Amanda McCulloch

Day OBJECTIVES Discuss experiences with and understandings of cancer Identify what they already know and still want to learn about cancer Define cancer Explain the connection between cell cycle and cancer Explain the basic genetics of cancer

9th Grade Biology Week of 03.31.14

MATERIALS HW Due

Periods 1, 3, 4, 7
NOTES TO SELF

M 3.31

Inspire presentation Cancer treatment articles

Cancer Webquest

Print articles Check webquest

Distinguish between benign and malignant Explain angiogenesis and metastasis T 4.1 Investigate these objectives through a case study of a patient with ovarian cancer Identify traditional cancer treatments (surgery, radiation, chemotherapy) Discuss knowledge about new treatments for cancer (from HW articles immunotherapy, targeted therapies) Decide on treatment for case study patient W 4.2 Explain the role of telomeres and telomerase in cancer cells and stem cells Define stem cell Identify the major types of stem cells (totipotent, pluripotent, multipotent, oligopotent, unipotent) Identify when and where you can find stem cells (embryo, fetus, adult) Explain the role of stem cells in science Discuss the controversy over stem cells Explore the Nobel Prize winning research into stem cells Quiz F 4.4 Investigate and discuss current state of stem cell research Quiz Stem cell research Inspire presentation Think about Prepare Nobel Prize brochure/letter worksheet Inspire presentation Cancer Treatment Articles & Questions

T 4.3

Inspire presentation Nobel Prize worksheet Stem cell research resources

Cancer Print quiz brochure/letter

Amanda McCulloch Cancer

9th Grade Biology MONDAY, MARCH 24, 2014

OVERVIEW/ RATIONALE

Periods 1, 3, 4, 7 50 minutes

Students previously studied cell division (cell cycle and mitosis.) This weeks lessons will apply students previous knowledge to help them to better understand stem cells and cancer (cells that do not have a normal cell cycles). ENDURING UNDERSTANDINGS Cancer cells exhibit uncontrolled growth because their cell cycles are no longer regulated. GOALS/OBJECTIVES Students will - Review the cell cycle - Discuss experiences with and understandings of cancer - Identify what they already know and still want to learn about cancer - Define cancer STANDARDS MATERIALS Inspire presentation, news articles OPENER Mitosis and cell cycle review questions. Review mitosis Review cell cycle (worksheets from Friday and cell cycle game at NobelPrize.org) Discuss basics of cancer (what students learned from webquest HW over the weekend) and personal feelings/ideas/words that come to mind when you hear cancer make Wordle Introduce Abby (case study patient) CLOSURE HW handout and announcement ACCOMODATIONS ASSESSMENT/EVALUATION Check HW from weekend Personal reflections / notes 3rd period 15/30 did HW (how can I improve this?) 4th period 15/30 did HW (how can I improve this?) These two classes also had the lowest average quiz grades from cell division quiz (68%, 70% respectively) How can I motivate my students? 7th period 23/26 did HW! This class had a 77% average on quiz (equal to 1st period average) What is going on with my 3rd and 4th period classes that is different than 1st and 7th? PROCEDURES REVIEW BODY OF THE LESSON

December 9, 2012 In Girls Last Hope, Altered Immune Cells Beat Leukemia By DENISE GRADY PHILIPSBURG, Pa. Emma Whitehead has been bounding around the house lately, practicing somersaults and rugby-style tumbles. It is hard to believe, but last spring Emma, then 6, was near death from leukemia. She had relapsed twice after chemotherapy, and doctors had run out of options. Desperate to save her, her parents sought an experimental treatment at the Childrens Hospital of Philadelphia, one that had never before been tried in a child, or in anyone with the type of leukemia Emma had. The experiment used a disabled form of the virus that causes AIDS to reprogram Emmas immune system genetically to kill cancer cells. The treatment very nearly killed her. But she emerged from it cancer-free, and about seven months later is still in complete remission. She is the first child and one of the first humans ever in whom new techniques have given a patients own immune system the lasting ability to fight cancer. Emma had been ill with acute lymphoblastic leukemia since 2010, when she was 5, said her parents, Kari and Tom. She is their only child. She is among just a dozen patients with advanced leukemia to have received the experimental treatment, which was developed at the University of Pennsylvania. Our goal is to have a cure, but we cant say that word, said Dr. Carl June. He hopes the new treatment will eventually replace bone-marrow transplantation, an even more arduous, risky and expensive procedure that is now the last hope when other treatments fail in leukemia and related diseases. The president of Novartis Oncology, called the research fantastic and said it had the potential to revolutionize the treatment of leukemia and related blood cancers. The same approach, reprogramming the patients immune system, may eventually be used against tumors like breast and prostate cancer. To perform the treatment, doctors remove millions of the patients T-cells a type of white blood cell and insert new genes that enable the T-cells to kill cancer cells. The technique employs a disabled form of H.I.V. because it is very good at carrying genetic material into T-cells. The new genes program the T-cells to attack B-cells, a normal part of the immune system that turn malignant in leukemia. The altered T-cells are then dripped back into the patients veins, and if all goes well they multiply and start destroying the cancer. A sign that the treatment is working is that the patient becomes terribly ill, with raging fevers and chills a reaction that oncologists call shake and bake. Its medical name is cytokine-release syndrome, referring to the natural chemicals that pour out of cells in the immune system as they are being activated, causing fevers and other symptoms. The storm can also flood the lungs and cause perilous drops in blood pressure effects that nearly killed Emma. Steroids sometimes reduce the reaction, but they did not help Emma. Her temperature hit 105. She wound up on a ventilator, unconscious and swollen, surrounded by friends and family who had come to say goodbye. But at the last minute, blood tests gave the researchers a clue: her level of one of the cytokines, interleukin-6 or IL-6, had shot up. Doctors had never seen such a spike before and thought it might be what was making her so sick. Dr. June knew that a drug could lower IL-6 his daughter takes it for rheumatoid arthritis. It had never been used for a crisis like Emmas, but there was little to lose. Her oncologist ordered the drug. The response, he said, was amazing. Within hours, Emma began to stabilize. She woke up a week later, on the day she turned 7; the intensive-care staff sang Happy Birthday. Since then, the research team has used the same drug, tocilizumab, in several other patients. In patients with lasting remissions after the treatment, the altered T-cells persist in the bloodstream, though in smaller numbers than when they were fighting the disease. Dr. Michel Sadelain, who conducts similar studies at the SloanKettering Institute, said: These T-cells are living drugs. With a pill, you take it, its eliminated from your body and you have to take it again. But T-cells, he said, could potentially be given only once. The Pennsylvania researchers said they were surprised to find any big drug company interested in their work, because a new batch of T-cells must be created custom for each patient. Custom drugs tend to be extremely expensive. A prime example is the Novartis drug Gleevec, which won rapid approval in 2001 for use against certain types of leukemia and gastrointestinal tumors. It can cost more than $5,000 a month, depending on the dosage.

Dr. June said that producing engineered T-cells costs about $20,000 per patient far less than the cost of a bonemarrow transplant. Scaling up the procedure should make it even less expensive, he said, but he added, Our costs do not include any profit margin, or other research costs. The research is still in its early stages, and many questions remain. The researchers are not entirely sure why the treatment works, or why it sometimes fails. One patient had a remission after being treated only twice, and even then the reaction was so delayed that it took the researchers by surprise. For the patients who had no response whatsoever, the team suspects a flawed batch of T-cells. The child who had a temporary remission apparently relapsed because not all of her leukemic cells had the marker that was targeted by the altered T-cells. It is not clear whether a patients body needs the altered T-cells forever. The cells do have a drawback: they destroy healthy B-cells as well as cancerous ones, leaving patients vulnerable to certain types of infections, so Emma and the other patients need regular treatments with immune globulins to prevent illness. So far, her parents say, Emma seems to have taken it all in stride. She went back to school this year with her secondgrade classmates, and though her grades are high and she reads about 50 books a month, she insists impishly that her favorite subjects are lunch and recess. 1. Define these terms in your own words using context clues, or dictionaries. Relapse Remission Leukemia Chemotherapy Persist T-cell B-cell 2. What type of cancer does Emma Whitehead have? What body system are the cells part of? 4. There are at least 2 other treatments mentioned in the article that Emmas doctors tried before this new procedure. A) What were they? (List names) B) What was the goal of each? Treatment Name Goal

5. Explain how doctors perform immunotherapy treatment for cancer patients. Use the words HIV, virus, T-cell, B-cell, identify, attack, mitosis.

6. Now take everything you wrote in your explanation above, and say it in a way your grandmother would understand.

7. How is immunotherapy different than chemotherapy?

8. Immunotherapy research is still in its early stages. What are some questions that still remain? (at least 3)

Targeted breast cancer therapies coming to the forefront in treatment: Researchers uncovering more effective methods as they learn more about intricacies of disease October 20, 2012 | By Scott Dance, The Baltimore Sun If there ever was a right time to be diagnosed with breast cancer, Beth Thompson found one. In February 2006, the pea-size tumor in her right breast was too small for a clinical trial of Herceptin, a targeted therapy that had proved effective in advanced stages of the aggressive cancer Thompson had. She underwent surgery and chemotherapy, but the cancer continued to grow. Her doctor encouraged her to consider Herceptin, a drug developed by Genetech. Herceptin targets a protein that fuels her cancer's growth. Unlike chemotherapy, which kills all rapidly growing cells, from cancer cells to bone marrow cells and hair follicles, targeted cancer therapies target just cancer cells and molecules that help them multiply and spread. Soon even more targeted therapies will be available for newly diagnosed breast cancer patients, offering hope that it can become more of a manageable chronic disease and less of a killer. "Years ago, just knowing that a patient had breast cancer, knowing the size of the tumor, and knowing if it had or had not spread outside the breast, that's what we called part of the staging assessment. That information alone was all we needed to make treatment decisions," said Dr. Antonio Wolff, a professor of oncology at the Johns Hopkins University School of Medicine and Thompson's physician. But decades of research investment, Wolff said, have "translated into real improvements in the lives of women who unfortunately are still diagnosed with breast cancer." The latest results from that research are two new drugs: Perjeta, used along with Herceptin to treat what is known as HER-2 positive breast cancer, and Affinitor, a drug already used for kidney cancer and shown to be an effective supplement to hormonal treatments for the most common type of breast cancer. Both received FDA approval this year for advanced cases of breast cancer and are undergoing clinical trials in early-stage cases. For some patients, the treatments mean they could lead normal lives with normal life expectancies. For others, it could mean that when one treatment's effectiveness begins to wane, there are other options that can keep cancer in check for longer. "The aim is that you have someone on an effective treatment as nontoxic and non-troublesome as possible," said Dr. Roisin Connolly, an assistant professor of oncology at Hopkins. Researchers are doing comprehensive genetic analysis of many patients breast cancers. A study published last month in the journal Nature laid out many of these findings. These findings help develop targeted therapies. The research laid out four distinct types of breast cancer: Luminal A and luminal B, two types of hormone-driven cancers that receive similar treatments but can have vast differences in tumor size and likelihood of spreading or recurring; HER2-enriched cancer, in which patients, like Thompson, are found to have an excess of a gene known as HER2 that promotes the cancer's spread; "Triple-negative" cancers, which test negative for the other three types. Oncologists theorize that this category could eventually be broken down into further subtypes because of variation among "triple-negative" tumors. Most are known as "basal-like" because they are similar to the basal cells that line mammary ducts. Basal-like cancer behaves similarly to ovarian cancer. Such cancer is more prevalent among both younger and black women. An estimated 227,000 women are expected to be diagnosed with breast cancer this year, with 40,000 deaths, according to the National Cancer Institute. As treatments have improved and awareness has increased, mortality rates from breast cancer have fallen in recent decades. For white women, the annual rate fell from about 31 per 100,000 in 1987 to about 22 in 2007, according to the cancer institute. The rate didn't fall as much among black women, dropping from 35 per 100,000 in 1987 to about 31 in 2007. In the realm of cancer research, much is known about breast cancer relative to other cancers, making targeted therapies more advanced, said Dr. Otis Brawley, chief medical officer for the American Cancer Society. But more could be done, he said, pointing out that the federal cancer institute funds only about 10 percent of research proposals. "In breast cancer, we understand more about the targets than almost any other cancer," Brawley said. "I see a lot of progress. I'm not at all satisfied with the pace of that progress."

Part of the difficulty is that the deeper researchers delve into breast cancer types, the fewer patients their findings may help, doctors said. That also makes it difficult for researchers to get a large enough sample of patients from which to draw conclusions. Studies pull from hospital cancer centers across the country to gather a large enough pool of cases. The treatments also are costly and not a quick fix. For Herceptin, for example, a full course is administered for a year and costs about $50,000. Combined with Perjeta, the new companion drug, the price rises above $100,000. Still, patients are eager to embrace new treatments, Thompson said. A former nurse, Thompson started working as a nurse educator and navigator at Hopkins' breast center after completing her treatment, helping others learn more about their options. Many go to their oncologists after doing their own research, asking specifically about targeted therapies that are in clinical trials, despite the time and costs involved. "A year seems like a long time to not be able to put cancer behind you, but at the same time, they're glad to have that arrow in their quiver," Thompson said. "This is the best shot for what we call a curative model." 1. Define these terms in your own words using context clues, or dictionaries. Diagnose Aggressive Chemotherapy Targeted Cancer Therapies Staging Assessment Oncology Genetic Analysis Hormone Mortality Rate 2. What experimental drug helped Beth Thompson beat her aggressive breast cancer? 3. There are at least 2 other treatments mentioned in the article that Beths doctors tried before this experimental drug. A) What were they? (List names) B) What was the goal of each? Treatment Name Goal

4. Explain how targeted cancer therapies differ from chemotherapy.

5. Do patients typically take targeted cancer therapies alone or in conjunction with other drugs? Use examples from the article to support your answer.

6. What does Dr. Roisin Connolly note is the aim of cancer therapies?

7. According to the National Cancer Institute (NCI), there are nearly 40 different types of targeted cancer therapies available for patients. Use the NCI website to name and briefly describe one of these therapies. (http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted) Treatment Name Specific Target Cancer(s) this drug treats

Amanda McCulloch Cancer

9th Grade Biology TUESDAY, APRIL 1, 2014

Periods 1, 3, 4, 7 50 minutes

OVERVIEW/ RATIONALE Students previously studied cell division (cell cycle and mitosis.) This weeks lessons will apply students previous knowledge to help them to better understand stem cells and cancer (cells that do not have a normal cell cycles). ENDURING UNDERSTANDINGS Cancer is a genetic disease induced by inherited, environmental, and viral factors. Tumors (mass of uncontrolled cell growth) can be benign (harmless) or malignant (harmful). When cancer spreads from one body part to another, it is called metastasis. GOALS/OBJECTIVES Students will be able to - Explain the connection between cell cycle and cancer - Explain the basic genetics of cancer - Distinguish between benign and malignant - Explain angiogenesis and metastasis - Investigate these objectives through a case study of a patient with ovarian cancer STANDARDS MATERIALS Inspire presentation OPENER Warm up Uncontrolled growth of abnormal cells Define cancer Chemo, Radiation, Surgery Identify three standard cancer treatments Immunotherapy, Targeted Cancer Therapies Name the new therapy you read about last night. BODY OF THE LESSON Give official definition from cancer for student notes (ACS definition) http://www.youtube.com/watch?v=LEpTTolebqo#t=26 Distinguish between normal cell division and unregulated cell division Review cell cycle, checkpoints, cyclins/CDKs (http://science.education.nih.gov/supplements/nih1/cancer/activities/activity2_animations.htm) Explain what happens when proteins that control checkpoints no longer function - mutation in gene that codes for cell cycle protein - cell cycle out of control and tumor forms Discuss ovarian cancer and CA-125 blood protein (marker for ovarian cancer) Examine pathology of breast cancer (note the difference in size and shape of cancer cells) Discuss genetics of cancer Cancer arises from the accumulation of genetic changes (mutations) Where do these mutations come from? Inherited from a parent Acquired during a persons lifetime Environmental factors (UV radiation from the sun, X-rays, toxins in cigarette smoke) Viruses Mistake made as DNA copies itself during cell division Most cancers have a minimum of 6-9 different genes mutated. Genetic vs. Hereditary Disease Not a hereditary disease we do not pass on cancer to offspring HOWEVER, we can inherit dispositions (susceptibility) to cancer Many genes that are mutated in cancer are involved in regulating the cell cycle PROCEDURES REVIEW

Amanda McCulloch Cancer

9th Grade Biology TUESDAY, APRIL 1, 2014

Periods 1, 3, 4, 7 50 minutes

Discuss oncogenes and tumor suppressor genes (http://science.education.nih.gov/supplements/nih1/cancer/activities/activity2_animations.htm) Discuss process of moving from benign to malignant tumor Start benign and small angiogenesis (nutrients, metastasis) malignant (video) ACCOMODATIONS ASSESSMENT/EVALUATION Personal reflections / notes

Amanda McCulloch Cancer/Stem Cells

9th Grade Biology WEDNESDAY, APRIL 2, 2014

Periods 1, 3, 4, 7 50 minutes

OVERVIEW/ RATIONALE Students previously studied cell division (cell cycle and mitosis.) This weeks lessons will apply students previous knowledge to help them to better understand stem cells and cancer (cells that do not have a normal cell cycles). ENDURING UNDERSTANDINGS Cancer is a genetic disease induced by inherited, environmental, and viral factors. Tumors (mass of uncontrolled cell growth) can be benign (harmless) or malignant (harmful). When cancer spreads from one body part to another, it is called metastasis. GOALS/OBJECTIVES Students will be able to Identify traditional cancer treatments (surgery, radiation, chemotherapy) Discuss knowledge about new treatments for cancer (from HW articles immunotherapy, targeted therapies) Decide on treatment for case study patient Explain the role of telomeres and telomerase in cancer cells and stem cells Define stem cell STANDARDS MATERIALS Inspire presentation OPENER Warm Up 1) benign (versus malignant) 1) A tumor that has not invaded neighboring tissue or spread is considered _________. 2) cell cycle (cyclins, CDKs proteins) 2) Cells become cancerous when the genes that control the ___________ get mutated. 3) inherited, environmental, viruses 3) What can cause these genetic mutations? BODY OF THE LESSON Plan a course of treatment for Abby (case study patient) - review possible treatments (chemo, radiation, surgery) - jigsaw new treatments (immunotherapy, targeted cancer therapies) - discuss in small groups/with neighbors - identify pros and cons of each treatment type Make the connection between cancer cells and stem cells - cell cycles messed up - divide indefinitely - both express telomerase Video to introduce telomerase: http://www.youtube.com/watch?v=qQCecSuPa1w Have students Define Telomeres: region of repetitive nucleotide sequences at each end of a chromatid, which protects the end of the chromosome from deterioration or from fusion with neighboring chromosomes Define Telomerase: an enzyme that adds DNA sequence repeats to the telomere regions Identify types of cells that express telomerase (stem cells, cancer cells, germ cells) Telomerase and aging? What are stem cells? - Cells that can divide and make identical copies of themselves forever (self-renew) - They can become any or almost any cell (they are unspecialized/undifferentiated) - Two main types: embryonic stem cells & adult stem cells PROCEDURES REVIEW

Amanda McCulloch Cancer/Stem Cells

9th Grade Biology WEDNESDAY, APRIL 2, 2014

ACCOMODATIONS ASSESSMENT/EVALUATION

Periods 1, 3, 4, 7 50 minutes

Exit ticket Personal reflections / notes I feel like students are more harsh than teachers are when discussing student peer editing/grading (5th period IB/ES student) 7th period very talkative I do not know how to show/I am not comfortable with showing I am upset/angry

Amanda McCulloch Stem Cells

9th Grade Biology THURSDAY, APRIL 3, 2014

Periods 1, 3, 4, 7 50 minutes

OVERVIEW/ RATIONALE Students previously studied cell division (cell cycle and mitosis.) This weeks lessons will apply students previous knowledge to help them to better understand stem cells and cancer (cells that do not have a normal cell cycles). ENDURING UNDERSTANDINGS Cancer is a genetic disease induced by inherited, environmental, and viral factors. Tumors (mass of uncontrolled cell growth) can be benign (harmless) or malignant (harmful). When cancer spreads from one body part to another, it is called metastasis. GOALS/OBJECTIVES Students will be able to Identify the major types of stem cells (totipotent, pluripotent, multipotent, oligopotent, unipotent) Identify when and where you can find stem cells (embryo, fetus, adult) Explain the role of stem cells in science Discuss the controversy over stem cells Explore the Nobel Prize winning research into stem cells MATERIALS Inspire presentation PROCEDURES OPENER REVIEW Review telomerase & cells expressing it BODY OF THE LESSON Totipotent Stem Cells: have the potential to give rise to any and all human cells, such as brain, liver, blood or heart cells (can even give rise to an entire functional organism) Pluripotent Stem Cells: can give rise to all tissue types BUT cannot give rise to an entire organism Multipotent Stem Cells: can give rise to a limited range of cells within a tissue type Adult Stem Cells: multipotent stem cell in adult humans that is used to replace cells that have died or lost function (undifferentiated cell present in differentiated tissue) - hematopoetic (blood) - neural - endothelial - muscle - mesenchymal - gastrointestinal - epidermal cells Adult Stem Cells: multipotent stem cell in adult humans that is used to replace cells that have died or lost function (undifferentiated cell present in differentiated tissue) - hematopoetic (blood) - neural - endothelial - muscle - mesenchymal - gastrointestinal - epidermal cells Why is stem cell research important? 1) possible treatment for a variety of diseases 2) help us understand how cells work 3) test how cells respond to substances (drugs, chemicals) 4) use stem cells to understand genetics Why is stem cell research controversial? - stem cells are derived from blastocyst (early stage of fetal development) * Is an embryo a person? * Is it morally acceptable to use embryos for research? * When do we become human beings?

Names ______________________________________________________________ Period ______ Date _________________ Nobel Prize Documentary Unlocking the Secrets of Our Cells By understanding how cells grow and communicate in the body, we can treat diseases that would otherwise be incurable. Directions: As we watch the video, answer the guiding questions below. What disease does Mark suffer from (general explanation)? What research do Sir John B. Gurdon and Shinya Yamanaka perform that could possibly lead to a cure for Mark? Where do all 200 different types of cells in the body come from? ________________________________ Pluripotent stem cells can become ________________________________ cell type in the body. Sir John B. Gurdon What question did Sir John B. Gurdon answer in his PhD research?

Was an answer to this question already published? YES or NO What variable did Gurdon change compared to the studies of Briggs and Kings?

Explain the basic procedure Gurdon used in his research.

Write a one-sentence summary of what Gurdon accomplished.

Gurdons research proved / disproved the hypothesis put forth by Briggs and Kings. (circle) What new field of research developed from Gurdons research?

What does Professor Robert MacLaren note is controversial about stem cell research?

Names ______________________________________________________________ Period ______ Date _________________ Shinya Yamanaka What problem did Yamanaka want to resolve?

How did his research team attempt to answer this problem?

Did his research team succeed right away? YES or NO What procedure worked?

What were these new cells named? __________________________________________ How does Professor Robert MacLaren plan to use these iPS cells?

If you could correct any disease or disorder with iPS cells, which would you choose?

What do you think about the process of scientific research?