Cancer and Chemotherapy

Cancer

• Cancer is a disease involving abnormal cell division and tissue invasion.
• "Karkinoma", the Greek term for crab, is the origin of the word cancer.
• Tumors, also known as neoplasms, represent new tissue growths.

Introduction: Terminology

• Differentiation refers to how each cell type specializes and carries out specific functions.
• Tissue structure reflects its function.
• Mitosis, part of the cell cycle, requires genetic control through DNA and RNA.
• Mutation involves the alteration of DNA in a parent cell, which is then passed onto offspring cells.
• Apoptosis refers to programmed cell death.
• Genetic elements control apoptosis.

Benign and Malignant Tumors

• Benign tumors involve differentiated cells reproducing at a higher rate than normal.
• Benign tumors are encapsulated.
• Benign tumors cause tissue damage.
• Tissue damage from benign tumors results from compression of adjacent structures.
• Benign tumors can be life-threatening in the brain.
• Malignant tumors consist of undifferentiated, nonfunctional cells.
• Malignant tumors exhibit rapid reproduction with abnormal mitotic figures.
• Malignant tumors can infiltrate or spread into surrounding tissue.
• Malignant tumors spread to distant sites.

Benign vs. Malignant Tumors

• Benign tumors grow slowly, have a well-defined capsule, and are non-invasive.
• Benign tumors are usually well-differentiated, have a low mitotic index, and do not metastasize.
• Malignant tumors grow rapidly, lack a capsule, and are invasive.
• Malignant tumors are poorly differentiated, have a high mitotic index, and can spread (metastasize).

Malignant Tumors: Cancer

• Malignant Tumors lack control of mitosis and do not undergo apoptosis.
• Malignant Tumors do not have normal organization or differentiation.
• Malignant Tumors lack contact inhibition.
• Malignant Tumors have abnormal cell membranes.
• Malignant Tumors have altered surface antigens.
• Malignant Tumors do not adhere to each other.
• Malignant Tumors often break loose from mass
• Malignant Tumors can invade other tissues and may spread to distant sites.

Malignant Tumors: Cancer (Cont'd)

• Malignant tumors compress blood vessels.
• Compression leads to necrosis and inflammation around the tumor.
• Tumor cells may secrete enzymes or hormones.
• Tumor cell secretion can break down of proteins and cells.
• Secretion can manifest systemic effects, such as altered calcium levels.
• Inflammation and loss of normal cells lead to progressive reduction in organ integrity and function.
• Angiogenesis is when some tumor cells secrete growth factors which stimulate the development of new capillaries in the tumor.

Classification and Nomenclature

• Benign tumors are often named after the tissues they originate from with the suffix "-oma"
• Lipoma, Leiomyoma, and Meningioma are all examples of Benign tumors.
• Benign tumors can progress to cancer.
• Several malignant tumors have unique names such as Hodgkin's disease, Wilms' tumor, and Leukemia.

Classification and Nomenclature (Cont.)

• Malignant tumors are named according to the tissues from which they arise.
• Carcinomas arise from Epithelial tissue.
• Adenocarcinomas arise from ductal or glandular tissue.
• Sarcomas arise from Mesenchymal tissue.
• Lymphomas arise from Lymphatic tissue.
• Leukemia arises from blood-forming cells..

Carcinoma in Situ

• Carcinoma in situ (CIS) refers to preinvasive epithelial malignant tumors of glandular or epithelial origin that haven't broken through the basement membrane or invaded the surrounding stroma.

Biology of Cancer Cells

• Cancer is predominantly a disease of aging
• Multiple mutations are required before cancer can develop.
• Clonal proliferation or expansion happens when, as a result of a mutation, a cell aqures a selective advantage over its neighbors.
• Selective advantage can manifest as an Increased growth rate or decreased apoptosis.

Biology of Cancer Cells (Cont.)

• Transformation of normal cells includes a decreased need for growth factors to multiply.
• Transformed cells also lack contact inhibition
• Transformed cells have Anchorage independence, and immortality.

Genomic Instability

• Increased tendency for genomic mutations during life cycle of the cell, increases the Risk for cancer increases.
• Caretaker genes Encode proteins that repair damaged DNA.

Genomic Instability (Cont.)

• Increased silencing or modulation of gene functioning can result from Promoter regions of genes being altered.
• Altering genes leads to silencing or altered gene expression
• Chromosome instability includes Increase in malignant cells
• Chromosome instability results in chromosome loss, loss of heterozygosity, and chromosome amplification

Telomeres and Immortality

• Body cells are not immortal.
• Body cells can only divide a limited number of times.
• Telomeres are protective caps on each chromosome.
• Telomeres are held in place by telomerase.
• Telomeres Block cell division and prevent immortality.
• Telomeres become smaller with each cell division.
• Cancer cells can activate telomerase which results in Unlimited division and proliferation.

Angiogenesis

• Angiogenesis includes the Growth of new vessels.
• Advanced cancers can secrete angiogenic factors (VEGF)
• Angiogenesis includes Vascular endothelial GF, Platelet-derived GF, and Basic fibroblast GF.

Inflammation and Cancer

• Chronic inflammation is an important factor in the development of cancer as Cytokine release happens from inflammatory cells.
• Helicobacter pylori causes Chronic inflammation which is associated with Peptic ulcer disease, Stomach carcinoma, and Mucosa-associated lymphoid tissue lymphomas.

Inflammation and Cancer (Cont.)

• Tumor-associated macrophage (TAM) are Key cells that promote tumor survival.
• The Presence of TAMs frequently correlates with a worse prognosis.
• TAMs Mimic M2 phenotype, Have diminished cytotoxic response and Develop the capacity to block T-cytotoxic cell and NK cell functions.
• TAMs Produce cytokines that are advantageous for tumor growth and spread.

Immune System and Cancer

• The normal human immune system protects against cancer.
• Immunosuppression fosters cancer.
• Non-Hodgkin lymphoma (10x) and Kaposi sarcoma (1000x) can result from immunosuppression.
• The Release of immunosuppressive factors into the tumor microenvironment increases resistance of the tumor to chemotherapy and radiotherapy

Viruses and Cancer

• Hepatitis B and C viruses, Epstein-Barr virus (EBV), Kaposi sarcoma herpesvirus (KSHV), Human papillomavirus (HPV) and Human T-cell leukemia-lymphoma virus (HTLV) are Implicated in cancer.

Metastasis

• Metastasis is the Spread of cancer from a primary site of origin to a distant site.
• Direct invasion of contiguous organs happens via local spread.
• Metastases to distant organs happen by spread through Lymphatics and blood..
• Metastasis Requires great efficiency and Usually occurs late

Local Spread

• Invasion by cancer cells is due to Cellular multiplication, Release of lytic enzymes, Decreased cell-to-cell adhesion and Increased motility.

Distant Metastases

• Distant Metastases happen through vascular and lymphatic pathways..
• Cancer can Selectivity occurs at different sites, for example Breast cancer goes to bones, Lymphomas goes to spleen.
• Dormancy is when tumors will not grow or spread for an extended time.

Seeding

• Seeding refers to the spread of cancer cells occurring in body fluids or along membranes, usually in body cavities.
• Tumor cells can break away and travel easily with the movement of fluid and tissue.
• The peritoneal membrane is an example that encourages dispersion of ovarian tumor cells.
• Excessive handling of the area containing malignant cells during procedures and surgery, dislodges the malignant cells leading to further spread.

Warning Signs of Cancer

• General warning signs of cancer include unusual bleeding or discharge.
• Change in bowel or bladder habits.
• Changes to the skin.
• A sore that does not heal, weight loss or anemia.
• Persistent fatigue, cough, or solid and painless lump.

Clinical Manifestations

• Early stages of malignancy usually have little to no pain..
• Pain in general can be Influenced by fear, anxiety, sleep loss, fatigue, and overall physical deterioration
• The mechanisms for pain in cancer include Pressure, Obstruction, Invasion of sensitive structures, Stretching of visceral surfaces, Tissue destruction and Inflammation/Infection.

Clinical Manifestations (Cont.)

• Fatigue is the most frequently reported symptom.
• Subjective clinical manifestations include Tiredness, weakness, lack of energy, exhaustion, lethargy, inability to concentrate, depression, sleepiness, boredom, and lack of motivation
• Suggested causes of fatigue include Sleep disturbance, Biochemical changes secondary to disease and treatment, Psychosocial factors, Level of activity, Nutritional status, and Environmental factors.

Clinical Manifestations (Cont.)

• Syndrome of cachexia represents the Most severe form of malnutrition including anorexia, early satiety, weight loss, anemia, asthenia, taste alterations, and altered protein, lipid, and carbohydrate metabolism
• Anemia is a decrease of hemoglobin in the blood via Chronic bleeding resulting in iron deficiency, Severe malnutrition, Medical therapies, and Malignancy in blood-forming organs.

Clinical Manifestations (Cont.)

• Direct tumor invasion to the bone marrow causes Leukopenia and thrombocytopenia.
• Chemotherapy drugs are toxic to the bone marrow
• Infection risk increases when the absolute neutrophil and lymphocyte counts fall.

Clinical Manifestations (Cont.)

• Gastrointestinal manifestations include Oral ulcers caused by decreased cell turnover from chemotherapy and radiation, Malabsorption, Diarrhea and Therapy-induced nausea.
• Hair and skin manifestations include Alopecia from chemotherapy (usually temporary) as well as Skin breakdown and dryness.

Diagnosis

• Diagnosis depends on the current Manifestations based on site, tumor size so Diagnostic testing is necessary.
• Diagnostic testing is also necessary alongside site and size of the tumor.
• Complete blood count (CBC) detects problems related to cancer ,and monitors the systemic effects of chemotherapy and radiation.
• Tumor markers in the blood include enzymes, antigens, or hormones produced by neoplastic cells to test PSA.
• Diagnostic imaging includes methods like x-ray, ultrasound, MRI, PET scans, CT scans.
• Cytologic testing looks at samples of cells and is used to screen and confirm a diagnosis.

Staging

• Microscopic analysis happens so a staging system can be based on the presence of metastasis..
• The levels of metastasis are categorized, including Stage I: No metastasis; Stage II: Local invasion; Stage III: Spread to regional structures; and Stage IV: Distant metastasis..
• World Health Organization's TNM system categorizes tumors with T for tumor spread, N for node involvement, and M for the presence of distant metastasis.

Tumor Markers

• Tumor cell markers, also known as biologic markers, are substances cancer cells produce
• These markers show up on either tumor cells, blood, CSF, or even urine.
• Hormones, enzymes, genes, antigens, and antibodies are all markers that can show up
• Tumor markers are used for Screening and identifying individuals as high risk for cancer.
• Tumor markers also help in Diagnosing specific types of tumors and Observing clinical course of cancer.
• A Problem that may arise is false positives and negatives.

Histology

• Tumors are classified based on immunohistochemical analysis of protein.
• Protein markers help determine genetic analysis for better treatment of tumors.
• Enhanced characterization then further divides those cancers into prognostically relevant smaller breast cancer groups.

Cancer Treatment

• Surgery can be conducted To prevent cancer (colon polyps), Biopsy for diagnosis and staging, Lymph node sampling, and Palliative surgery.
• Radiation has the Goals including eradicating cancer without excessive toxicity and avoiding damage to normal structures.
• Ionizing radiation damages the cancer cell's DNA

Cancer Treatment (Cont.)

• Chemotherapy Takes advantage of specific vulnerabilities in target cancer cells.
• Chemotherapy is Usually given in combinations designed to attack a cancer from many different weaknesses at the same time.

Chemotherapy

• Induction chemotherapy aids in Shrinkage and disappearance of tumors.
• Adjuvant chemotherapy aids in Eliminating micrometastasis after surgery.
• Neoadjuvant therapy is Given before localized treatment to shrink tumor

Immunotherapy

• Vaccines against oncogenic viruses provide protection and prevent the onset of viral-induced tumors.
• Numerous potential therapeutic vaccines have been tested with little success
• Allogeneic cancer cell vaccines continue to be tested

Cancer Treatment

• Targeted disruption is Used in combination with chemotherapy which makes it Highly specific.
• Targeted disruption also includes Inactivating oncogenes, Blocking angiogenesis, Affecting cell metabolism, Inducing apoptosis, and Neutralizing cytokines/chemokines.

Genetics, Epigenetics, and Tissue

• Environmental-lifestyle factors and genetic factors result in cancer.
• Patterns of cancer are environmental, not genetic.
• Genetic alterations and abnormalities drive cancer at the cell level while Factors are influenced by the greater external environment.

Incidence Trends

• Cancer is a major cause of morbidity and mortality worldwide.
• The incidence and mortality are decreasing in the United States.
• The most frequently diagnosed cancers are prostate cancer and breast cancer.

Cancer Incidence

• Prostate, lung and colorectal cancer are the most common cancers in men.
• Breast, lung and colorectal cancer are the most common cancers in women.

Mortality Trends

• Death rates have decreased by children.
• Death rates have decreased by adults in some cancer types.
• Death rates are increasing for cancers of pancreas, liver, and uterus and for melanoma of the skin in men.

Environmental-Lifestyle Factors

• Tobacco is a leading cause of preventable death in the United States.
• Tobacco is a Multipotent carcinogenic mixture.
• Tobacco smoking is linked to cancers of the lung, lower urinary tract, upper aerodigestive tract, liver, kidney, pancreas, cervix, uterus and myeloid leukemia.
• Secondhand smoke (ETS) is also harmful and contains many toxic chemicals.
• Cigar and pipe smoking are equally harmful

Environmental-Lifestyle Factors (Cont.)

• Cooking of fat, meat, or protein produces carcinogenic substances.
• Naturally occurring carcinogens include alkaloids or mold byproducts.
• Nutrigenomics looks at the Study of nutrition on the phenotypic variability of individuals based on genomic differences.

Nutrition and Cancer

• Many cellular processes are affected by nutrition.
• Nutrition can Silence genes that should be active or activating genes that should be silence
• Nutrition can Alter hormonal axes, influence cellular proliferation, and affect phenotypes or expression of key genes.

Nutrition and Cancer (Cont.)

• Xenobiotics (drugs, pesticides, food additives) have Toxic, mutagenic, and carcinogenic chemicals in food.
• The Two defense system for countering effects of Xenobiotics are Phase I activation and Phase II detoxification enzymes.

Nutrition and Cancer (Cont.)

• Dietary components can be activated into carcinogens or can prevent cancer
• The Pathways to cancer affected by diet include Cell cycle control, Differentiation, DNA repair, Gene silencing, Inflammation, Apoptosis, and Carcinogen metabolism

Obesity

• Obesity is Correlated with the body mass index (BMI).
• Three factors related to obesity and cancer are insulin-IGF-1 axis, sex hormones and adipokines or adipocyte-derived cytokines,
• The Mechanism of obesity-associated cancer risks is unclear.

Alcohol Consumption

• Alcohol Consumption is a Risk factor of oral cavity, pharynx, larynx, esophagus, liver, colorectum, and breast cancers.
• Genetic Factors are also involved.
• There is No "safe limit" of alcohol intake.

Physical Activity

• Physical activity Reduces cancer risk (breast, colon, other).
• Physical activity Decreases insulin and insulin-like growth factors, obesity, inflammatory mediators and free radicals, and Increases gut motility.

Ionizing Radiation

• Emission comes from x-rays, radioisotopes, radon, and other radioactive sources.
• Exposure causes cell death, gene mutations, and chromosome aberrations.
• Mutations in germ cells are heritable.
• The Increased use of diagnostic testing is a current concern.

Radiation-Induced Cancer

• Targeted effects: Chromosome aberrations, cell transformation, gene expression, alternative targets, mutagenesis in somatic cells.
• Biology is affected in nonirradiated cells, effects occur both in and on the microenvironment.
• Nontargeted effects includes Bystander effects, and Genomic instability.

Radiation-Induced Cancer (Cont.)

• Radiation includes Acute, latent, and microenvironmental effects.
• Organs with highly proliferative cells are especially affected by acute radiation exposure..
• Nontargeted radiation effects alter cell and tissue.
• Microenvironment changes = Radiation-induced cancers have latent periods that usually run from 5-10 years.

Ultraviolet Radiation

• Ultraviolet Radiation Causes basal cell carcinoma, squamous cell carcinoma, and melanoma (increased incidence).
• The Principal source from which the radiation comes is sunlight.
• The radiation released from this source includes Ultraviolet A (UVA) and ultraviolet B (UVB)
• Release of Tumor Necrosis Factor alpha (TNF-α) is released in the epidermis, and Produces ROS (reactive oxygen species)
• Promotes skin inflammation and release of free radicals

Electromagnetic Radiation (EMR)

• Electromagnetic Radiation (EMR) is Non-ionizing, low-frequency radiation
• Microwaves, radar, cell phones, and power frequency radiation associated with electricity and radio waves, fluorescent lights, computers, and other electric equipment produce EMR.
• While EMR is present among many devices, it May or may not be carcinogenic

Infection, Sexual and Reproductive Behavior

• The Top cancer-causing infections include Human papillomavirus (HPV), Helicobacter pylori (H. pylori) and Hepatitis B (HBV).
• Helicobacter pylori (H. pylori) Causes 85 to 89 percent of all stomach cancers.
• HBV and HCV account for a large majority of liver cancers.

Human Papillomavirus (HPV)

• Human Papillomavirus is the Most common STD in the United States
• 50% of the sexually active population carries related traces.
• HPV Spreads through skin contact; oral, vaginal, or rectal sex
• There are 150 related viruses: High risk results in cancer,.while low risk does not cause cancer.
• HPV Causes six types of cancer, Cervix, Penis, Vulva,Anus and Oropharynx (tongue and tonsils).

Air Pollution

• Particulate matter includes Particles and liquid droplets made up of acids, organic chemicals, metal, and dust particles.
• The makeup of Particulate matter is Carcinogenic and causes lung cancer,
• Particulate matter Also includes a High proportion of mutagenic agents.
• Primary particles are emitted directly from source ,including from construction sites and smoke stacks..
• Secondary particles are emitted from power plants, industries, and automobiles.

Air Pollution (Cont.)

• Indoor pollution tends to be Generally worse than outdoor pollution.
• Tobacco smoke (passive) causes formation of reactive oxygen free radicals and thus DNA damage.
• Radon gas trapped in houses forms decay products that are carcinogenic.
• Exposures from heating and cooking sources and asbestos are a hazard.
• Inorganic arsenic is also a hazard.

Chemical and Occupational Hazards

• Present in air, soil, water, household products, toys, workplaces, and homes.
• Upper respiratory passages, lung, bladder, peritoneum are easily targeted.
• A Substantial number of occupational carcinogenic agents exists, including Asbestos (mesothelioma and lung cancer).
• Dyes, rubber, paint, explosives, rubber cement, heavy metals, and air pollution are also occupational carcinogenic agents.

Prevention of Cancer

• Preventing cancer includes Avoiding or limiting alcohol use, Getting regular exercise and physical activity, Maintaining an appropriate/ideal body mass index, Maintaining healthy dietary habits, and Getting regular colorectal screening after age 50 .
• Getting regular mammography screening age 40 through 74, Pap tests yearly from age 21-65 if normal results is also included.
• Further options towards sunscreen, regular skin exams, smoke cessation, along with a low-dose helical computed tomography of lungs are good measures.

Questions cover mechanisms of chemotherapy side effects like leukopenia and oral ulcers. It also tests knowledge of cancer staging using the TNM system, including metastasis and lymph node involvement.