Neoplasia Flashcards

Question

What are the 4 steps of invasion?

Answer 1

* **Loosening of cell-cell contacts** - inactivation of E-cadherin through a variety of pathways * **Degradation of ECM -** basement membranes and interstitial matrix degradation is mediated by proteolytic enzymes secreted by tumor cells & stromal cells, such as matrix metalloproteases and cathepsins * **Attachment to novel ECM components** - proteolytic enzymes also release growth factors sequestered in the ECM & generate chemotactic and angiogenic fragments from cleavage of ECM glycoproteins * **Migration of tumor cells**

Answer 2

* **once in the blood stream, cancer cells are still vulnerable** * Mechanical shear stress from blood flow * Apoptosis stimulated by loss of adhesion (anoikis) * And the innate and acquired immune system, if the cell can be identified as foreign * **Once they reach target site they extravastate** * Within the blood, tumor cells tend to cluster via homotypic adhesions between tumor cells or heterotypic between tumor cells & WBC/platelets. These may create **emboli** * Many tumors arrest in the first capillary bed they encounter (lung, liver, most commonly) * Solid tumor cells often display **CD44** adhesion molecule, which is the same vehicle used by T cells to extravastate in inflammation * **Tropism** * ****Certain tumors tend to target tissues for metastatic spread * Prostate prefers spread to bone * Bronchogenic CA spread to adrenal brain * Neuroblastoma spread to liver bone * Skeletal muscle and spleen rarely sites of metastasis

Answer 3

* **Hematogenous** * ****This is typical route of metastasis for **sarcomas**, but it is also the favored route for certain types of carcinoma, such as those originating in kideny renal cell carcinoma. Because of their thinner walls, veins are more frequently invaded than are arteries, and metastasis tends to follow the pattern of venous flow * Remember that uveal melanoma is a sarcoma and behaves as one * **Lymphatic** * ****Lymphatic can transport tumor cells to lymph nodes and then to other parts of the body. This is the **most common route of metasis for carcinomas.** * Uncommon for a sarcoma to metastasize via this route. * Lymphatic system does eventually drain to systemic venous via the **azygous vein**, and therefore these metastatic cells can eventually spread through the hematogenous route

Answer 4

Common in retinoblastoma

Answer 5

* The **TNM Classification of Malignant Tumors (TNM)** is a cancer staging notation system that describes the stage of a solid tumor with alphanumeric codes * **T** desribes the size of orginial (primary) **tumor** and whether it has invaded nearby tissue * size or direct extent of the primary tumor * **Tx**: tumor cannot be evaluated * **Tis**: carcinoma in situ * **To**: no signs of tumor * **T1, T2, T3, T4**: size and/or extension of the primary tumor * **N** describes nearby (regional) lymph **nodes** that are involved * Degree of spread to regional lymph nodes * **Nx**: lymph nodes cannot be evaluated * **No**: tumor cells absent from regional lymph nodes * **N1**: regional lymph node metastasis present; at some sites, tumor spread to closest or small number of regional lymph nodes * **N2**: tumor spread to an extent betwen N1 & N3 (N2 not used at all sites) * **N3**: tumor spread to more distant or numerous regional lymph nodes (N3 is not used at all sites) * **M** describes distant **metastases** * ****Presence of distant metastasis * **Mo:** no distant metasis * **M1:** metastasis to distant organs (beyond regional lymph nodes) * **Mx:** used variable to mean mutliple sites in different organs

Answer 6

* **G** (1-4): the grade of the cancer cells (ex. they are "low grade" to "high grade". High grade = poorly differentiated * **S** (0-3): elevation of serum tumor markers * **R** (0-2): the completeness of the operation (resection-boundaries free of cancer cells or not) * **L** (0-1): invasion into lymphatic vessels * **V** (0-2): invastion into vein (no, microscopic, macroscopic) * **C** (1-5): a modifier of the **certainty** (quality) of the last mentioned paramter

Answer 7

* **c:** stage given by clinical examination of the pt. The c-prefix is implicit in absence of the p-prefix * **p:** stage given by pathologic examination of surgical specimen * **y:** stage assessed after chemotherapy and/or radiation therapy; in other words, the individual neoadjuvant therapy of some kind (ex. tamoxifen) * **r:** stage for a recurrent tumor in an individual that had some period of time free from the disease * **a:** Stage determined at autopsy * **u:** stage determined ultrasonography or endosonography

Answer 8

* small, low-grade cancer, no metastasis, no spread to regional lymph nodes, cancer completely removed, resection material seen by pathologist: pT1 pNo Mo Ro G1; this grouping of T,N, and M, would be considered stage 1 * **pT1** - smallest detectable tumor (seen by pathologist) * **pNo** - lymph nodes resected and pathologist found no tumor cells * **Mo** - no metastases * **Ro** - resection complete with no tumor at surgical margins * **G1** - abnormal but minimal anaplasia

Answer 9

* If a pt develops mets from their primary tumor (ex. lung cancer) to a vital (ex. liver or brain) and it is the mets that lead to their demise, they did not die of liver cancer or brain cancer. They died of lung cancer metastatic to the liver or brain.

Answer 10

* Benign does not mean inconsequential (unimportant) * **Spenoid ridge meningioma** - most common primary brain tumor * Potentially blinding * Reduced acuity, afferent defect and acquired red-green color vision defect

Answer 11

* **Self suficiency in growth signals -** cells can proliferate without external stimuli - **oncogenes** * **Insensitivity to growth inhibition signals** - usually due to inactivation of **tumor supressor genes** * **The Warburg Effect -** cancer cells switch from oxidative phosphorylation (26 ATPs) to aerobic glycolysis (2 ATPs). Why? b/c the cell wishes to use most of the available metabolic intermediates to fabricate cell components for building new cells, rather than burn them up for just ATP * **Evasion of apoptosis -** malignant cells evade apoptosis (which is worrisome thing as we try to develop ways for retinal ganglion cells to avoid apoptosis in glaucoma * **Limitless Replicative potential -** essentially de-differentiated (which is worrisome thign as we try to develop ways for retinal ganglion cells to avoid apoptosis in glaucoma) * **Sustained angiogenesis** - anti-VEGF, currently used to inhibit neovascularization in macular degeneration, was first explored to as avenue to kill tumors * **Ability to invade and or metastasize** - ability to evade host immune response

Answer 12

* **Oncogenes -** mutated genes that promote autonomous cell growth * Their un-matured counterparts are called **proto-onocogenes** - products of proto-oncogenes promote cell growth but are regulated * Oncogenes encode **oncroproteins** that can promote cell growth in the absence of the usually required growth-promoting cell signals * It is the main signaling pathways that are altered including: * Receptor tyrosine kinase pathway, G-protein receptor pathway, the WNT pathway, the Notch pathway, the Hedgehog pathway, the TFG-beta/SMAD pathway and the NF-kB pathway

Answer 13

* TP53, a tumor suppressor gene, located on chromosome 17p, regulates cell cycle progression, DNA repair, cellular senescence and apoptosis * It is the most frequently mutated gene underlying human cancers

Answer 14

* the first quintessential tumor suppressor gene and knudson's 2-hit hypothesis

Answer 15

* Chemical * Radiation * Inflammation * Microbial (Bacteria & viral - both RNA & DNA)

Answer 16

* Chemical carcinogens have highly reactive electrophile groups that directly damage DNA, leading to mutation & eventually cancer * Direct-acting agents do not require metabolic conversion to become carcinogenic, while indirect-acting agents are not active until converted to an ultimate carcinogen by endogenous metabolic pathways * After exposure of a cell to a mutagen or an initiator, tumorigenesis can be enhanced by exposure to promoters, which stimulate proliferation of the mutated cells * Ex. of human carcinogens are direct-acting agents (ex. alkylating agents used for chemotherapy), indirect acting agents (eg. benzo[a]pyrene, azo dyes, aflatoxin) and promotor or agents that cause pathologic hyperplasia of the endometrium or regenerative activity in the liver

Answer 17

* Ionizing radiation causes chromosome breakage, translocations, and, less frequently, point mutations, leading to genetic damge and carcinogenesis * UV rays induce formation of pyrimidine dimers within DNA, leading to mutations. Therefore, UV rays can give rise to squamous cell carcinomas & melanomas of the skin. Individuals with defects in the repair of pyrimidine dimers suffer from xerodema pigmentosa and are particularly high risk. * Exposure to radiation during imaging procedures such as CT scans, pan-dental x-rays is linked to a very small, but measurable,increase in cancer risk in children

Answer 18

* Acquired conditions that predisopose to cancer can be divided into chronic inflammations, precursor lesions, and immunodeficiency states. Chronic inflammation disorders and precursor lesions span a diverse set of conditions that are all associated with increased cellular replication, which appears to create a "fertile" soil for the development of malignant tumors. * Indeed, repeated rounds of cell division may be required for neoplastic transformation, in that proliferating cells are the most at risk for accumulating the genetic lesions that lead to carcinogenesis * Tumors arising in the context of chronic inflammation are most carcinomas, but also include mesothelioma and several kinds of lymphomas * Immunodeficiency states predispose to virus-induced cancers

Answer 19

* Pt who are immunodeficient & those who have deficits in T-cell immunity (ex. AIDS), are at increased risk for cancers, especially those caused by **oncogenic viruses.** * These virally associated tumors include mainly lymphomas, but also certain carcinomas & even some sarcomas and sarcoma-like proliferations

Answer 20

* Compare the size of 25 year old thymus (left) to that of an 80 year old (right). Each is normal for pt age and is outlined with red arrows * B/c our immune system weakens & fail to target precancerous cells

Answer 21

* **HPV:** an important cause of benign warts, cervical cancer, and oropharyngeal cancer * Oncogenic types of HPV encode 2 viral oncoproteins, E6 & E7, that bind to p53 and Rb, respectively, with high affinity and neutralize their function * HPV cancers can be prevented by vaccination against high-risk HPV types * **Hepatitis B virus and hepatitis C virus:** cause of between 70% and 85% of liver CA * **Oncogenic effects** are multifactorial dominant effect seems to be immunologically mediated chronic inflammation, hepatocellular injury, and reparative hepatocyte proliferation * **HBx protein** of HBV and the HCV core protein can activate signal transduction pathways that also may contribute to carcinogenesis. New medications can cure Hep-C * **H. pylori** (cause of stomach ulcers) implicated in gastric adenocarcinoma and MALT lymphoma * Pathogenesis of H. pylori-induced gastric cancers is multifactorial, including chronic inflammation and reparative gastric cell proliferation * H. pylori pathogenecity genes, such as CagA, also may contribute by stimulating growth factor pathway * **Chronic H. pylori infection** leads to polyclonal B-cell proliferations that may give rise to a monoclonal B-cell tumor (MALT lymphoma) of the stomach as a result of accumulation of mutations

Answer 22

* Surgery * Radiation (general or focused) * Adjuvant ( general chemo or receptor-targeted therapy)

Answer 23

* Estrogen receptors * Progesterone receptors * **HER2** - human epidermal growth factor receptor 2. It causes these cells to grow and spread faster than the one with normal levels of the protein * **Triple negative breast cancer** - If all 3 receptors are negative. Absent targetable receptors, general chemo is usually required. (All 3 receptor fuel the growth of breast cancer) * Those with **BRCA1 or BRCA2** mutations are at increased risk of triple negative breast cancer

Answer 24

* Researcher using fruitflies, bred to mimic genetic mutations in cancer pt. * He sequences DNA from pt tumor to look for errors and then replicates those errors into fruit flies to create "fly avatars". The fly develops tumor and thats when the drug testing comes in. * By doing this he comes up with a cocktail of 2 to 3 drugs that work together against the tumor. He passes on his findings to pt & the pt oncologist

Answer 25

* Researchers used monolconal antibodies to treat pt with **B cell lymphomas** * Each B cell have a unique receptor (BCR) on the surface which helps them respond to different types of infections * As lymphoma express the same type of BCR. By targeting this BCR we can eliminate lymphoma. * To test this, they produced monoclonal antibodies specific for unique BCR expressed by a pt lymphoma cells aka **anti-idiotype therapy.** * This was successful but technique is too difficult & costly for clinics.

Answer 26

* **Cancer-associated retinopathy** is characterized by * painless and progressive visual loss * photopsia (Visual distortion) * ceco-central scotoma * loss of rod & cone function * demonstrated by **electroretinography** due to production of autoantibodies against retinal antigens stimulated by a systemic, non-ocular tumor. * Anti-retinal antibody testing is commercially available * **VF:** central, cecocentral, or equatorial scotomas * **Fundus angiography:** usually normal. Rarely show areas of leakAge if vasculitis or macular edema present * **OCT:** retinal thinning * **Electroretinogram (ERG):** Full field ERG almost always abnormal (attenuated or absent photopic and scotopic response). In CAR where mainly the cones are affected, full field ERG could be normal but multifocal ERG will be abnormal * **FAF:** Parafoveal ring with enhanced autofluorescence with normal autofluorescence within the ring and hypoautofluoresence outside the ring * **The malignancy most commonly associated with this disorder** * small-cell lung cancer * followed by gynecologic (uterine & cervical) & breast cancers. * Occasional cases have been associated with non-small lung cancer, hodgkin lymphoma, and pancreatic, prostate, bladder, laryngeal, and colon cancers

Answer 27

Ceco-central VF loss

Answer 28

* **Cancer metastasis that appear in and around the eye are usually from** * Breast cancer (w) * Lung cancer (m) * **Other less common sites include** * the prostate * the kidney * the thyroid * gastrointestinal tract * lymphoma and luekemia can also metastasize to the eye and orbit

Answer 29

normally permeable vessels (episclera, choroid, ciliary body) If primary unknown,usually difficult to determine source from biops of a met in the eye

Neoplasia Flashcards

(55 cards)