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CELLULAR CHARACTERISTICS Eukaryotic and prokaryotic cells differ in many important ways.

The primary distinction between the two types of cells is that eukaryotes have a nucleus as well as organelles, while prokaryotes do not. In fact, the word eukaryote literally means "true nucleus." Other differences between eukaryotes and prokaryotes include cell size, cell wall structure and genetics.

embryonic tissue. Many of these tumors are most common in children.

TYPES OF CELLULAR ABERRATIONS Genetic disturbances Degeneration and infiltration Disorders in cell growth (malignant growth, atrophy and hypertrophy

CELLULAR ACTIVITIES y y y Reproduces Reacts to stimuli Moves by either ameboid motion or by means cilia or flagella

EPIDEMIOLOGY y y y Gender Age Economic status

ALTERATION IN CELLULAR FUNCTION y y y y y Aging cell Atrophy Hypertrophy Hyperplasia Neoplastic changes

ETIOLOGY y y y y y y y Genetic factors Immune system factors Viruses Hormonal factors Preparative action on target tissue making them susceptible to CA Permissive influence on CA development allowing process to progress Conditioning effect on the tumor

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. These are the histology and the location, respectively. Examples of general categories include:
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CARCINOGENESIS y a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes on cellular and genetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.

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Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer. Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells. Lymphoma and leukemia: Malignancies derived from hematopoietic (blood-forming) cells Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the testicle and ovary; in fetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull). Blastic tumor or blastoma: A tumor (usually malignant) which resembles an immature or

4 STAGES OF CANCER CELL GROWTH/ MULTI STEP TO CARCINOGENESIS Initiation Promotion Progression Metastasis

tumor- a tumor can be benign, pre-malignant, or malignant, or can represent a lesion with no cancerous potential whatsoever. neoplasm (benign & malignant)- A tumor. An abnormal growth of tissue. The word neoplasm is not synonymous with cancer. carcinogen are a class of substances that are directly responsible for damaging DNA, promoting or aiding cancer. Tobacco, asbestos, arsenic, radiation such as gamma and x-rays, the sun, and compounds in car exhaust fumes are all examples of carcinogens. When our bodies are exposed to carcinogens, free radicals are formed that try to steal electrons from other molecules in the body. Theses free radicals damage cells and affect their ability to function normally.

involuntary weight loss involving both fat and muscle, due to shifts in metabolism caused by tumour byproducts and cytokines.

BREAST CA UTERINE CA FALLOPIAN TUBE CA OVARIAN CA COLORECTAL CA LUNG CA PROSTATE CA LEUKEMIA RETINOBLASTOMA PREVENTION & CONTROL OF CA IN ALL LEVELS y y Primary prevention Secondary prevention

y PATHOPHYSIOLOGY OF CANCER SIGNS & SYMPTOMS CA CELL PROLIFERATION y y y y y pressure obstruction pain effusion ulceration in necrosis

PARANEOPLASTIC SYNDROME is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors (by hormones or cytokines) excreted by tumor cells or by an immune response against the tumor. y y y anemia hypercalcemia DIC

WARNING SIGNALS OF CA DIAGNOSTIC TESTS TUMOR MARKER IDENTIFICATION y HCG (human chorionic gonadotropin)- HCG is a glycoprotein consisting of subunits a e b, which are nonconvalently linked. The hormone is normally produced by the syncytiotrophoblastic cells of the placenta and is elevated in pregnancy. Its most important uses as a tumor marker are in gestational trophoblastic disease and germ cell tumors. CA 125- is often elevated in patients with ovarian cancer, its level following the patient's clinical course. PSA (prostate specific antigen)-is prostate-specific, not cancer-specific. A variety of conditions can raise PSA levels: prostatitis (prostate inflammation), benign prostatic hypertrophy (prostate enlargement), and prostate cancer. PAP (prostatic acid phosphatase)-This enzyme is found in high concentraitions in the normal

y ANOREXIA & CACHEXIA SYNDROME Cachexia is a debilitating state of involuntary weight loss complicating malignant, infectious, and inflammatory diseases and contributing significantly to mortality. Anorexia, also a frequent complication of these diseases, is a major contributor to the development of cachexia, although the pattern of weight loss in cachexia differs from that seen with pure nutrient deprivation. Cachexia has been defined as y

prostate as well as in primary and metastatic prostate cancers. Alpha fetoprotein (AFP)- is a marker for hepatocellular and germ cell (nonseminoma) carcinoma.1 It is a glycoprotein produced in large amounts during fetal life and is homologous to albumin. AFP is elevated in normal pregnancy, benign liver disease (hepatitis, cirrhosis), as well as in cancer. CEA (carcinoembryonic antigen)-was first indentified in colon cancer, an abnormal CEA blood level is specific neither for colon cancer nor for malignancy in general. Elevated CEA levels are found in a variety of cancers other than colonic, including pancreatic, gastric, lung, and breast. It is also detected in benign conditions including cirrhosis, inflamatory bowel disease, chronic lung disease, and pancreatitis.

added to each letter to indicate the size or extent of the primary tumor and the extent of cancer spread. Primary Tumor (T) TX T0 Tis

Primary tumor cannot be evaluated No evidence of primary tumor Carcinoma in situ (CIS; abnormal cells are present but have not spread to neighboring tissue; although not cancer, CIS may become cancer and is sometimes called preinvasive cancer) Size and/or extent of the primary tumor

T1, T2, T3, T4

POSITRON EMISSION TOMOGRAPHY (PET SCAN) RADIOIMMUNO CONJUGATES BIOPSY y y y y Excisional biopsy Incisional biopsy Needle biopsy Exfoliative cytology

Regional Lymph Nodes (N) NX N0 Regional lymph nodes cannot be evaluated No regional lymph node involvement Involvement of regional lymph nodes (number of lymph nodes and/or extent of spread)

N1, N2, N3

TUMOR STAGING AND GRADING


The American Joint Committee on Cancer recommends the following guidelines for grading tumors (1): Grade GX G1 G2 G3 G4 Grade cannot be assessed (Undetermined grade) Well-differentiated (Low grade) Moderately differentiated (Intermediate grade) Poorly differentiated (High grade) Undifferentiated (High grade)

Distant Metastasis (M) MX M0 M1 Distant metastasis cannot be evaluated No distant metastasis Distant metastasis is present

For example, breast cancer classified as T3 N2 M0 refers to a large tumor that has spread outside the breast to nearby lymph nodes but not to other parts of the body. Prostate cancer T2 N0 M0 means that the tumor is located only in the prostate and has not spread to the lymph nodes or any other part of the body. For many cancers, TNM combinations correspond to one of five stages. Criteria for stages differ for different types of cancer. For example, bladder cancer T3 N0 M0 is stage III, whereas colon cancer T3 N0 M0 is stage II. Stage Stage Carcinoma in situ. Definition

TNM SYSTEM IN BREAST CA The TNM system is based on the extent of the tumor (T), the extent of spread to the lymph nodes(N), and the presence of distant metastasis (M). A number is

0 Stage I, Stage II, and Stage III y

Higher numbers indicate more extensive disease: Larger tumor size and/or spread of the cancer beyond the organ in which it first developed to nearby lymph nodes and/or organs adjacent to the location of the primary tumor.

Stage The cancer has spread to another organ(s). IV

SURGICAL INTERVENTION y Chemotherapy- utilizes chemicals that interfere with the cell division process - damaging proteins or DNA - so that cancer cells will commit suicide. These treatments target any rapidly dividing cells (not necessarily just cancer cells), but normal cells usually can recover from any chemical-induced damage while cancer cells cannot. Chemotherapy is generally used to treat cancer that has spread or metastasized because the medicines travel throughout the entire body. It is a necessary treatment for some forms of leukemia and lymphoma. Chemotherapy treatment occurs in cycles so the body has time to heal between doses. However, there are still common side effects such as hair loss, nausea, fatigue, and vomiting. Combination therapies often include multiple types of chemotherapy or chemotherapy combined with other treatment options. Radiation therapy- destroys cancer by focusing high-energy rays on the cancer cells. This causes damage to the molecules that make up the cancer cells and leads them to commit suicide. Radiotherapy utilizes high-energy gamma-rays that are emitted from metals such as radium or highenergy x-rays that are created in a special machine. Early radiation treatments caused severe sideeffects because the energy beams would damage normal, healthy tissue, but technologies have improved so that beams can be more accurately targeted. Radiotherapy is used as a standalone treatment to shrink a tumor or destroy cancer cells (including those associated with leukemia and

lymphoma), and it is also used in combination with other cancer treatments. Biotherapy- It uses drugs aimed at the patient's immune system to help fight cancer throughout the body. IMMUNOTHERAPY focuses on stimulating the patient's own immune system to fight cancer. Immunotherapy can reach most cells in the body and is used to treat cancer that has metastasized, or it can be placed in one area of the body to localize the treatment. INTERFERONS are proteins that boost the immune system to help fight cancer. Interferon stops them from dividing and stops the cells from developing new blood vessels, therefore stopping their growth. INTERLEUKINS are proteins that help coordinate the cells of the immune system to in turn help them distinguish and fight cancer cells.MONOCLONAL ANTIBODIES target foreign proteins on the cancer cell and are effective in women with breast cancer who have certain cell characteristics. GENE THERAPY is a promising therapy that can correct gene mutations in cancer and other non-cancerous conditions. It has had much negative publicity over the years as stem cells were gathered from unborn fetuses or in a more positive light - banked cord blood. Clinical trials are still underway but now that scientists have learned how to make these precious stem cells in the lab, this treatment's future looks brighter than ever.TUMOR VACCINES are just as promising as gene therapy and are currently being studied both for treatment, where the vaccine can stimulate the immune system to fight against specific tumors and kill them, or to prevent certain cancers in people who are at high risk for developing them. MERCK'S HPV VACCINE for young girls is a good example as this vaccine can prevent some women from contracting cervical cancer later on.Gene therapy- The goal of gene therapy is to replace damaged genes with ones that work to address a root cause of cancer: damage to DNA. For example, researchers are trying to replace the damaged gene that signals cells to stop dividing (the p53 gene) with a copy of a working gene. Other gene-based therapies focus on further damaging cancer cell DNA to the point where the cell commits suicide. Gene therapy is a very young field and has not yet resulted in any successful treatments. Bone marrow transplant

There are three kinds of bone marrow transplants:

Autologous bone marrow transplant: "Auto" means "self." Stem cells are removed from you before you receive high-dose chemotherapy or radiation treatment. After these treatments are done, your stems cells are put back in your body. This is called a "rescue" transplant. Allogeneic bone marrow transplant: "Allo" means "other." Stem cells are removed from another person, called a donor. Most times, the donor must have the same genetic makeup as the patient, so that their blood is a "match" to yours. Special blood tests are done to determine if a donor is a good match for you. A brother or sister is most likely to be a good match. However, sometimes parents, children, and other relatives may be good matches. Donors who are not related to the patient may be found through national bone marrow registries. Umbilical cord blood transplant: Stem cells are removed from a newborn baby's umbilical cord immediately after being born. The stem cells are stored until they are needed for a transplant. Umbilical cord blood cells are so immature, there is less of a concern that they will not match.

Alkylating agents Alkylating agents directly damage DNA to prevent the cancer cell from reproducing. As a class of drugs, these agents are not phase-specific; in other words, they work in all phases of the cell cycle. Alkylating agents are used to treat many different cancers, including acute and chronic leukemia, lymphoma, Hodgkin disease, multiple myeloma, sarcoma, as well as cancers of the lung, breast, and ovary. Because these drugs damage DNA, they can cause long-term damage to the bone marrow. In a few rare cases, this can eventually lead to acute leukemia. The risk of leukemia from alkylating agents is "dose-dependent," meaning that the risk is small with lower doses, but goes up as the total amount of the drug used gets higher. The risk of leukemia after getting alkylating agents is highest 5 to 10 years after treatment. There are many different alkylating agents, including: Nitrogen mustards: such as mechlorethamine (nitrogen mustard), chlorambucil, cyclophosphamide (Cytoxan), ifosfamide, and melphalan y Nitrosoureas: which include streptozocin, carmustine (BCNU), and lomustine y Alkyl sulfonates: busulfan y Triazines: dacarbazine (DTIC), and temozolomide (Temodar) y Ethylenimines: thiotepa and altretamine (hexamethylmelamine) The platinum drugs (cisplatin, carboplatin, and oxalaplatin) are sometimes grouped with alkylating agents because they kill cells in a similar way. These drugs are less likely than the alkylating agents to cause leukemia.
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Alternative therapies

COMPLEMENTARY AND ALTERNATIVE THERAPIES What are the different types of chemotherapy drugs? Chemotherapy drugs can be divided into several groups based on factors such as how they work, their chemical structure, and their relationship to another drug. Some chemotherapy drugs are grouped together because they were derived from the same plant. Because some drugs act in more than one way, they may belong to more than one group. Knowing how the drug works is important in predicting side effects. This helps oncologists decide which drugs are likely to work well together. If more than one drug will be used, this information also helps them plan exactly when each of the drugs should be given (in which order and how often).

Antimetabolites Antimetabolites are a class of drugs that interfere with DNA and RNA growth by substituting for the normal building blocks of RNA and DNA. These agents damage cells during the S phase. They are commonly used to treat leukemias, tumors of the breast, ovary, and the intestinal tract, as well as other cancers. Examples of antimetabolites include 5-fluorouracil (5FU), capecitabine (Xeloda), 6-mercaptopurine (6-MP), methotrexate, gemcitabine (Gemzar), cytarabine (AraC), fludarabine, and pemetrexed (Alimta).

Anti-tumor antibiotics Anthracyclines Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in DNA replication. These agents work in all phases of the cell cycle. Thus, they are widely used for a variety of cancers. A major consideration when giving these drugs is that they can permanently damage the heart if given in high doses. For this reason, lifetime dose limits are often placed on these drugs. Examples of anthracyclines include daunorubicin, doxorubicin (Adriamycin), epirubicin, and idarubicin. Other anti-tumor antibiotics include the drugs actinomycin-D, bleomycin, and mitomycin-C. Mitoxantrone is an anti-tumor antibiotic that is similar to doxorubicin in many ways, including the potential for damaging the heart. This drug also acts as a topoisomerase II inhibitor (see below), and can lead to treatment-related leukemia. Mitoxantrone is used to treat prostate cancer, breast cancer, lymphoma, and leukemia.

needed for cell reproduction. These drugs work during the M phase of the cell cycle, but can damage cells in all phases. They are used to treat many different types of cancer including breast, lung, myelomas, lymphomas, and leukemias. These drugs are known for their potential to cause peripheral nerve damage, which can be a dose-limiting side effect. Examples of mitotic inhibitors include:
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Taxanes: paclitaxel (Taxol) and docetaxel (Taxotere) Epothilones: ixabepilone (Ixempra) Vinca alkaloids: vinblastine (Velban), vincristine (Oncovin), and vinorelbine (Navelbine) Estramustine (Emcyt)

Corticosteroids Steroids are natural hormones and hormone-like drugs that are useful in treating some types of cancer (lymphoma, leukemias, and multiple myeloma), as well as other illnesses. When these drugs are used to kill cancer cells or slow their growth, they are considered chemotherapy drugs. Corticosteroids are also commonly used as anti-emetics to help prevent nausea and vomiting caused by chemotherapy. They are used before chemotherapy to help prevent severe allergic reactions (hypersensitivity reactions), too. When a corticosteroid is used to prevent vomiting or allergic reactions, it is not considered chemotherapy. Examples include prednisone, methylprednisolone (Solumedrol) and dexamethasone (Decadron).

Topoisomerase inhibitors These drugs interfere with enzymes called topoisomerases, which help separate the strands of DNA so they can be copied. They are used to treat certain leukemias, as well as lung, ovarian, gastrointestinal, and other cancers. Examples of topoisomerase I inhibitors include topotecan and irinotecan (CPT-11). Examples of topoisomerase II inhibitors include etoposide (VP-16) and teniposide. Mitoxantrone also inhibits topoisomerase II. Treatment with topoisomerase II inhibitors increases the risk of a second cancer -- acute myelogenous leukemia (AML). With this type of drug, secondary leukemia can be seen as early as 2 to 3 years after the drug is given.

Mitotic inhibitors Mitotic inhibitors are often plant alkaloids and other compounds derived from natural products. They can stop mitosis or inhibit enzymes from making proteins

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