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3 - Physio Genetics > Neoplasms > Flashcards

Flashcards in Neoplasms Deck (45):


new growth



the growth itself



determination of cell's fate, specialization



cell division and growth of new cells



programmed death, remodeling


benign vs malignant tumors

-When differentiated cells mutate, they form differentiated tumors— benign tumors
-When undifferentiated cells mutate, they form rapidly dividing tumors— malignant tumors


phases of cell cycle

-G1 (gap 1) – postmitosis – 0 DNA synthesis, cell growth phase
-DNA Synthesis (S phase)
-G2 (gap2) – premitosis, 0 DNA synthesis
-M – mitosis
-G0 – quiescence, resting phase


checkpoints in the cell cycle

-Three major checkpoints are found in the G1, G2 and M phases
-For many cells, the G1 checkpoint seems to be the most important, “restriction point”
-If a cell receives a go-ahead signal at the G1 checkpoints, it will usually complete the cycle and divide
-If it doesn’t, it will switch into a nondividing state called the G0 phase
-Nerve and muscle cells never divide. Other cells, such as liver cells, can be “called back” to the cell cycle by certain environmental cues, such as growth factors released during injury


permanent cell vs stable cell

-permanent = cant undergo cell division --> always in G0
-stable = can be called back into division --> can go from G0 to G1


protein kinases and cyclins

-Particular protein kinases give the go-ahead signals for mitosis
-To active such a kinase, it must be attached to a cyclin.
-Therefore they are called cyclin-dependent kinases or Cdks.
-For instance, there is a cyclin that rises during S and G2 phases and then falls abruptly during M phase. It attaches to a Cdk and creates a complex called MPF (maturation promoting factor)
-Thus we can think of MPF as “M-phase promoting factor”
-During anaphase, MPF helps switch itself off by initiating a process that leads to the destruction of its own cyclin.


G1 checkpoint

-there are at least three CDK proteins and several cyclins at this checkpoint


genes that control the checkpoints

1. Genes that turn off or decrease the rate of cell division (Tumor suppressor genes)
2. Genes that turn on or increase the rate of cell division (Proto-oncogenes)


tumor suppressor genes function

-Some tumor suppressor proteins normally repair damaged DNA
-Some tumor suppressor proteins control the adhesion of cells to each other or to the extracellular matrix; proper cell anchorage is crucial in normal tissue
-Other tumor suppressor proteins are components of cell signaling pathways that inhibit the cell cycle.



-Genes that code for normal proteins used in cell division (Growth factors, Growth factor receptors, G proteins, Enzymes that produce second messengers, Genes that turn the production of these proteins on and off)
-Mutated form of a proto-oncogene is called oncogene
-Oncogenes promote cancer


two key genes for controlling cell division

1. Ras proto-oncogen
2. p53 tumor suppressor gene
Mutation in ras occurs in about 30% of human cancers
Mutation in p53 in more than 50%


tumor suppressing gene - p53

-The protein coded by this gene is called p53 as well.

-In at least three ways, p53 prevents a cell from passing on mutations due to DNA damage
1. This protein indirectly blocks the ability of cyclins
p53 induces the expression of another gene called P21.
p21 inactivate Cdk.
2. p53 protein can directly turn on genes involved in DNA repair
3. When DNA damage is irreparable, p53 activates “suicide” genes, whose protein products cause cell death by apoptosis.
-Normal function of TP53 inhibits angiogenesis necessary for tumor development


Li-fraumeni syndrome

-mutation of p53 on chromosome 17, with high rate of many types of tumor


tumor suppressor gene: Rb

-Rb gene prevents the cell from entering S-phase until the appropriate growth signals are present
-Mutation of Rb gene on chromosome 13→ Retinoblastoma, cancer of the retina


Genes that regulate apoptosis

-There are genes regulate apoptosis
Mutation of these genes modify apoptosis
1. bcl-2: Prevents apoptosis
2. bax, bad, bcl-xS, bid and p53: Promote apoptosis
3. c-myc: When associated with p53 leads to apoptosis, When associated with bcl-2 inhibits apoptosis



-Telomeres: DNA sequences at the ends of the chromosomes
-The enzymes that duplicate DNA attach here
-The end of the telomere does not get duplicated


events in transformation

-Initiation – exposure to carcinogenic agents
-Promotion – induction of unregulated growth
-Progression – tumor cells acquire malignant phenotype


epidemiology of neoplasia

-90% of neoplasm arise from epithelium because (It proliferates rapidly – high turnover, It encounters the environmental carcinogen)
-The remainder arise from mesenchymal cells


"carcinoma" vs. "sarcoma"

-Epithelial tissue: tissue name + “carcinoma”
-Mesenchymal tissue: tissue name + “sarcoma”


benign tumors

-Contain cells that look like normal tissue cells
-May perform the normal function of the tissue (like secreting hormones) (This may lead to oversecretion)
-Usually have a capsule around them
Usually do not invade neighboring tissues
-They can damage nearby organs by compressing them


malignant tumors

-Contain cells that do not look like normal adult cells
-These cells divide rapidly and mutate faster and can change type
-The tumor does not have clear boundaries and sends “legs” out into surrounding tissue (the word cancer means “crab” and is based on these crablike legs)
-Do not perform the normal functions of the organ
-May secrete hormones associated with other tissues (paraneoplastic disorders)
-Can compress and/or destroy the surrounding tissues
-Can metastasize to distant region


generalized effects of cancer

Cancer cachexia syndrome (Weight loss, Muscle wasting, Weakness, Anorexia, Anemia, bone breakdown)


cancer changes in organ function

-Benign tumors may cause overproduction of normal organ secretions
-Malignant tumors may occasionally cause overproduction (as in thyroid cancer), but more commonly decrease production of normal organ secretions


local effects of tumor growth

-Compression of blood vessels (Superior vena cava syndrome, Portal hypertension)
-Compression of lymph vessels (Edema, ascites, effusion
-Compression of hollow organs
-Compression of nerves (Pain, paralysis)


leading cause of death in US

-adult = heart disease, cancer, CVA
-children = accident, cancer, congenital anomaly


most common cancer location in males and females

-males = prostate, lung and bronchus, colon and rectum
-females = breast, lung and bronchus, colon and rectum


cancer mortality by site and sex

-males = lung and bronchus, prostate, colon and rectum
-females = lung and bronchus, breast, colon and rectum


cancer risk based on affected relatives

-1 = 1-%
-2 = 25%
-3 = 30%


predisposition to cancer

-Geography and racial factor
-Exposure to carcinogen agents
-Hereditary predisposition (personal or family history)
-Acquired pareneoplastic disorder


geographic and racial factors affecting cancer

-Stomach cancer: Japan > USA
-Liver hepatoma: Asia > USA
-Breast cancer: USA > Japan
-Prostate cancer: African-American > Caucasian
-Ashkenazi Jews: Tay-Sachs disease, Niemann-Pick disease, Gaucher disease (all lysosomal dzs)


carcinogen agents

-Chemical carcinogen
-Oncogenic viruses
-Loss of immune regulation


carcinogen vs protocarcinogen

-Carcinogens are the chemicals that directly modify DNA (cause mutation) and therefore cause cancer
-Protocarcinogens are carcinogens that require metabolic conversion to form active carcinogen



-Initiation: carcinogens can be mutagens that cause cancer by modifying DNA
-Promotion: this steps need promotors. Mutated cells are stimulated to divide
-Progression: tumor cells compete with one another and develop more mutations which make them more aggressive


important chemical carcinogens

-Cigarette smoke: multiple cancer
-Nitrosamine: gastric cancer
-Polycyclic aromatic hydrocarbons: bronchogenic carcinoma
-Asbestos: bronchogenic carcinoma, mesothelioma
-Arsenic: squamous cell carcinoma of:
skin and lung, angiocarcinoma of liver
-Alkalating agents: leukemia, lymphoma



-UV radiation (UVB sunlight is the most carcinogenic radiation, Produces pyrimidine dimers in DNA, Ex. Xeroderma Pigmentosum)
-Ionizing radiation (X-ray and γ-ray, protons, neutrons, α and β particles --> Cell in mitosis or G2 of the cell cycle are most sensitive, Ex. Atomic bomb: leukemias, thyroid cancer, Uranium miners: lung cancer)


oncogenic viruses

-RNA viruses
-The human T-cell leukemia virus (HTLV-1) → Adult T cell leukemia/lymphoma (ATLL) (This virus is found in Japan and the Caribbean more commonly)
-DNA viruses
-Hepatitis B virus (HBV) → hepatocellular carcinoma
-Kaposi-sarcoma-associated herpesvirus (HHV8) → Kaposi sarcoma
-Human papilloma virus (HPV) (Benign squamous papilloma (warts), Cervical and vulvar cancer)
-Epstein-Barr virus (EBV)



-Diagnosed between 1–3 years of age
-40% due to an AD trait
-60% are sporadic cases


hereditary retinoblastoma

-Children of family with this trait have 50% chance of inheriting a gene for retinoblastoma and a 90% chance of developing RB
-Usually in both eyes
-High risk for other cancers especially osteosacroma and fibrosacroma, which often occurs following successful surgical cure of retinoblastoma.


sporadic form of retinoblastoma

-Mutations occur in both copies of the RB1 (the gene encode protein pRB)
-Tumors form generally in only one eye
-No increased risk of other cancers


routine screening in primary care

-PAP (Cervical)
-Colonoscopy (Colon)
-Mammogram (Breast)
-Lung Cancer Screening (controversial)



-Product of the AHRQ
-Search for recommendations and guidelines
-Does not always align with all other organizations providing recommendations