CEXP 538 Module 11 PDF

CEXP 538 CANCER Fall 2024 Module 11 OUTLINE CANCER INTRODUCTION ETIOLOGY TREATMENT RISK FACTORS PHYSICAL ACTIVITY  CANCER: INTRODUCTION  CANCER Introduction The origin of the word cancer is credited to the Greek physi...

CEXP 538 CANCER Fall 2024 Module 11 OUTLINE CANCER INTRODUCTION ETIOLOGY TREATMENT RISK FACTORS PHYSICAL ACTIVITY  CANCER: INTRODUCTION  CANCER Introduction The origin of the word cancer is credited to the Greek physician Hippocrates (460-370 BC,“Father of Medicine”) Hippocrates used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. In Greek, these words refer to a crab, most likely applied to the disease because the finger-like spreading projections from a cancer called to mind the shape of a crab The Roman physician, Celsus (25 BC - 50 AD), later translated the Greek term into cancer, the Latin word for crab Galen (130-200 AD), another Greek physician, used the word oncos (Greek for swelling) to describe tumor  CANCER Introduction Disease caused when cells divide uncontrollably and spread into surrounding tissues Can start almost anywhere in the human body Normally, human cells grow and multiply (through a process called cell division) to form new cells as the body needs them. When cells grow old or become damaged, they die, and new cells take their place. Sometimes this orderly process breaks down, and abnormal or damaged cells grow and multiply when they shouldn’t. These cells may form tumors, which are lumps of tissue.  CANCER Introduction Cancerous (malignant) tumors Spread into, or invade, nearby tissues and can travel to distant places in the body to form new tumors (metastasis) Can be solid tumors, but cancers of the blood, such as leukemias are not Sometimes return or grow back Benign tumors Do not spread into, or invade, nearby tissues When removed usually don’t grow back, whereas cancerous tumors sometimes do Can sometimes be quite large Some can cause serious symptoms or be life threatening, such as those in the brain  CANCER Prevalence/Mortality (Siegel et al., 2024) Cancer is the second leading cause of death in the US The National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) program have collected data since 1973  CANCER Incidence (Siegel et al., 2024)  CANCER Prevalence/Mortality (Siegel et al., 2024)  The number of averted deaths is twice as large for men than for women because the death rate in men peaked higher, declined faster, and remains higher  CANCER Prevalence/Mortality (Siegel et al., 2024)  CANCER Incidence (Siegel et al., 2024)  CANCER: ETIOLOGY  CANCER Introduction Cancer cells Normal Cells grow in the absence of signals telling them to grow only grow when they receive such signals invade into nearby areas and spread to other areas ignore signals that normally tell cells to stop of the body dividing or to die (a process known as programmed tell blood vessels to grow toward tumors because cell death, or apoptosis) they supply tumors with oxygen and nutrients and stop growing when they encounter other cells remove waste products from tumors most do not move around the body. hide from the immune system which normally eliminates damaged or abnormal cells. trick the immune system into helping cancer cells stay alive and grow–some even convince immune cells to protect the tumor instead of attacking it accumulate multiple changes in their chromosomes, such as duplications and deletions of chromosome parts. Some cancer cells have double the normal number of chromosomes. rely on different kinds of nutrients than normal cells. In addition, some cancer cells make energy from nutrients in a different way than most normal cells. This lets cancer cells grow more quickly.  Treatment Many times, cancer cells rely so heavily on these abnormal behaviors that they can’t survive without them. Researchers have taken advantage of this fact, developing therapies that target the abnormal features of cancer cells. For example, some cancer therapies prevent blood vessels from growing toward tumors, essentially starving the tumor of needed nutrients.  CANCER Etiology Caused by certain changes to GENES: ○ Basic physical units of inheritance ○ Arranged in long strands of tightly packed DNA called chromosomes “Drivers of Cancer” PROTO-ONCOGENES ○ involved in normal cell growth and division ○ when these genes are altered in certain ways or are more active than normal, they may become cancer-causing gene, or ONCOGENES, which allow cells to grow and survive when they should not Normal cells contain TUMOR SUPPRESSOR GENES which prevent growth of oncogenes become inactivated ○ Cells with certain alterations in tumor suppressor genes may divide in an uncontrolled manner DNA REPAIR GENES ○ Mutations in these genes tend to develop additional mutations in other genes and changes in their chromosomes, such as duplications and deletions of chromosome parts.  Treatment Certain mutations commonly occur in many types of cancer Many cancer treatments available that target gene mutations found in cancer. A few of these treatments can be used by anyone with a cancer that has the targeted mutation, no matter where the cancer started growing.  CANCER Etiology Hyperplasia occurs when cells within a tissue multiply faster than normal and extra cells build up. However, the cells and the way the tissue is organized still look normal under a microscope. Hyperplasia can be caused by several factors or conditions, including chronic irritation. Dysplasia is a more advanced condition than hyperplasia. In dysplasia, there is also a buildup of extra cells. But the cells look abnormal and there are changes in how the tissue is organized. In general, the more abnormal the cells and tissue look, the greater the chance that cancer will form. Some types of dysplasia may need to be monitored or treated, but others do not. An example of dysplasia is an abnormal mole (called a dysplastic nevus) that forms on the skin. A dysplastic nevus can turn into melanoma, although most do not. Carcinoma in situ is an even more advanced condition. ○ Although it is sometimes called stage 0 cancer, it is not cancer because the abnormal cells do not invade nearby tissue the way that cancer cells do. But because some carcinomas in situ may become cancer, they are usually treated.  CANCER Etiology Granulocytes ○ Basophils, Eosinophils, Neutrophils Mast cells ○ defense against parasites ○ found in tissues and can mediate allergic reactions by releasing inflammatory chemicals like histamine Monocytes (including macrophages) ○ ingest and degrade bacteria ○ notify other immune cells of the problem ○ recycle dead cells, like red blood cells, and clearing away cellular debris Dendritic cells (DC) ○ important antigen-presenting cell (APC) Natural killer (NK) cells ○ important for recognizing and killing virus-infected cells or tumor cells  Treatment Some cancer treatments help the immune system better detect and kill cancer cells.  CANCER Etiology Metastasis Cancer cells break away from where they first formed and form new tumors in other parts of the body. Metastatic cancer has the same name and the same type of cancer cells as the original, or primary, cancer Metastatic cancer cells and cells of the original cancer usually have some molecular features in common, such as the presence of specific chromosome changes  Treatment The primary goal of treatment for metastatic cancer is to control the growth of the cancer or to relieve symptoms it is causing. Metastatic tumors can cause severe damage to how the body functions, and most people who die of cancer die of metastatic disease  CANCER Treatment Goal Complete remission (no evidence of disease) Signs and symptoms of the disease have disappeared Cancer can return or the original treatments can produce adverse effects; thus, cancer survivors are often monitored for many years after active treatment ends. Cancer treatment varies according to the type, stage, and other factors. The most common treatments are as follows: Surgery: Some cancers are removed by surgery (also called resection). Though typically performed with scalpels or lasers, other techniques involve the destruction of cells with extreme cold (cryosurgery) or heat (hyperthermia). Chemotherapy: This treatment involves the use of powerful medications to kill rapidly dividing cells in the body or slow their rate of growth. It can also be used to shrink tumors before surgery or in order to relieve pain and pressure. Radiotherapy: In this treatment, high doses of ionizing radiation are directed specifically at the tumor or, following surgery, to the area where cancer occurred. It damages and eventually destroys rapidly dividing cells in that region of the body. Targeted biologic, hormonal, or immune therapies: monoclonal antibodies, hormones, vaccines, or bacteria to stimulate immune or other mechanisms to act against cancer cells. treatments that use drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells. may have fewer side effects than other types of cancer treatment Many patients receive more than one type of therapy  CANCER Sides Effects of Treatment RESPIRATORY DISEASE Anemia Memory or Concentration Problems Ascites Mouth and Throat Problems Bleeding and Bruising (Thrombocytopenia) Nausea and Vomiting Bowel Obstruction Nerve Problems (Peripheral Neuropathy) Cachexia Nutrition Problems Constipation Organ-Related Inflammation and Delirium Immunotherapy Diarrhea Edema (Swelling) Pain Fatigue Sexual Health Issues in Men Fertility Issues in Boys and Men Sexual Health Issues in Women Fertility Issues in Girls and Women Skin and Nail Changes Flu-Like Symptoms Sleep Problems Hair Loss (Alopecia) Urinary and Bladder Problems Infection and Neutropenia Weight Changes and Malnutrition Lymphedema  CANCER Sides Effects of Treatment RESPIRATORY DISEASE  CANCER Types Carcinoma ○ formed by epithelial cells, which are the cells that cover the inside and outside surfaces of the body ○ Adenocarcinomas form in epithelial cells that produce fluids or mucus, such as glandular tissue (i.e., breast, colon, or prostate cancer). ○ Basal cell carcinomas form in epithelial cells in the base or basal level of the epidermis (i.e., skin cancer). ○ Squamous cell carcinomas form in epithelial cells that lie beneath the outer surface of the skin (i.e., skin cancer). ○ Transitional cell carcinomas form in epithelial cells that function to stretch an organ such as the bladder. Sarcoma ○ form in bone and soft tissues, including muscle, fat, blood vessels, lymph vessels, and fibrous tissue (such as tendons and ligaments)  CANCER Types Leukemia ○ begin in the blood-forming tissue of the bone marrow are called leukemias Lymphoma ○ begins in lymphocytes (T cells or B cells). Multiple Myeloma ○ abnormal plasma cells, called myeloma cells, build up in the bone marrow and form tumors in bones all through the body Melanoma ○ begins in cells that become melanocytes, which are specialized cells that make melanin (the pigment that gives skin its color) Brain and Spinal Cord Tumors ○ tumors are named based on the type of cell in which they formed and where the tumor first formed in the central nervous system  CANCER Staging Stage 0 ○ Carcinoma in situ Stage 1–3 ○ Cancer is present. The higher the number, the larger the tumor ○ Stage 3 cancer indicates that it has spread to nearby tissues. Stage 4 ○ Cancer has spread to distant parts of the body.  CANCER Risk Factors https://www.youtube.com/watch?v=XSTabmQhAOc&t=106s Age Alcohol Cancer-Causing Substances Chronic Inflammation Diet Hormones Immunosuppression Infectious Agents Obesity Radiation Sunlight Tobacco  CANCER: PHYSICAL ACTIVITY  CANCER Effects of physical activity Alteration to metabolic pathways and growth factors (i.e., insulin and insulin-like growth factor [IGF] axis pathways) Reduction in sex-steroid synthesis Improved immune function Reduced systemic inflammation and oxidative damage; Interrupting angiogenesis in the tumor Interestingly, exercise may be more or less effective at altering tumorigenesis depending on the molecular characteristics of the tumor. This variability in effectiveness suggests a potential precision-medicine approach for exercise in the clinical management of cancer  CANCER Effects of physical activity May exert a protective effect through changes in the amount and/or activity of adipose or skeletal muscle tissue Excess adipose tissue can generate signals that the body is in a state of energy surplus, which supports cell proliferation and can contribute to an oncogenic state Adipose tissue can also serve as an additional energy source if storage depots are located near cancer cells, fueling their growth and survival Numerous studies report that reductions in metabolic hormones and adipocytokines from exercise training are mediated by reductions in body fat and alterations in these metabolic and inflammatory pathways interrupt or slow cancer progression Signaling cascades from skeletal muscle might also play a role in slowing cancer progression Cytokines (myokines) and peptides are released by contracting skeletal muscle Chronic exposure to these cytokines and peptides may play a protective role in chronic conditions fueled by low-grade inflammation or metabolic dysfunction, including cancer  CANCER Effects of physical activity (Liguori et al., 2021; McTiernan et al., 2019) Higher volumes of PA are associated with lower risk of developing 13 types of cancer (e.g., primary cancer prevention) and a reduction of cancer-related mortality in individuals with several common cancers (e.g., secondary cancer prevention Exercise, a subset of PA, has also been shown to help mitigate the side effects of cancer therapy and improve functional measures in individuals with cancer  CANCER Effects of physical activity (McTiernan et al., 2019)  CANCER Effects of physical activity (Schmitz et al., 2019)  CANCER Effects of physical activity (Schmitz et al., 2019) In a nationally representative sample of cancer survivors, only 8% engaged in 150 min ⋅ wk-1 of moderate-to-vigorous intensity exercise A similar study demonstrated that breast cancer survivors engaged in a daily average of 1 min of moderate-to-vigorous intensity exercise, spending most of their day in sedentary (66%) or light intensity activities (33%)  CANCER Effects of physical activity (Schmitz et al., 2019) Eastern Cooperative Oncology Group  CANCER Effects of physical activity (Schmitz et al., 2019) What are some potential barriers to these programs?  CANCER Effects of physical activity (Liguori et al., 2021) Sample Cancer History Questions What kind of cancer? Whether the individual is currently receiving cancer treatment (and if so, what agents)? Whether the cancer was removed or is still present? If the individual has any symptoms or side effects attributed to cancer treatment? Including: ○ Neuropathy ○ Lymphedema ○ Ostomy ○ Bone metastases ○ Any other symptom the individual believes may influence their ability to exercise  CANCER Effects of physical activity Arm morbidity and upper extremity lymphedema Survivors with established upper extremity lymphedema should wear a compression garment during resistance exercise, progress weight slowly, and should consider working with a certified health fitness professional. There is no upper limit on the amount that breast cancer survivors with or at risk for lymphedema can lift. The safety of exercise for lower extremity lymphedema remains unknown.  CANCER Effects of physical activity Bone metastases Selected modalities for exercise should avoid direct musculoskeletal loading to metastatic lesions or loading of muscles that are proximal to metastatic lesions. Bone pain should be monitored during and after exercise. If bone pain worsens, exercise should be ceased; if pain does not improve with cessation of exercise, referral to medical provider is encouraged. Neuropathy Systematic assessment of falls may be informative in older cancer survivors (85) or those with a history of falls and/or significant neuropathy of the lower extremities. Weight-bearing activities should be carefully selected to reduce risk of falls. Neuropathy symptoms should be monitored during and after exercise. If neuropathy worsens, exercise should be ceased or alternative exercises considered; if neuropathy symptoms do not improve with cessation of exercise, referral to medical provider is encouraged. Ostomy Cancer survivors with an ostomy should adhere to infection risk reduction practices. Resistance exercise should start with low resistance and progress slowly. Avoid contact sports and exercises that cause excessive intra-abdominal pressure (e.g., Valsalva maneuver). There is no empirical evidence to support this recommendation, and it is based on expert opinion.  CANCER Effects of physical activity (Campbell et al., 2019) CANCER  CANCER Resources ACSM https://members.acsm.org/ItemDetail?iProductCode=CES23 Exercise is Medicine https://www.exerciseismedicine.org/eim-in-action/moving-through-cancer/ American Physical Therapy Association https://oncologypt.org/oncology-for/ Cancer Exercise Specialist https://ceti.teachable.com/courses/cancer-exercise-specialist-live-training-mar-1-31-2024/lectur es/52305733  RESEARCH IN PHYSICAL ACTIVITY Strength of the Evidence Temporal Sequence Onset of exercise program ○ Before, during, after ○ Short-term vs. long-term side effects Strength of Association ↓risk ↓side effects Consistency of Results Biological Plausibility Metabolic pathways, hormones, CVD,immune system Risk, mortality, side effects Dose Response Inverse relationship between risk and treatment side effects? FITT  MODULE ASSIGNMENT Please summarize a research article related to physical activity and cancer. Choose a type of physical activity, such as walking, jogging, resistance, yoga, HIIT, Tai Chi, or a specific sport, to demonstrate the effects on a specific type of cancer. Use the template to guide and organize your assignment. Please upload your document to the appropriate D2L dropbox. The assignment is due by Sunday, November 17, 2024 @11:59pm. Final Presentation The student will give a 10-minute presentation facilitating the understanding of the effects of physical activity on the prevention and management of a chronic disease. Use the outline below to guide your presentation: 1. Choose one of the chronic diseases that have been discussed during the semester: a. CAD b. Hypertension c. Dyslipidemia d. Diabetes e. Obesity f. COPD, Asthma g. Musculoskeletal health–Sarcopenia, Arthritis, Osteoporosis, Back pain h. Cancer i. Chronic Kidney Disease j. Brain-health and Brain-related disorders–Parkinson’s disease, Mental health 2. Choose one of the following types of physical activity: a. Aerobic training (Biking, walking, running, swimming, etc.) i. Continuous ii. Non-continuous b. Resistance training (Dumbbells, resistance bands, etc.) c. Combined training d. Flexibility training (Static, dynamic) e. Neuromuscular training i. Yoga ii. Tai Chi iii. Dual-task training iv. Speed, agility, quickness f. Multicomponent, multimodal g. Evidence-based program h. Sport of your choice Final Presentation 3. The presentation should address: a. The chronic disease b. The benefits of the activity for the specific chronic disease c. A brief summary (similar to the research article summary assignments during the semester) of a research article to support your rationale for its benefits d. Exercise training considerations for this type of physical activity which may include: i. General FITT prescription ii. Special considerations 4. The presentation should be no longer than 10 minutes. Please email me @ [email protected] your topic and research article by Sunday, November 17, 2024 @ 11:59 p.m. November 25–Bublis, Foster, Mount, Stefanek, Nicholson December 2–Cenexant, Flint, Parkins, Malone, Tegtmeier REFERENCES Dishman, R.K., Heath, G.W., Schmidt, M.D., & Lee, I.M. (2021). Physical activity epidemiology. Human Kinetics, Inc. Liguori, G. (2021). ACSM's Guidelines for Exercise Testing and Prescription (11th Edition). American College of Sports Medicine. Wolters Kluwer. MCTIERNAN, ANNE; FRIEDENREICH, CHRISTINE M.; KATZMARZYK, PETER T.; POWELL, KENNETH E.; MACKO, RICHARD; BUCHNER, DAVID; PESCATELLO, LINDA S.; BLOODGOOD, BONNY; TENNANT, BETHANY; VAUX-BJERKE, ALISON; GEORGE, STEPHANIE M.; TROIANO, RICHARD P.; PIERCY, KATRINA L.. Physical Activity in Cancer Prevention and Survival: A Systematic Review. Medicine & Science in Sports & Exercise 51(6):p 1252-1261, June 2019. | DOI: 10.1249/MSS.0000000000001937 National Cancer Institute. (2024). https://www.cancer.gov/about-cancer/understanding/what-is-cancer Schmitz, K.H., Campbell, A.M., Stuiver, M.M., Pinto, B.M., Schwartz, A.L., Morris, G.S., Ligibel, J.A., Cheville, A., Galvão, D.A., Alfano, C.M., Patel, A.V., Hue, T., Gerber, L.H., Sallis, R., Gusani, N.J., Stout, N.L., Chan, L., Flowers, F., Doyle, C., Helmrich, S., Bain, W., Sokolof, J., Winters-Stone, K.M., Campbell, K.L. and Matthews, C.E. (2019), Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer. CA A Cancer J Clin, 69: 468-484. https://doi.org/10.3322/caac.21579 Scott, J. M., Dolan, L. B., Norton, L., Charles, J. B., & Jones, L. W. (2019). Multisystem Toxicity in Cancer: Lessons from NASA's Countermeasures Program. Cell, 179(5), 1003–1009. https://doi.org/10.1016/j.cell.2019.10.024 Siegel, R. L., Giaquinto, A. N., & Jemal, A. (2024). Cancer statistics, 2024. CA: a cancer journal for clinicians, 74(1), 12–49. https://doi.org/10.3322/caac.21820 Thompson, W. R. (2025). Acsm's: clinical exercise physiology, 2e. Lippincott Williams & Wilkins,