Cancer Flashcards
G1
G1 phase: cell grows larger, organelles duplicated
S phase
DNA and centrosome (microtubule- organizing structure) copied in nucleus
G2 phase
growth, proteins and organelles are made, preparation for mitosis
M phase
cell divides copied DNA and cytoplasm to make two new cells
Late g2
DNA is copied, so chromosomes in nucleus are two connected copies: sister chromatids
Two centrioles
prophase
Chromosomes begin to condense
Mitotic spindle forms (made of microtubules)
Nucleolus (where ribosomes are made) disappears
prometaphase
Mitotic spindle begins to organize chromosomes
Nuclear envelope breaks down
spindle anatomy
Microtubules bind to chromosomes at the kinetochore
Centromere is where the sister chromatids join together
Aster: structure of microtubules bound to chromosomes
metaphase
All chromosomes aligned at the metaphase plate
Two kinetochores of each chromosome should be attached to microtubules from opposite spindle poles
Spindle checkpoint: cell checks that sister chromatids will separate evenly
anaphase
Sister chromatids split - this is driven by motor proteins that “walk” along the microtubule tracks
telophase
Mitotic spindle is broken down
Two new nuclei form, nuclear membranes reappear
Chromosomes decondense
cytokinesis
Starts in anaphase/telophase
Separation of the cytoplasm
An actin ring forms a cleavage furrow
how cyclins work
Cyclin dependent kinases (CDK) - when bound to cyclin its active (phosphorylates targets) Kinase: adds a phosphate group CDK default function is to be inactive
G1 regulation
cycD, cycE
Phosphorylates Rb protein→ can’t inhibit DNA replication
s regulation
cycA
Activates DNA replication
G2 regulation
Cyc B
Activates mitosis/cell division
oncogenes
Cancer is a disease of uncontrolled cell division: cyclins expressed at high levels or overactive growth factor receptor
Proto-oncogene (normal cell growth) → oncogene (overactive, cancer-promoting) gene
how gene can mutate
AA mutation, amplification (cell gains extra copies of a gene), error in DNA repair where a proto-oncogene is attached to a different gene. This then makes an unregulated, new protein
oncogenes result from the activation (turning on) of proto-oncogenes
tumor suppressor genes
Genes that normally block cell cycle progression: tumor suppressors
Tumor protein p53 is involved in cellular response to DNA damage
Primarily acts at G1 checkpoint where it blocks progression in response to damaged DNA
tumor suppressor genes cause cancer when they are inactivated (turned off)
normal p53 protein
detects and binds damaged DNA. halts cell at g1 checkpoint, repairs it or apoptosis
what causes cancerous cell 4
Mutation that turns proto-oncogenes into oncogenes
- Change in AA sequence, Amplification, DNA repair error
Mutation causes a change in Ras and Raf structure
- Ras is a G protein - Switches between active and inactive forms
Ras protein is stuck in “active” form, unable to switch to “inactive” form
- Prompts cell division even in absence of growth factor
- missing or bad p53 (no stopping the mutations)
benign vs malignant
- Benign Tumor - Mass of cells that divide excessively but don’t have potential to invade other tissues
Is not considered cancerous yet - Malignant Tumor - Mass of cells that divide excessively and can invade other tissues (Metastasis)
- Offspring from original mutated cell may have enough mutations to become cancerous
causes of cancer 6
- smoking and tobaccco (radioactive)
- diet and physical activity (18% of cancer is due to fatness)
- UV rays, or xray and gamma ray
- radon
- viruses (15-20%) since they can insert genes OR alter cell behaviour
- HIV/AIDS are more likely to get kaposi sarcoma, non-hodgkin lymphoma, cervical cancer
inherited cancer
- 5-10%
- breast and ovarian
- lynch, colorectal, li fraumeni syndrome (see card)
breast anatomy
- Each female breast contains 15-20 sections called lobes
- Each lobe contains smaller sacs called lobules
- Lobules/glandular tissue produce breast milk
- Ducts carry milk to the nipple
- Connect the lobes and lobules to the nipple
- Fatty adipose tissue and connective fibrous tissue which surrounds the lobules and ducts
lymph and breast
- Lymphatic System: Part of immune system that protects the body from disease and infection
- Made from lymph vessels found throughout body
- Vessels carry lymph/clear fluid to lymph nodes to trap or remove harmful substances from body
Ex. Cancer cells, bacteria - Axillary nodes are closest nodes to breast, found in armpit; Internal mammary nodes under breastbone
- In case of breast cancer, cancer cells can enter lymph vessels and grow in lymph nodes
- Vessels carry lymph away from breast
signs of breast cancer 7
New lump in breast or underarm Thickening or swelling of breast Irritation or dimpling Redness or flaky skin in nipple area Nipple discharge other than breast milk (ex. blood) Size or shape change Pain
BRCA genes
5-10% of breast cancers are hereditary and involve mutations in BRCA1 or BRCA2 genes
BRCA genes function to repair cell damage and keep breast, ovarian, and other cells growing normally
Everyone has two copies of the BRCA1 and BRCA2 genes passed from their mother and father
Cancer occurs when both copies are mutated
Mutations are inherited through generations
Linked to a strong history of breast and ovarian cancer
invasive breast cancer, 3
Begins when cells in the breast such as those lining the ducts and lobules grow abnormally, growing out of control and invading surrounding tissue
Invasive Ductal Carcinoma (IDC): Starts in ducts and accounts for 80% of breast cancers
Invasive Lobular Carcinoma (ILC): Starts in lobules and accounts for 10% of breast cancers
Major molecular subtypes
Depend on presence of estrogen-receptor (ER), progesterone-receptor (PR), and human epidermal growth factor receptor-2 (HER2)
Estrogen and progesterone are needed for normal breast development
HER2 deals with cell growth and repair in healthy breast cells
Luminal A: ER/PR positive, HER2 negative, slow-growing, have best prognosis
Luminal B: ER/PR positive, HER2 positive, fast-growing, aggressive
Triple-negative: Negative/No receptors, most common with BRCA1 mutation
HER2-positive: ER/PR negative, HER2 positive, energizes cell growth, worse prognosis
Normal-like: ER/PR positive, HER2 negative, slightly worse prognosis than luminal A
metastasis
Invasion: Cancer cells from the primary tumor escape and spread in surrounding connective tissues of the organ
Intravasation: Cells cross vessel wall of organ and enter bloodstream or lymphatic system
Survival: Cells survive in circulation
Extravasation: Cells leave bloodstream and enter another organ through endothelial barrier
Colonization: Secondary tumor develops in target organ
detection and diagnosis of breast cancer 6
Breast Screening: Process of checking a woman’s breasts for cancer before there are signs or symptoms of disease
Clinical Breast Exam (CBE): Exam by doctor or nurse; using hands to feel for lumps or abnormalities
Mammogram: Place breast on plastic plate and take an X-ray; best option for early detection; encouraged for women to get them annually starting at age 45, every 2 years for 55 years and older
Breast MRI: Uses magnets and radio waves to take pictures of the breast; may appear abnormal even without the presence of cancer; used only for high-risk patients
Breast Ultrasound: Uses soundwaves to take images of the breast tissue
Biopsy: Removal of tissue or fluid from breast to be tested for cancer presence
stages of breast cancer
Stage 0: Abnormal cells with potential to become cancerous
Stage I: Early-stage; cancer cells break through a small part of tissue
Invasive breast cancer
Stage II: Cancer is beginning to spread to nearby tissues and lymph nodes
First area of spread outside of breast tissue is axillary node
Stage III: Continuous growth; larger infected areas
Stage IV: Metastatic cancer; spread to other areas of the body
cancer treatment
Surgery: Make an incision in the breast tissue and remove the tumor cells, remove most if tumor is too large
Chemotherapy: Cytotoxic drugs to kill and slow cancer cell growth
Radiation Therapy: High doses of radiation to kill and slow cancer cell growth by damaging their DNA
Targeted Therapy: Use of drugs to target proteins that control how cancer cells divide, grow, and spread
Immunotherapy: Inhibit immune system checkpoints for stimulation or injection of immune-like substances to make the immune system work harder to find tumor cells
most common treatments
Stem Cell Therapy: Procedure restoring blood-forming cells destroyed by high doses of chemotherapy or radiation therapy
Hormone Therapy: Drugs that block body’s ability to make certain hormones to stop or slow cancer growth
Ex. Anti-estrogen therapy blocks the production of estrogen in women
Ex. Aromatase inhibitors block the production of estrogen in postmenopausal women
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oral manifestations
Depending on the type of cancer and treatments, oral manifestations will vary
Most common side effects seen in almost all cancers and treatments include:
Xerostomia
Decreased salivary flow
Leads to increased dental caries
Mucositis
Oral candidiasis
Red/white lumps found within the oral cavity
Pain
Gingival bleeding
Oral dysesthesia
high risk groups
Tobacco and Alcohol Use One of the strongest risk factors for oral cavity and oropharyngeal cancers Human Papillomavirus (HPV) Infection HPV Infection found in 2 out of 3 oropharyngeal cancers Gender Twice as common in men than in women Excess Body Weight/Poor Nutrition Age UV Light Genetic Syndromes Fanconi Anemia Dyskeratosis Congenita
patient bone thing
Osteochemonecrosis is defined as medicine-induced osteonecrosis, or death of the jawbone
Osteochemonecrosis is a form of osteoporosis
Osteoporosis: Condition where bones lose strength and thickness (density)
Weakens bones, more likely to break/fracture
Osteoporosis can occur due to a lack of estrogen levels within the body
Estrogen protects against bone loss and helps to keep bones strong
Low levels of estrogen are connected to cancer treatments such as chemotherapy and hormone therapies such as anti-estrogen therapies
Tamoxifen: Anti-estrogen modulator, blocking the effect of estrogen on cancer cells to stop growth but can increase the risk of osteoporosis in postmenopausal women
Bisphosphonates: Taken to stop cancer spread to the bone and reduce risk of fracture
Side effect is osteochemonecrosis
BP therapy management
Stress the importance of routine dental care to keep a healthy oral cavity and reduce infection
Careful management of oral health and relevant dental procedures can decrease risk of osteonecrosis
Considering the patient’s cancer status, further consultation with a specialist or oncologist prior to any essential dental treatments is encouraged
In non-cancer patients, it is suggested that a patient on bisphosphonate therapy to stop taking the medicine 3 months prior to an invasive dental procedure such as an extraction and to prescribe an antibiotic such as Amoxicillin
detecting oral cancer
Dentist will check lips, gingiva, inside of cheeks and roof/floor of mouth
Appears as a red/white patch, sore that bleeds easily and doesn’t heal, a thick lump or a rough/crusted area
Other signs include numbness, pain, or change in the bite
If there are signs of cancer present, refer the patient to an oncologist for a biopsy
Dentists can only detect cancer but cannot diagnose it
pre chemo
Dental professionals should ensure the patient has all infected teeth removed, gum disease treated, cavities filled and crowns/bridges restored prior to chemotherapy
The patient should use extra-soft nylon bristle brushes and gentle flossing to remove plaque
5000 ppm fluoride toothpaste/gel to mitigate risk of caries
Topical management of xerostomia and oral lesions if need be
during chemo, 4
If patients have a port under skin for medication or feeding, they are often taking anti-blood clotting medications
This can increase bleeding during dental procedures and risk of infection
Weakened immune system which can have bacteria in mouth spread to the rest of the body easily
Infection: Manifests as a sore or sticky, white film. Contact doctor since this can delay cancer treatment.
Xerostomia: recommend use of artificial saliva/fluoride rinse to reduce tooth decay
Sensitive gums/ gum disease: minor tissue swelling from chemotherapy. Treat by topical anti-inflammatory, steroid/antibacterial/antifungal rinse.
Jaw pain: common during radiation therapy near head/neck. Treat using muscle relaxants, exercises and anti-inflammatory medication.
mucositis
Mucositis is when your mouth or gut is sore and inflamed
Occurs because chemotherapy works to destroy rapid growth cells and some healthy cells are also affected
Prevention: Suck on ice chips for 30 minutes before and during chemotherapy to keep oral cavity moist
Rinse with alkaline saline mouthwash that includes ½ teaspoon of baking soda and ½ teaspoon salt in 16 ounces of water. Rinse 5 times /day
Also can give saliva substitutes, topical anesthetics, cellulose film-forming agents, antacid solution
Post- treatment
Patient should visit the dentist regularly, since the effects of cancer treatment can include tooth decay as a result of dry mouth
Brush twice a day with fluoride toothpaste + floss
Avoid tobacco and alcohol
Eat nutritious foods to boost immune system