Flashcards in Neoplasia 2 Definitions Deck (66):
T (14, 18) Translocation is most likely a ... ?
follicular B-cell lymphomas have a t(14;18) translocation that fuses the BCL2 gene from chromosome 18 with the active IgH locus on chromosome 14 resulting in overproduction of anti-apoptotic BCL2
Describe a lymphoma
Follicular lymphoma usually presents with painless, generalized, very slowly progressive enlargement of lymph nodes at an average age of 60. It is equally common in men and women, but twice as common in whites as blacks and Asians
What is the best treatment of Lymphomas according to nichols ?
Why do lymphomas grow really slow ?
Lymphocytes are subjected to apoptosis at a slow rate and the resulting decrease in apoptosis causes a very slow accumulation of excess lymphocytes over many years
What normally inhibits angiogenesis ?
thrombospondin-1 (induced by p53) and destruction of HIF-1alpha (by VHL)
How does hypoxia induce angiogenesis ?
Tumoral hypoxia calls off VHL, so that HIF-1alpha starts VEGF production and growth of irregular leaky blood vessels, a process mediated by VEGF.
What is the angiogenic switch ?
The conversion from the normal “make-no-new-vessels” to the “OK-full-steam-ahead-make-new-blood-vessels” milieu is called the angiogenic switch
What actually happens in the angiogenic switch ?
The angiogenic switch is mediated by HIF-1alpha, basic FGF, loss of p53, decreased thrombomodulin-1, and overcoming anti-angiogenic factors (angiostatin, endostatin, vasculostatin).
What is an anti-VEGF agent ?
What are the 4 steps of malignancy ?
(1) detachment of tumor cells from each other, (2) degradation of basement membrane and extracellular matrix, (3) attachment of tumor cells to basement membrane, and (4) migration of the escaped malignant cells through the interstitium.
How do tumor cells detach from each other ?
Detachment of tumor cells from each other is mediated in part by down-regulation of E-cadherin or mutated catenin.
How do tumor cells degrade the basement membrane ?
Degradation of basement membrane (type IV collagen) and extracellular matrix by performed by matrix metalloproteinases (especially MMP-9).
What mediates attachment of tumor cells to the basement membrane ?
Attachment of tumor cells to exposed basement membrane components is mediated by laminin and fibronectin receptors.
How do tumor cells migrate through the basement membrane and the extracellular matrix ?
Migration through basement membrane and extracellular matrix is mediated by binding to various factors such as autocrine motility factor
What is the metastasis pattern of colon cancer ?
Colon cancer typically metastasizes to local lymph nodes and then liver
What is the metastasis pattern of prostate cancer
prostate and breast cancers typically metastasize to local lymph nodes and then bone
What determines the area a tumor will typically metastasize to ?
haracteristic patterns are due to a combination of drainage pathways and organ tropism
How does organ trophism determine metastasizing patterns ?
The mechanisms of metastatic organ tropism include differential concentration of endothelial cell ligands for adhesion molecules in different organs and chemokines such as CXCR4 and CCR7 receptors in the case of breast cancer.
What is tumor embolus ?
Tumor cells that invade veins generally pass through the right heart and go to lungs, where they stop and elicit formation of blood clot around them
What happens to the blood clots that are formed in a tumor embolus ? What is the end result of a tumor embolus ?
Fibroblasts organize the blood clot part of this. The obstruction of small pulmonary blood vessels can eventually lead to pulmonary hypertension and right heart failure.
What are the classes of chemical carcinogens ?
Chemicals that cause cancer can be categorized as initiators or promoters, and direct or indirect.
What do initiators do ?
Initiators cause mutations, which become irreversible in the progeny of the mutated cell, if not reversed
After a mutation is initiated what does a promoter do ?
Promoters cause reversible proliferation of initiated cells.
What are direct carcinogens ?
Direct chemical carcinogens are few, generally reactive electrophiles
What are indirect carcinogens ?
Indirect chemical carcinogens require metabolic activation of procarcinogens commonly by cytochrome P450-dependent mono-oxygenases
What are common general carcinogens
Chemical carcinogens include estrogen, alcohol, anti-cancer drugs, asbestos, polycyclic and heterocyclic aromatic hydrocarbons, aromatic amines, amides, azo dyes and many other substance
What does UV light cause ?
What does radiation cause ?
What does HPV cause ?
Human papilloma virus (HPV) causes uterine cervical cancer and cancers of the mouth and upper respiratory tract. The development of a vaccine for HPV has made it possible to prevent many of these cancers.
What do Hep C and Hep B cause ?
Hepatitis C virus (HCV) and hepatitis B virus (HBV) cause hepatic cancer.
What does Epstein-Barr virus (EBV) cause ?
Epstein-Barr virus (EBV) causes lymphoma in immunocompromised patients
What does Helicobacter pylori cause ?
Helicobacter pylori causes gastric carcinoma and lymphoma.
How does the immune system respond to cancer ?
immune response recognizes some tumor antigens, mutated oncogene products, products of other mutated genes, overly or aberrantly expressed proteins, oncogenic viral products, oncofetal antigens (e.g. CEA, AFP), altered cell surface glycolipids or glycoproteins (e.g. CA-125, CA-19-9) and cell type specific differentiation antigens
What is the principle immune cell involved int he cancer immune response ?
The principal effector mechanism is by CD8+ cytotoxic lymphocytes. Others included natural killer cells (activated by IL-2), macrophages (activated) and antibodies.
How do tumor cells evade the immune response ?
Tumor can resist immune surveillance and response by selective outgrowth of Ag-negative cells, decreased expression of MHC molecules, lack of co-stimulation, and antigen masking.
* Tumors can engage the T cell inhibitory receptor, CTLA-4, or activate regulatory T cells that suppress immune responses.
What is an immunosuppressant that tumors secrete ?
How can tumor cells induce immune cell apoptosis ?
Some tumors express FasL, which can engage Fas on immune cells and induce the immune cell to commit suicide (apoptosis)
How can a benign tumor cause damage ?
5 common ways
1. They can impinge on adjacent structures.
2. They can cause obstruction of, for instance, the intestine.
3. They can have functional activity (e.g. hormones).
4. Surface ulceration can lead to bleeding or infection. Tumors can infarct or rupture.
5. They can compress an artery or vein and infarct an adjacent tissue or organ.
What are paraneoplastic syndromes ?
Symptoms not attributable to direct effects of tumor (or hormones native
to the primary tumor organ) are called paraneoplastic. Paraneoplastic syndromes occur in about 10% of cancer patients
What is cachexia ?
cachexia (wasting), which is in a class by itself. If cachexia were counted, the incidence would approach 100% for serious malignancies. Cachexia is a catabolic state of severe wasting mediated by tumor necrosis factor.
Other than cancer what can cause cachexia ?
Cancer is the most common cause, but AIDS, end-stage heart disease and end-stage lung disease also cause cachexia
What causes hypoglycemia ?
hypoglycemia (due to tumor insulin)
What causes carcinoid syndrome
carcinoid syndrome (due to serotonin)
Eaton-Lambert syndrome (resembling myasthenia gravis).
What is Hypecalcemia due to in cancer patients ?
Hypercalcemia frequently occurs in cancer patients. When it is due to lytic bone metastases, however, that is not counted as paraneoplastic
When is Hypercalcemia paraneoplastic
When it is caused by parathyroid hormone-related protein (PTHRP) and other substances released by tumors, it is counted as paraneoplastic.
What is the most common cancer related to hypercalcemia ?
Squamous cell carcinoma is the most common lung cancer type to cause hypercalcemia
What are the symptoms of hypercalcemia ?
Symptoms of hypercalcemia include nausea, vomiting, constipation, polyuria, disorientation, lethargy and seizures. Treatments include hydration and bisphosphonates.
What is the most common source of ACTH causing cushings syndrome ?
Pituitary adenomas are the most common source of ACTH causing Cushing syndrome. Small cell carcinoma is also a common source
weight gain, central obesity, moon face (fat deposition), weakness, hirsutism, hypertension, glucose intolerance, depression, psychosis, broad red abdominal striae, buffalo hump dorsal neck fat deposition, plethora, osteoporosis, menstrual irregularity, muscle wasting, and other manifestations
Pituitary Adenoma causing cushingos syndrome
attacks of cutaneous flushing (deep red erythema of face and neck, which may go on to persistent erythema or cyanosis), diarrhea, cramps, nausea, vomiting, cough, and other manifestations.
Carcinoid causing cushings
When do colonic adenomas have an increased chance of malignancy ?
anything below 10 mm will have an increased risk of malignancy
What dietary component is most associated with colon cancer
Low intake of unabsorbable vegtable fiber and high intake of refined carbohydrate and fat. Animal protein in the form of red meat has a strong association with colon cancer.
What are the 5 risks of colon cancer ?
1. charred red meat
2. criciferous vegtables
3. Inadequate intake of folate
4. Limited Caloric intake
What is the most common type of lung cancer ?
Adenocarcinoma of the lung. 87% are in the subpleural space
What is tumor stage ?
Tumor stage is the anatomic extent of tumor, including primary tumor size, extent of lymph node and distant metastases.
What is tumor grade ?
Tumor grade is a qualitative assessment of the differentiation of a tumor (extent to which the microscopic appearance resembles normal tissue at the primary site).
What is the relation between stage and grade ?
Basically, tumor stage is a radiologic thing and tumor grade is a pathologist thing. For most tumors, stage carries far more prognosis than grade.
What are the two aspects of making a cancer diagnosis ?
(1) discovery by symptoms, signs, radiology or serum markers, and second (2) specific actionable diagnosis by biopsy or cytology.
What are serum tumor markers ?
Serum tumor markers include PSA, CA-125, CA-19-9, HCG, AFP, CEA and immunoglobulins).
catabolic state of severe wasting mediated by tumor necrosis factor
symptoms not attributable to direct effects of tumor (or hormones native to the primary tumor organ)
Tumor Grade ?
qualitative microscopic assessment of the differentiation of a tumor
Tumor Stage ?
anatomic extent of tumor, including primary tumor size, extent of lymph node and distant metastases
tissue sample obtained by surgical or endoscopic forceps, incision or excision