Biology of Cancer - Ch.1

Hyperplasia

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

Sir Percival Pott

- 1775, England- first epidemiology of cancer, chimney sweeps contracted scrotal cancer from exposure to tars in soot of the chimney. First recommendations on prevention- washing, clothing etc.

Gardner's syndrome

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

Kidney Cancer

-Causes: unknown-Kidney stones only recently have been associated with calcifying nanoparticles (CNPs) -There is some evidence that nitrosamines can cause kidney cancer. -Phyletic studies: Studies of other phyla of animals. In this case the causation of kidney cancer in Frogs (Lucke adenocarcinoma) may shed light on the possibility of a herpesvirus in the causation of human kidney cancer. -Etiology= causation.-are multi-factorial (many) for a given cancer -Routes of metastasis= lymphatics and bloodstream. -Staging of tumors = 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.

Metaplasia

-Change -One adult cell type replaced by another -smokers exhibit this because all their tall sexy ciliated columnar cells in their blackened, dirty, filthy, disgusting lungs are replaced by flattened, ugly, alien cells call squamous.

Pancreatic Cancer

-Evidence suggests a strong role for nitrosamines in causation . -nitrate containing meats - hot dogs, preserved sandwich style ham, turkey. You can even get these meats smoked in order to contain additional carcinogens -Nitrosamines and smoking are great high risk factors for pancreatic cancer and contain some of the most powerful carcinogens known. -Obesity is a known risk factor o Insulin-like Growth Factor (IGF) -1 is an important growth factor that you need to stimulate and nurture your mutated cancer cells. It may help you get diabetes (a risk factor for pancreatic cancer) as well. Cancer cells have increased levels IGF receptors on their surface which increases their response to , insulin and IGF-1. -soft drinks o high levels of phosphate as phosphoric acid o high calcium-phosphate diet allows you to grow billions of calcifying nanoparticles which lodge in the pancreatic ducts and tissues and produce calcification or deposits of calcium phosphate. -Alcohol oPancreatic Calcinosis is most frequent in alcoholic pancreatitis oAlcohol is a known tumor promoter. -Smoking is a recognized risk factor for pancreatitis and the progression of pancreatitis can be measured by the appearance of calcification.

Anaplasia

-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".

Neuroblastoma

-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.

Stomach Cancer

-adenocarcinoma -cancer is fatal in 90% of cases -half to two thirds of the world's population is infected with a bacterium associated with non-cardia gastric cancer.

Tumor Suppressor Genes

-are NORMAL genes whose deletion or loss of function can likewise lead to cancer. -produce genes tat either directly or indirectly exert a restraining influence on cell proliferation and survival.

Sarcomas

-are cancers that originate in the supporting tissues such as bone, cartilage, blood vessels, fat, fibrous tissue, and muscle. -rarest form of human cancers, accounting for about 1% of the total

Lymphomas (tumor of lymphocytes WBCs) and Leukemias (cancer in which malignant blood cells proliferate mainly in the bloodstream.

-arise from cells of lymphatic and blood origin.

Carcinomas

-arise from epithelial cells that form covering layers over external and internal body surfaces. -by far the most common type of malignant tumor, accounting for roughly 90% of all human cancers.

Colon Cancer

-exhibit a reproducible series of sequential mutations that bring about the progression of the cancer from a benign polyp to adenocarcinoma. -mutagens are believed to be present in the foods we eat (charcoal broiled, fried foods) or produced within the gut from chemical reactions with preservatives in the foods we eat. -Promoters such as bile acids induce cell division of the mutated cancer cells, allowing for selection of additional mutations. -Symptoms: outward signs of disease. these include changes in bowel habits-, blood in stool, pain, obstruction= blockage of colon.

Oncogenes

-genes whose presence can lead to cancer. -arise by mutation form normal genes that code for proteins involved in stimulating cell proliferation and survival -abnormal genes whose activity can lead to cancer

Proto-oncogenes

-normal cellular genes that are important regulators of normal cellular processes, they promote growth. alterations in the expression of these cells result in oncogenes -can be transformed into oncogenes by activating (gain-of-function) mutations

Dysplasia

-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.

Leukemia

-uncontrolled growth of blood cells. -Acute: rapid onset -Bimodal Incidence: Two age groups develop this (young and old) -most pts die of opportunistic infection (not enough diversity in WBC), anemia (not enough RBC) and bleeding (not enough platelets).

Squamous cell cancer

= malignant cancer of epidermal cells. -Solar damage is the most common etiology. The margins are 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. -If this is not effective, chemotherapy and local irradiation may be necessary. -signs and symptoms are reddened, scaly or plaque-like areas that: o are slightly elevated o can develop an ulcer o change over time into a hard pale pink to white nodule o can develop a scaly crust or a wart-like surface o arise from old scars, change colour, begin to bleed, ulcerate, drain, or become painful o commonly appear on face, ears, neck, forearms, backs of hands, and legs

Colon polyp:

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.

pleiotrophic

An allele that has more than one effect on phenotype. -example, inactivation of a single gene, coding for the P53 protein, will cause genomic instability, evasion of apoptosis and increased angiogenesis

Warburg Effect

An observation made in 1925 by Dr. Otto Warburg is that cancer cells (most) do not respire! They use anerobic glycolysis to obtain 2 ATP from one glucose molecule. Normal cells fully oxidize or "burn" glucose to yield 38 molecules per glucose. Why? Can we target and kill cancer cells because of this difference?

-Mouse mammary tumor virus (discovered by Bittner)- recent studies found 30-70% of HUMAN breast cancer tissue samples contain this mouse virus -Identification of human papillomavirus DNA gene sequences in human breast cancer.

Are any viruses associated with the cause of breast cancer?

Ductal Carcinomas

Breast Ca originating from milk ducts

Lobular Carcinomas

Breast cancer originating from milk supplying lobules

1. uncontrolled growth (division beyond the normal limits), 2. invasion (intrusion on and destruction of adjacent tissues), and sometimes 3. metastasis (spread to other locations in the body via lymph or blood). Layman's term of tumor-can be benign or malignant. Note: The development of cancers requires progression (accumulation of malignant properties over time)

Cancer or malignant neoplasm is a class of diseases in which a group of cells display at least What three properties?

FYI

Cancer-causing mutation can be triggered by chemicals, radiation, or infectious agents, or they may arise spontaneously, arise from errors in DNA replication, or be inherited. Regardless of these differences in how they arise, caner-related mutations affect the same two classes of genes: 1. Oncogenes 2. tumor suppressor genes.

Stomach Cancer FYI

China and Asia are high incidence areas of stomach cancer. Antibiotic therapy to eradicated H. pylori has decreased the incidence of non-cardia stomach cancer by 40%! Don't delay ulcer treatment. There is a suggestion that eradication of H. pylori increases the risk for the cardia form of stomach cancer.

a tyrosine kinase which Gleevec can target successfully. However, resistance to the drug eventually occurs.

Chronic leukemias such as chronic myelogenous leukemia (CML) exhibit a specific gene fusion that produces What?

Mesenchymal cell

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

The reproduction of peer reviewed articles

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

epigenetic changes (changes in the histone patterns on genes and micro RNAs), others by inflammation or hypoxia (low oxygen levels in the tumor).

Not all the changes in the developing ca cell are mutations, some are brought about by what?

a 'liquid biopsy,' which essentially involves sampling of circulating tumor cells (CTC) and/or cell free nucleic acids (cfDNA, including microRNA (miRNA)) present in blood and lymph [12-16].The rationale for liquid biopsy is that tumors shed cells and/or genetic fragments into the circulation, theoretically making the blood representative of not only the primary tumor but also distant metastases

Possible Solution to Core Needle Biopsy?

Liver cancer, melanoma, kidney and thyroid. For some of them, the obesity epidemic may be a factor. In obesity high levels of TNF alpha and IL-6 (inflammatory cytokines) are produced. Obesity results in a persistent inflammatory state, activating STAT3 which can function as a tumor-promoting transcription factor.

Some cancers that are increasing in frequency are what?

Neuroblastoma FYI

Some forms of this tumor can undergo spontaneous regression- change into benign ganglioneuromas which can be removed. We can make neuroblastoma cells differentiate and stop growing in the laboratory by adding cyclic AMP- the second messenger molecule for hormones. The cells transform from a rounded, fast growing little buggar to cells with long dendritic processes resembling the typical nerve cell

Non-cardia

Stomach cancer occurs in any area of stomach except the top inch.

actinic cheilitis,

The most aggressive form of keratosis, appears on the lips and can evolve into squamous cell carcinoma. When this happens, roughly one-fifth of these carcinomas metastasize.

Pathology= study of disease (pathos).

The pathologist must identify the type of cancer the patient is suffering from. Often the clinician or oncologist (cancer physician) can diagnose the type of cancer from symptoms and placement- for example melanoma of the skin. However, the physician can not tell for sure if the cancer has metastasized or exactly what its classification is until the pathologist studies a sample or biopsy. Historically, the pathologist would classify the cancer and examine the regional lymph nodes microscopically. Today, molecular techniques are applied to examine the genetics and phenotype of the cancer cell so that custom treatments can be applied. In this chapter you will learn the terminology the pathologist, clinician, and researcher use.

Malignant neoplasia (nasty new growths).

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

Drugs: are DNA poisons Monoclonal Antibodies: not poisonous; proteins-human, safe for therapy

What are key differences between drugs and monoclonal antibodies?

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. *Two tumor suppressor genes have been identified whose loss (inherited mutations) leads to a high incidence of early onset breast cancer. *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.

What are the Risk factors of Breast Cancer?

1. Acquisition of self-sufficiency in growth signals, leading to unchecked growth. Cancer cells produce their own growth factors or altered receptors that do not need the growth factors. 2. Loss of sensitivity to anti-growth signals, also leading to unchecked growth. Normal cells require ligand binding to receptors to signal growth. 3. Loss of capacity for apoptosis (cell suicide) thus allowing growth despite genetic errors. -Apoptosis is programmed cell death. 4. Loss of capacity for senescence, leading to limitless replicative potential (immortality). -Senescence is aging. 5. Acquisition of sustained angiogenesis, allowing the tumor to grow beyond the limitations of passive nutrient diffusion. -Angiogenesis is the development of blood vessels. 6. Acquisition of ability to invade neighboring tissues ( the defining property of invasive carcinoma) with acquisition of ability to build metastases at distant sites, the classical property of malignant tumors (carcinomas or others). Cancer cells secrete a variety of enzymes that digest surrounding tissues. 7. Loss of capacity to repair genetic errors, leading to an increased mutation rate (genomic instability), thus accelerating all the other changes. -mutations in the genes that control repair of are repair -EX: PL-1-programmed death ligan 8. Cancer cell suppression of the immune system 9. Epithelial to mesenchymal transition (EMT): Most cancers originate from epithelial cells as they are the most exposed to carcinogens (skin, linings of intestine and lung, ductal/secretory tissues of breast, pancreas). 10. Warburg Effect: 11. Epigenetic modifications -Newest but least understood hallmarks:

What are the hallmarks of Cancer?

Ductal: Derived from epithelial cells lining the ducts that drain milk from the lobes. Lobular: Derived from the lobes of the gland.

What are the main types of breast cancer?

-Increase doses of poisonous drugs -acute leukemia divides rapidly, so sucks up all the poisions -young enough to recover from chemo

What are two reasons for success with Leukemia?

Benign Tumor: not cancer -tumor cells grow only locally and cannot spread by invasion or metastasis Malignant Tumor: cancer -cells invade neighboring tissue, enter blood vessels, and metastasize to different sites.

What is the difference between Benign and Malignant tumors?

Skin Cancer most cases however are not deadly

What is the most common type of cancer? Accounts for roughly half of all human cancers.

Metastasis

What is the most outstanding (the ultimate) hallmark of cancer?

Allow cancer to grow more rapidly

What might happen if one blocked the cytokines to prevent the cachexia?

Influenza -immune system is immature or old and also vitamin D deficiency

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

Lung Cancer -cause the most deaths because they are detected late in development and have often spread to distant sites in the body. Colorectal, Breast and Pancrease are the next few.

Which type of cancer causes the most cancer deaths?

occurred because the patient was immunosuppressed

Why is Aspergillus presented in cancerous lung? Did the fungus cause the lung cancer?

Monocytes Osteopontin

____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 ___.

Melanoma

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.

Carcinoma in situ

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.

Ascites tumor

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

Neoplasia

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

Teratocarcinoma

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

Benign neoplasia (benign= kind)

are non-invasive growths, usually encapsulated with fibronectin- hence it looks like a cacoon. When the pathologist slices and dices a "kindly" cacoon of tissue he/she sees highly differentiated, specialized and well ordered cells with few mitoses. He does not see any tissues sneaking across the natural borders (basement membranes etc.) between tissues.

Epithelial cells

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

Bile acids

are secreted from the gall bladder into the intestine in order to solubilize fats for absorption. High fat diet= high levels of promoters. -induce cell division of the mutated cancer cells in the colon

Septicemia

bacterial infection of the blood usually seen in immuno-compromised cancer patients following chemotherapy.

Malignant melanoma

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

Adenocarcinoma

cancer of glandular (adenoma) epithelial cells.

Epigenetic modifications

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.

Colostomy

colon sewn to opening in abdomen= artificial anus.

Cancer

comes from the Latin or Greek word for crab - the appearance it makes as it invades, grow and anchors itself to underlying tissues. -is the layman's term for scientifically correct malignant neoplasia.

Osteosarcomas (bone cancers)

diagnosed in Egyptian mummies. In the middle ages references were made to inherited cancers:"cancer families". References to cancer villages probably reflected environmental causes such as a polluted well.

Regional lymph nodes

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

Pneumonia

infection in the lung, often by bacteria- lung cancer symptom.

Metastasis

invasion/spread of cancer cells into adjacent or distant tissues, often occurring via the lymphatics and blood vessels.

Osteopontin

is a biomarker for pancreatic adenocarcinoma (Koopmann

Aspergillus

is a common mold or fungus.

Mohs surgery

is a precise surgical technique used to treat skin cancer. During Mohs surgery, layers of cancer-containing skin are progressively removed and examined until only cancer-free tissue remains

Actinic keratosis

is a scaly or crusty bump that forms on the skin, also known as solar keratosis, sun spots, or precancerous spots. -The scale or crust is horn-like, dry, and rough- often first detected by touch. -may itch or produce a pricking or tender sensation, especially after being in the sun. -may be a precursor of squamous cell cancer.

Neoplasia

is an abnormal type of tissue growth in which cells proliferate in an uncontrolled, relatively autonomous fashion, leading to a continual increase in the number of dividing cells. -this loss of growth control creates a proliferating mass of abnormal cells called a neoplasm or tumor.

Myeloma

malignant tumors of bone marrow cells

Tumor markers

molecules synthesized by tumors that indicates their presence. -are used in the detection, diagnosis, and management of some types of cancer -this alone is usually not enough to diagnose cancer. -are usually combined with other tests, such as a biopsy, to diagnose cancer. Classic Examples: -CEA= carcinoembryonic antigen, used in prognosis of colon cancer -HCG= human choriogonadotrophic hormone. Seen in testicular tumors that are derived from trophoblast tissue. -ACTH= 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). -PSA= prostate specific antigen Cutting Edge Example: Exosomes that contain certain micro RNAs

Prognosis

outlook of the disease; whether curable and at what stage of the disease.

Small cell carcinoma

poorly differentiated lung cancer with poor prognosis.

Quackery

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

Anastamosis

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

Biopsy

sampling a piece of tissue for analysis by pathology or genetic means.

Bone marrow

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.

Micro-Metastasis

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

Cardia

stomach cancer occurs in top inch of stomach connecting to esophagus.

Complete regression

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

Stroma

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.

Progression

transition from less to more aggressive cancer over time. Many factors can affect the length of time- genetic susceptibility, mutation of tumor suppressor genes, host nutrition, immune status, age of host, psychological well-being, excessive time on the internet, too little diving, skiing or tennis.

Plasias

types of growths. The pathologist can relate to the doctor just how messed up the tissue organization is by the following terms: -hyperplasia -Metaplasia -Anaplasia -Dysplasia -Carcinoma in site

Chemotherapy

use of chemicals that usually interfere with DNA synthesis and induce apoptosis in the cancer cell. -These drugs or chemicals are usually mutagens and toxic to any rapidly dividing cell= hair loss, nausea, diarrhea.

Cachexia

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