Patho Ch 11 (cancer)

what is neoplasia?

means "new growth" but can also refer to malignancy which is cancer

what does neoplasia result in?

abnormality of cellular growth/ tumor, and altered expression of cellular genes

what is a benign tumor?

a non-invasive/ non-metastatic tumor that does not directly kill the host but may be life-threatening due to location

describe the structure of benign tumors

well differentiated, slower growth, encapsulated, no necrotic tissue, and more closely resembles original tissue

what is a malignant tumor?

an invasive, metastatic and deadly growth

describe the structure of malignant tumors

poorly differentiated, anaplasia, grows rapidly, replicated uncontrollably, frequently necrotic, and dysfunctional tissue

what may a malignant tumor originate from?

stem cells

what does the suffix -oma mean?

indicated a benign tumor (some exceptions)

what does carcinoma and sarcoma mean?

malignant tumor

what is carcinoma a tumor of?

malignant tumor of epithelial tissue

what is adenocarcinoma a tumor of?

malignant tumor of ductal or glandular tissues

what is sarcoma a tumor of?

malignant tumor of mesenchymal tissue

what is lymphoma a tumor of?

a malignant tumor of lymphatic tissue

what is leukemia a tumor of?

a malignant tumor of blood-forming cells

what are exceptions to the benign -oma rule?

lymphomas, hepatomas, melanomas (all malignant)

why are malignant tumors considered antisocial?

they ignore extrinsic and intrinsic growth/ death signals and replicate on their own indefinitely

what is the second leading cause of death in the US?

cancer

when do most cancer deaths occur?

individuals over the age of 55

what is the risk of men developing cancer?

1 in 2

what is the risk of women developing cancer?

1 in 3

what are the lifestyle factors that contribute to 1/3 of cancer-related deaths?

tobacco use, nutrition, obesity, sun exposure, and sexual exposure to HPV (cervical cancer)

what percent of cancers have a 5-year survival rate?

68%

what types of cancers does tobacco use have linkages to?

pancreatic, kidney, bladder, mouth, esophageal, and cervical cancers

what viruses may be cancer risk factors?

oncoviruses

how is tobacco a complete carinogen?

it initiates tissue damage and promotes replication

what chemicals are cancer risk factors?

organic solvents, asbestos, heavy metals, formaldehyde, and chemotherapy agents

what biological factors are also cancer risk factors?

chronic irritation/ inflammation, age, hormones

what nutritional factors may be cancer risk factors?

fat, fiber, alcohol, and antioxidant intake

what is a carcinogen?

a potential cancer-causing agent

what is a proto-oncogene?

a gene that enhances growth promotion/ replication

what is an oncogene?

a proto-oncogene in mutant form that promotes replication and ignores regulatory cell signals

what is a tumor suppressor gene?

a gene that inhibit cell proliferation (cancers arise when these are inactivated)

how is HIF-1a affected when tumor suppressor genes are inactivated?

increased expression leading to increased VEGF expression causing a tumor to grow its own blood vessels

what are mitogens?

extracellular growth signals that promote replication through autocrine or paracrine function

what are mitogen receptors?

extracellular receptors that bind and transfer message of mitogens

what happens if there is a mutation in mitogen receptors?

may cause increased responsiveness, increased number of receptors, or increased affinity for mitogens causing increased proliferation signals (cancer can develop)

what are cytoplasmic signaling pathways?

intracellular enzymatic cascades that promote a cell response (ex: replication)

what happens if there is abnormal function in cytoplasmic signaling pathways?

survival signals remain on and lead to uncontrolled proliferation and resistance to apoptosis (tumors develop)

what is the purpose of marker genes?

indicate whether an individual is at risk for cancer and the predicted aggressiveness

what is p53 an example of?

tumor supressor gene

what is the function of p53?

programs cell death under normal conditions or in response to radiation/ chemo. also slows replication

what is BRCA 1 and 2 marker genes for?

breast/ ovarian cancers

what is APC a marker gene for?

colorectal cancers

what is DLC a marker gene for?

live cancer

what is VHL a marker gene for?

kidney/ renal cancers

what is carcinogenesis?

process by which normal cells are transformed into cancer cells

how is cancer multifactorial?

various factors may lead to cancer (ex: environmental, hereditary, or infections)

what are the phases of carcinogenesis?

initiation -> promotion -> progression

what is the initiation phase of carcinogenesis?

mutations or abnormalities in proto-oncogenes and tumor supressor genes that lead to increased replication factors and promotion of cancer growth

what are the 2 agents of cause in the initiation phase of carcinogensis?

complete carcinogens (cause and initiate cell damage/ mutations promoting cancer) and partial carcinogens (promote growth factors)

what is the promotion phase in carcinogensis?

proliferation continues under activation of another oncogene or inactivation of a tumor supressor gene (mutations continue and promote drug resistance/ invasion)

what two hormones stimulate growth and encourage tumor progression in the promotion phase?

estrogen and testosterone

why is telomerase sometimes activated during the promotion phase?

allows for immortality as it can repair cancerous DNA leading to indefinite replication

what is the progression phase in carcinogenesis?

tumor cells begin to develop malignant characteristic and invade near by tissue/become metastatic

how are laminin receptors important during progression?

increases invasiveness/ metastatic potential by allow cancer cells to attach to adjacent tissues

how are lytic enzymes important in progression?

increase invasiveness/ metastatic potential by damaging adjacent cells and allow cancer a portal of entry

why is anchorage independency important in the progression phase?

allows cancer cells to move elsewhere in the body rather than staying in one spot

what are common ways cancers can become metastatic?

by invading circulatory or lymphatic systems

what is angiogenesis?

ability of cancer tumors forming their on blood vessels to promote growth

how are tumors parent tissue identified?

examining marker cells in blood circulation or biopsy

what is the purpose of grading and staging tumors?

to predict the malignancy of tumors and guide therapeutic management/ treatment mechanisms

what does grading assess?

microscopic view of tissues and their degree of anaplasia (how different it looks from normal tissue)

what does staging assess?

location and spread pattern, tumor size, local growth, involvement of lymph nodes and organs, and any distant metastasis

what to results of staging determine?

prognosis and treatment protocol

what is the TNM system?

tumor size, node involvement, metastasis (pneumonic for staging tumors)

what is carcinoma in situ?

early-stage cancers that have not invaded surrounding tissues or broken through the basement membrane

what are the possible outcomes of carcinomas in situ?

remain stable, progress into invasive/ metastasis cancers, or regress and disappear

what are warning signs of cancer?

1. unusual bleeding or discharge

2. change in bowel/ bladder habits

3. change in a wart or mole

4. a sore that does not heal

5. unexplained weight loss

6. anemia, low hemoglobin, or persistent fatigue

7. persistent cough or hoarseness without reason

8. solid painless lump

what are the common side effects of cancer and cancer therapy?

anemia, bone density loss, cachexia, cardia and pulmonary damage, fatigue, GI problems, hair loss, infections, infertility, lymphedema, pain

what are systemic effects of malignant tumors?

weight loss and cachexia, anemia, severe fatigue, effusions (fluid in places it is not meant to be), infections, bleeding, paraneoplastic syndrome

what are local effects of malignant tumors?

pain, obstruction, tissue necrosis

what is cachexia?

a multiorgan energy-wasting syndrome causing overall weight loss and generalized weakness (most severe form of malnutrition)

what are paraneoplastic syndromes?

abnormal autoimmune response to cancer via production of hormones/ cytokines in a tumor

what are examples of paraneoplastic syndromes?

hypercalcemia, cushing syndrome caused by excessive ACTH secretion, hyponatremia and water overload caused by excess ADH secretion

what are the main types of cancer therapy?

surgery, radiation, and chemotherapy

what are emerging cancer therapies?

immunotherapy, targeted molecular therapies, and stem cell transplants

how are majority of solid tumors treated?

surgically to remove tumor and cause minimal damage to other body cells (radiation/ chemotherapy may follow to kill and remaining or missed cancer cells)

what is radiation therapy?

mechanism that damages nuclear DNA to induce apoptosis or cause cell death in tumor cells while also killing a few normal cells

why is radiation therapy given in small doses over several treatments?

cell-cycle specific as cancer cells are easier to kill in certain phases and allows normal body cells to recover from damage

what is chemotherapy?

systemic administration of anticancer chemicals to treat cancers in known or suspected area in the body

what is a con of chemotherapy?

most drugs are cytotoxic and also kills normal cells, and bone marrow supression

when is chemotherapy most effective?

on rapidly dividing cells or in combination with antiangiogenic drugs

why is chemotherapy given over several courses?

to ensure all cancer cells are killed

what does immunotherapy primarily involve?

interferons, interleukins, and monoclonal antibodies

what are interferons?

glycoproteins produced by immune cells in response to viral infections

what are interleukins?

peptides produced and secreted by WBCs (aka lymphokines/ cytokines)

what are monoclonal antibodies?

antibodies with identical structure that bind with specific target antigens

when is immunotherapy used?

commonly alongside surgery, radiation, and chemotherapy

what are the causes of bone marrow suppression?

invasion/ destruction of bone marrow cell, poor nutrition, or chemotherapy

what causes hair loss ad sloughing of mucosal membranes?

chemotherapy and radiation

what does damaged mucosa cause?

primary source of cancer pain and anorexia, also provide a portal for infections

when is stem cell transplantation used?

for life threatening disorders affecting the bone marrow, WBCs, RBCs, or platelets (used in malignant and nonmalignant disorders)

what is the purpose of stem cell transplantation?

to restore bone marrow function