PATHOS - WEEK 2 - Neoplasm and Cancer

Chemotherapy

Antineoplastic drugs Can be used alone or in combination with surgery or radiation Usually combination of two to four drugs Given at periodic intervals Classifications include •Antimitotics, anti-metabolites, alkylating agents, antibiotics Drugs interfere with protein synthesis and/or DNA replication Adverse effects Bone marrow depression; nausea; epithelial damage; damage to specific areas (kidney, lungs, heart, liver)

Cancer spread

Local spread Direct extension Seeding Metastasis

Progression to neoplasm

Cancer - disorder of altered cell differentiation and growth. Cells do not divide/grow properly and differentiating poorly can lead to development of cancer. Cellular alteration - dysplasia - precancerous, calls are little more disorganized and little differentiated. totally undifferentiated is neoplasm. In-situ neoplasm - initial site when dysplasia becomes neoplasia. Invasive neoplasm - growing into new tissues, outside of initial growth area. Growth is uncoordinated, no control mechanisms. Does not have signaling systems in the body. no regulatory control over cell growth and division.

Carcinogens

Cancer causing substances / things in the environment.

Cancer

Cellular based disease. Chronic illness. Risk for cancer increases w/ age. 55-60years old.

Cell replication

Cellular proliferation and differentiation is under control of genes. Neoplastic / cancerous cells ignore genetic control results in : excessive cellular proliferation (autonomy) and loss of cellular differentiation (anaplasia)

Chronic inflammation and Cancer

Chronic inflammation is an important factor in the develop of cancer. Cytokines (histamine) release from inflammatory cells Free radicals - damages DNA Decrease response to DNA damage

Goals for cancer treatment

Curative - not too far ahead, helps get rid of the body of cancer and being placed in remission Control - cannot cure, but try to keep it controlled and stop growing Palliative - too far along, no hope/ no cure. Keep the individual comfortable during last months of life.

Radiation therapy

May be used alone or combined with other therapies Causes mutations/alterations in target DNA Most effective in rapidly dividing cells Some types of cancers are radio-resistant May be used as an adjuvant therapy prior to surgery to shrink tumor Adverse effects Bone marrow depression; epithelial damage; infertility; GI upset

Genes that control apoptosis

when mutated, apoptosis cannot occur as usual, leading to build up of abnormal and damaged cells

Genes that regulate repair of DNA damage

when mutated, damage DNA continues to replicate which contains mutations

Warning signs of cancer

1. Unusual bleeding or discharge anywhere in the body 2. change in bowel or bladder habits 3. a change in a wart or mole 4. a sore that does not heal 5. unexplained weight loss 6. anemia or low hemoglobin, & persistent fatigue 7. persistent cough or hoarseness without reason 8. a solid lump, often painless, in the breast or testes or anywhere on the body

Acquired vs. Innate

Acquired - Mutations that occur in somatic cells are not passed down to progeny Innate - Mutations that occur in germline cells may be passed to future generations

Benign vs. Malignant tumors

Benign: similar to origin cells, differentiated Malignant: varied in size and shape. undifferentiated. Benign: relatively slow growth, expanding mass, encapsulated. Malignant: Rapid growth, cells not adhesive, infiltrate tissues, no capsules. Benign: remains localized Malignant: invades nearby tissues, metastasizes to distant sites through blood and lymph vessels Benign: rare systemic effects Malignant: often present w/ systemic effects Benign: only life threatening in the brain Malignant: yes, by tissue destruction and spread of tumors

Immunity and Cancer risk

Cell-mediated immunity recognizes some tumor cells and destroys these. (CD4 - T-lypmhocyte / cytotoxic T cell - responsible for finding abnormal cells and destroying them) Immunization for cervical cancer and hepatitis is recommended to reduce cancer risk from infection. Immune suppression increases the risk of cancer

Cancer treatments

Depends on cancer type, location, and staging: Chemotherapy Radiation Surgery: To remove some or all tumor Immunotherapy Hormones Palliative care

Common diseases and cancer

GERD - Esophageal cancer Chronic Pancreatitis - Pancreatic cancer Common conditions related to chronic inflammation are likely to develop into cancer.

Protooncogenes

Genes required for proliferation, when mutated it is called oncogene. cancer causing gene, which allows for extensive proliferation.

Malignant tumors pt. 1

Grows extremely rapidly and spreads very quickly. Very undifferentiated. May not look like tissue of origin. Unrecognizable. Not encapsulated. Can spread easily, branch off and break off by traveling through the lymphatic systems or blood vessels to distant sites, where they can seed and start metastatic tumor / secondary tumor in different location. Malignant tumor can build own blood supply (angiogenesis), steals blood and nutrients from nearby tissues, causing those tissues to become ischemic and necrotic. Some tumors may exhibits enzymes and toxics, which can try to kill tumor tissues but also cause damage to normal/healthy tissue. Some malignant tumors can release hormones which can micmic normal body hormones and can lead to problems. Malignant neoplasm are less well-differentiated tumors that have lost the ability to control cell proliferation and differentiation.

Tumor suppressor gene

Helps w/ suppression of proliferation of cancer. When mutated, it cannot suppress tumors, allowing tumors to grow more rapidly.

Malignant tumors pt.2

Lack control of mitosis , does not undergo apoptosis No organization or differentiation No contact inhibition - when cells overgrow, body signals cells that they're over-replicating and starts apoptosis. Malignant tumors lose the ability to sense contact inhibition. Abnormal cell membranes Altered surface antigens Do not adhere to each other - often breaks loose from mass, invades other tissues and may spread to distant sites.

Local spread

Malignant tumor starts to spread and grow, initially invade are of where it initially started. IE bowel cancer, cancerous cells located within the bowel tissue

Tumors

Mass of cells due to overgrowth. Neoplasm : benign vs. malignant. -oma - benign tumor -carcinoma - malignant epithelial tissue -sarcoma - malignant connective tissue Tumors are checked by biopsy to determine benign / malignant.

Altered genes

Mutations to these genes can lead to cancerous tissues: Mutator genes Protooncogenes Tumor suppression genes Genes that control apoptosis Genes that regulate repair of DNA damage

Local effects of tumors

Pain: may be absent until very late stages, occurs when tumor is well-advanced. Severity depends on type of tumor (tumor pushing onto nerve/blood vessel causing pain) Tissue integrity: Compressed and eroded blood vessels. Ulceration and necrosis Frank bleeding and hemorrhage. Obstruction: Blockage of air in bronchus, obstruction of colon. can affect breathing, blood flow and impede movement.

Diagnostic testing

Radiographic, ultrasound, MRI, CT scans: visualizing changes in tissues or organs Cytologic tests require biopsy or cell sample: Histologic and cytologic examinations to determine degree of differentiation and tumor type. Most dependable confirmation of malignancy Biopsy is the best diagnostic way to determine malignancy

Surgery

Removal of tumor and surrounding tissue May be done with laparoscope and several small incisions Minimizes tissue damage Improves recovery time Removal of adequate surrounding tissue may result in changes in function. if tumor is small enough, surgery can remove the entire tumor and little of the surrounding tissue to make sure there are no cancerous cells left. Debulking - removes parts of the tumor and removes the rest by chemo/radiation therapy. May also do debunking if it is obstructing surrounding tissue.

Diagnostic Screening

Secondary Prevention Routine screening : essential for early detection, Following treatment to detect any further tumors Self-examination : Early detection if done consistently, breast, testicular, skin are important Blood tests : Measure blood cell levels during treatment (H/H, RBCs and WBCs) May detect tumor markers, e.g., PSA test,

Areas of control - indications of what cancer needs to survive

Self-sufficiency in growth signals Insensitivity to antigrowth signals Evading apoptosis Limitless replicative potential Sustained angiogenesis Tissue invasion and metastasis

Mutator genes

Some genes within the genome, when they become mutated, they lead to other mutated cell to develop more rapidly. Like a control gene that helps mutations from occurring. When issue occurs, more mutations will occur on faster basis. When this mutator gene is mutated, leads to other mutated genes to develop more rapidly.

Malignant tumors pt.3

Tumor can compress blood vessels, leading to necrosis and inflammation around tumor Tumor cells may secrete enzymes or hormones, break down of proteins and cells. systemic affects such as altered calcium levels. Inflammation and loss of normal cells. Lead to progressive reduction in organ integrity and fx. Angiogenesis - some tumor secrete growth hormones. stimulates the development of new capillaries in tumor. pulls blood, oxygen and nutrients away from tissues towards tumor.

Benign tumors

Very slow growing. Encapsulated. Can show growth then regress/shrink. Stays relatively localized when grows. Encapsulation keeps all the cancer cells tightly together. No cell shedding, no metastasis to different site of body with benign tumors. Cells within the capsule are fairly well-differentiated, resembles tissue of origin. Not dangerous Fatty tissue - lipoma Cherry hemangioma - little benign tumors of the blood vessels

Systemic effects of malignant tumors

Weight loss and cachexia: Anorexia, fatigue, pain, stress Increased demands on the body from tumor cells Anemia: Caused by blood loss at tumor site Nutritional deficits may reduce hemoglobin synthesis. Severe fatigue: Caused by inflammatory changes, cachexia, anemia Stress of treatment schedule Psychological factors Effusions: Inflammation causes fluid buildup in body cavities. IE, fluid in peritoneal cavity leads to ascites. Fluid in the Lungs leads to pneumonia. Infections: Occur frequently as resistance declines Bleeding: Tumor cells may erode the blood vessels. Paraneoplastic syndrome: Associated with certain tumor types Tumor cells release substances that affect neurological function and may have hormonal effects. Affects glandular functions Tumor may release their own substances/hormones that can act like hormones on the body.

Cancerous cells

Well-differentated cells cannot become cancerous cells. These are typically the cardiac muscles and nerve tissues. Cancerous cells are typically the cells that has the ability to reproduce quickly and often. (skin, blood, liver etc) Undifferentiated cells also known as stem cells might be trigged by abnormal process to produce large amount of progenitor cells (usually progenitor helps regenerate RBC and WBCs, skin cells, etc) When progenitor cells mutate/malfunction, it will rapidly dive and produce large number of cancer cells.

Seeding / Metatasis

When those cancer cells break off from malignant tumor, moves by blood stream / lymphatic system, movs throughout the body and is going to break off somewhere else now and starts seeding. Finds new location and begins dividing and replicating new malignant cells onto that new location is known as metastatic / secondary tumor. Metastasis - when seeding occurs and secondary malignant tumor starts to grow.

Cancer cell differentiation

anaplasia - irreversible. describes the loss of cell differentiation in cancerous cells. undifferentiated cancer cells are marked by morphological changes, including variations in size, shape, condition known as pleomorphism. Changes in nucleus and DNA. these adaptations occur during rapidly uncontrollable division.

TNM staging

classifies cancer according to tumor size, node involvement, metastasis important to know how far along the pt is and allow for better prognosis and treatment.

Direct extension

tumor has grown past the basement membrane of that tissue and is now invading surface and surrounding tissue IE, bowel cancerous cells can move up towards bladder