question

Three properties of cancer:

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1) uncontrolled cell division 2) invasion of surrounding tissue 3)metastasis (spread to other locations in the body via lymph or blood)

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Eight hallmark biological properties of malignant tumor cells:

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1)Acquisition of self-sufficiency in growth signals 2)Loss of sensitivity to anti-growth signals 3)Loss of capacity for apoptosis (cell suicide) 4)Loss of capacity for senescence (aging) 5)Acquisition of sustained angiogenesis (blood vessel growth) 6)Secrete enzymes to digest surrounding tissue that builds metastasis 7) lack of ability to repair genetic errors 8)suppression of the immune system

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What steps are not needed in Leukemia development?

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tissue invasion and displacement to distant sites

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Inactivation of a single gene, coding for the P53 protein:

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will cause genomic instability, evasion of apoptosis and increased angiogenesis

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Epithelial to mesenchymal transition (EMT)

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originate from epithelial cells as they are the most exposed to carcinogens (skin, linings of intestine and lung, ductal/secretory tissues of breast, pancreas)

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Epithelial cells

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are non-motile, unipolar, oriented, linked up with other epithelial cells via tight junctions, social, sit on top of a basement membrane

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Mesenchymal cell

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full transformation or progression to a highly malignant cell results in a cell that becomes motile, bipolar, disoriented, anti-social, cell that lacks tight junctions and moves about freely in the body

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Warburg Effect

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- cancer cells use anerobic glycolysis to obtain 2 ATP from one glucose molecule. Normal cells fully oxidize or "burn" glucose to yield 38 molecules per glucose -they do not respire but may be target to kill them ***

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Epigenetic modifications

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changes in chromatin (DNA+histones) by histone acetylases and deacetylases, micro RNA regulation of cell phenotypes. These modification patterns can be inherited and/or induced in utero by diet

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Cancers that are increasing in frequency:

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Liver cancer, melanoma, kidney and thyroid. For some of them, the obesity epidemic may be a factor

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Malignant melanoma

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can be a very aggressive and deadly skin cancer, but it is often caught early before it spreads and kills.

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Melanoma

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a cancer of pigmented epithelial cells, caused by excessive ultraviolet light exposure in early childhood. Again early detection- any changes in a mole should be examined immediately

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ABC's of Melanoma

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Asymmetry, Border, Color, Diameter

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Actinic keratosis

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-a scaly or crusty bump that forms on the skin, also known as solar keratosis, sun spots, or precancerous spots - may be a precursor of squamous cell cancer. About 10 to 15 percent of active lesions, which are redder and more tender than the rest will take the next step and progress to squamous cell carcinomas

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actinic cheilitis

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appears on the lips and can evolve into squamous cell carcinoma. When this happens, roughly one-fifth of these carcinomas metastasize. This seldom occurs prior to 60 years of age and the cancer enlarges so slowly and metastasizes so late that one population study found no deaths and minimal morbidity from the carcinomas.

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Figure 2 " Trends in Death Rates"

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Stomach decreasing incidence= refrigeration, anti-oxidants. Uterine decreasing= early detection, Pap smear. Breast/Colon slight decrease= early detection, education about the role of a high fat/low fiber diet. Lung increasing=smoking. Slight decrease in 1990 due to education and decrease in smoking among men

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Neoplasia

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a new growth or swelling (Could be either benign or malignant).

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Benign neoplasia

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non-invasive growths, usually encapsulated with fibronectin- looks like a cacoon. highly differentiated, specialized and well ordered cells with few mitoses. no tissues sneaking across the natural borders (basement membranes etc.) between tissues.

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Malignant neoplasia

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truly cancerous growths have broken out of the cacoon and invaded other tissues (metastasized). look nasty because they are de-differentiated or embryonic-like, have large nuclei seen among cells that are disorganized

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How does a pathologist differeniate maligiant vs benign?

answer

A bone marrow sample is taken (that does hurt) and the pathologist asks: Are there many white blood cells in the bone marrow? Also used are immunophenotyping techniques such as the flow cytometer .

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Why does a leukemia patient (with many lymphocytes) die if untreated?

answer

patient dies from secondary infection

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Hyperplasia

answer

(more) increased cell numbers (gobs of cells in the tissue- but maybe not cancer).

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Metaplasia

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change)one adult cell type replaced by another. Smokers exhibit this because all their tall sexy ciliated columnar cells in their blackened, dirty, filty, disgusting lungs (cough, cough) are replaced by flattened, ugly, alien cells called squamous.

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Anaplasia

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(loss) Although this would make a good name for a daughter, the term really means loss of differentiation or specialization of cells as judged by microscopic or biochemical analysis. "Anaplasia darling, you seem to have lost your special dress- along with your memory".

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Dysplasia

answer

the orderly arrangement of nicely differentiated cells in a tissue is changed. A bad hair day for cells in a tissue-plasia here, plasia there, dys plasia in dat wrong place. Weird looking cells are mixed in with well behaved cells in a tissue.

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Carcinoma in situ

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a confusing term since it translates as: cancer in place. Did we not say that the hallmark of cancer is invasion of adjacent tissues? Well, apparently when pathologists see really, truly aberrant dysplastic, anaplastic cells in a tissue they get all anxious and say it sure as hell looks like cancer in a spot of tissue- cut it out before it does invade or spread.

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-oma suffix

answer

often -but NOT always-means that the tumor is benign: For example: Lipoma, chondroma, neuroma, fibroma are all nice terms to hear from the oncologist. Exceptions are: Melanoma (skin), hepatoma (liver) and synovioma (lining of joints)- these are all malignant even though they end in the suffix -oma. Whose your moma?

question

-carcinoma, -sarcoma, -blastoma.

answer

These indicate malignant growths in epithelia, connective and a variety of tissues respectively. Blastomas look like the innner cell of the blastocyst, hence their name.

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Ascites tumor

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a malignant tumor of any type that has been adapted to grow in the peritoneal cavity of animals.

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Metastasis

answer

a malignant tumor of any type that has been adapted to grow in the peritoneal cavity of animals

question

Stroma

answer

the blood supply and connective tissue which must grow from the host to afford a lifeline. The tumor causes the surrounding capillaries to sprout like weeds in a garden and grow toward it so it can be nourished.

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Teratocarcinoma

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a real terror. These are malignant tumors of all three germ layers and can develop an occasional eye, teeth, hair.

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Tumor markers

answer

molecules synthesized by tumors that indicates their presence

question

CEA

answer

carcinoembryonic antigen, used in prognosis of colon cancer

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HCG

answer

human choriogonadotrophic hormone. Seen in testicular tumors that are derived from trophoblast tissue

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ACTH

answer

adrenocorticotropic hormone. Seen in some squamous cell cancers of the lung. If these tumors produce this hormone the patient's face may look like a big round balloon (Cushing's syndrome)

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PSA

answer

prostate specific antigen

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Osteosarcomas

answer

bone cancer

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Why extended latent period after exposure to tars and other chemicals required before cancer is clinically evident?

answer

time for mutagens to accumulate

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proto-oncogenes

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can convert to oncogenes through mutation

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cancers develop from a single cell that :

answer

suffers repeated mutations or amplifications in a series of growth regulatory genes.

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How might scientists prove that cancers arise from a single cell?

answer

by using molecular markers

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Why are cancers genetically unstable?

answer

they have accumulated mutagens in major cell cycle regulating genes

question

cancers must become vascularized by

answer

the process of angiogenesis

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Describe the genetic makeup of a cancer cell?

answer

cancers become genetically unstable and heterogeneous

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Breast Cancer: Ductal

answer

Derived from epithelial cells lining the ducts that drain milk from the lobes

question

Breast Cancer: Lobular

answer

Derived from the lobes of the gland

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Breast Cancer: Risk Factor

answer

Female, late age, early menstruation, late menopause, few children (all relate to hormonal exposure). Obesity and lack of physical activity (high estrogen levels) and alcohol - both tumor promoters -10% of breast cancer cases are due to mutations of either the BRCA1 gene or BRCA2 genes. Women who inherit these genes may elect mastectomy or surgical removal of the breast, or prevention by taking Tamoxifen (estrogen blocker) because of their high risk

question

Are any viruses associated with the cause of breast cancer? Why would finding a virus associated with a human cancer be of tremendous importance?

answer

-Rous Sarcoma Virus -Human Papilloma Virus -Mouse Mammary Tumor Virus

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Human papilloma viruses (HPVs)

answer

-accepted as being carcinogenic in human cervical and anogenital cancers -HPVs may be transmitted by hand from the female perineum to the breast

question

What is the most abundant source of an anti-cancer hormone? What is the hormone and how does it work? Does the hormone prevent any other diseases?

answer

Steroid D through regulation of cellular proliferation and differentiation as well as inhibition of angiogenesis

question

Regional lymph nodes

answer

immune organs draining the tissue fluid (lymph) from a region such as the breast. They are filtering devices and trap cancer cells

question

What organs do physicians routinely remove for biopsy in a breast cancer patient other than the breast tissue itself?

answer

sentinel lymph node

question

Why do we not test for inherited mutations for breast cancer?

answer

Only 5% of breast cancer is due to familial inherited predisposition.- only when a strong family history is present

question

What two genes are usually mutated in breast cancer?

answer

BRCA1 and BRCA 2

question

Colon Cancer- page 257 text

answer

Most are adenocarcinomas arising from epithelial cells, a few are from stromal cells of the intestine and are called gastrointestinal stromal tumors or GIST

question

Describe the progression of colon cancer.

answer

Colon cancers exhibit a reproducible series of sequential mutations that bring about the progression of the cancer from a benign polyp to adenocarcinoma

question

What preservative do we eat almost daily that is implicated in causing colon, brain, stomach and pancreatic cancers? Why do we eat it? Do any preservatives actually prevent cancers?

answer

Nitrates and Nitrites are used as antimicrobials while antioxidants can reduce oxidative species produced by the mitochondira

question

What induces cell division of cancer cells in the colon, allowing for selection of additional mutagens?

answer

Promoters such as bile acids

question

Bile acids

answer

are secreted from the gall bladder into the intestine in order to solubilize fats for absorption. High fat diet= high levels of promoters.

question

Colon

answer

lower portion of the intestinal tract

question

Colon polyp

answer

A growth that projects, often on a stalk from the lining of the intestine or rectum. Almost always benign, but may if atypical progress to cancer

question

Gardner's syndrome

answer

autosomal dominant inherited (familial) mutation. Familial polyposis is a hereditary predisposition to develop polyps and cancer of the colon

question

Do normal people w/o the inherited gene develop polyps? What can they do if they are found?

answer

yes, they can be scraped out through rectal access

question

Anastamosis

answer

reconnection of intestine end to end after removing tumor or section of the colon containing too many polyps

question

Colostomy

answer

colon sewn to opening in abdomen= artificial anus

question

Micro-metastasis

answer

spread of tumor cells, not detectable as a tumor for months to years later

question

Cachexia

answer

-wasting, anorexia of cancer patient due to cytokines released by immune cells -Cancers cause the release of cachectic substances that cause weight loss -Cachectic substances are immunotransmitters such as tumor necrosis factor

question

What might happen if one blocked the cytokines to prevent the cachexia? Why is an immunotransmitter molecule called tumor necrosis factor?

answer

-reverse outcome with stable body mass -because this cytokine induces apoptosis

question

Quackery

answer

practice of selling non-working cures to cancer patients/families

question

How does one tell quackery from science? What is the litmus test of good science?

answer

clincial trials and dose relationships

question

Leukemia

answer

uncontrolled growth of blood cells

question

What might explain this distribution? What other major infectious illness exhibits this bimodal distribution in terms of death?

answer

the young and old typically have a compromised immune system, many autoimmune and pathogenic diseases are susceptible at this bimodel incidence

question

What are key differences between drugs and monoclonal antibodies?

answer

one is synthetically made of non self molecules while the other is created by the immune system for a specific antigen reponse

question

What are two reasons for success with acute childhood leukemia?

answer

early detection and clinical trials

question

How does Gleevec work as a drug?

answer

Chronic leukemias such as chronic myelogenous leukemia (CML) exhibit a specific gene fusion that produces a tyrosine kinase which can target successfully. However, resistance to the drug eventually occurs.

question

Bone marrow

answer

site of growth and development of blood cells, especially the stem cells that give rise to immune cells. Invasion and displacement of bone marrow by malignant cells prevents normal functioning and replacement of immune cell types

question

Aspergillus is a common mold or fungus. Why is it presented in this cancerous lung? Did the fungus cause the lung cancer?

answer

No, this is a post secondary infection from a compromised immune system

question

Complete regression

answer

term used by physicians to indicate after chemotherapy that the cancer is no longer detectable. In many cases micro-metastasis has occurred

question

Routes of metastasis

answer

lymphatics and bloodstream. How would the clinician know if the cancer had spread- lymph node analysis or wait and see (fingers crossed approach).

question

Staging of tumors

answer

tumors are graded depending on their degree of differentiation, whether they have invaded local or distant lymph nodes. Stage 1 have the best prognosis, stage 4 the worse.

question

Squamous cell cancer

answer

-malignant cancer of epidermal cells -Solar damage is the most common etiology -usually indistinct and the surface smooth, but the lesion can be scaly. A wide variety of colors and textures can be present. Characteristics include possible ulceration, fibrosis, and hyperpigmentation. SCC can metastasize and should receive early treatment to prevent this. Many varieties of SCC exist, and treatment can be excision or Mohs' surgery

question

signs and symptoms of squamous cell carcinoma are reddened, scaly or plaque-like areas that:

answer

-are slightly elevated -can develop an ulcer -change over time into a hard pale pink to white nodule -can develop a scaly crust or a wart-like surface -arise from old scars, change colour, begin to bleed, ulcerate, drain, or become painful commonly appear on face, ears, neck, forearms, backs of hands, and legs

question

Adenocarcinoma

answer

cancer of glandular (adenoma) epithelial cells. This description of the cell type within the cancer is used to classify stomach, breast, colon cancers etc as to their cell type

question

What are the two deadliest cancers?

answer

Stomach and pancreatic cancer is fatal in 90% of cases

question

What preservative is implicated in the causation of the two most deadly cancers? Can you avoid this preservative? What bacterium is implicated in the causation of stomach cancer? Does Dr. Hartmann follow a health diet?

answer

-Helobacterial pylori - Salt -No

question

Neuroblastoma

answer

-Most common tumor of children in the US. A tumor of undifferentiated or embryonic nerve cells. It occurs in infants and young children. It is rarely found in children older than 10 years. The cells of this cancer usually resemble very primitive developing nerve cells found in an embryo or fetus -can release hormones causing strange changes in the body. The child may have constant diarrhea. Functions of the brain, such as opsoclonus (rotary movements of the eyes) and myoclonus (spastic jerks of the muscles) may also occur. These changes are called paraneoplastic syndromes

question

Pancreatic Cancer (adenocarcinoma) Etiology:

answer

Evidence suggests a strong role for nitrosamines in causation processed meats, no exercise, soft drinks, alcohol

question

Monocytes

answer

migrate from the blood into the pancreas to remove the calcification laid down by the calcifying nanoparticles with that "food" from your soft drinks. In order to bind to the calcium-phosphate surrounded nanons and engulf them, they convert to macrophages and secrete osteopontin (Keating and Hartmann, two patents submitted 2008). Osteopontin is a biomarker for pancreatic adenocarcinoma

question

Pancreatic Calcinosis

answer

most frequent in alcoholic pancreatitis

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