CANCER INTERVENTION JUSTIFICATION Individual Rough Draft

DIRECTIONS PAGE 1. Complete the INDIVIDUAL RESEARCH (this document). *Please use the sources that were assigned to you (see Pilot). a. Due Tuesday at the beginning of class: Research on specific cancer type b. Due Thursday at the beginning of class: General characteristics of cancer 2. Combine your INDIVIDUAL RESEARCH with your group to create your FINAL CANCER INTERVENTION JUSTIFICATION. Due date TBA. a. CANCER STORY - Combine your research on your specific cancer type and general characteristics of cancer with your group. As a group, 1000 word (maximum) description telling the STORY of your cancer. You may use pictures or graphics to illustrate your point. You must use ALL sources (cite using APA). Use 12 point, Times New Roman, 1 margin, and please make youre your formatting is professional. Please address the following questions: i. How do the cells in your cancer become cancerous? ii. Once the initial cell becomes cancerous, what happens next? iii. How does your cancer spread? iv. How can your cancer be treated? v. What happens if your cancer is untreated? b. INVERVENTION JUSTIFICATION - Write a 1000 word (maximum) INTERVENTION JUSTIFICATION. i. Given what you told in your story, why did you pick your specific intervention focus (early detection, prevention)? ii. How will your intervention change the story?

CANCER INTERVENTION JUSTIFICATION Individual Rough Draft

INDIVIDUAL RESEARCH Specific Cancer Type Cheyenne Benson Melanoma

A. ABCDEs of Melanoma 1. Asymmetry If its got symmetry, its a mimicry 2. Borders Kansas is fine, borders like Benin? Hardly benign 3. Color If it comes in all shades, youve got it in spades 4. Diameter Too far across? Worse than Hamas 5. Evolving If its changed, an appointment must be arranged B. What IS Melanoma? 1. Dangerous most dangerous form of skin cancer kills 8,790 people in US a year causes most skin cancer deaths, despite not being most common C. Warning Signs 1. Self-exams Spots that wont stop bleeding or oozing (basal and squamous) Ugly duckling: be suspicious if it looks or feels different than a mole D. Causes and Risk Factors 1. Sun Exposure UVA and UVB rays cause damage to DNA (which as we know causes cancer) 2. Dysplastic Nevi Abnormal moles, but not melanoma: harmless 3. Skin Type Fairer skin at higher risk 4. Personal History Any type of skin cancer, if had once, can reoccur 5. Weakened immune system HIV/AIDS, chemotherapy, organ transplant, extreme sun exposure immune system has harder time fighting cancer

CANCER INTERVENTION JUSTIFICATION Individual Rough Draft 6. Family History People who have family members with Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM) are at a much higher risk of developing Melanoma 7. Genes Mutations in BRAF (growth control protein) and p53 genes found in 2/3 of melanoma cells analyzed, genetic link E. Prevention Guidelines 1. Stay out of the sun! Seek shade from 10-4 Do not burn Do not use tanning beds Use UVA and UVB blocking sunscreen SPF 15 every day (30 for high exposure) Reapply sunscreen after swimming and sweating 2. Keep newborns out of the sun 3. Perform self-examinations and get checked yearly by physicians F. Types 1. Superficial Spreading Melanoma Most common (70%), often in the young Grows along top layer of skin for a long time before penetrating deeper Can occur in benign mole, mostly in legs for women, trunk in men, lower back for both 2. Lentigo Maligna Mostly found in elderly, most common in Hawaii Also in situ (starts in top layer of skin), like SSM Found on face, ears, arms, and upper trunk 3. Acral Lentiginous Melanoma Also in situ, but penetrates much faster/found mostly in African-Americans and Asians Found under nails, soles of feet, and palms of hands 4. Nodular Melanoma Usually already invasive by time of diagnosis 10-15% of cases, most aggressive frequent locations are trunk, legs, and arms, mainly of elderly, as well as scalp in men G. Stages 1. Tis: tumor in situ, T1a through T4b determined by measuring tumor in mm and any ulceration Stage Tis. The tumor is in situ and remains non-invasive in the epidermis. Stage T1a. The tumor is invasive but less than or equal to 1.0 mm. Stage T1b. The tumor is less than or equal to 1 mm thick. It is ulcerated. Stage T2a. The tumor is 1.01-2.0 mm thick without ulceration. Stage T2b. The tumor is 1.01-2.0 mm thick with ulceration.

CANCER INTERVENTION JUSTIFICATION Individual Rough Draft Stage T3a. The melanoma is 2.01-4.0 mm thick without ulceration. Stage T3b. The melanoma is 2.01-4.0 mm thick with ulceration. Stage T4a. The tumor is thicker than 4.0 mm without ulceration Stage T4b. The tumor is thicker than 4.0 mm with ulceration. 2. Stages 3 and 4 Tumor has spread to lymph nodes, ulceration still measured, any metastases by sentinel node Tumor has spread past lymph nodes in area, gone into major organs (frequency: liver, brain, bone, and gastrointestinal tract) H. Treatments 1. Outpatient Surgery Melanoma simply removed surgically if it has not metastasized (sometimes sentinel node removed as well as precaution) Can be done cosmetically as well 2. Setting the Margins Margins around tumor are surgically removed as well, based on size of the tumor When there is an in situ melanoma, the surgeon excises 0.5-1 centimeter of the normal skin surrounding the tumor and takes off the skin layers down to the fat. In removing an invasive melanoma that is 1 mm or less in Breslows thickness, the margins of surrounding skin are extended to 1 cm and the excision goes through all skin layers and down to the fascia (the layer of tissue covering the muscles). If the melanoma is 1.01 to 2 mm thick, a margin of 1-2 cm is taken. If the melanoma is 2.01 mm thick or greater, a margin of 2 cm is taken. 3. Mohs Micrographic Surgery Was considered most effective at removing basal cell and squamous cell tumors, now being used for melanoma as well One layer of tissue of tumor removed at a time After each layer removal, margins re-checked whittling the tumor down 4. Stage 3 and 4 Treatments are more desperate and intense Chemotherapy Immunotherapy/Biotherapy (target cancer cells and mark them for destruction) Gene therapy (injecting correct genes) Chemical peeling (peeling layers of tumor off using chemicals) Laser therapy (used to carve tissue off for people with thin blood) Photodynamic therapy (cancer cells absorb certain light, marks them for destruction by drug) Radiation therapy (radiation applied to site of tumor to stop cell growth)

CANCER INTERVENTION JUSTIFICATION Individual Rough Draft I. What is skin cancer? 1. Uncontrolled growth of abnormal skin cells Occurs when DNA in skin is damaged and goes unrepaired This is usually caused by exposure to sunlight from outdoors/tanning beds (UV radiation) Damage to DNA causes cancer cells to divide uncontrollably, making a tumor 2. Actinic Keratosis Most common precancer (wart-like protrusions that develop in skin that gets a lot of sun) Untreated, these can advance to squamous cell carcinoma Estimated to be more than 58 million Americans with AK (also called Solar Keratosis, SK) 3. Basal Cell Carcinoma Most common form of skin cancer Cancer that occurs in deepest layer of epidermis (outermost layer of skin) Almost never metastasizes, but can be disfiguring if not treated promptly 4. Dysplastic Nevi Atypical but benign moles that resemble melanoma in appearance Appear to be passed down genetically The more dysplastic nevi a person has, the higher their chance of developing melanoma 5. Melanoma (see notes above) Most deadly form of skin cancer Very deadly because it metastasizes and shuts down organs where it spreads Treatable if detected early One of the more easily detected forms of cancer (ABCDE) 6. Squamous Cell Carcinoma Cancer in the squamous cells, which are in the epidermis Looks like a wart or sore, may weep, bleed or crust Caused by cumulative UV exposure across a lifetime Disfiguring if allowed to grow, can become deadly J. Prevention 1. Tanning Every time you get a tan, your skin is being exposed to UVR (UV rays) UVR damage the DNA in skin cells, tanning is an attempt to block out UVR to save cells Tanning bed users: 2.5 times more likely to get SCC and 1.5 times more likely to get BCC Only one sunburn increases risk of melanoma, five sunburns doubles lifetime risk 2. Sunscreen Sun Protection Factor: skin exposed to UVB w/out burning w/ protection vs w/o protection SPF 15 prevents sunburn 15 times longer than if no protection was used SPF 15 blocks 93% of UVB rays, SPF 30 blocks 97%, SPF 50, 98% Even on overcast days, 70-80% of UVR still gets through

CANCER INTERVENTION JUSTIFICATION Individual Rough Draft

INDIVIDUAL RESEARCH General Characteristics of Cancer Cheyenne Melanoma

[Due Thursday, 3/6/2014 at the beginning of class] Please research general characteristics of cancer. Use the sources assigned to you (posted on Pilot). Take outline notes using the template below you may MODIFY this as needed (recall the outline notes model for cell division). A. Nature of Cancer 1. Tumors Many different types of tumors Cancer is a tumor Some tumors are benign, some are not Cancer tumors are malignant 2. Examples Nevus (plural nevi), like dysplastic nevi in melanoma Vocal cord modules: another form of benign tumor Tumor is not defined as malignant or benign based on size Salivary gland tumors: can be enormous, but benign 3. Malignance and Metastases Malignant tumor: known as a cancer Malignance determined by invasiveness Nevus: round, smooth, non-invasive Melanoma: bumpy, rough borders, invading in three dimensions, will get into blood When a malignant tumor reaches a blood vessel and travels to new organs: metastasis Metastases: causes of death in cancer Tumors must recruit blood vessels in order to grow greater than 1/10th inch in diameter Dont all just metastasize through blood: colon to liver gets through hepatic portal vein All tumors have an abnormal ratio between cell birth and cell death, in normal cells, for every death of a cell a new one is born, for tumors, there is too much cell birth and too little cell death (apoptosis!) Only takes slight imbalance in ratio to produce monstrous size over time Normal cells: mitosis produces two cells, one dies as left-over Tumor: mitosis produces two cells, both stay alive

CANCER INTERVENTION JUSTIFICATION Individual Rough Draft 4. Types of tumors 5. Q&A Q: How is it possible to determine when a benign tumor will become malignant? A: Really no way to predict, can estimate probability, though. Q: Are cancer cells selective in tissues they chose for metastasis? A: Yes, certain cancers only grow in certain tissues in metastatic form. Prostate cancer generally goes to bone marrow, colon cancer generally goes to liver: dont know the reason for it, dont understand basis of metastasis in fact Q: Is it more difficult to control a massive malignant tumor or a metastic one? A: Bigger is not necessarily a problem, some tumors taken out have weighed 250 pounds. Its only a real problem after metastasis has occurred, because you cant take out somebodys liver or lung. Q: Can we cause cells to stop multiplying? A: Yes, thats what cancer therapy is, preventative drugs do this. Unfortunately, this also stops normal cells from growing. B. Theories on what causes cancer 1. In the past Some people thought cancers were caused by viruses Other people thought bacteria/infectious agents caused cancer Some thought it was the immune system going kaput 1. Based on: most cancers appear in middle-age when immune strength decreases Others thought it was a mutation in a specific gene (ding ding ding) 2. Now Cancer is, in essence, a genetic disease, but different than typical genetic diseases Typical genetic diseases: environment doesnt matter, doesnt affect disease Some genes cause increased risk towards a condition, but environment determines outcome Cancer: even more complex than just genes, or just environment and genes Cancer requires more than one mutation: no single mutation causes cancer, its accumulative 3. Clonal Expansion Start out with a bunch of normal cells One of those cells mutates That cell divides and creates two more cells: the ratio is no longer 1:1 The number of this mutant cell grows faster than the normal cells Benign i. Non-invasive, non-life-threatening Malignant ii. Locally invasive, dangerous, can invade surrounding tissues Metastatic iii. Becomes REALLY malignant, spreads

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CANCER INTERVENTION JUSTIFICATION Individual Rough Draft These new mutated cells are clones of the original Once this bunch of mutant cells form a benign tumor, cells in that tumor can mutate again Through a second wave of clonal expansion, this double-mutated cell multiplies This dangerously damaged cell forms a malignant tumor One of the cells in this malignant tumor can mutate again, causing it to be a triple mutant This triple mutant multiplies elsewhere, is metastatic Successive waves of clonal mutations, layering problem over problem Non-hereditary Typically, mutations causing cancer are not inherited but rather acquired after birth Only hereditary mutations are ones that occur in egg and sperm cells Since gametes are very small percent of total cells, genetic cancers are rare Genes mutated in Cancer Oncogenes 1. Normally stimulates cell growth when circumstances call for it Suppressor genes 1. Normally inhibits cell growth when circumstances call for it Repair genes 1. Normally find mutations in genes and correct them When all three of these types of genes are mutated, thats when a cell becomes cancerous Why has evolution done such a crappy job with our DNA system? That would eliminate variety in a population Mistakes are vital for causing good mutations If you had no mutations at all, the species would never advance Everybody has mutations in genetic code, just not usually bad ones Example: Colon cancer Most cases of colon cancer are non-familial: other family members dont have it Two main types of familial colon cancer: FAP and HNPCC FAP: polyposis, HNPCC: non-polyposis Polyps: benign tumors FAP: mostly caused by mutation in ACP (Suppressor gene) Other hereditary colon cancers: repair gene defects HNPCC: mutation in mismatch repair genes NORMALLY: 1. When mistake is made, protein calls another protein which gets rid of affected strand 2. Polymerase comes by and adds the right nucleotides again NOT-SO-NORMALLY: 1. If patient has mutation in proteins working in mismatch repair, bad things happen 2. Or rather, good things dont happen 3. Cell accumulates mutations much more quickly, unchecked and unfixed

CANCER INTERVENTION JUSTIFICATION Individual Rough Draft This is why in FAP it takes around forty years for tumors to become malignant, slowly mutating over time, while HNPCC occurs much faster as repair proteins dont work 8. So heres how it goes Using colon cancer as an example: Normal cells A mutation in suppressive gene (APC), forms benign tumor Benign tumor cells mutate in oncogene (K-Ras), grow really fast Big benign tumor mutates again, suppressive gene (Smad-4 or p-53) Now a malignant tumor, oncogene (PRL-3) mutates, BAD BAD BAD Lots of bad and unlikely mutations piling up gradually 9. Student Suzanne Baker discovered role of p-53 in cancer P-53 mutation found in melanoma! 10. P-53 with melanoma as an example Mutagen: sunlight Sunlight causes C to change to T (typical mutation caused by sunlight) This mutation occurs in p-53 gene (60% of this mutation causes skin cancer) Other mutagens for p-53 include cigarette smoke, aflatoxin, and other unknowns 11. How does p-53 work? Binds to specific gene sequences (adjacent to their controls) Recruits RNA polymerase This polymerase makes mRNA This section of code makes two proteins: WAF1 and PUMA If all else fails, cell commits apoptosis to protect organism from cancer 12. Oncogenes Oncogenes often activated by chromosome translocations Remember Philadelphia chromosome? Yeah: translocation Remember Gleevec? Protein-centered drug 13. Q&A 2 Q: How come mutagens produce such specificity in mutations? A: Mutagens are chemicals, and chemicals bind to specific sections of DNA based on electric charges which direct them to different cell components (only bad if mutates something like repair gene) Q: If someone had a familial cancer, can you fix the mutated gene so it cant be passed on? A: In theory, yes, in practice, no. Ethical complications, but you can use PGR and IVF to select embryonic cell without mutation (My Sisters Keeper!) Prevention notes: mostly only tumors on skin are visible, if you feel a tumor consult a doctor right away, ABCDE Q: Why isnt cancer more common in children, whose cells divide more often? A: Cancer not so much about amount of cell division, something more than just cell division, but we dont understand. Q: In cancer cells, are there multiple mutations that stop apoptosis, or is just p-53 enough? A: Yes, all cancers need several mutations to completely become cancerous 14. The End

CANCER INTERVENTION JUSTIFICATION Individual Rough Draft

Cancer Story Cheyenne Benson Ben French AJ Landolfi

Once upon a time, Melanie went walking on a mountain trail. The day was hot and sunny, and she had neglected to put on sunscreen because she didnt know about the risks of exposing her skin to UVR (UV Rays are comprised of UVA and UVB rays, both of which are harmful to skin, but UVB triggers the tanning response of increasing melanin in human skin). As she was walking, the UVR mutated some of the DNA in her skin cells. Normally, this would not be an issue, however, the UVR mutated her DNA in a way that caused damage to proteins vital to control of the cell cycle. Skin cells normally provide the body with a barrier from foreign objects and helps the body to keep water in. If a skin cell goes through pre-programmed cell death, or apoptosis, which happens when a cell stops functioning normally, the surrounding cells notice and it triggers mitosis. Though skin cells spend most of their life in interphase, they will occasionally undergo mitosis to fill the spot of another cell. This is when the skin cell divides, producing two daughter cells. To grow, the cell must first undergo growth phase one. This is where the cell grows, as the name implies. A protein named Ras cyclin checks the cell to make sure it has grown enough before proceeding to the next phase, synthesis. This is when the DNA is copied, and the protein p53 oversees the process to ensure that no errors are made. ATM/Nibrin inspects the DNA afterwards, as a double precaution. The cell then enters a second growth phase. To begin mitosis, the chromosomes condense in the nucleus. Next, spindle fibers attach to the chromosomes and begin pulling the chromosomes apart. As they are pulled apart, the spindle fibers also pull the sister chromatids to the edges of the cell. Next, the nucleus begins to grow more, and the nuclear membrane begins to form the two separate nuclei, and they slowly separate. This is the technical end of mitosis, but the cells are not fully divided. The next, and final part, of cell division is cytokinesis. Cytokinesis is when the cytoplasm also grows, and the cell membrane grows between the nuclei, completely separating them and forming the two daughter cells. What causes cancer is the mutation of DNA vital to the proteins that oversee the cell cycle. There are three types of genes that, when mutated, dramatically increase the risk of cancer because they are the very genes in charge of preventing cancer. Oncogenes are genes that control proteins that trigger cell growth, suppressive genes code for proteins that tell the cell to stop growing, and repair genes code for proteins that fix mutations in DNA. Often cancer is not caused by a single mutation in one of these three genes, but several, which completely shuts down a cells ability to properly go through the cell cycle. Because it requires multiple mutations in DNA to produce cancer, tumors (especially those of skin cancer) will often begin as benign. Through clonal expansion, and further mutation, a malignant tumor can emerge if the benign tumor is continuously exposed to carcinogens, such as UV Rays. As the malignant tumor grows, pieces can break off and move through the lymph node system and/or the bloodstream. As both the lymph node system and the bloodstream are connected throughout the body, the chunk of cancer cells can get anywhere, including the liver, brain, bones, and the gastrointestinal tract. From there, the cells can find a place to dock and continue the growth. This is called metastasization.

CANCER INTERVENTION JUSTIFICATION Individual Rough Draft Melanies DNA became sufficiently mutated by the UVR, and so her skin cells began to form a malignant melanoma tumor. Her DNA responsible for producing the proteins that regulate cell growth and correct mutations was damaged and failed to produce the proteins. Her cancer cells, unhindered by the neat and orderly cell cycle, began to multiply out of control. Normally after a cell undergoes mitosis, the unneeded daughter cell goes through apoptosis. This maintains the perfect 1:1 ratio of cell life to cell death, so that there are never more cells than the body needs, or too few. However, with cancer, the second daughter cells remain alive, causing cancer to grow exponentially. This uncontrolled growth is what produces the tumor. Melanie should expect the physical symptoms to start once the tumors begin to change or disrupt the function of other organs. If Melanie notices the abnormal growth under her skin (marked by asymmetry, irregular borders and changing or mixed colors) in time, she can catch melanoma in the early stages and get the malignant tumor removed with minimal damage and she can live a healthy (if more sun-cautious) life. However, if Melanie catches the cancer when it has metastasized (which can be found by examining a sentinel lymph node) she could die. .
at the end of the mountain trail, she gets mauled by a bear and her cancer no longer matters.