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NURS 5315 Cancer Biology fully solved
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anaplasia - answer not differentiated, nucleus has irregular shape, size, tissue structure is abnormal. metastasis - answer the spread of cancer cells from the site of the original tumor to distant tissues and organs through other blood or lymphatic vessels. benign tumor - answer tumor that grows slowly has a well-defined capsule, non-invasive, well-differentiated, low mitotic index, does not metastasize. Malignant tumor (cancer) - answer tumor that is rapid-growing, not encapsulated, invasive, poorly differentiated (anaplasia), has a high mitotic index can spread distantly. carcinomas - answer cancers that arise in the epithelial tissues carcinoma in situ (CIS) - answer "in its original place", cancer cells have not spread beyond where they first formed. Objectives Cancer Biology: - answer Describe how cancer cells differ from normal cells, Discuss the genetic basis of cancer, including the role of oncogenes and tumor suppressing genes, Define the origins of cancer based on nomenclature (carcinoma, sarcoma, blastoma, carcinoma in situ) Student Responsibility: Determine tumors that produce biologic markers and "connect" the marker to the specific tumor. Link the pathology
of cancer with clinical manifestations of cancer - including paraneoplastic syndromes, cachexia, fatigue, immune suppression and systemic effects of cancer. Describe the core concepts of metastasis including mechanisms and patterns of metastasis. Identify the TNM staging for cancer. Benign Tumor: - answer Slow growth, well-define capsule, a noninvasive, well differentiated, low mitotic index, does not metastasize malignant tumor (cancer): - answer rapid growth, not encapsulated, invasive, poorly differentiated: anaplasia, high mitotic index, can spread distantly (metastasis) anaplasia: - answer not differentiated, nucleus has a regular shape, size, tissues structure is abnormal metastasis: - answer the spread of cancer cells from the site of the original tumor to distant tissues and organs through either blood or lymphatic vessels carcinomas: - answer cancers arising in epithelial tissue carcinoma in situ: - answer "in its original place", cancer cells not spread beyond where they first formed adenocarcinoma: - answer cancer arising from ductal or glandular structures sarcoma: - answer cancer arising from mesenchymal tissue
Highest cancer death rate for men: - answer prostate cancer it has 10% death rate Highest cancer death rate for women: - answer Lung cancer 26% death rate Second highest cancer date rate in women: - answer breast cancer has 16% death rate Cancer Cell Hallmarks (from circular diagram): - answer Cancer Cell Hallmarks (from circular diagram): - answer Resist cell death: Apoptosis is regulated by the intrinsic pathway (monitors sell stress ) any extrinsic pathway (activated through plasma membrane receptor complex linked to intracellular activation of apoptosis known as the death receptor). Apoptotic pathways are dysregulated in most cancers. Anti apoptotic mols are overexpressed or under expressed Duty mutations. Cancer Cell Hallmarks (from circular diagram): Deregulate cellular energetics
- answer Cancer Cell Hallmarks (from circular diagram): sustaining proliferative signaling: - answer Normal cell proliferation: Growth factors bind to specific receptors on the cell surface receptors signal cytoplasmic molecules to undergo activation (Regulating DNA synthesis, entrance into the cell cycle, changes in expression of genes for cell metabolism) Proliferation is stopped by decreased levels of growth factors in the environment or inactivation of signaling pathway components
proto oncogenes: - answer genes that encode components of receptor mediated pathways designed to regulate normal cell proliferation. cancer cells express mutated or overexpressed forms of these genes (oncogenes) oncogenes : - answer Mutated or overexpressed proto oncogenes....Independent of normal regulatory mechanisms-->so goes into unregulated expression of proliferation signals -->uncontrolled cell growth. Oncogenes - answer activated by gene amplification increased expression of an uncle gene or drug resistant genes. Human epidermal growth factor receptor 2 (HER2): - answer AKA epidermal growth factor receptor gene in breast cancer production. Is up-regulated and hyper -esponsive to low levels of EGF. Cancer Cell Hallmarks (from circular diagram): avoiding immune destruction - answer Cancer Cell Hallmarks (from circular diagram): evading growth suppressors - answer Uncontrolled cancer cell proliferation due to inactivation of tumor suppressor gene. tumor suppressor genes : - answer AKA anti oncogenes. regulate the cell cycle, inhibit proliferation resulting from growth signals, stop cell division when cells are damaged, prevent mutation Cancer Cell Hallmarks (from circular diagram): enabling replicative immortality: - answer Hallmark of cancer cells have an unlimited lifespan and continue to divide for years. Normal cells can divide a limited number of times --> become old -->stop dividing -->apoptosis
reprogram, cellular metabolism in order to most effectively support neoplastic proliferation. Even in the presence of adequate oxygen,cancer cells don't use oxphos but are reprogrammed to glycolysis (Warberg effect)...even under normal oxygen conditions -->Aerobic glycolysis Cancer Cell Hallmarks (from circular diagram): (**Still emerging as a hallmark) Escape immune system: - answer allows cancer cells to evade immunological destruction, in particular by T and B lymphocytes, macrophages, and natural killer cells Progression from normal to neoplasm: - answer normal epithelium-->low- grade epitheilial neoplasia-->High grade intraepithelial neoplasia-->invasive carcinoma Carcinoma in situ: - answer Pre invasive epithelial tumors of glandular or squamous cell origins. incrementally develops into cancer as it accumulates genetic mutations --> abnormal growth, increased proliferation rate. Occurs frequently in the cervix, skin, oral cavity, esophagus, bronchus. in glandular epithelium : stomach, endometrium, breast, large bowel. CIS can vary from low grade to high grade dysplasia. high grade dysplasia CIS: - answer highest likelihood of becoming invasive cancer Oncogenes: - answer are mutated versions of proto-oncogenes, which are normal genes in charge of positive regulation of the cell-cycle. The protein products of proto-oncogenes stimulate cell growth and division - they're like a gas pedal in a car.
Tumor suppressor genes: - answer are in charge of negative regulation of the cell cycle, so their protein products stop its progression and promote apoptosis or cell death. Tumor suppressor genes - answer are involved in DNA repair mechanisms and inhibiting transcription factors that try to push the cell along in the cell cycle
- so they're like the brake pedal in a car. Molecular basis for Cancer: - answer Acquired (environmental) DNA damaging agents: Chemicals, Radiation, viruses-->Normal Cell-->DNA Damage--
successful DNA repair OR Failure of DNA repair-->Mutations in the Genome of somatic cells due to Inherited mutations in 1) genes affecting DNA repair,
- genes affecting cell growth or apoptosis-->1. Activation of growth promoting oncogenesUnregulated cell proliferation 2. Inactivation of tumor suppressor genesunregulated cell proliferation 3. Alterations in genes that regulate apoptosisdecreased apoptosis-->This all leads to clonal expansion--
Tumor Progression--> Malignant Neoplasm Normal cells transform and become cancer cells - answer Behave autonomously, do not follow "usual" cell control mechanism. No contact inhibition - thus when come up against/contact other cells, continue to grow. Do not need an anchor for continued growth - thus are able to grow in a suspension. Have long life span. Lack differentiation (anaplasia). Do not acquire specialized functions or organization. Cells are pleomorphic (size, shape isn't uniform). More non-differentiated, more malignant Cancer cell Metabolism - answer Rapidly dividing, able to survive in a sub- optimal environment that normal cells unable to tolerate. Because dividing rapidly, use nutrients that are then not available to normal cells. Have ability to perform glycolysis without using mitochondria to generate "usual" ATP - but able to generate "normal" number ATP molecules. Despite anaerobic metabolic pathway, able form lipids and other cell building blocks
Heterogeneity: - answer the quality or state of being diverse in character or content. Cancer cells - answer can develop from cancer stem cells. Cancer Stem Cells: - answer Only rare cells within a cancer can initiate cancer regrowth. In laboratory experiments it takes as many as 100,000 breast cancer cells injected into a mouse mammary fat pad to form a new cancer. If the breast cancer cells are sorted, one rare subtype (shown here in red) is much more proficient at forming new cancers. Conventional chemotherapy - answer can destroy the bulk of a cancer. However, if the cancer stem cells (red cells) are not destroyed, the cancer may regrow. If therapies can be devised that kill the cancer stem cells, then durable long-term responses may be achieved Tumor-Induced Angiogenesis: - answer process similar to Wound healing. Malignant tumors secrete angiogenic factors and tissue remodeling matrix metalo proteinases (MMPs)that actively induce the formation of new blood vessels. New blood vessels are formed from both local endothelial cells and circulating precursor cells recruit from the bone marrow circulating platelets can also increase regulatory proteins in the tumor. Treatments targeting loose endothelial juntions: - answer The vessels formed within tumors differ from those in healthy tissue.-->They originate from endothelial sprouting from existing cappilaries and irregular branching , rather than regular branching seen in healthy tissues. -->The Inter endothelial cell contact is less tight so the vessels are more porous and prone to hemorrhage, as well as allowing passage of tumor cells into the vascular system.
BFGF and BFGFR: - answer basic fibroblast growth factor and its receptor respectively; PDGF and PDGFR: - answer platelet derived growth factor and its receptor respectively V EGF and VEGFR: - answer Vascular endothelial growth factor in its receptor respectively Carcinoma in situ: - answer Pre invasive cancer; Atypical cells. Have not penetrated basement membrane, no local invasion. Fate of carcinoma in situ: - answer May remain where they are and not change. / May progress to invade and metastasize. / May regress and go away. More dysplastic the cells are the more likely to be invasive Cancer—Genetic Basis - answer Changes in cell's genes cause cell to become a cancer cell. Basic theory = gene changes occur fairly constantly over time. When a critical number mutations occur--> becomes cancer Normal to cancerous cell transition - answer As mutations occur and cells become a cancer → has advantage over normal surrounding cells → clonal proliferation → cancer in situ → potential for advancing
- answer Oncogenes - answer Proto-oncogenes: genes encode components of receptor- mediated pathways designed to regulate normal cellular proliferation;
Oncogene exampleD cycling, - answer Oncogene example HER2 (ERBB-2): human epidermal growth factor receptor 2: - answer oncogene in breast CA this is upregulated and is hyperresponsive to low levels of EGF (epidermal growth factor). Tumor suppressing genes - answer Genes that inhibit or decelerate proliferation (hit the brakes) Suppress oncogenes - decrease cell growth, mutation, replication Examples of tumor suppressing genes: TP53: - answer also called the guardian of the genome. It is a caretaker gene, responsible for the maintenance of genomic integrity. Li-Fraumeni syndrome - answer is a very rare inheritable loss-of-function mutation in TP53 in one allele, 25-fold increase of developing malignancy at early age (<50 years). Breast cancer, brain tumors, acute leukemia, soft tissue sarcomas, bone sarcoma Oncogene example RB gene (retinoblastoma): - answer Mutations in RB lead to persistent cell growth. ~ 50% children with retinoblastoma have the inheritable form of mutated RB gene. BRAC: BRCA1 and BRCA2 (Breast cancer type 1 &2 susceptibility protein genes)
- answer are responsible for DNA repair. End result of tumor suppressing gene changes = - answer loss of caretaker gene function. Gene mutations generally occur in somatic cells therefore cannot be inherited BUT predisposing mutations ARE inherited
Biological Tumor Markers: Purpose/Use - answer Surveillance, diagnosis, therapy, assess recovery, assess recurrence. Produced by benign and malignant tumor cells. Generally found on (or in) tumor cell, serum, spinal fluid, urine If Biological Tumor Markers causes symptoms - answer paraneoplastic syndrome Alpha fetoprotein (AFB) - - answer serum marker for liver, germ cell tumors Prostate-specific antigen (PSA) - - answer serum marker for prostate tumors Beta human chorionic gonadotropin ( β -HCG) - - answer germ cell, choriocarcinoma Carcinoembryonic antigen (CEA) - - answer serum marker for numerous tumors (e.g. colon, lung, breast...) Bence Jones Protein - - answer urine marker for multiple myeloma BRCA1 and BRCA2 - gene mutations; - answer breast, ovarian CA Neuron-specific enolase (NSE) - - answer serum marker for small cell lung cancer and neuroblastoma HCG: human chorionic gonadotropin (hCG), hormone, - answer made up of an alpha and beta subunit. There are two common types of hCG tests. Usually,
Interaction of PD-L1 (programmed death-ligand 1) on the tumor cells with PD- 1 (programmed cell death protein 1) on a T-cell - answer reduces T-cell function signals to prevent the immune system from attacking the tumor cells Metastasis: - answer Not all cancer cells have ability. Tend to be tissue selective: ex lung cancer goes to brain, liver, bone Epithelial-Mesenchymal Transition (EMT): - answer The model for transition to metastatic cancer cells. Originate from highly differentiated in polarized epithelial cells that form structured sheets stabilized by adherence is to neighboring cells into a basement membrane along the cells basal surface. Normally occurs in wound healing and embryonic development. Cells have suppressed expression , a loss of polarity , increased migratory capacity, an elevated resistance to apoptosis , the ability to re differentiate into other cell types. In order to move to distant sites (metastasize), cells must - answer Outgrow, alter immediate limiting environment, Access local blood, lymphatic vessels, Survive in circulation, Attach, grow in new environment, May survive but not proliferate...
- answer Matastasis: - answer cancer cells undergoing oncogenic mutations --> they acquire the epigenome instability -->become to be more aggressive and then they can release the prerequisite-->have the micro environment -->through the EMT (endothelial-mesenchymal transition) -->intravasation--> and then they go into the bloodstream and life in transit and then they can go through the circulation to the secondary place and through a process called the HOMING (attachment/attraction) extravasation-->to survival signals and then go to the second sight and that second site has the micro environment as
supported survival and then they stay there and through the full colonization and become to be secondary tumor. Patterns of Metastasis of Cancers: - answer Common metastatic cancers: - answer Lung, colorectal, testicular, prostate, breast, head and neck, ovarian, sarcoma, and melanoma cancers Breast cancer metastasis pattern: - answer cells spreads through bloodstream to bones but rarely to kidney or spleen. Lymphomas pattern of metastasis: - answer often spread to the spleen but uncommon to bone Clinical Manifestations of cancer: - answer symptoms that can be a result of the malignancy itself, or of the treatment of CA (chemo, radiation) Paraneoplastic syndromes: - answer rare disorders that are triggered by an altered immune system response to a neoplasm. They are defined as clinical syndromes involving nonmetastatic systemic effects that accompany malignant disease. These syndromes are collections of symptoms that result from substances produced by the tumor, and they occur remotely from the tumor itself. The symptoms may be endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous in nature. Cachexia, - answer a multiorgan syndrome that That includes many symptoms including anorexia, early satiety, weight loss, anemia, market weakness, taste alterations, altered protein, lipid, and carbohydrate metabolism. It is most severe form of malnutrition associated with cancer an
Therapy - goals - answer Remove cancer cells, Stop cancer cell growth, Kill cancer cells New Therapy Targetting the Hallmarks: ex: Immunotherapy targeting therapies... - answer takes advantage of checkpoint inhibitor..immune system will recognize the CA cell again and destroy it. Angiogenesis targeting therapies: - answer inhibitors of VGF signalling and block formation of blood vessels. Immunotherapy: - answer A treatment that uses the bodies natural defenses to fight cancer. It uses substances made by the body or in a laboratory to improve or restore immune system function. Immunotherapy may work by: 1. Stopping or slowing the growth of cancer cells 2.Stopping cancer from spreading to other parts of the body 3.Helping the immune system work better at destroying cancer cells There are several types of immunotherapy, including: - answer Monoclonal antibodies, Non-specific immunotherapies, Oncolytic virus therapy, T-cell therapy: chimeric antigen receptor (CAR) T-cell therapy., Cancer vaccines: prevention vaccines and treatment vaccines. Interferons such as interferon alpha (Roferon-A [2a], Intron A [2b], Alferon [2a]). - answer Side effects of interferon treatment may include flu-like symptoms, an increased risk of infection, rashes, and thinning hair. Interleukins: such as IL-2 (aldesleukin, brand name Proleukin). - answer It is used to treat kidney cancer and skin cancer, including melanoma. Common side effects of IL-2 treatment include weight gain and low blood pressure, flu- like symptoms.
Cancer in Age Group: Cancer in Children: - answer Most common cancers: leukemia and brain tumor (61% for 0-14 yrs), solid tumors, such as neuroblastoma and soft tissue or bone sarcomas are less common. Cancer in Age Group: Adolescents (15-19y): - answer Hodgkin lymphomas most common. Leukemia, thyroid carcinoma, brain tumors, and germ cell tumors also are common. Cancer in Age Group Children Etiology: - answer genetic factors, environmental factors; Diagnosis during active growth periods; Prognosis: ~85% are cured. Cancer in Age Groups: Elders - answer Incidence increases with age. Cancer supported by changes in immune system, immunocompetence, longer time exposed to potential gene mutations. More likely develop solid tissue/organ cancers
