L19, L20, L22, L24- Neoplasia Flashcards
the 2 most common cancers in men are (1), and in women are (2)
1- prostate, lung
2- breast, lung
(also these cause the most cancer deaths by gender)
list some causes of atrophy
- dec workload
- dec blood supply
- loss of innervation
- interruption of trophic signals (hormones)
- aging
list some causes of hypertrophy
- inc functional demand (i.e. myocardial hypertrophy in HTN)
- physiological hypertrophy (hormonal, i.e. sex organs at puberty)
list some causes of hyperplasia
-inc functional demand (ex. inc RBCs at high altitudes)
-persistent cell injury (ex. skin in calluses)
-hormonal stimulation (endometrium)
[note stem cells are effected to generate more cells]
In dysplasia there is a variation in the shape and size of (1) and (2). (2) also undergoes some of the following, (3). The (4) of cells in tissue will also be altered.
1- cells (cellular pleomorphism)
2- nuclei (nuclear pleomorphism)
3- enlargement, irregularity, hyperchromatism (inc DNA - inc nuclear-cytoplasmic ratio)
4- disordered arrangement (loss of polarity)
(T/F) metaplasia and dysplasia are considered precancerous
F- although both are reversible cell adaptations, only dysplasia is considered premalignant
define aplasia
absence of an organ (only rudimentary organ present)
define hypoplasia
reduced size of cell/organ due to incomplete development
define agenesis
complete lack of organ
list the 4 properties that define a neoplasm
1- abnormal mass of tissue
2- growth Exceeds normal rate
3- growth is Uncoordinated like normal
4- growth Persists (in same excessive manner) even after removal of stimulus that evoked change
All neoplasms have two basic components: (1) and (2) [include definition]. Classification and behavior of tumors are based on (1/2) and their growth/spread are dependent on (1/2).
1/3- parenchyma: the neoplastic cells (classification + behavior)
2/4- stroma: CT, BVs, and various cells of adaptive/innate immune system (metastasis)
Define Benign Tumors [include general nomenclature]
- gross and microscopic appearances imply tumor will remain localized (no spreading), local surgical removal required
- no evidence of necrosis or hemorrhage
- suffix of -oma, ex. lipoma, fibroma, angioma (exceptions are melanoma, lymphoma)
list and define the 4 terms used to describe Benign Tumor architecture
- Adenoma, forms a gland
- Cystadenoma, adenoma with cystic (fluid filled) space
- Papilloma, contain finger like projections
- Polyp, elevated mucosal lesions
(1) are malignant tumors of mesenchymal origin
(2) are malignant tumors of epithelial origin
1- sarcoma (sar = fleshy)
2- carcinoma
(T/F) although most tumors usually contain cells of a single neoplastic clone, some may show divergent differentiation => mixed tumors which are always malignant
F- mixed tumors can be benign or malignant
define a teratoma
- tumor with cells of two or more germ layers
- originate from totipotent germ cells (usually from ovary or testes)
- they differentiate into all cell types in the body
- ex. usually composed of haphazard bone, epithelium, muscle, fat, nerve, ect
____ is ectopic rests of tissue (include ex)
Choristoma, ex. normal pancreatic tissue in submucosa of stomach/duodenum
____ is disorganized, benign mass composed of normal tissue indigenous to involved site (include ex)
Hamartoma, ex. pulmonary nodule (tissue is indigenous to the lung, just disorganized mass)
____ is a fluid filled space
cyst
(1) is the smooth muscle prefix
(2) is the skeletal muscle prefix
1- leiomyo- (-oma, -sarcoma)
2- rhabdomyo- (-oma, -sarcoma)
pleomorphic adenoma refers to…
benign tumor of the salivary glands
Wilms tumor refers to….
- aka Nephroblastoma
- malignant tumor of renal anlage (a precursor or rudimentary state of the kidney)
benign teratoma is referred to as (1)
malignant teratoma is referred to as (2)
1- mature teratoma, dermal cyst
2- immature teratoma, teratocarcinoma
fibromatosis, aka (1), is defined as (2)
1- desmoid tumor
2- soft tissue tumor of proliferating fibroblasts; appear benign, invade locally, no metastasis
(1) is a tumor of low grade malignant potential and are composed of (2)
1- carcinoid tumor
2- neuroendocrine cells
define Leukoplakia
white patch on mucous membrane- inflammatory or neoplastic
some tumors are productive and are describe as (1) or (2)
some tumors grow in specific/opposite directions (based on gross appearance), called (3) and (4)
1- serous (fluid/water like production)
2- mucinous (thick mucin production)
3- endophytic- grows inwards
4- exophytic- grows outwards
(1) define medullary tumor
(2) define desmoplastic
1- soft cellular tumor, minimal CT
2- dense fibrous stroma in tumor
(1) are tumors thought to arise from embryonic tissue and therefore mostly affect (2). Their cells are describe as (3). Include 4 examples: (4).
1- blastoma
2- children
3- small, blue, round
4- retinoblastoma, hepatoblastoma, neuroblastoma, nephroblastoma (Wilm’s tumor)
list the 4 characteristics that are used to define neoplasms
- differentiation / anaplasia
- rate of growth
- invasion
- metastasis
define anaplasia
- lack of cell differentiation
- usually used for an invasive neoplasm
Differentiation of a tumor (how close is it to the normal functional tissue it originates from) is defined as one of the following terms: (1)
-benign tumors are considered (2)
1- well, moderately, poorly differentiated
2- well differentiated
NOTE- the better the differentiation the higher the functional ability (resembles closely to normal cells)
the rate of growth tumors:
- benign tumors are (1)
- malignant tumors are (2)
1- slow growing
2- fast growing
Note- exception is benign leiomyoma that grow fast in pregnancy
Rate of growth of a tumor has a (1) relationship with differentiation and correlated highly with (2). In fast growing tumors (3) maybe evident.
1- inverse (well diff. = slow growth, poor diff. = fast growth)
2- blood supply
3- central necrosis
rate of growth of a tumor is measure microscopically by….
- mitotic count
- proliferation markers: Ki67
benign tumors are (non-/invasive)
malignant tumors are (non-/invasive)
1- non-invasive (just growth and expansion, putting pressure on surrounding tissue w/o invasion)
2- invasive
carcinomas (epithelial tumors) are termed (1) as long as the basement membrane remains intact; (2) is the major feature of (1)
1- carcinoma in situ (severe dysplasia, intraepithelial neoplasia)
2- reversible cell adaptation
metastasis can occur via one of the following….
- seeding in body cavities (usually peritoneal)
- lymphatic spread
- hematogenous spread (favored by sarcomas, liver and lungs are frequent deposition sites)
Monoclonality of neoplastic cells by examining (1) isoforms. If one isoform is detected, (2) is assumed; if greater than one isoform is detected, (3) is assumed.
1- glucose-6 phosphate dehydrogenase (G6PD)
2- neoplasia (derived from single stem cell)
3- hyperplasia (derived from multiple stem cells)
Growth Fraction = ….
(no. cycling cells) / (no. total cells)
Tumors with (high/low) growth fractions are susceptible to chemotherapy because of (2)
1- high
2- proliferating cells have an earlier (or easier) mortality
cell loss in tumors is much less than cell production, but mechanisms of cell loss include….
- apoptosis
- ischemia
- host defense mechanisms
(1) is the time required for a tumor to double in volume/mass, and it depends on (2) and (3)
1- doubling time
2- growth fraction
3- cell loss factor
Clinically detectable tumors are (1) in mass, which is equal to (2) number of cells and (3) doubling events from single cell (excluding cell loss).
It only takes (4) doubling events from this detectable stage for a tumor to become (5) in size and (6) in action.
1- 1 gram
2- 10^8 - 10^9
3- 30
4- 10
5- 1 kg
6- lethal
with time tumors develop subpopulations that vary in the following….
(note the rate at which they are generated are variable)
- antigenicity
- invasiveness
- metastatic potential
- growth factor requirement
list the extensive number of properties transformed cells have (hint- 7)
- autonomous (self growth signals / active oncogenes)
- resistant to growth inhibitory signals (tumor suppressor genes)
- resistant to apoptosis
- genomic instability (poor/defective DNA repair)
- unrestricted proliferation (telomerase reactivation)
- angiogenesis, invasion, metastasis
- immuno-surveillance evasion
unmutated genes that promote cell growth are called….
- proto-oncogenes (once mutated and active they become oncogenes, making oncoproteins)
- less mutations required than tumor suppressor genes (1 v 2)
- Tyr Kinase is most common affected pathway, but all signalling pathways can be affected
Tumor suppressor genes act by transforming cells to (1); the best four examples include (2). Note these genes require (3) in order to be considered dysfunctional.
1- Go phase
2- RB, p53 (TP53), TGF-β, APC
3- mutations on both alleles (Kundson’s two hit hypothesis- only one mutation for oncogenes)
evasion of apoptosis by tumor cells are usually through the dysfunction of the (1) pathway, commonly through the loss of (2), overexpression of (3) that inhibits (2), or overexpression of (4)
1- intrinsic / mitochondrial pathway
2- p53 (TP53 mutation) –> loss of pro-apoptotic function
3- MDM2 (inhibits p53)
4- anti-apoptotic members of BCL2 family: BCL2, BCL-XL, MCL1
list the 3 stem cell-like properties of tumor cells (that lead to limitless replicative potential / immortality)
1) evasion of senescence: avoid genetic/epigenetic alterations that trigger senescence (no signal that a cell is old and needs to die)
2) evasion of mitotic crisis: telomerase reactivation, avoids mitotic catastrophe => immortality
3) self-renewal: after cell division, at least one of the daughter cells are a stem cell
(1) is the concept where malignant cells prefer aerobic glycolysis over oxidative phosphorylation. In cancer cells there is increased conversion of glucose to (2), a mechanism that can be detected with (3) and a nonmetabolized derivative of glucose that prefers growing cells. (4) are responsible for inducing (1).
1- Warburg metabolism
2- lactose
3- PET (positron emission tomography)
4- oncoproteins (RAS, MYC, mutated GF-Rs)
In nutritional deficiency of normal cells (1) occurs for energy production and (2) occurs if (1) fails. In cancer cells, (3) is avoided and sustain growth on (4).
1- digestion/cannibalization of cell organelles (C sources)
2- cell death (apoptosis)
3- Autophagy (aka (1))
4- marginal nutritional / environmental conditions
discuss the role of oncometabolites
Oncometabolites are the products of oncoproteins, and at high levels they can lead to epigenetic changes and oncogenic gene expression (ex. mutated isocitrate dehydrogenase / IDH)
list the 6 steps of cancer enabled chronic inflammation
1) release of proliferation promoting factors
2) removal of growth suppressors
3) enhanced resistance to cell death
4) angiogenesis
5) activating invasion and metastasis
6) evasion of immune destruction
in chronic inflammation, tumor cell growth can be encouraged by factors released from…
infiltrating leukocytes and activated stromal cells (variety of GFs)
in chronic inflammation, tumor cell growth resists suppression due to…
- epithelial cell growth suppression
- limited cell-cell / cell-ECM interactions
- proteases degrade adhesion molecules => removal of barrier of growth
in chronic inflammation, tumor cells resist cell death by…
integrins from macrophages detach from basement membranes and cell-cell interactions
in chronic inflammation, angiogenesis is promoted by….
VEGF
in chronic inflammation, invasion and metastasis of tumor cells can be activated by (1) and (2)
- protease remodeling of ECM
- TGF-β promoting epithelial to mesenchymal transition
in chronic inflammation, tumor cell growth evade immune destruction by…
TGF-β favoring recruitment of immunosuppressive Treg cell OR suppression of Tc cells
HNPCC, aka (1), is the result of an inherited mutation in (2) genes. Patient’s genomes show (3), which is characterized by (4).
1- hereditary nonpolyposis colon cancer
2- DNA mismatch repair
3- microsatellite instability (MSI)
4- changes in length of short tandem repeating sequences
Xeroderma Pigmentosum results from a defect in (1) and increased risk of (2) due to (3)
1- nucleotide excision repair pathway
2- skin cancer (SCC)
3- UV light
(1), (2), (3) are disorders with hypersensitivities to DNA-damaging agents like ionizing radiation or DNA cross-linking agents like chemotherapeutic drugs
- bloom syndrome
- ataxia-telangiectasia (ALL- acute lymphoblastic leukemia)
- Fanconi anemia (AML- acute myelogenous leukemia)
Angiogenic factors in tumor angiogenesis are produced by (1) and (2). It has a dueling effect on tumor cell growth based on (3) and (4).
1- tumor cells
2- infiltration inflammatory cells (macrophages)
3- inc perfusion of nutrient and oxygen supply
4- new endothelial cells stimulating growth of adjacent cells via IGF (insulin) and PDGF (platelet-derived)
the main types of angiogenic factors are….
- FGF (fibroblast)
- VEGF (vascular endothelial)
- PDGF (platelet derived)
- HIF1α (hypoxia inducible factor 1α)
list the phases of metastasis
1) invasion of ECM
2) movement through intersitial tissue
3) vascular dissemination and homing of tumor cells
Invasion of tumor cells into ECM starts with (1) due to reduced number of (2). Then there is degradation of ECM by (3) enzymes. Tumor cells will then (4) ECM protein components, which include (5). Finally, (6) of tumor cells through the ECM is mediated by (7).
1- detachment of tumor cells
2- reduced E-cadherins (for adhesion)
3- collagenase, cathepsin B (very little seen in benign tumors)
4- attach
5- laminin receptors, integrins
6- movement
7- autocrine motility factors, cleavage products (of collagen, IGF)
Tumor cells disseminate in vasculature (including (1)) in the (2) or (3) forms. These cells will choose the next site in a process called (4) which is based on the following factors: (5).
1- BVs, lymphatics
2- single cell
3- multiple cell emboli (w/ platelets and WBCs)
4- homing
5- presence/absence of specific molecules, chemokines, unfavorable environment (ex. muscle)
list some general forms of tumor Ags (recognized forms of non-self in tumor cells)
(presented via MHC-I to Tc cells)
- products of mutated oncogenes and tumor suppressor genes
- overexpressed cellular proteins
- Ags from oncogenic DNA viruses
- oncofetal Ags at high levels
- altered cell surface proteins (glycolipids/glycoproteins)
- cell type specific differentiation Ags
The main mechanism of tumor cell destruction is presentation of tumor Ag by (1) to (2) cells. (2) are inhibited in (3) associated neoplasms.
1- MHC-I
2- Tc cells
3- virus-associated neoplasms (ex. EBV, HPV)
Alternate mechanisms to tumor destruction include:
- NK cells activated by (1) and destroying through (2) and (3)
- macrophages activated by (4)
- (5)
1- IL-2, IL-12 2- direct killing 3- ADCC (AB dep. cell mediated cytotoxicity) 4- IFN-γ 5- humoral destruction by complement
tumor cells can escape immune surveillance by….
- lost/reduced expression of MHC Ags
- outgrowth of antigenic negative clones
- inc production of proteins that promote immunosuppression (inhibit Tc)
tumors with high number of _____ have better prognoses
infiltrating lymphocytes- Tc cells, Th1 cells
list the 4 general carcinogenic agents
- chemical
- physical
- oncogenic virus
- bacterial infection
Chemical carcinogens are (highly/poorly) reactive and usually work along side (2). Direct acting agents are described as (3); indirect are described as (4).
1- highly reactive (w/ DNA, RNA, proteins –> mutagens)
2- physical agents (radiation) or oncogenic viruses
3- weak carcinogens, dose and time dependent
4- require metabolic conversion via P450 in liver
list the extensive number of chemical carcinogens (and their associated cancer, hint- 7)
- direct acting alkylating agents (cyclophosphamide –> leukemia)
- polycyclic aromatic hydrocarbons (tobacco –> lung CA)
- aromatic amines + azo dyes (–> hepatocellular/bladder CA)
- nitrosamines + amides (–> gastric CA)
- asbestos (–> mesothelioma, lung CA)
- β-Naphthylamine (–> urinary bladder CA)
- aflatoxin B1 via fava beans (–> hepatocellular CA)
Chemical carcinogenesis requires both a (1) to cause DNA mutation, and a (2) to cause (3).
1- initiator (causes initial permanent DNA damage)
2- promoter (at DNA, RNA, or protein level)
3- clonal expansion
Note- both required, but initiated cell can produce tumor if promoter is delayed for several mos-yrs
radiation carcinogens includes…
- UV rays
- Ionizing Radiation: electromagnetic or particulate radiation
UV radiation increases cancer risk depending on (1). Its mechanisms include (2), (3), (4). Examples include (5).
1- intensity and quantity of exposure
2- DNA damage
3- pyrimidine dimer formation (UVB light)
4- nucleotide excision repair (NER) mechanism is overwhelmed
5- SCC, BCC, melanoma
Ionizing Radiation includes (1) and (2). Radiant energy has the following 5 effects: (3).
- atomic bomb results in increased (4)
- therapeutic irradiation results in (5)
1- electromagnetic radiation (X-rays)
2- particulate radiation (α/β particles, protons/neutrons)
3- DNA damage, protein alteration, enzyme inactivation, membrane injury, macromolecule ionization => free radicals
4- leukemia
5- thyroid CA
Ionizing Radiation:
- damage depends on (1) of the organ/tissue
- (2) is most frequent, (3) is also seen in younger populations
- less frequent occurrences include (4)
- resistant organs/tissues include (5)
1- vulnerability of tissue 2- leukemia 3- papillary carcinoma of thyroid 4- breast, lungs, salivary glands 5- skin, bone, GI tract
list 3 common DNA oncogenic viruses and the cancers they may cause
- HPV: papilloma (skin/larynx), cervical CA
- EBV: nasopharyngeal CA, Burkitt’s lymphoma
- HBV: hepatocellular CA
HPV is a (DNA/RNA) virus and is oncogenic because of its production of (2) in affected cells that are involved in (3). The net effect of HPV is (4).
1- DNA virus
2/3- proteins (early proteins- E6/E7) that bind/inhibit products of tumor suppressor genes (involved in cell cycle)
4- immortalized cells + removal of restraints on cell proliferation
EBV is a (DNA/RNA) virus that infects (2) and (3) cells. Although the infection is latent, the infected cells are considered (4), which is worsened by (5). (6) is the most common tumor that presents as (7).
1- DNA 2- B lymphocytes (oropharynx) 3- epithelial cells (oropharynx) 4- immortal, propagate indefinitely 5- accumulation of more mutations => unchecked proliferation 6- Burkitt lymphoma, acquired t(8;14) 7- rapidly enlarging jaw masses
RNA oncogenic viruses are always (1) and have the following three types: (2)
1- retroviruses
2- acute transforming (quick cancer onset, viral oncogenes), slow transforming (no viral oncogenes, slow cancer development), HTLV-1 (human T-cell leukemia virus)
HHV-8 is a (DNA/RNA) virus that causes (2) cancer
1- DNA
2- Kaposi’s sarcoma
(1) is the only RNA virus implicated in human cancer, specifically (2)/(3), usually after 40-60 yr latent period. (4) protein stimulates proliferation, increased cell survival, interfere with cell cycle by causing (5). Initial proliferation is described as (6) and (7) leads to outgrowth of monoclonal leukemia.
1- HTLV-1 (human T-cell leukemia virus) 2- adult T-cell leukemia 3- lymphoma 4- viral Tax protein 5- genomic instability via interference with DNA repair functions 6- non-malignant, polyclonal 7- secondary mutations
H. Pylori is associated with the following cancers: (1). Its mechanism involves (2).
1- B cell lymphoma, MALToma, gastric adenocarcinoma
2- inc epithelial cell proliferation in chronic inflammation background
compare Driver and Passenger mutations
Driver: directly contribute to cancer development/progression, usually clustered w/in cancer genes
Passenger- acquired mutations with no effect on cell behavior, at random locations through out genome
- Burkitt’s lymphoma is caused by (1) DNA error
- CML is caused by (2) DNA error
- KRAS colon CA is caused by (3) DNA error
- Neuroblastoma is caused by (4) DNA error
- Retinoblastoma is caused by (5) DNA error
1- balanced translocation, t(8;14) 2- balanced translocation, t(9;22) 3- point mutation 4- gene amplification (NMYC) 5- deletion (del13q14)
(1) mutation is the most common mutation in human cancers. (1) are (2) type proteins and are activated by (3), which results in (4). This process also occurs with (5) gene.
1- RAS (oncogene - point mutation)
2- membrane-associated G proteins (bind GDP/GTP)
3- TK receptors
4- downstream gene activation => rapid cell growth
5- TP53 (p53, tumor suppressor gene)
(1) DNA event is the cause of CML, which activates (2) to increase (3) to activate (4)
1- t(9;22) translocation
2- BCR-ABL chimeric protein
3- TK activation
4- GF signaling pathways
(1) DNA event is the cause of Burkitt’s lymphoma, which leads to increased (2) resulting in increased (3)
1- t(8;14) translocation
2- MYC protein
3- pro-growth gene expression
Amplification of genes (cancer related) is common in (1) cancer via (2) gene which activates (3) AND in (4) via (5) gene.
1- Neuroblastoma
2- N-MYC
3- expression of genes involved in cell growth and telomerase
4/5- Breast Cancer, HER2 amplification
list the 5 types of mutated Oncoproteins
- GFs (ex. PDGF in astrocytoma)
- GFRs
- signal trasduction proteins (ABL, RAS)
- nuclear regulatory factors (transcription factors / amplification - CMYC, NMYC)
- cyclin and cyclin dependent kinases (cell cycle dysregulation)
list the other common tumor suppressor genes and associated cancers [besides RB, TP53]
- NF1 –> hereditary neurofibromatosis
- BRCA1/2 –> breast/ovarian CA
- APC –> adenomatous polyps in colon
- DCC –> deleted in colon CA
- WT-1 –> Wilm’s tumor
the most common mutations in HNPCC are in (1) and (2) genes and they are consider (3) genes in general for cancer predisposition
1/2- MSH2, MLH1
3- mutator / caretaker genes, involved in DNA repair (mismatch repair in this case)
(T/F) changes in epigenetics can also cause cancer through a change in gene expression
T- DNA methylation, acetylation, deacetylation, miRNA can all affect gene expression
list the clinical features of malignancy
- grading and staging of cancer
- effect of tumor on host
- tumor Dx
list the three reasons for grading and staging cancer
- Tx decisions
- determine prognosis
- research purposes
A cancer Grade is a measure of (1), with one of the following grades: (2). Grade is also based on (3) in addition to (1). The issues with tumor grading are (4).
1- differentiation
2- well, moderately, poorly
3- mitosis (mitotic figures), necrosis
4- variation in histology in different bodily areas + observer variation
which is more important, tumor grading or staging
Staging
A cancer’s Stage is a measure of (1), based on the following: (2)
1- spread (extent of spread)
2- size of primary tumor (T), extent of spread to regional lymph nodes (N), presence/absence of metastasis (M)
list the effects of tumor on the host (hint- 6)
- Local: location/impingement of surrounding tissue
- Functional: hormone production
- Acute Sxs: infarctions, rupture
- Constitutional Sxs: fever, wasting
- Paraneoplastic syndrome
- metastasis + its consequences
Local effects of some benign and malignant tumors:
- GI/UG tumors –> (1)
- just GI tumors –> (2)
- ovarian tumors –> (3)
- Pituitary adenoma –> (4)
- skin neoplasmas –> (5)
- submucosal leiomyoma –> (6)
1- bleeding / melena, hematuria
2- bowel obstruction
3- torsion (uterine tube –> cuts off blood supply)
4- destruction of remaining gland => hypopituitarism
5- ulcerations + secondary infections (b/c prone to trauma)
6- bleeding (close to endometrial lining –> inc menses)
what is a common local effect of a bronchogenic carcinoma (explain)
mass impingement and eroding of main bronchus => hemoptysis (blood-tinged cough)
Uterine leiomyomas are masses within (1). If located near the surface they can have the following local effects: (2). If located towards the periphery, (3) can be the effects. Leiomyomas are not caused by (4), but they are highly dependent on it.
1- myometrium (SM)
2- bleeding (inc in menstrual cycle), disrupted implantation / infertility
3- obstruction to surrounding structures, ex. bladder, rectum
4- Estrogen (therefore they have waxing/waning of size)
(1) is the presentation of a tumor mass in the myocardium. Common signs and symptoms are (2) caused by (3).
1- Atrial Myxomas
2- chest pain, dizziness, fainting, palpitations
3- mitral/tricuspid valvular stenosis
list the two main local effects of a renal cell carcinoma
1- invasion of renal pelvis –> hematuria
2- invasion to surrounding tissue –> paresthesia if it compresses spinal nerves (kidney is retroperitoneal)
Hormonal effects of tumors are more likely in (benign/malignant) tumors. A (2) tumor has general production of hormones leading to (3) syndrome.
1- benign b/c fully differentiated
2- neuroendocrine (carcinoid)
3- carcinoid syndrome (low malignancy risk)
what are the hormonal complications of a β cell adenoma in the pancreas
(insulinoma) inc insulin production and release => fatal hypoglycemia
(1) tumors have different symptomatology depending the hormone type produced. Most common is (2) production leading to (3) syndrome. Increased production of (4) causes high BP, muscle cramps, ect.
1- adrenal adenomas (adrenal cortex)
2- cortisol
3- Cushing syndrome
4- aldosterone
(1) is a cancer complication defined as loss of fat and lean body mass with the following as symptoms: (2). (1) is not due to the nutritional demand of tumors, but due to the following factors: (3), (4), (5). Fat and lean muscle loss is equal due to (6) and (7).
1- cachexia
2- anorexia, weakness, anemia
3- dec food intake
4- reduced synthesis/storage of fat + inc mobilization of FAs from adipocytes
5- TNF-α
6- inc basal metabolic rate
7- systemic inflammation (inc acute phase proteins)
(1) is a cancer complication that correlates with tumor growth as it disappears following treatment and reappears with recurrence. It is due to the release of (2), examples include (3) and (4).
1- fever
2- pyrogens
3- IL-1
4- TNF-α
define paraneoplastic syndromes and discuss their importance
- Sxs (of cancer Pts) that aren’t explained by local, distant, or hormonal effects (by affected tissue)
- It is important as it may: i) be earliest manifestation of occult neoplasm; ii) cause significant / lethal issues; iii) mimic metastatic disease; iv) lead to wrong Dx
(1) cancer is the best example of tumors causing paraneoplastic syndrome, as it is a (2) type tumor and can have any one of the following symptomatolgies: (3)
1- bronchogenic carcinoma (small cell carcinoma of the lung)
2- neuroendocrine (tissue)
3- Cushing’s Syndrome, SIADH, Myasthenia, Acanthosis nigricans, hypertrophic osteoarthropathy, venous thrombosis
____ is the gold standard for a cancer Dx
biopsy and microscopic tissue examination
list the sampling methods for cancer testing
- biopsy
- excision
- fine needle aspiration cytology
- smear
- body fluid
FNAC process is described as (1). It is useful for assessing (2) lesions, often for the following tissues: (3). These (4) tissues can go through FNAC if it is image guided.
(fine needle aspiration cytology)
1- aspiration of cells + attendent fluid –> stained smear (cytologic examination)
2- palpable / radiologically accessible lesions
3- thyroid, breast, salivary glands, lumps/bumps
4- liver, lung (deeper tissues)
Cytologic smear is most useful in (1) cancer detection. It is also used on the following body fluids: (2)
1- cervical cancer
2- pleural/peritoneal fluid, CSF, sputum, urine
list some laboratory techniques used for cancer Dx
- immunocytochemistry
- EM
- flow cytometric analysis: maturation markers in lymphoma/leukemia, DNA ploidy
- cytogenetics
- molecular diagnostic techniques
(1) detects nuclear/cytoplasmic proteins or surface markers with aid of specific Ab. It is used in tumor diagnosis to detect (2). This can be important for (3).
1- immunocytochemistry
2- cell of origin (especially with undifferentiated malignant tumors to see origin of metastatic tumors)
3- prognosis and therapeutic significance
list the various immunochemistry stains used
- epithelium: keratin (many types)
- melanoma: S-100/HMB45/Melan A
- mesenchyme: vimentin
- muscle: desmin
- neuroendocrine cells: chromogranin
- prostatic epithelium: PSA
- thyroid follicular cells- thyroglobulin
describe the factors for use of EM in cancer Dx
- detect cell of origin using cytoplasmic features of specialization
- instrumentation is a bit rarer and expense
(1) is the technique of staining a suspension of single cells with fluorescent surface markers using (2), then molecules are separated by (3) and (4). It useful in detection (5) and (6) cancers.
1- flow cytometric analysis 2- specific Abs (note multiple Ags can be used at once unlike immunihistochemistry) 3- size 4- fluorescent intensity 5- lymphoma 6- leukemia
list some of the molecular diagnostic techniques for cancer
- PCR / sequencing
- gene mutations (deletions, pt mutations)
- gene amplification
- gene rearrangement
- mRNA detection
Indicate what the following biochemical tumor markers are for:
(1) PSA
(2) CEA
(3) AFP
(4) HCG
(5) calcitonin
1- (prostate specific Ag) prostate adenocarcinoma
2- (carcino-embryonic Ag) colon / pancreatic / breast / gastric adenocarcinoma
3- (α-fetoprotein) hepatocellular carcinoma
4- (human chorionic gonadotropin) trophoblastic tumors, nonseminomatous testicular tumors
5- medullary carinoma thyroid
list some of the environmental influencers of cancer
- food/diet, high in fat (GI CA)
- infectious agent (virus, bacteria), HPV, EBV (Burkitts)
- smoking (pharynx/larynx, mouth, lung, esophagus, pancreas, bladder)
- EtOH (liver CA)
- sunlight (melanoma, BCC)
- radiation (leukemia, thyroid CA)
the peak age group for cancer is (1) range; possibly die to (2) and (3) as aging factors
1- 55-75 y/o
2- accentuated somatic mutation
3- decline in immune competence
childhood tumors are commonly describe as….
small, round, blue cell tumors (neuroblastoma, Wilms / nephroblastoma, retinoblastoma, many sarcomas)
list the some of the Inherited Cancer Syndrome and its associated gene mutations
- multiple endocrine neoplasia: MEN1, RET
- Li-Fraumenii syndrome: p53
- familial adenomatous polyposis: APC
list the 4 phases of a malignant tumor
1) transformation: normal cell –> malignant cell
2) growth of transformed cell: + angiogenesis, progression/heterogeneity
3) local invasion
4) distant metastasis
HPV Proteins:
- E6 effects (1)
- E7 effects (2)
1- TERT –> inc telomerase, inhibits p53
2- inhibits p21 –> inc CDK-4/cyclin-D –> inhibits RB-E2F
Both => immortilized cells, inc cell proliferation, genomic instability
RB binds (1) to inhibit its action in (2). Mutated RB will free up (1), allowing for (3)
1- E2F
2- G1 –> S phase transformation
3- unchecked proliferation
p53 functions to sense (1), and responds by (2) and if (2) fails, it allows (3) to occur.
1- DNA damage
2- slows cell cycle –> allowing more time for DNA repair
3- p53 upregulates BAX to inhibit BCL2 => activation of intrinsic apoptosis
compare clinical and pathological staging
Clinical- based on evidence acquired prior to decision of definitive treatment
Pathological- (more accurate), based on evidence during surgery (lymph nodes) and by pathologist observation of tissue samples
