms









6

Cell characteristics

Rate of growth

Mode of growth

Metastasis



Benign



Malignant



Well differentiated



Undifferentiated



Resemble tissue of origin



Anaplasia, atypical structure



No resemblance to tissue of origin



Variable



More undifferentiated= faster growth



Grows by invasion



Infiltrates surrounding tissues



Gains access to blood and lymph channels to metastasize to other areas



Progressive, still



Grows by expansion without invading surrounding tissues



Encapsulates



None

Other Characteristics of Malignant Neoplasms



Tend to grow rapidly and spread widely



Have the potential to kill regardless of their original location



Tend to compress blood vessels and outgrow their blood supply, causing ischemia and tissue necrosis



Rob normal tissues of essential nutrients



Liberate enzymes and toxins that destroy tumor tissue and normal tissue o

Solid or hematologic 

Solid tumor confined to a specific tissue or organ o



Hematologic Cancer o



As the growth of the primary solid tumor progresses, cells detach from the original tumor mass, invade the surrounding tissue, and enter the blood and lymph systems to spread to distant sites, (a process termed metastasis)

involve cells normally found in the blood and lymph, thereby making them disseminated disease from the beginning.

Lecture Notes o

Can grow indefinitely if they have a blood supply 

Won’t stop even if other cells nearby

Types of Tumors



7

Adding the suffix -oma to the parenchymal tissue type from which the growth originated o

Adenoma: benign tumor of glandular epithelial tissue

o

Adenocarcinoma: malignant tumor of glandular epithelial tissue

o

Carcinoma: malignant tumor of epithelial tissue

o

Osteoma: benign tumor of bone tissue

o

Sarcoma: malignant tumors of mesenchymal origin

o

Papilloma's: benign microscopic or macroscopic finger-like projections growing on a surface



Question

 Which of the following does not apply to benign tumor cells?  A. A slow, progressive rate of growth that may come to a standstill or regress  B. An expansive manner of growth  C. Liberate enzymes and toxins that destroy tumor tissue and normal tissue  D. Composed of well-differentiated cells that resemble the cells of the tissue of origin  Rationale: Liberating enzymes and toxins that destroy tumor tissue and normal tissue is an ability that characterizes metastatic tumor cells.

Methods by which Cancer Spreads



Direct invasion and extension o

Cancercrablike 

8

Because cancer grows and spread by sending crablike projections into the surrounding tissue

 

Seeding of cancer cells in body cavities o



Most cancers synthesize and secrete enzymes that break down proteins and contribute to the infiltration, invasion, and penetration of the surrounding tissues

Occurs when tumor sheds cells into body cavities

Metastatic spread through the blood or lymph pathways o

Sentinel node 

First node to test if cancer is malignant 

Initial lymph node to which the primary tumor drains

Mechanisms of Tumor Metastasis



9

The mechanism by which a malignant tumor initially penetrates a confining basement membrane and then invades the surrounding extracellular environment involves several steps. 1.The tumor first acquires the ability to bind components of the extracellular matrix. These interactions are mediated by the expression of a number of adhesion molecules. 2. The tumor undergoes epithelial–mesenchymal transition (EMT) and traverses the basement membrane. 3. Proteolytic enzymes are then released from the tumor cells, and the extracellular matrix is degraded. 4. After moving through the extracellular environment, the invading cancer penetrates blood vessels and lymphatics by the same mechanisms. 5. After survival in blood vessels or

lymphatics, the tumor exits the vascular system. 6. It establishes micrometastases at the site where it leaves the vasculature. 7. These micrometastases grow into gross masses of metastatic tumor.

Factors Affecting Tumor Growth



Once cells have an adequate blood supply, the rate of tissue growth in normal and cancerous tissue depends on three factors o

Number of cells that are actively dividing

o

Duration of the cell cycle

o

Number of cells that are being lost compared with the number of new cells being produced 

Cancer cells do not die on schedule; thus, a greater percentage of cells are actively engaged in cycling than in normal tissue

Genes that Control Cell Growth and Replication



Proto-oncogenes o

Normal genes that become cancer-causing oncogenes 



Tumor suppressor genes o



Encode growth factors

When less active→ creates an environment in which cancer is promoted

Genes that control programmed cell death or apoptosis o

Can also be shut off



Genes that regulate repair of damaged DNA



Genetic and molecular mechanisms that increase susceptibility to cancer or facilitate cancer include defects in DNA repair mechanisms, defects in growth factor signaling pathways, evasion of apoptosis, development of sustained angiogenesis, and invasion and metastasis.

Host and Environmental Factors Leading to Cancer



Heredity



Hormones



Carcinogens o

Chemical 

10

Tobacco, Alcohol, Dietary

o



Ionizing Radiation



Ultraviolet Radiation

HPV, Hepatitis B and C, and HIV

Immunologic mechanisms o





Oncogenic viruses o



Radiation

Kaposi Sarcoma associated with AIDS

Micro-environmental effects o

Multiple cell types, cytokines, and growth factors

Clinical Manifestations of Cancer



Tissue Integrity o

o 

Cancer disrupts tissue integrity causing 

Compressed and eroded blood vessels;



ulceration and necrosis;



frank bleeding and hemorrhage



Example sore that does not heal

Cancer invades and compresses adjacent structures with no regard for normal anatomic boundaries

Anorexia and Cachexia 

o

o

Weight loss and wasting of body fat and muscle tissue; profound weakness, anorexia, and anemia

Fatigue and sleep disorders 

Are two of the most frequent side effects experienced by people with cancer.



Cancer related fatigue is characterized by feelings of tiredness, weakness, and lack of energy and is distinct from normal tiredness experienced by healthy people

Anemia 

Related to blood loss, hemolysis, impaired red blood cell production, or treatment effects

Paraneoplastic Syndromes o

11

Example blood in stool of colorectal cancer

Systemic Manifestations o





Inappropriate hormone release, circulating hematopoietic, neurological, and dermatological factors

 Cancer Screening and Health Promotion



Secondary prevention measure for early recognition of cancer in an otherwise asymptomatic population



o

Mammography

o

Pap smear

o

Colon and rectal exams

o

PSA

Tumor Markers o

AFP: liver cancers

o

CEA: colorectal, pancreas, lung cancers

o

PSA: prostate cancer

Staging and Grading of Cancer



T (Tumor)



Size and local spread of primary tumor



N (Nodes)



Involvement of regional lymph nodes



M (Metastasis)



Extend of metastasis

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Cancer





Goals of Cancer Treatment o

Curative

o

Control

o

Palliative

Cancer Management o

Surgery

o

Radiation

o

Chemotherapy

o

Hormonal therapy

o

Stem cell transplant

Notes on The Board



Metastatic Site o

BBONE

o

BBRAIN

o

LLUNG

o

LLIVER



Primary Site where tumor came from



Breast cancer cells can metastasize to other organs

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