Cancer Exam 4

Skin cancer(percent) and lung cancer

50% of cases but lowest death

>25% death due to lung cancer

hyertrophy

an increase in the size of cells, leading to tissue enlargement. - exercise, lifting

hyperplasia

an increase in the number of cells in a tissue, often leading to increased tissue volume. - callous

metaplasia

the transformation of one cell type into another, often in response to chronic irritation or injury. - reversisble

dysplasia

the abnormal development or growth of cells, tissues, or organs, which can be a precursor to cancer. - non reversible

neoplasia

the process of abnormal and uncontrolled cell growth, which may lead to the formation of tumors.

atrophy

the decrease in size or wasting away of a tissue or organ due to various factors such as disuse, lack of nutrients, or disease.

How does age influence cancer rates?

Age is a significant factor in cancer rates, as the risk of developing cancer generally increases with age due to the accumulation of genetic mutations and longer exposure to carcinogens.

Neoplasm

An abnormal growth of tissue that can result in the formation of tumors, which may be benign or malignant.

Benign

A benign tumor is a non-cancerous growth that does not invade nearby tissues or spread to other parts of the body. They are usually not life-threatening and can be removed surgically if necessary.

A benign tumor typically grows slowly and is often surrounded by a fibrous capsule, making it distinct from surrounding tissues.

Can reactivate, can be functinal(can produce something), space limiting

malignant

A malignant tumor is cancerous, capable of invading nearby tissues and spreading to other parts of the body, often leading to serious health issues.

can lead to metastasis

is not faster growth, there is just no pause before S phase (after G1)

Are benign tumors always safe?

No, while benign tumors are generally non-cancerous and not life-threatening, they can still cause complications depending on their location and size.

Naming cancers

Site of origin(3)

1. carcinoma(90%)- from epithealial cells

2. Sarcoma(1)- bone, cartilage, vessels

3. lymphoma/leaukemia- 9%- blood

Prefixs of cancers

are often derived from Greek or Latin roots that indicate the type of tissue or origin, such as 'neuro-' for nerve tissue and 'hepat-' for liver tissue. adeno for gland, osteo for bone, and myelo- for bone marrow.

suffix of cancers

are commonly used to denote the nature of the tumor, such as '-oma' indicating a tumor that is usually benign, or '-sarcoma' indicating a malignant tumor that arises from connective tissues. there are some exceptions

• What is the importance of five-year survival rates and mitotic index in terms of cancer prognosis?

Five-year survival rates indicate the percentage of patients who live at least five years after diagnosis, serving as a key metric for assessing treatment effectiveness and prognosis. The mitotic index reflects the number of cells undergoing mitosis in a tumor; a higher index often correlates with more aggressive cancer behavior and poorer prognosis.

What can pathologic exam or surgical intervention add to classifying tumors

Pathologic exams and surgical interventions provide critical information regarding tumor type, grade, and stage, allowing for more accurate classification and tailored treatment plans. They can reveal the presence of specific markers or mutations that guide prognosis and treatment decisions.

Oncogene

A type of gene that has the potential to cause cancer when mutated or expressed at high levels, often promoting cell growth and proliferation. Oncogenes can lead to uncontrolled cell division, contributing to tumor formation and cancer progression.

Oncogenes normal functions

Oncogenes normally play essential roles in cell growth and division, regulating signals that control these processes. When mutated or overexpressed, they can disrupt normal cellular functions and lead to malignancy.

growth factors, GF receptors, signaling cascades, transcription factors

Tumor suppressor gene

A gene that normally acts to prevent uncontrolled cell growth and division, helping to maintain normal cellular function. Tumor suppressor genes can be inactivated by mutations, leading to increased risk of cancer. They help regulate cell cycle, repair DNA, and promote apoptosis.

Tumor supressor functions

repair enzyme, apoptosis, control growth

Be able to list and define some of the major phenotypical changes that occur in tumor cells as compared to normal cells

Tumor cells show increased proliferation, altered metabolic processes, evasion of apoptosis, loss of contact inhibition, and enhanced angiogenesis compared to normal cells. These changes often result in uncontrolled growth and the potential to invade surrounding tissues.

cancer cells grow well when disturbed and adapt to varying conditions, exhibiting changes in morphology and increased motility.

Cyclin and CDK regulation

Cyclins are proteins that regulate the cell cycle by activating cyclin-dependent kinases (CDKs). This activation controls transitions between different phases of the cell cycle, ensuring proper cell division and growth. Cyclin and CDK regulation involves the coordination of cyclins with CDKs to oversee cell cycle phases, facilitating orderly cell division and maintaining cellular integrity.

cyclin needs a threshold level to interact with CDK

• Understand the basics of normal cell cycle, and what and how it is regulated

The normal cell cycle is comprised of distinct phases: G1 (growth), S (DNA synthesis), G2 (preparation for mitosis), and M (mitosis). Cell cycle regulation involves checkpoints that ensure proper progression through these phases, with key proteins such as cyclins and CDKs coordinating the transitions.

How is this regulation “messed-up” in cancer cells

In cancer cells, the regulation of the cell cycle is disrupted, often due to mutations in genes encoding cyclins and CDKs, leading to unchecked proliferation and bypassing of critical checkpoints. This can result in continuous cell division and a higher likelihood of accumulating further genetic alterations.

Apoptosis and enzyme that activates it

Apoptosis is a programmed cell death process crucial for maintaining cellular homeostasis, and it is often activated by caspases, a family of cysteine proteases. These enzymes play a central role in the execution phase of apoptosis, leading to the systematic dismantling of cellular components.

2 pathways of apoptosis

1. intrinsic/internal- signifiicant dna damage

   • p53 increase can activate it

   • Bc12 inhibits APoptosis

2. external- via death receptors

How does a cell normally deal with DNA mutations and damage?

A cell typically manages DNA mutations and damage through mechanisms such as DNA repair pathways, cell cycle checkpoints, and apoptosis if the damage is irreparable. Key proteins like p53 play a crucial role in sensing DNA damage and initiating repair or triggering cell death.

Examples of DNA damage

include base alterations, double-strand breaks, and cross-links. These alterations can arise from environmental factors, radiation, or replication errors. Additionally, they may result from oxidative stress and chemical exposure.

too many chromosomes, toow few, deletions, translocations

decrease in adhesion molecule expression-metasisis, increaase in mobility of carbs, allows cells to clump, decrease in GAP junction proteins

Immune system response to cancer

The immune system responds to cancer through recognizing and attacking cancerous cells via immune surveillance, utilizing mechanisms such as cytotoxic T cells, natural killer cells, and the production of antibodies. However, cancer cells can develop evasion strategies to escape detection. This involves the immune system identifying and destroying tumor cells through various effector mechanisms, including the activation of CD8+ T cells and macrophages, while sometimes facing challenges from the tumor microenvironment.

Innate and acquired

immunity are the two main components of the immune system. Innate immunity provides immediate, non-specific defense, while acquired immunity generates a tailored response against specific pathogens, involving lymphocytes and antibodies. B(plasma and antibodies) and T cell response(cytotoxic c)

What is the immune surveillance theory? Plus examples

The immune surveillance theory posits that the immune system continuously monitors and eliminates emerging tumor cells, preventing the development of cancer. It suggests that immune cells recognize and destroy abnormal cells before they can form clinically detectable tumors.

people on immune suppressent therapies, and HIV patients have a higher risk of developing cancer

• What is the difference between tumor-associated and tumor-specific transplantation antigens; why are they important to the immune system

Tumor-associated antigens are proteins expressed on both normal and cancerous cells, while tumor-specific antigens are unique to cancer cells.

Tumor associated cells are expressed in low numbers normally(or just in fetal cells)

Tumor specific antigens are new antigens produced by the tumor

Understanding these differences is crucial for developing targeted immunotherapies and enhancing the immune system's ability to distinguish between normal and malignant cells.

Why are they important?

allows immune system to target transformed cells, stimulate antibodies response via vaccination, and help develop personalized cancer therapies.

Why might the immune system fail in its recognition or response to cancer

The immune system may fail to recognize or respond to cancer due to various factors, including the tumor's ability to hide from immune detection by downregulating antigen presentation, producing immunosuppressive factors, or creating a hostile microenvironment that inhibits immune cell function.

Tumor escape

is the process by which tumors evade detection and destruction by the immune system, allowing for continued growth and metastasis.

Tumor escape mechanisms

blocks CTL interactions

induces tumor to down-regulate the antigen

some tumors kill T cells

hard to acess cancerous cells

natural selection- capscase proteins pathways are disregulated

down regulation of MHC class 1

expression on tumor cells, reducing their visibility to cytotoxic T lymphocytes (CTLs) and facilitating immune evasion. APC can fail to recognize the tumor cells, leading to decreased antitumor immune responses. tumor gets by without being detected

angiogenesis

cells can stimulate their own vascularizationto ensure a sufficient blood supply for nutrients and oxygen in tumor growth.

VEGF- a key protein that promotes angiogenesis by stimulating blood vessel formation. vascular epitheal growth factor

statins

are a class of drugs used to exhibit anti-cancer properties by inhibiting tumor growth and improving immune response.

Avastin- approved for colon cancer, lung, cervical, etc.

it attaches to vegf receptos to inhibit it- there are few side effects

vasculogenisis

the formation of new blood vessels from endothelial progenitor cells, distinct from angiogenesis.

How is angiogenesis regulated, how do tumor cells influence this process

Angiogenesis is regulated by a balance of pro-angiogenic factors like VEGF and anti-angiogenic factors. Tumor cells influence this process by secreting growth factors that promote blood vessel formation, ensuring adequate nutrient supply for their growth.

Tumor cells initiate their own vascularization by releasing signaling molecules that enhance angiogenesis and recruit surrounding endothelial cells.

What inhibts this process?

Angiostatin, Canstatin, and Endostatine—actively
inhibit this process
– May be useful to limit tumor growth and movement
– Avastin—an angiogenesis inhibiting drug approved in the
late 2000’s for colon cancer

What are the major steps in the process of invasion and metastasis

Invasion and metastasis involve several key steps: local invasion of tumor cells through the surrounding tissue, entry into the bloodstream (intravasation), survival in circulation, extravasation into new tissues, and colonization of distant sites to form metastases.

Steps of metastisis

1. Tumor cells invade surrounding tissue,
   including the vessels

2. The cells are transported to distant sites
   in the vessels

3. The cells exit the vessel

4. Enter/migrate into the new tissue or organ

Mechanism of metastasis

Decreased adhesiveness at the primary site
– Increased cell motility
– Increased production of proteases
• Cells from the primary tumor have
different abilities to meet these
requirements—therefore, cells in the
secondary tumor can be more “fit”!

• What factors can influence the location of metastatic cells

Factors influencing the location of metastatic cells include blood flow patterns, organ-specific microenvironments, the presence of specific growth factors and receptors, and the interactions between metastatic cells and the host tissue.

Final deposition of cells and seed and soil hypo

– Circulatory patterns are the largest
influence
• Cells are typically seeded in the first capillary
bed they encounter
• e.g.—colon cancerliver

– “Seed and soil” hypothesis—some organ
preference do to compatible environments
• e.g.—prostate cancerbone (bone produces
comatible growth factors

What kind of information do we routinely “analyze” with regards to cancer?

We routinely analyze tumor characteristics such as genetic mutations, protein expression, and histological features to understand cancer behavior, prognosis, and response to treatment.

Age, locaction, genetics,

5 Ds of cancer- death, disease, disability, discomfort, dissatisfaction, destitution

• What are some of the basic concepts of statistical analysis

Population

sample- subset of population

sample size- min # of subjects needed

p-value- are the outcomes similar or not

• probability that observed results are due to chance
  - represents statistical significance in hypothesis testing

• smaller=less likely its due to chance