Cells/cancer Flashcards
Tumor
Benign or malignant
Neoplasm
Global term for mass may be malignant or benign
Benign tumor
Non-cancerous growth
Malignant tumor
Cancerous
Cancer
Any malignant growth or tumor caused by an abnormal division of cells
Features of a benign tumor
Slow growth
well-defined capsule
non-invasive
Well differentiated
Low mitotic index
Does not metastasize
Features of a malignant tumor
Rapid growth
Not encapsulated
Invasive
Poorly differentiated anaplastic
High mitotic index
Can spread distantly by metastasis
Cancer cells versus normal cells
Cancer cells do not follow usual cellular control mechanisms, no contact inhibition don’t need a anchor they can grow in suspension and have a long lifespan
They lack differentiation (anaplasia) do not acquire specialized function or organization cells are pleomorphic size and shape is not uniform non-differentiated more malignant
Metabolism divide rapidly able to survive and sub optimal environments where normal cells would die. Use nutrients so none are available for normal cells. Can perform glycolysis without using mitochondria to generate usual ATP but still generate normal numbers of ATP molecules. Despite using anaerobic metabolic pathways, they are able to form lipids and other cellular building blocks or normal cells cannot do this.
Stem cells, normal cells, regenerate, using adults stem cells whereas cancer cells are heterogeneous using cancer, stem cells
Cancer formation
DNA is damaged cell fail to repair activation or growth promoting on genes and inactivation of tumor, suppressing genes results and unregulated cell proliferation alteration in genes that regulate apoptosis clonal expansion (angiogenesis, cells elude immune system and continue to mutate) cells, progressive, tumor, malignancy, or metastasis
-Oma
Tumor or cancer
Carcinoma
Arising from epithelial tissue
Sarcoma
Arising from mesenchymal tissue
Adenocarcinoma
Airing from ducts or glands
Leukemia
Cancer of blood forming cells
Lymphoma
Cancer of lymphatic tissue
Blastomas
Malignancy in precursor cells or blasts common in children
Carcinoma in Situ
Original place has not spread a pre-invasive cancer atypical cells may not have penetrated the basement membrane of the organ no local invasion, but has potential to remain where it is and not change or progress to invade in metastasize or regress and go away the more dysplastic, the more likely it is to be invasive
Oncogenes
Oncogenes are mutated or over-express proto-oncogenes (genes encode components of receptor mediated pathways designed to regular normal cellular proliferation) which are independent of normal regulatory mechanisms they may amplify make numerous copies of mutated genes. This is important for both prognosis and therapy.
Role of inflammatory suppression and cancer
Tumor, suppressing genes (antioncogenes) inhibit or decelerate cellular proliferation suppress oncogenes decrease cellular, growth, mutation, and replication
Role of inflammatory progression, and cancer
Cancer cells use the inflammatory response to their benefit, using the healing and proliferation pathways to support growth and progression. They have the ability to produce chemotactic signals, attracting macrophages producing mediators, decreasing inflammation, increasing proliferation, and angiogenesis
Macrophages decreases toxic response do not kill the cancer cells
T regulatory self change there is no cancer cell destruction. There is production of cytokines lead into cancer, cell proliferation, and spread.
Paraneoplastic syndrome
Rare sometimes the first symptom that there is cancer present, cause not by the cancer itself, but by the inflammatory response caused by the cancer or worsen by the cancer may be life-threatening includes Cushing’s disease syndrome of inappropriate anti-diuretic hormone, hypercalcemia hypoglycemia, polycythemia osteomalacia myasthenia disorders of the central nervous system or peripheral nervous system, acanthosis nigricans, dermatomyositis, hypertrophic osteoarthropathy and clubbing of the fingers Venous thrombosis (trousseau phenomenon) DIC, non-bacterial thrombotic, endocarditis, red cell aplasia nephrotic syndrome
Cachexia
Complex metabolic syndrome associated with muscle loss with or without fat loss in cancer in involves systemic, inflammation negative protein and energy, balance and loss of lean muscle mass again with or without wasting of adipose occurs in 50 to 80% of individuals with cancer implicated in 20% of death related to cancer
Mechanisms include anorexia, decrease secretions of anabolic hormones altered metabolic response with abnormal protein, lipid and carb metabolism. It appears the mitochondria and sarcoplasm reticulum have a role.
Alpha fetoprotein tumor marker
Liver and germs cell tumors
Prostate specific antigen
Prostate CA 
Carcinoembrynoic antigen
Numerous-colon, lung, breast
Bence jones protein
Urine marker for multiple myeloma
Neuron specific enolase
Serum marker for small cell lung CA and neuroblastoma
BRCA 1 and BRCA 2
Gene mutation for breast and ovarian CA
Cancer staging
TNM
tumor spread, node- degree of lymph node involvement and metastasis presence of distance metastasis
Childhood cancer
Rare but leading cause of death most originate in the mesodermal germ layer fast growing 80% metastasis 85% cured leukemia is most common in kids under 14. Brain and CNS next aged 15-19 Hodgkin and non Hodgkin lymphomas, germ cell tumors, thyroid, sarcomas
Adult cancer
The more inflammation an individual has the more prone to cancers they will be as we age we accumulate inflammation
Lung cancer
Risk factors-smoking, environmental exposures, chronic inflammation, ionizing radiation, genetic susceptibility, 85% of lung cancer is squamous cell, adenocarcinoma, large cell and undifferentiated
Types-squamous, adenocarinoma, large cell and small cell
Small cell- neuroendormcrine most common 15% of all lung cancers repair growth and metastasis worse prognosis paraneoplastic syndrome hyponatremia, cushings, hypocalcemia, carcinoid syndrome, lambert Eaton myasthenic syndrome
Metastasis to brain and beyond common
Esophageal cancer
6th leading cause of death worldwide
Types-squamous cell carcinoma (esophageal cancer belt) and adenocarcinoma
Adenocarcinoma seen more in developed countries, poorer prognosis 5 years survival less than 20%,
Squamous cell- due to low fruit and veggie intake. Low zinc, hot food, and beverages, smoking, lifestyle, environment, overweight, obesity, Barrett’s, GERD
Metastasis common to lymph, liver, lung, bone, adrenal, brain
Colon cancer
3rs most common CA death early detection means survival
Risk- genetics, family hx, familial adenomatous polyposis, T2DM, IBD greater than 10 years, smoking, obesity, physical inactivity, processed meats, high fat, red meats, low fiber
S/s- polyps, early tumor asymptomatic, late symptoms depend on location, range from discomfort to pain, change in bowel habits, transverse and descending colon may have obstruction, transverse and ascending may have anemia, sigmoid rectum descending may have BRB, blood in stool
Patho- polyp of CRC, 10-15 years
Screening!!
Metastasis to liver, lung, urinary, lymph, stomach
Pancreatic cancer
Poor prognosis-late stage when diagnosis and poor treatment
Most common pancreatic ductal adenocarcinoma
Risk- DM2, pancreatitis, smoking, obesity, age >65, alcohol, family history, BRCA2, K Ras gene, lynch syndrome, familial atypical mult mole melanoma syndrome (FAMM)
Early stage asymptomatic, late stage- abdominal pain, lateral abdominal, back, loss of appetite, weight loss, jaundice, light colored stool, dark colored urine, itching; fatigue, arm leg pain or edema due to clot
Metastatic to liver, stomach, perineum
Ovarian cancer
Risk- age greater than 63 years, more common in whites, genetic mutation BRCA 1 and 2
No sx until advanced then GI symptoms
Metastasis to peritoneal, diaphragm, omentum, liver
Endometrial cancer
Uterine most common in post menopausal women late 50-early 60s prolonged exposure to estrogen without opposing progesterone, obesity, DM, HTN, gallbladder disease, family hx of colon endometrial or ovarian CA
Arises from glandular epithelium of uterine lining
Vaginal bleeding post menopause is never a good sign, weight loss late stages
Metastasis to lung, lymph, liver, ovary
Testicular cancer
Young to middle aged men. Cure rate 90% risk factors ?
Maybe genetics hx of cryptorchidism, abn testicular development, HIV/AIDS, Klinefelter syndrome
Painless mass with Mets, lumbar pain can cause CNS symptoms
Metastasis to lung, liver, lymph
Prostate cancer
Men 65+, advanced age, family history, genetic BRCA 1 and 2 mutations other tumor suppressors, +- diet, infection, hormones, trauma, urinary reflux, dietary carcinogens, inflammation
No sx until advanced usually bladder outlet obstruction can lead to rectal obstruction
Imbalance estrogen and androgen in prostate epithelial cells cancer cells proliferate
Metastasis to liver; bone particularly lumbar spine, brain follow sx of organ
Breast cancer
White women highest rate black women highest mortality
HR + and HER2 negative (most common) 10% triple negative 10% HR + HER2 *
Risk greater than 55 years, genetics BRCA 1 and 2 and family history, alcohol, radiation, hormone use, obesity
Screening mammograms
Polycystic ovarian syndrome
Obesity
3X risk of uterine CA increased metabolic syndrome and DM
An ovulation, obesity, hirsutism, hyperabdrogenism, infertility 20% asymptotic, insulin resistance, LH, DJEA, testosterone, androstenedione, prolactin, leptin, maybe decreased Insulin like growth factor 1 receptors HLD, DM, CVD, endometrial hyperplasia, carcinoma, OSA, NFLD, gestational DM
hyperandrogenic states
Atrophy
Decrease in size and function
Multiple causes, disuse, decrease metabolic supply
Normal examples in Children-thymus, tonsils, brain, senescent, kidney, ovaries
Patho changes- spinal cord injuries, prolonged bed rest, poor nutrition
Hypertrophy
Increase in size
Overuse, increased strain, increase protein synthesis and metabolic demand
Normal changes- uterus breast in pregnancy
Patho changes- excessive weight lifting, cardiomyopathy
Hyperplasia
Increase in number of cells
Size of organ increases
Normal change- endometrial thinking In prep for pregnancy
Patho change- BPH, anemia state bone marrow hyperplasia
Metaplasia
One cell type replaced by another
Allows cells to better tolerate environment
Not normal
Patho changes- GERD/lung cancer
Dysplasia
Disorganized cellular growth
Chronic irritant exposure
Not normal
Precancerous or cancerous respiratory cervical
Hypoxic ischemia cellular injury
Decreased blood supply decreased oxygen
Mitochondrial injury
Cytochromes are damaged hemoproteins-reduction and oxidation->gaining and losing electrons utilizing enzymes and other proteins help to transfer energy within cell
Failure of calcium and sodium and potassium and sodium pumps
Endoplasmic reticulum protein factory for the cell fails to work
Cytoskeleton failure that cannot be reversed
Calcium influx injury
Calcium into the cell increase sodium increases in extra cellular potassium increase in cellular edema d/t increase of sodium in cell damage to cell membrane proteins ATP nucleic acid RNA, increase in intracellular calcium activated enzymes resulting in cellular death
How do we know there is cellular injury
Lysosomes digest cytoplasmic reticulum, and nuclear components, lysosomes leak into the blood, hydrolysis, elevated lactate, troponin and transminases in labs
Reperfusion injury
Oxygen is reintroduced to the cell first cells have to have had decrease in O2, increase ATP to the cell, cell is injured cannot handle influx of energy, creates increase in ROS, and oxidative stress this is usually broken down but due to the injury the cell isn’t able to work as fast as needed results in damage to cell membrane
Oxidative stress
Chronic inflammation over time, aging, DM, cancer, autoimmune,
Reactive oxidative species subset of -free radicals (hydroxyl radicals, superoxide, H2O2 and NO) pathological cell communication
Electrically charged- missing a paired electron and it goes around looking for it, binding to carbs, lipids, proteins and DNA, antioxidant enzymes decrease free radicals like vitamin C, E and flavonoids, beta carotene
Chemical agents that can cause cell In jury
Cell membrane affected
Calcium influx
Multiple small insults over time or one large one
Therapeutic drugs- Tylenol small vs large dose can cause hepatotoxicity
Non therapeutic drugs-arsenic-replaces phosphate in ATP damaging mitochondria, cyanide-blocks use of O2 intracellularly
Lead
Found in soil, dust, water
Disrupts calcium homeostasis, cells uptake lead instead other elements (zinc, iron, magnesium) vitamin D no safe level in kids
Neuro, MS, endo, reproductive, dental problems
Mercury
Liquid at room temp, ok if in a vessel, contaminates in soil can be inhaled via skin, water, fish, seafood. Binds with protein lipid soluble can cross BBB, accumulates in the brain causes overproduction of NO and other free radicals cellular necrosis speeds apoptosis
Ethanol
Absorbed in stomach and small intestine-liver-detoxified liver enzymes convert to acetaldehyde when the alcohol is metabolized it generates ROS, they damage the proteins of DNA and lipids causing cell death and necrosis, body also identifies it as a carb and choose it over nutritional sources alcohol nutritional deficiency (mg, B6, Thiamine, folic) this alters protein synthesis
Peripheral and brain neuropathy, wernickes, hepatotoxicity, cirrhosis, impaired mitochondrial function portal HTN
Carbon monoxide
Colorless odorless gas, wood burning, combustible engine exhaust, propane, charcoal cooking
Binds to hgb carboxyhemoglobin this is very stubborn and hard to get off the hgb and cannot carry o2 when bonded cells don’t get o2 resulting in injury ischemia and death positing js considered with CO2 greater than 10%
Feel BAD, dizziness, confusion, SOB. Increase o2 hyperbaric
Physical agents that harm cells
Temperature hypothermia slows everything down no ATP production means cellular death
Hyperthermia speeds metabolism increasing the release of ROS, cells cannot keep up and results in injury and death
Radiation- gamma, xray, neutron
Increase activity in the cell, disorganized cellular function
Stochastic -no threshold level of dose safe like in nuclear weapons
Deterministic- safe dose
Mechanical stress that cause cellular injury
Cells are rearranged, interferes with communication and protein synthesis
Compression, crush, pressure, tension, stretching, torsions, twisting, shearing or pulling
Necrosis
Atypical not planned cell components leak from cellular membrane into ECF rules In Release of inflammatory substances
Apoptosis
Programmed cell death expected and planned requires ATP does not result in release of inflammatory substances
Autophagy
Cell destruction for survival cells are stressed lysosome go to work to catabolism cellular components savings good and getting rid of autophaging the bad stuff
Requires energy also happens in CA and dementia
