Update
In Oncology the beginning...sperm meets the egg...
Sperm + egg = zygote
1 cell, 2 cells, 4 cells, 8, 16, 32, 64, 128 100 trillion cells Blastocyst 3 germ layers (first evidence of differentiation)
Differentiation
The process of growing up Start out as an immature, undifferentiated, embryonic stem cell and go through various stages of differentiation to become a mature, fully differentiated adult cell
Ectoderm (epithelial cells)
"the outer layer exposed to the environment..." Skin cells--keratinocytes, melanocytes, squamous cells, basal cells Epithelial cells lining body cavities (what body cavities?--think about it!) Epithelial cells line the bronchioles of the lung, the esophagus, the stomach, the GI tract, the vagina, the prostate gland, the bladder, even the ductal linings of the breast (The nervous system also arises from the ectoderm--but it's different--more later)
Endoderm
"innards" Glands (thyroid, anterior pituitary, pancreas, glands that produce milk in the breast, glands that produce mucous in the stomach and colon and lungs) The prefix for gland is "adeno"...
Mesoderm
"filler in the middle" Bones Muscle Lymph tissue Cartilage Fat Bone marrow
Maturation and differentiation--an example in the bone marrow (2 cell lines)
Example of maturation and differentiation
Stem cells Myeloblast (BM) Promyeloctye (BM) Myelocyte (BM) Metamyelocyte (juvenile) (BM) Band neutrophil (BM and PB) Segmented neutrophil (BM and PB)
Loss of control of normal maturation and differentiation in the bone marrow
Leukemia ("white blood") Acute (total loss of control of differentiation) vs. chronic (partial loss of control of differentiation) Which cell line is involved? Myeloid cell line? AML, CML Acute myelocytic (myeloblastic) leukemia (AML), chronic myelocytic leukemia (CML) Lymphoid cell line? ALL, CLL Acute lymphocytic (lymphoblastic) leukemia (ALL), chronic lymphocytic leukemia (CLL)
Back to the basics--Neoplasms
A neoplasm is a "new growth" Once this growth is removed, the pathologist determines whether it is a benign new growth or a malignant new growth All tumors have to have a name, so...
Nomenclature--is it a benign tumor?
Add "oma" to the tissue type Gland--adenoma; a glandular tumor of the thyroid is a thyroid adenoma; pituitary adenoma; adenoma of the breast Bone--osteoma Fatty tumor--lipoma Cartilage--chondroma Smooth muscle--leiomyoma (a smooth muscle benign tumor of the uterus is called a leiomyoma or FIBROID)
Besides nomenclature, what makes a benign tumor "benign"?
It grows slowly Histologically the cells are mature and they "stick" together The rate of division is slow The benign tumor cells may function as normal cells and produce hormones from that tissue, over and above the usual output (thyroid adenomas producing excessive thyroid hormone causing hyperthyroidism; pituitary adenomas producing excessive prolactin causing loss of libido, lactation, and amenorrhea; adrenal adenomas producing excess cortisol and causing Cushing's syndrome)
Benign tumor of the meninges covering the brain
Meningioma Even tho' tumors are histologically benign, they can behave badly by virtue of their location (brain) causing increased intracranial pressure or by virtue of their ability to produce excess hormones Insulinoma--benign tumor of the beta cells of the pancreas wreaking havoc with insulin levels and hypoglycemia
Other characteristics of benign tumors
They can be removed and they don't come back (usually) They generally don't progress to a malignancy The cells do not "shed" and travel throughout the body to seed somewhere else (i.e., they don't metastasize) There are exceptions to all rules of course Neurofibromatosis (Von Recklinghausen's disease)--too many to remove and occasionally they will develop into a malignant tumor
Naming malignant tumors...
Is it a carcinoma or a sarcoma? Carcinomas arise from ectodermal and endodermal derivatives Skin and epithelial cells--lung linings (bronchogenic carcinoma), lining of the breast ducts (ductal carcinoma) Glands lining of the GI tract (adenocarcinoma of the colon); glands located in the bronchioles (adenocarcinoma of the lungs)
More nomenclature
Bronchogenic carcinoma (lung cancer) is subdivided into 2 types Small cell carcinoma (oat cell)(Kulchitsky cell) Non-small cell carcinoma--includes large cell carcinoma, squamous cell carcinoma, and adenocarcinoma
Lung cancer statistics in women
Bigger threat than breast cancer and all other gynecological cancers combined 87% of lung cancers are due to smoking Killed nearly 70,000 women in 2003 Between 1930 and 1997 the death rate from lung cancer rose 600 percent for women, while the rate for men during that period decreased slightly Genetic, metabolic and hormonal factors explain the wide gap between women and men
Naming tumors...
Type of cell can be used as a descriptor Squamous cell carcinoma of the skin, lung, rectum Basal cell carcinoma of the skin Melanocyte of the skin is a melanocarcinoma OR melanoma (shortened version but a misnomer)
Quick digression: Characteristics of a malignant melanoma
Asymmetrical; appearance of a new mole after 40 Borderline irregular; bleeding Color variation Diameter greater than 6 mm Elevation, erythema Funny feeling, fast growing
Incidence of squamous cell carcinoma and basal cell carcinoma has nearly tripled in the last 30 years among women below the age of 40 Rate of BCC and SCC rose to 32 per 100,000 women under 40 in 2003, from 13 per 100,000 in the late 1970s Beach and tanning salons are the culprits American Academy of Dermatology recently found that only half of the 18- to 24-year olds protect themselves from the sun 61% of women 18 and older think they look better with a tan
(Dr. Leslie Christenson, Mayo Clinic; JAMA September 2005).
Naming malignant tumors...
Is it a sarcoma? Sarcomas arise from mesodermal derivatives Bones, muscle, cartilage, lymph tissue, bone marrow, fat
Naming tumors
Sarcomas Bone? Osteosarcoma Cartilage? Chondrosarcoma Fat? Liposarcoma Lymph? Lymphosarcoma (shortened to "lymphoma"--another misnomer as you might think it is a "benign" tumor)
Another digression...
Lymphomas are also divided into 2 major types... Hodgkin's lymphoma (HL) NON-Hodgkin's lymphoma (NHL) Histologic characteristics distinguish the two; presentation is more aggressive with the NHL; age is usually young adults with HL; the very young or the very old are more likely to have NHL
Mesoderm--sarcomas
Chondrosarcoma (cartilage)
Rhabdomyosarcoma Rhabdo = skeletal Myo = muscle
Nomenclature--is it a malignant tumor?
Malignancies are also named and defined by their level of differentiation Immature, embryonic="blast" retino "blast" oma, glio "blast" oma, neuro "blast" oma--rapid growing tumors Undifferentiated--looks embryonic and it may be difficult to determine where the tissue of origin is Poorly-differentiated Well-differentiated
Characteristics of malignant tumors
Malignant--invasive, lack of cohesiveness (basis for the Pap smear), proliferates rapidly Malignant tumors have the capacity to metastasize 72% of lung cancers (especially small cell carcinomas) have mets at dx; 57% of colorectal cancers; 34% of breast cancers The more primitive the tumor (undifferentiated, the more likely it will metastasize)--eg, oat cell, small cell of lung
Brain tumors have their own special nomenclature
Not called carcinomas even though the nervous system is an ectodermal derivative Cell type + "oma" Astrocyte + oma = astrocytoma Glioblastoma multiforme Medulloblastoma Ependymal cell + oma = ependymoma Oligodendrocyte + glioma= oligodengroglioma Brain stem glioma
Grading and staging malignant tumors
Grade I-IV or V--establishes the aggressiveness of the tumor The lower your grade, the better Example: Brain tumors--Grade I astrocytoma vs. Grade IV astrocytoma (glioblastoma multiforme)
Grading and staging
Staging--Stages I-IV establishes the amount of tumor in the body The lower your stage, the less tumor in the body Example: Hodgkin's disease--Stage I (one group of lymph nodes) Also give the stage a letter--IA (without symptoms), IB (with symptoms)
TNM system--tumor size, node involvement, metastases Example: Breast cancer T1, N1, M0 Tumor size, one lymph node group, no distant metastases Staging--T1, N0, M0 is Stage I, Stage IIA is T0, N1, M0, Stage IIB is T2, N1, M0 for examples
Back to the basics of the biology of cancer...
Biologists estimate that more than 100 million billion cells must cooperate to keep a human being healthy over the course of an 80-year lifespan Who's responsible for this maturation and differentiation of cells?
Your genes...
Highly regulated control systems located in the genetic code All cancer cells have serious problems with their DNA; alterations to the DNA inside cells results in cells that have "superpowers"; they can grow anywhere and can continue to divide indefinitely Normal human cells stop dividing after 50-70 generations
Proto-oncogenes
Genes responsible for manufacturing proteins for normal cell growth; turned off and on when needed HER-2/neu is a protooncogene involved with cell growth; when this gene is amplified, cells grow much faster; present in 20-30% of primary breast cancers Amplification of this gene correlates with a poor prognosis in patients with breast cancer
Targeted therapies
Biological response modifiers Monoclonal antibody that targets the HER2/neu proto-oncogene Trastuzumab (Herceptin) for breast cancer patients
Oncogenes
Oncogenes responsible for uncontrolled proliferation of cell growth Suppressor genes--p53 ( a mutation or dysfunction of this suppressor gene is found in the majority of tumors); BRCA mutations and breast and ovarian cancers (ovarian cancer occurs in 2 in 5 women with a BRCA mutation) Normal risk for a lifetime for ovarian cancer without the BRCA mutation is 1 in 75 BRCA gene and breast cancer
Apoptosis--preprogrammed cell suicide
Programmed cell death observed in healthy cells Cancer cells bypass this mechanism altho' some cells of the immune system can sometimes successfully command the cancer cell to self-destruct COX-2 inhibitors and apoptosis--breast and colon cancer Vioxx (rofecoxib) was removed from the market for clotting problems in CV patients (high doses, long-term use for greater than 18 months) Continues to be studied for cancer prevention Aspirin and other COX inhibitors are also being studied EBV produces substances that resemble Bcl-2 (a protein that inhibits apoptosis) and subsequently block cell suicide
Tyrosine kinase
An enzyme required for the uncontrolled growth of cancer cells Targeted therapies--a new class of drugs called the signal transduction inhibitors Inhibit the tyrosine kinase signal Imatinib (Gleevec)--CML Gefitinib (Iressa)--lung cancer (investigational for other cancers)
Epidermal growth factor receptors (EGFR); angiogenesis
Epidermal growth factor (EGF) can fuel the fire, so to speak, as can supplying the tumors with blood vessels Drugs that block the receptor (EGFR) can slow down the growth of tumors Tarceva (erlotinib) (Lung cancer) Cetuximab (Erbitux)--colon cancer (Martha Stewart and ImClone) Bevacizumab (Avastin)--inhibits angiogenesis
Targeted therapies
Thalidomide (Thalomid) inhibits growth factors (IL-6) and angiogenesis (as exhibited in appendage growth when given during the first trimester of pregnancy in the 50's and 60's) Rituximab (Rituxan)--targets a protein marker on B lymphocytes--CD 20. Used to treat B-cell lymphomas
Targeted therapies
Some malignant tumors, especially that those are "male only" and "female only" have receptors for their respective hormones Breast cancer and estrogen receptors ER+ or ER-; If the tumor is ER+ then changing the hormonal milieu is often very beneficial Drugs include nolvadex (Tamoxifen), raloxifene (Evista) --both drugs block estrogen receptors Is there a problem with that? Tamoxifen (agonist/antagonist) Aromatase inhibitors--letrozole (Femara)--inhibits an enzyme that converts estrogen to its most potent form; other aromatase inhibitors
Changing the hormonal milieu in prostate cancer patients is common--blocking testosterone, blocking gonadotropin releasing factor/hormone (Lupron) In the "old days" men with prostate cancer were given estrogen (DES) to change their hormonal environment
Let's change gears for a moment and talk about "normal proliferation"... Normal growth, maturation and differentiation of cells
Normal proliferation...most occurs during fetal life; as adults, cells divide as needed to replace lost cells--epithelial cells do the most dividing
Dividing cells are more prone to the loss of the control of growth and DNA mutations The older the cells, the more prone to loss of control--who gets skin cancer? Skin (epithelial) cells--how often? Sunlight and turnover Sunburns as a kid Is sunlight a double-edged sword?
Vitamin D and other epithelial cell cancers...
Liquid sunshine...
Normal proliferation--cells lining the bronchioles
Respiratory cells--how often? Cigars, cigarettes, cigarillos, pipes, passive smoking Asbestos
Normal proliferation--cells lining the gastrointestinal tract
How often do you replace cell lining the gastrointestinal tract Sloughing cells and dead bacteria Genetics and cellular turnover time High fat diet, low fiber diet, high nitrosamines
Breast ductal linings--prolonged hormone stimulation?
Estrogen or progesterone? New evidence? Maybe progesterone in PMF LIFETIME exposure to hormones Long period of periods When did you start your periods, when did you stop your periods? Did you have a period of not having periods? Women's Health Initiative And, now what about hormones?
Like when you were pregnant...
Number of kids Kids before the age of 20
Or breast feeding...
Age and risk for breast cancer
1/2044 @ 20 1/249 @ 30 1/67 @ 40 1/36@50 1/29 @ 60 1/24 @ 70 1/9 @ 80 1/8 @ 90
Prostate epithelial cells...
The older you are, the higher the risk Epithelial cells and turnover A lifetime of testosterone The prostate increases in size with aging
So, then...what are the 5 most common cancers in the U.S.?
Skin Lung GI Breast Prostate All of which have epithelial cells that continue to grow throughout life-- "exposed to the environment, exposed to hormones" and have the potential for growth disturbances
Other tissues that divide constantly
Bone marrow White blood cells Red blood cells Platelets Leukemia is a cancer of the bone marrow AML (t15:17) CML (Ph chromosome--t9:20) In children, the lymphocyte is the most rapidly dividing cell--hence, ALL is most common in kids
Bone turnover
Bone growth spurts During the first year And at puberty Older adult also has more bone turnover Highest risk for bone cancer is as an adolescent and as an older adult Adult with Paget's disease Big dogs vs. small dogs
Tissues that have the capacity to divide but only do so as necessary...
Liver undergoing active regeneration due to ETOH abuse Hepatitis B and C--active hepatitis Inflammation and cancer
Renal tubular cells
Acute tubular necrosis (ATN) with acute renal failure Renal tubular cells have the capacity to regenerate
Tissues that "never" have the capacity to divide--well, almost never...
Neurons--brain tumors involving neurons are RARE The majority of brain tumors involve the "glial" or supporting cells of the central nervous system Myocardial cells--cancers of the heart muscle are extremely rare Skeletal muscle cells in teenagers and adults-- tumors are rare
Factors that can cause a change in the growth of tissues...
Radiation Sunlight Chemicals--asbestos, benzene, nitrosamines, pesticides ? Viruses--HBV, HCV, HPV, EBV Bacteria (1)--Helicobacter pylori Genetics--who's yo' daddy (or momma)?
Factors that can cause a change in the growth of tissues...
Hormones--growth hormones such as insulin-like growth factor, growth hormone, estrogen, progesterone, testosterone Obesity--increased hormone production in fat tissue-- especially abdominal fat tissue Chronic inflammation--ulcerative colitis, celiac disease, Crohn's disease, rheumatoid arthritis, hepatitis
Growth disturbances
May be precursors to the "loss of control" and the development of cancer Fertile soils, so to speak BUT, the growth disturbances are NOT cancer, and they are reversible once the inciting stimulus is removed What are these growth disturbances? Regeneration, hyperplasia, metaplasia, dysplasia
Growth disturbances
Regeneration--regrowth of damaged tissues (cuts, burns, the ovary following ovulation, skin damaged by sunlight, chronic liver infection with viruses, chronic alcohol and the liver) Chronic hepatitis C + alcohol = high risk (100 x greater) for the loss of the control of growth resulting in hepatocellular carcinoma and cirrhosis
HPV and cancer
Cervical cancer Cancer of the vulva Rectal cancer Penile cancer Oral cancer
Growth disturbances
Chronic inflammation and regeneration Helicobacter pylori Gastric ulcers Gastric carcinoma
Growth disturbances
hyperplasia too many cells Physiologic hyperplasia--breast cells at puberty Pathologic hyperplasia--atypical hyperplasia of the breast
Growth disturbances
Metaplasia substitution of one adult cell for another adult cell Normal cells lining the bronchii--ciliated columnar cells; with constant trauma (smoking, for example)--the cells will "change" to cells that can take the trauma-- squamous cells; this change is known as squamous metaplasia Barrett's esophagus--stomach cells lining the esophagus (columnar epithelial cells)(normal lining of the esophagus is squamous epithelium) Acid reflux and irritation of the lower esophagus might play a BIG role Take those PPIs!!
Metaplasia (the substitution of one adult cell for another adult cell usually as an adaptive substitution)--intestinal metaplasia and Barrett's esophagus (intestinal metaplasia vs. the normal stratified squamous cells of the lower 1/3 of the esophagus)
Growth disturbances
dysplasia--abnormal cell size and architectural arrangement of cells
cervical dysplasia; dysplastic nevus (mole) low-grade vs. high-grade dysplasia in patients with ulcerative colitis
Growth disturbances
All of the aforementioned growth disturbances are considered "reversible" If the inciting stimulus is removed How long do the changes take? An example of cervical cancer Changes may take 16-25 years Human papilloma virus initiates the changes Co-infected with HIV or HSV? promotes the changes
CANCER PREVENTION
Annual check-ups--breast, prostate, skin Colonoscopies every 10 years Pap smears HPV vaccine is now available!! YES! When should it be given? Eat right Exercise Stop smoking Lose weight
Mammograms every year starting at 40**
Everybody over 50--colonoscopies every 10 years
Yearly stool samples for occult blood
Guys, get those prostates checked! (starting at age 40)
Comments from patients during rectal exams:
James Ralph)
(Dr.
"Find Amelia Earhart yet?" "Can you hear me NOW?" "Hey, now I know how a muppet feels..." "How long have you been in politics?" "Remind me never to become an altar boy." "Could you write me a note for my wife, saying that my head is not, in fact, up there?"
Young guys, examine those testicles!!
Heat and testicular cancer? Undescended testicles Plastic diapers? Laptops?
Weight loss...
Abdominal obesity and cancer... inflammation
NHL -- +95% Breast (PMF) 112% Pancreatic -- +176% Kidney -- +375% Colorectal -- +46% Ovarian -- +51% Uterine -- +525%
Breast cancer prevention
Failure to limit adult weight gain may account for one-third of all breast cancers (Thompson HJ,
Cancer Prevention Laboratory @ Colorado State University, Fort Collins, CO)
Weight gain of more than 11 pounds as an adult, along with less than 30 minutes of physical activity daily, is linked to an increased risk of breast cancer
Cancer prevention
Does HT increase your risk of breast cancer? HT--yes, slightly ET only--no, maybe Fat tissue and hormones?
Foods and cancer protection
Indole-3 carbinols--huh? Brassica veggies Broccoli, Brussels sprouts Cabbage May reverse the changes observed with cervical dysplasia
And don't forget your cauliflower...
"Cauliflower is nothing but a cabbage with a college education." ---Mark Twain (1835-1910)
Do forget your french fries... acrylamides (?)
Is soy protective? Depends on when you add it to your diet...
Add 25 gm of soy products per day--soy beans, soy milk, soy burgers, soy sauce (not!) at puberty NOT at menopause
Cut back on grilling...if you have to grill, marinate the meat (in a sweetened oil and vinegar sauce overnight to reduce HCA formation)
Most of the HCAs are found in the crisp black outer crust of the steak or meat that has been grilled, so the more the meat is well done, the higher the risk. Microwave to precook it before grilling. Microwaving evaporates much of the water, zapping the HCAs in the process Flip the burgers constantly Add fruit to the meat before it is grilled, such as ground tart cherries, and reduce the HCA content by up to 90%.
(Science News 155;264:1999)
Cut back on the booze...
Folic acid supplements Alcohol is on the list of "probable cause" for cancers of the colon, rectum and breast; "convincing cause" of cancers of the mouth and pharynx, larynx, esophagus, liver, and "possible cause" for lung cancer.
Sip a bit of tea...
Green or black--but not herbal tea. Polyphenols--catechins may have a couple of ways they protect against cancer Decrease the division of cells Increase the excretion of carcinogens Anti-angiogenesis BMJ 318:1086, 1999; Nature 398:381, 1999; Medical Tribune 39#9:13, 1998 and 40#9:2, 1999.
Coffee enemas
With the re-emergence of complementary and alternative therapies, daily coffee enemas have re-emerged as detoxifying agents in an alternative cancer therapy program known as the Gonzalez/Kelley treatment regimen for pancreatic cancer.. The mechanism of action --smooth muscle relaxation of the hepatic ducts resulting in increased secretion of toxins from the liver into the GI tract and out of the body. Rectal administration only
Better yet...
Combine tomatoes with broccoli-- synergistic action Eat whole foods, not supplements! Cook the tomatoes--increase potency Add a bit of olive oil...
Eat grapes...
Loaded with ellagic acid which blocks the body's production of enzymes necessary to stimulate cancer cell growth Packed with phenols and antioxidants as well Other foods: apples, strawberries, raspberries
Colon cancer prevention--dietary changes
Don't forget fiber Vitamin D detoxifies our digestive juices Increased folic acid converts homocysteine to methionine which protects DNA from damage Calcium also plays a role in colon cancer prevention
Exercise
Stop smoking
Chemicals and by-products of cigarette smoke Head and neck cancer Lung cancer Bladder cancer Cervical cancer in the presence of HPV
Vitamin D
Get that prostate out in the sun But don't do it halfassed...
P S A -- a p r o t e i n l o c a t
Get the whole thing out in the sun where there is plenty of vitamin D!!
Thank you.
Barb Bancroft, RN, MSN, PNP
[e-mail] www.barbbancroft.com