1 - Cancer + Cellular Regulation Flashcards
What is a neoplasm?
a neoplasm (aka a tumor) is an abnormal mass of cells which grow and divide w/o response to normal regulatory controls
Define proliferation
normal cells divide to develop normal tissues to replace lost / damaged normal tissues
Define differentiation
cells acquire functions that are different from those of their original cell from which they came; cell maturation
Describe contact inhibition
Normal cells respect the boundaries of surrounding cells and won’t grow into their space; growth is inhibited through physical contact w surrounding membranes
What is a biopsy? Identify the 3 types of biopsies.
definitive means of diagnosing cancer; piece of tissue is surgically removed from the suspect area for histological examination.
this examination helps determine whether the tissue is benign or malignant, the anatomical tissue from which the tumor arises, and the degree of cellular differentiation
3 TYPES: needle, incisional, excisional
What is chemotherapy?
use of chemicals as a systemic therapy for cancer
What is radiation therapy?
local treatment modality for cancer
use of radiation in a controlled way to prevent the continued growth of highly mitotic cancer cells
Define cachexia
weakness + wasting of the body due to cancer
What is pancytopenia?
marked decrease in the # of RBCs, WBCs, and platelets
What is neutropenia?
What is the normal range of neutrophils?
neutrophil count of less than 1 to 1.5 x 10^9 / L (normal range is 2.2 – 7.7)
What is thrombocytopenia?
reduction of platelets below 150 x 10^9 / L
Define myelosuppression (bone marrow suppression).
decrease in bone marrow activity resulting in the reduced production of blood cells
common side effect of chemotherapy
What is a carcinogen?
cancer-causing agents capable of producing cellular alterations; anything that promotes carcinogenesis
What is stomatitis?
inflammation of the mouth + lips; inflammed, sore mouth
What is mucositis?
painful inflammation and ulceration of the mucous membranes lining the digestive tract; usually as an adverse effect of chemotherapy + radiotherapy
What is alopecia?
partial or complete (reversible) loss of hair resulting from normal aging, endocrine disorders, drug rxns, anticancer medications, or skin diseases
What are CSFs (colony stimulating factors)?
glycoproteins that stimulate the production, maturation, regulation, and activation of cells of the hematological system
also stimulate the production, maturation, and release of blood cells from the bone marrow + their functional ability
What is the function of proto-oncogenes?
Promote growth + regulate normal cellular processes; start the cell cycle
What is the function of tumor suppressor genes?
Supresses growth + ends the cell cycle; also sense if a mutation is taking place
What is an oncogene?
An oncogene is a mutated cell growth regulator that promotes tumor growth; a cancer causing gene
What is cellular regulation?
All functions carried out w/in a cell to maintain homeostasis, including intracellular responses to extracellular signals.
What is cancer?
The unregulated and uncontrolled growth of cells.
What are the top 3 types of cancers that occur in males?
1) prostate
2) lung and bronchus
3) colorectal
What are the top 3 types of cancers that occur in females?
1) breast
2) lung and bronchus
3) colorectal
What are the 3 most common forms of cancer in childhood?
1) leukemia
2) brain tumors
3) lymphomas
Define + describe the current theory of cancer formation.
The current theory of cancer formation states that cancer occurs as a result of multiple + sequential mutations that impair a cell’s ability to control its cell cycle + replication
Identify the 4 characteristics of malignant cells.
1) proliferation w/o limits
2) evasion of apoptosis
3) acquisition of vasculature (angiogenesis)
4) ability to invade other tissues and metastasize
Define metastasis.
Metastasis occurs when tumor cells break free of a tissue and are circulated to distant tissues in the blood and / or lymph; results in secondary tumors
What is the most common site of metastasis? What is the second most common site?
The most common site of metastasis is the lungs because the pulmonary capillaries are often the first beds encountered by systemic tumor cells.
Second most common site is the liver.
Provide 2 examples of mutated tumour suppressor genes.
1) BRCA1 - genetic mutation; mutated to breast + ovarian cancer
2) P53 - most mutated gene in all of human cancer
What is carcinogenesis?
Process by which normal cells become transformed into malignant cells; initially involves mutations in DNA
What are the 5 types of DNA mutations that occur in carcinogenesis?
genetic (ex - BRCA1) chemical environmental (ex - UV) viral or immunological unidentified
Identify the 3 processes of cancer development.
Initiation
Promotion
Progression
What happens during initiation?
Normal cell gets altered / transformed by genetic mutations from multiple sources such as viruses, hormones, radiation, chemicals, genetic factors, or unknown factors.
This alteration leads to dysfunction in the cell’s differntiation and proliferation.
What happens during the promotion phase? Which hormones can impact promotion?
Cancer cell begins proliferating at tissue of origin.
Promotion can be enhanced by steroid homrones such as estrogen and testoseterone.
What happens during the progression phase?
Evidence of clinical disease is present, eventual evidence of regional spread and metastasis.
Which cancer is associated with the Epstein- Barr Virus?
Burkitt’s Lymphoma
Which cancer is associated with HIV?
Kaposi Sarcoma
Which cancer is associated with Hep B?
Hepatocelular carcinoma.
Hep B increased the risk of developing liver cancer by 300%.
Which cancer is associated with HPV?
Squamous Cell Carcinoma, especially in the cervix.
What is nutrient trapping?
Tumours rob the surrounding cells of nutrients
What are the 5 local signs of cancer found on assessment?
1) visible lesions
2) physical asymmetry
3) palpable masses
4) abnormal sounds
5) pain
what are the 5 systemic signs of cancer found on assessment?
1) anemia
2) bleeding
3) cachexia
4) fever
5) infections
How does anemia occur as a sign of cancer?
From blood loss, iron deficiency, or bone marrow suppression / invasion
How does bleeding occur as a symptom of cancer?
Bleeding occurs as a result of tumor necrosis and erosion of blood vessels, bone marrow suppression / invasion, or secondary to chemotherapy
How does cachexia occur as a symptom of cancer? How does cachexia affect the patient?
Cachexia occurs as a result of anorexia, increased catabolism (associated w release of cytokines), and nutrient trapping.
Cachexia almost behaves like a disease of its own. When you lose muscle mass you not only become weaker, but you lose the ability to tolerate the harsh side effects of cancer treatment. Pts w cachexia often feel both tired and nauseated, and increased nutrient intake cannot compensate for it.
Cachexia is associated with increased mortality rates of cancer pts.
What is the lifetime probability of cancer in Canada?
44%.
What do anemia, bleeding, and infections have in common?
These symptoms are signs that the cancer or cancer therapy has invaded or suppressed the bone marrow
What are paraneoplastic syndromes? Provide examples.
Paraneoplastic syndromes are characterized by symptoms that occur that cannot be attributed to the direct effects of the tumor or its spread (some type of quirky cancer).
Ex - abnormal hormone or cytokine secretion by a tumor such as ACTH, ADH, PTH
Identify the 3 ways in which malignant tumours spread.
1) invasion of neighbouring tissue
2) metastasis
3) seeding
Describe the process of invasion. How do tumor cells invade other tissues?
Invasion occurs when tumor cells grow into neighbouring or adjacent tissue.
Tumor cells lack adhesion molecules and can secrete enzymes that allow them to break down confining CT.
Identify one type of cancer that is known to spread through the process of invasion.
Cervical cancer.
Begins as a carcinoma in situ (non-invasive)
Breaks through the basement membrane and becomes a cervix-invasive carcinoma.
Spreads to the vagina
Widespread invasion to the urethra, uterus, colon, rectum, and urinary bladder.
What is a carcinoma in situ?
Lesion with all the histological features of cancer except invasion.
Define metastasis.
Metastasis occurs when tumor cells break free of a tissue and are circulated to distant tissues in the blood and / or lymph.
Secondary tumors form and can be either contained by local lymph nodes or attach to capillary beds they come across.
What are the 2 most common sites of metastasis?
The lungs are the most common site of metastasis because the pulmonary capillaries are often the first beds encountered by systemic tumor cells.
2nd most common is the liver.
Identify the 5 main sites of bloodborne metastasis.
1) brain + CSF
2) lungs
3) liver
4) adrenal glands
5) bones
What is seeding? Where does seeding most often occur?
Seeding involves the spreading of tumor cells along membranes or w/in fluids OTHER THAN blood or lymph.
The cancer cells are “sliding” along a biological membrane, typically the peritoneum, which wraps around our gut.
Identify a type of cancer that is typically spread by seeding. Where does this cancer typically spread to?
Ovarian cancer is typically spread by seeding.
The ovaries sit in the abdominal cavity and have lots of space around them. The only thing surrounding them is the peritoneum.
Cancer cells seed or slide along the peritoneum and form tiny secondary tumors as they spread along the membrane. Hundreds of secondary tumors can form around the bowels and eventually up to the liver.
Identify the 3 ways in which we classify cancerous tumors.
Tumors can be classified by:
1) anatomical site or tissue of origin
2) grading severity thru histological analysis
3) staging the extent of the disease
Where do carcinomas originate from?
Carcinomas originate from epithelial tissue.
either the ECTODERM (skin, glands, epithelium)
or the ENDODERM (mucous membrane of resp, GI, and GU tracts).
Where would a bronchogenic carcinoma originate from?
The mucous membrane of the respiratory tract.
Where do sarcomas originate from?
The mesoderm (muscle, bone, fat, CT)
Where do lymphomas + leukemias originate from?
The hematopoietic system (RBCs, WBCs, platelets, + stem cells in bone marrow)
Where does leukemia originate from?
Bone marrow
Where does lymphoma originate from?
Lymphocytes (WBCs)
Why do we grade cancer cells?
What is implied when we grade cells?
Grading gives us an idea of how “aggressive” the cancer is.
Grading also implies that we have taken a biopsy of the tumor and sent it for a histological analysis.
describe the 4 grades of abnormal cells: grade I grade II grade III grade IV
grade I: cells differ SLIGHTLY from normal cells; WELL differentiated
grade II: cells MORE abnormal and MODERATELY differentiated
grade III: cells VERY abnormal and POORLY differentiated
grade IV: cells are IMMATURE, PRIMITIVE, UNDIFFERENTIATED; cell of origin difficult to determine
What is staging?
Staging is the most important classification system of cancer. Determines the EXTENT of the disease (beginning or end?), the prognosis of a cancer and the most apropriate therapy.
What are the 5 clinical staging classifications? Describe them. Which are generally considered to be curable and which are not?
0: cancer in situ; cured if removed.
1: tumor limited to tissue of origin + localized growth; cured if removed.
2: limited local spread to lymph nodes; good chance of being cured if we remove primary tumor + surrounding lymph nodes
3: extension of stage 2, spread beyond local lymph nodes - generally not curable
4: metastasis. secondary tumor somewhere beyond a local node, lethal.
Describe the TNM classification system of cancer.
This system states that staging is based on 3 parameters:
T: primary tumour size + invasiveness
N: spread to lymph nodes
M: metastasis.
T or F: Any evidence of metastasis makes the cancer a stage 4.
True.
What is lymphoma?
Lymphoma is a generic term used to describe malignant tumors of the lymphocytes. 90% of Lymphomas involve B lymphocytes while the other 10% involve T lymphocytes.
What is the most common clinical manifestation of lymphoma? What are the most common lymph nodes affected by lymphoma?
Lymphadenopathy (enlarged lymph nodes) beginning in a single lymph node and eventually metastasizing to adjacent nodes and all over the body.
Most common nodes affected are the cervical, supraclavicular, and axillary.
What are the 7 risk factors for developing Lymphoma?
1) previous exposure to radiation (UV, x-rays)
2) chronic immusuppression
3) autoimmune disease
4) HIV
5) hepatitis B or C
6) helicobacter pylori infection
7) exposure to herbicides + pesticides (more common in farming communities)
What are lymph nodes?
Small, bean-shaped structures that filter the lymph passing through them
Trap germs + immune cells
Lymph nodes swell in the presence of infection
What is bone marrow?
Spongy material that produces blood cells.
What are the 7 clinical manifestations of lymphoma? Which of these are B symptoms?
1) lymphadenopathy (most common)
2) fatigue
3) itching
4) immunosuppression + frequent infections
5) weight loss (B symptom)
6) fever (B symptom)
7) nght sweats (B symptom)
What is a lumbar puncture? When might this be performed?
Thin needle is inserted into lower back.
Performed if specialist suspects lymphoma in the brain or spinal cord or if you need to have chemotherapy drugs that reach your CNS.
What are the 2 categories of Lymphoma?
Hodgkin’s Lymphoma (Hodgkin’s Disease)
Non-Hodgkin’s Lymphoma (~ 18 diseases)
Compare Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma in terms of their cellular origin.
Hodgkin’s Lymphoma: always in B lymphocytes
Non-Hodgkin’s Lymphoma: 90% in B lymphocytes, 10% in T lymphocytes
Compare Hodgkin’s and Non-Hodgkin’s Lymphoma in terms of their spread / extent.
Hodgkin’s Disease is localized to regional lymph nodes but may be bulky
Non-Hodgkin’s Lymphoma is disseminated and spreads more quickly.
What are B symptoms?
B symproms are characteristic symptoms of Hodgkin’s Lymphoma. They include fever, night sweats, and weight loss.
These symptoms are less common in Non-Hodgkin’s Lymphoma, but are still 40% likely to occur.
Compare Hodgkin’s Disease and Non-Hodgkin’s Lymphoma in terms of extranodal involvement (spreading outside of the lymph node system)
Hodgkin’s Lymphoma: rare
Non-Hodgkin’s Lymphoma: common (disseminated)
Hodgkin’s Lymphoma is staged differently than other types of cancer and required us to modify the TNM staging system.
Describe the following stages of Hodgkin's Lymphoma: Stage I Stage II Stage III Stage IV
Stage I: single lymph node involved
Stage II: involvement of 2 or more lymph node regions on the SAME SIDE of the diaphragm
Stage III: involvement of lymph node regions on BOTH SIDES of the diaphragm; can include single extranodal site, the spleen, or both
Stage IV: one or more extralymphatic organs or tissues w or w/o associated lymph node involvement
Identify the 7 diagnostic categories of study used to diagnose cancer.
1) cytology studies (PAP smear)
2) laboratory tests (CBC, liver + renal fucntion)
3) endoscopy (ex - sigmoidoscopic / colonoscopic, including fecal occult blood test)
4) radiological studies (chest radiography, MRI)
5) radioisotope scanning (bone, lung, liver, brain)
6) bone marrow aspiration
7) biopsies
What is the difference between a bone marrow biopsy and a bone marrow aspiration?
A bone marrow biopsy removes a small amount of bone and a small amount of fluid and cells from inside the bone marrow. A bone marrow aspiration removes only the marrow.
What is the ultimate goal of chemotherapy?
Produce 100% kill of neoplastic (cancer) cells while causing limited injury to normal tissues - especially the bone marrow and GI epithelium.
What is combination therapy? What is the purpose?
Combination therapy is chemotherapy involving a combination of drugs. Used to suppress drug resistance, increase cancer cell kill, and reduce adverse effects / toxicity to normal cells.
Which tissues are most affected by chemotherapy and why?
Chemotherapy is most harmful to rapidly dividing cells.
Therefore, the bone marrow, GI epithelium, and hair follicles are often heavily affected by chemotherapy. This results in alopecia, emesis, and bone marrow suppression.
In which situations is chemotherapy most often utilized?
Treatment of choice for disseminated cancers and several localized cancers.
What is the main goal of radiation therapy?
Deliver a dose large enough to kill cancer cells w/o causing intolerable damage to healthy tissue.
List 3 differences between radiation and chemotherapy in terms of their effect on the body and the cells.
chemotherapy side effects: alopecia due to killing of hair follicle cells, nausea, vomiting, and diarrhea due to killing of GI mucosa, myelosuppression, extravasation risk
radiation side effects include: skin inflammation, lesions of the GI mucosa, and fibrosis of the brain, peripheral neurons, and lungs (tissues w a low ability to regenerate).
In what situations would radiation be utilized?
Radiation relieves pain by causing tumor regression; can be used in palliative treatment.
Identify the 3 main dose-limiting side effects associated withh chemotherapy drugs.
alopecia
nausea, vomiting, diarrhea
myelosuppression
What is the nadir (nAY-der)
The lowest WBC count we are willing to tolerate when giving chemotherapy
Describe chemotherapeutic drugs in terms of their therapeutic index.
Almost all chemotherapeutic drugs have a narrow therapeutic index. This means that when the dose is high enough to provide therapeutic effects it’s also v/ close to the S/E dose. We try to prevent this by giving drugs in combination.
Describe chemotherapeutic drugs in terms of drug resistance.
Just like antibiotic resistance - if a cancer recurrence occurs after treating it w a certain medication, we need to find a new anticancer drug
Describe chemotherapeutic drugs in terms of dose-limiting adverse effects.
These include alopecia, nausea, vomiting, diarrhea, and myelosuppression.
This is why we give pts chemotherapy “rounds” as their body needs a break from the drugs.
Why are hair follicles, GI tract cells, and bone marrow cells most effected by chemotherapeutic drugs?
Because these cells are rapidly dividing and chemotherapeutic drugs target rapidly dividing cells.
T or F: a combination of chemotherapy drugs is usually more effective than single-drug therapy.
True (synergism).
Describe RCVP as a combination chemotherapy drug used to treat lymphoma. Which 4 drugs are included in this “cocktail”?
RCVP for lymphoma:
Rituximab
Cyclophosphamide
Vincristine
Prednisone (steroidal anti-inflammatory drug)
What is chemotherapy? What is another name for anti-cancer drugs?
The pharmacological treatment of cancer.
Antineoplastic drugs.
The 3 general goals of chemotherapy are to cure, control, or palliate the symptoms of cancer.
In which stage of cancer would the goal be to Cure?
In which stage of cancer would the goal be to Control?
In which stage of cancer would the goal be to provide Palliation?
CURE - early cancer; stage 2 or 3
CONTROL - after surgery + radiation to prevent resurgence
PALLIATION - stage 4, sometimes stage 3 - shrink a tumor to relieve pain, relieve obstruction, or to improve a pt’s QOL and wellbeing.
In which types of cancer would the goal be to Cure because they respond v/ well to chemotherapy?
Burkitt's lymphoma Wilms' tumor Neuroblastoma Acute lymphocytic leukemia Hodgkin's Lymphoma Testicular cancer
In which types of cancer would the goal be to Control it (such as after surgery + radiation to prevent resurgence)?
Breast cancer
Non-Hodgkin’s Lymphoma
Small cell lung cancer
Ovarian cancer
Antineoplastic drugs are divided into 2 groups based on where in the cell cycle they work. What are the 2 types?
Cell cycle-nonspecific (CCNS) - kill cells in any phase of the cell cycle
Cell cycle-specific (CCS) - kill cells only as they go through one specific phase of the cell cycle such as S or M
Why is chemotherapy sometimes referred to as adjunctive therapy?
Because it is most often intended to go with other therapies such as surgery + radiation therapy.
What is a drug’s emetic potential?
A drug’s emetic potential describes how greatly they will produce a nausea response.
Antimetabolites and mitotic inhibitors are what kind of neoplastic drugs?
Cell cycle-specific drugs
Cytotoxic antibodies and alkylating drugs are what kind of antineoplastic drugs?
CCNS drugs
Cytotoxic antibiotics and alkylating drugs are what kind of antineoplastic drugs?
CCNS drugs
What are the 5 functions of human cells?
1) creating fuel for the body
2) manufacturing proteins
3) transporting wastes
4) disposing of wastes
5) cellular growth of reproduction
What is dysplasia?
Abnormal growth patterns
Stem cells differentiate into osteocytes. What do osteocytes eventually differentiate into?
Bone
Stem cells differentiate into enterocytes. What do enterocytes differentiate into?
Intestines
Stem cells differentiate into neurons. What do neurons differentiate into?
Brain
Stem cells differentiate into hepatocytes. What do hepatocytes differentiate into?
Liver
What is a polypoid tumor?
“Ball on a string”
What is the function of the spleen?
10) Function of the spleen – stores healthy blood cells + filters out damaged blood cells, bacteria, and cell waste.
What is extravasation?
Leaking of an antineoplastic drug into surrounding tissues during IV administration.
Can result in permanent damage to nerves, tendons, muscles –> loss of limbs
skin grafting or amputation may be necessary
prevention through IV monitoring and discontinue IV at ANY sign of extravasation (pain, inflammation, etc)
