Chapter 6 (neoplasia)

Question 1

in the US what are the top 2 leading causes of death?

Answer 1

• cardiovascular

- cancer

Question 2

shared characteristics of cancers?

Answer 2

• cancer is a genetic disorder caused by DNA mutations. (can be environmental mutation or genetic) epigentic DNA modifications such as methylations and histone modifications can cause this, which themselves come from mutations of proteins that regulate them.
• genetic alterations are heritable and gives cancer cells an advantage for survival. The cancer cells out-compete their neighbors. The tumor comes from a single cells called “clonal”.
• epigenetic alterations to that affect cancer properties are called cancer hallmarks.

Question 3

describe malignant and benign neoplasm?

Answer 3

Bengin: innocent characteristics but can be lethal if they grow into surrounding vital tissues.
Malignant: The tumor can metastasize and invade surrounding tissues and cause damage.

Question 4

2hat are the 2 components of tumors?

Answer 4

• Parenchyma (neoplasic cells)

- Stroma (supporting host derived non-neoplastic stroma)

Question 5

Describe benign tumors?

Answer 5

designated by attaching the suffix “-oma” Fibrous tissue tumor that is benign = fibroma. Adenoma is used generally applied not only to benign epithelial neoplasms that produce glandlike structures and also those that lack glands.

Question 6

Describe malignant tumors?

Answer 6

-malignant neoplasm coming from solid organs are called “sarcoma” while those coming from mesencymal cells of the blood are called leukemias or lymphomas.
Examples: fat cells (liposarcoma),
-malignant neoplasma of epithelial cells are called carcinomas.

Most cells are usually resemble each other, from the single transformed progenitor cell that they came from.

Question 7

what are the 3 fundamental characteristics of benign and malignant neoplasms.

Answer 7

1. differentiation and anaplasia local invasion and metastasis.
   -Differentiation and anaplasia: Anaplasia is a lack of differentiation. Differentiation refers to the extent to which neoplasm resemble their parenchymal cells of origin.
   mitotic bodies are rare and the cells closely resemble the cell type that they came from. thyroid cancer for example may contain well structures follicles.
   Scirrhous tumors are defined by their abundant fibrous stroma.
   Malignant tumors are anaplastic. (which means they loose their shape and function).

Question 8

what are the morphologic features of anaplastic cells?

Answer 8

• pleomorphism: variation in size and shape
• nuclear abnormalities: dark-stained (hyperchromatism) variable size. nuclear to cytoplasmic ratio gets close to 1:1.
• Tumor giant cells: they are considerably larger than neighboring cells and may possess one enormous nuclei or several nuclei.
• Atypical mitosis:
• Loss of polarity

Question 9

benign tumors can secrete what?

Answer 9

the same material as their origin cell. can be from cancers of nonendocrine origin, may produce so-called ectopic hormones; ACTH made by lung cancer, PTH, Insulin, glucagon.

Question 10

describe dysplastic epithelium?

Answer 10

a loss in the uniformity of individual cells and their architectural orientation.
when dysplastic changes are severe and involve the entire thickness of the epithelium the lesion is referred to as carcinoma in situ, a preinvasive stage of cancer.

dysplasia is not cancer but it can mark the possibility of an invasive cancer developing.

Question 11

Describe the local invasion of a tumor?

Answer 11

malignant tumors can invade surrounding tissues. Benign tumors form a capsule and expand slowly. The rim of fibrous tissue that forms the capsule consist largely of ECM that is deposited by stromal cells such as fibroblasts, which are activated by hypoxic damage to parenchymal cells resulting from compression by expanding tumor.
This capsule makes the tumor discrete, movable and easy to remove via surgery.
Not all benign tumor have a capsule: leiomyoma of the uterus is discretely demarcated from the surrounding smooth muscle by a zone of compressed and attenuated normal myometrium.
Hemangiomas: a benign vascular neoplasms that are difficult to excise do to the lack of demarcation.

Question 12

what is it called when a patient has a hidden metastasis?

Answer 12

occult metastases. Larger tumors usually increase the chance of metastasis. But this is not always the case: basal cell carcinomas of the skin and most primary tumors of the CNS are very locally invasive.
lymphomas and leukemias are taken to be disseminated diseases at diagnosis and are always considered to be malignant.

Question 13

what are the 3 ways malignant neoplasms disseminate (spread)

Answer 13

-seeding withing body cavities (brain cancers may travel through the ventricles and into the meningeal surfaces) This type of seeding is typical of ovary cancer.
-lymphatic spread: This is more typical in carcinomas whereas hematogenous spread is favored by sarcomas. NOTE that cancers traveling in the lymph can “skip metastasis” can skip lymph node and may even end up in the blood circulation. the 1st node affected is called the SENTINEL lymph node and blue-dye or radiolabeled dye can be injected to detect it.
-Hematogenous spread: favored by sarcomas but carcinomas can use it as well. Veins are more easily penetrated. The liver and lungs are the most common place of hemntogenous semination.
Some carcinomas can grow withing veins reaching the heart.

Question 14

what are some of the predisposing conditions for neoplasm?

Answer 14

acquired conditions that predispose to cancer include disorders associated with chronic inflammation, immunodeficiency state, and precursor lesions.

Question 15

what are precursor lesions?

Answer 15

are localized disturbances of epithelial differentiation that are associated with an elevated risk for developing carcinoma. Their removal lowers the risk of cancer.

• squamous metaplasia and dysplasia of bronchial mucosa (smokers)
• endometrial hyperplasia and dysplasia seen in women with unopposed estrogenic stimulation (endometrial cancer)
• Leukoplakia of the oral cavity, vulva and penis: which may progress to squamous cell carcinoma
• Villous adenoma of the colon: associated with a high risk for progression to colorectal carcinoma.

Question 16

what are the 4 major functional classes of cancer genes?

Answer 16

• oncogenes. (overexpressed normal genes)
• tumor suppressor genes (divided as guardians, sense damage, governors; acts as brakes during division)
• Genes that regulate apoptosis (genes the prevent apoptosis are overexpressed).
• genes that allow for tumor-host interaction are mutated.

Often both alleles must be mutated for a gene to be absent.

Question 17

what are driver and passenger mutation?

Answer 17

Driver mutations are mutations that alter the function of cancer genes and thereby directly contribute to the development or progression of a given cancer.
Passenger mutations are acquired mutations that are neutral in terms of fitness and do not affect cellular behavior. passenger mutations may increase the likelihood for cancer.

Question 18

what mutations cause cancer?

Answer 18

-point mutations: can create oncogenes, the cardinal example is when RAS gene is turned into a cancer gene. TP53 is most affected by point mutations.

Question 19

what are the rearrangement that can activate proto-oncogenes?

Answer 19

• gene rearrangements result in overexpression of proto-oncogenes by removing them from their normal regulatory elements and placing them under control of an inappropriate highly active promoter or enhancer.
  1. Burkitt lymphoma: chromosome 8-14 translocation MYC gene overexpressed by the heavy chain promoter on 14
  2. follicular lymphoma: 14-18 translocation leads to overexpression of the anti-apoptotic gene BCL2 on 18.
  3. FUSION of genes: philadelphia (Ph) 22 and 9 (22=Ph),fusion of a protions of the BCR gene on 22 and abl gene on 9 = chronic myeloid leukemia.

Question 20

how does lymphoid tumors associate with gene rearrangements?

Answer 20

because normal lymphocytes express special enzymes that purposefully introduce DNA breaks during the processes of immunoglobulin or T cell receptor gene recombination. Repair of these DNA breaks is error-prone. sometimes the gene rearrangements can create oncogenes.

Question 21

describe gene amplifications?

Answer 21

proto-oncogenes can become oncogenes by gene amplifications with consequent overexpression and hyperactivity of otherwise normal proteins. DNA probes can readily detect the hundreds of copies of the gene.
2 patters are seen under the microscope: double minutes and homogeneously staining regions. Homogeneously staining regions are chromosomal segments with various lengths and uniform staining intensity after G banding
examples:
NMYC: amplified in neuroblastoma
HER2: amplified in breast cancer.

Question 22

list the genetic lesions that can lead to cancer?

Answer 22

• point mutations
• gene rearrangements
• Deletions
• gene amplifications
• aneuploidy: improper chromosomal separation causing multiple chromosomes in one cell
• microRNA

Question 23

what are the epigenetic modifications that can lead to cancer?

Answer 23

hypermethilation and mRNA.

Question 24

Describe how the Darwinian selection affects cancer?

Answer 24

cancers continue to evolve and they generally become more aggressive and acquire greater malignant potential called tumor PROGRESSION.

the heterogenecity of the cancer genes means that recurrent tumors are less responsive to the original cancer treatment drug.

Question 25

what are the hallmarks of cancer?

Answer 25

• self-sufficiency in growth signals
• insensitivity to growth-inhibitory signals
• altered cellular metabolism
• evasion of apoptosis
• limitless replicative potential (immortality)
• Sustained angiogenesis
• invasion and metastasis
• evasion of immune surveillance.

Question 26

how are tumor cells self-sufficient in their growth signals?

Answer 26

Cancers may secrete growth factors to induce stromal cells to produce growth factors in the tumor microenvironment. Normal cells do no express receptors for what they secrete, this rule may be broken in tumor cells. They can also signal stroma which signals them back to promote tumor growth.

The growth factor receptors can also be mutated causing them to be “stuck in the on position”

Question 27

Describe the ABL proto-oncoprotein mutation?

Answer 27

ABL has tyrosine kinase activity that is dampened by internal negative regulatory domains. In chronic myeloid leukemia a part of the ABL gene is translocated from its normal abode on chromosome 9 to 22 where it fuses with BCR (breakpoint cluster region). The fusion of BCR-ABL hybrid protein unleashes a constitutive tyrosine kinase activity.
the BCR-ABL activates all signals downstream of RAS making it a potent simulator of cell growth.

this was confirmed by the dramatic response of BCR-ABL kinase blocker to myeloid leukemia patients. this drug was imatinib.

This pathway shows the so called “oncogene addiction” where a tumor is dependent on a single signaling molecule.

Question 28

what regulates the progression of a cell through the cell cycle?

Answer 28

-cyclin-dependent kinases: (CDKs) which are activated by binding to cyclins so called because of the cyclic nature of the production and degradation.
CDK-cyclin complexes phosphorylate crucical target proteins that drive cells forward through the cell cycle. while cyclins arouse the CDKs, CDK inhibitors (CDKIs) of which there are many silence the CDKs and exert negative control over the cell cycle. These inhibitors downregulate by mitogenic signaling pathways thus promoting the progression of the cell cycle.

Question 29

why does the increased production of oncoproteisn do not by itself lead to sustained proliferation of cancer cells?

Answer 29

there are 2 built in mechanisms, cell senescence and apoptosis that oppose oncogene mediated cell growth which must be disabled to allow oncogene to proceed.

Question 30

Under what conditions does RB gene lead to retinoblastoma?

Answer 30

both alleles need to take a “hit” mutation;

1. one hit on both alleles.
2. In Familial cases, children inherit one defective copy of RB gene in the germline and the other copy is normal only need one “hit”. Because retinoblastoma families a single germ line mutation is sufficient to transmit disease risk the trait has an autosomal dominant inheritance pattern.
3. in psoradic cases both normal RB alleles are lost by somatic mutation in one of the retinoblasts.

Question 31

how does RB regulate the cell cycle?

Answer 31

it regulates G1/S checkpoint by binding to E2F in its hypophosphorylated state and inhibiting transcription. this prevent cyclin D transcription.
2 ways RB block E2F transcription:
1. E2f is prevented from interacting with transcriptional activators
2. RB recruits chromatin remodeling proteins such as histone deacetylases and histone methyltransferases which bind to promoters of E2F genes such as cyclin E.

With sufficient stimulation (EGF, PDGF), Cyclins D/CDK4,6 complex phosphorylates RB allowing transcription to occur.

Growth inhibitors like (TGF-b, p53) stimulate CDK inhibitors p16 inactivate cyclins D/CDK4,6.

Question 32

which virus can affect RB?

Answer 32

HPV: encode E7 protein what bind RB and render it nonfunctional.

Question 33

Describe the role of TP53 in the cell cycle?

Answer 33

p53 protein that thwarts neoplastic transformation by 3 interlocking mechanisms: 1. cell cycle arrest (quiescence), 2. permanent cell cycle arrest (senescence), 3. trigger programmed cell death.

p53 has a short life span as its degraded by MDM2 quite fast, During cell stress ATM(ataxia telangiectasia mutated) are activated that modify and release p53 from MDM2 allowing it to transcribe the target genes.

p53 controls the expression and activity of genes involved in cell cycle arrest DNA repair cellular senescence and apoptosis.

Question 34

what is the syndrome that patients develop if p53 is mutated?

Answer 34

Li-fraumeni syndrome making patients prone to additional cancers.

Question 35

contact inhibition description?

Answer 35

tumor cells can experience contact inhibition via E-cadherin via tumor suppressor gene NF2.
Also by E-cadherin ability to bind beta-catenin, a signaling protein.

Question 36

Describe APC (adenomatous polyposis coli).

Answer 36

The importance of E-cadherin and B-catenin is illustrated by the rare hereditary disease called adenomatous polyposis coli. numerous adenomatous polyps in the colon develop, and have a high chance of becoming colon cancers. The polys show loss of tumor suppressor gene APC.
APC normally destroys B-catenin. WNTs bind their receptors and prevent APC destruction complexes allowing B-catenin to enter the nucleus.
If APC is mutated B-catenin allows the transcription of growth promoting genes.

APC and b-catening are part of the WNT pathway. WNT blocks the destruction of it via APC.

Question 37

what are the metabolic changes in tumor cells?

Answer 37

the warburg effect or aerobic glycolysis results in fermentation and excessive glucose uptake. This can be used to detect cancers via the use of radioactively labeled sugars.
NOTE that this ineffective method of energy generation is also present in normal cells that are in embryonic tissues that are proliferating.
THUS: aerobic glycolysis provides rapidly dividing tumor cells with metabolic intermediated that are needed fro the synthesis of cellular components whereas mitochondrial oxidative phosphorylation does not.

Question 38

what does a cell do when it is unable to adapt to marginal environmental conditions that are related to nutrition?

Answer 38

They may start to eat their own organelles for energy: autophagy.

Question 39

how does tumor cells avoid cell death?

Answer 39

Tumor cells frequently have mutations to the genes that regulate apoptosis making the cells resistant to cell death. Apoptosis is an organized dismantling of cells that does not trigger inflammation and allows the components to be taken up by neighboring cells or phagocytes.
2 pathways to cell death; extrinsic (FAS + FASL) and intrinsic/mitochondrial.
During apoptosis mitochondrial membrane becomes permeable and cytochrome C is released causing apoptosis. Pro and anti-apoptoic pathways regulate permeability of the BCL2 protein family.
-Bax/Bak are pro-apoptotic
-BCL2 are anti-apoptotic proteins.
cytochrome C binds to caspase-9 which turn activates caspase-3.
Inhibitor of apoptosis proteins (IAPs) bind caspase 9 and prevent apoptosis.

Question 40

what proteins are affected during the loss of apoptosis ability by tumor cells?

Answer 40

amplification of MDM2 which inhibits p53 function.

• most common is the loss of p53 function via TP53 mutation or MDM2 overexpression.
• Overexpression of antiapoptotic members of the BCL2 family such as BLC2, BCL-XL and MCL1 which protect cells from the action of BAX and BAK the pro-apoptotic members of the BCL2 family.
• Follicular B-cell lymphomas BCL2 levels are high because of a 14;18 translocation that fuses the BCL2 gene with regulatory elements of the immunoglobulin heavy chain gene
• inhibitor of MDM2 (to activate p53) and inhibitors of BCL2 family members induce the death of cancer cells by stimulating the intrinsic pathway of apoptosis and are being developed as therapeutic agents.

Question 41

describe limitless replicative potential (immortality) of tumor cells.

Answer 41

The DNA of cell shortens with each division but telomerases fix this in stem cells, however in somatic cells these enzymes are disabled. Tumor cells have this enzyme reactivated.
If telomerases are significantly degraded they may be recognized as double stranded breaks and incorrectly joined together IF the RB and p53 are mutated in disabled.
In normal cells the shortening will eventually cause the activation of cell cycle checkpoints and stopping of cell division. cell with disabled checkpoints will continue to divide leading to mitotic crisis.

Question 42

what is the limit of how big tumors can grow?

Answer 42

solid tumor possesses all of the genetic aberrations that are required for malignant transformation, it cannot enlarge beyond 1-2mm in diameter unless it can induce angiogenesis (vessel formation). Tumors do need oxygen and nutrients and removal of waste products.
many tumors remain small of years until there is a switch to induce angiogenesis.
Hypoxia via HIF can induce VEGF (proangiogenic).

drugs used to stop angiogenesis (the development of new blood vessels from existing ones) have little affect.

Question 43

what are the 2 phases of invasion and metastasis?

Answer 43

1. ECM invasion

2. Vascular dissemination and homing of tumor cells.

Question 44

the process of metastasis?

Answer 44

1. loss of E-cadherin
2. local degradation of the basement membrane and intersitial connective tissue via matrix metaloproteinases (MMP) cathepsin D, urokinase.
3. changes in attachment of tumor cells to ECM proteins Normal epithelial cells have receptors such as intergrins for basement membrane laminin and collagens that are polarized at their basal surface help mainting the cell in resting differentiated state, and if lost apoptosis occurs, but tumors are resistant to this.
4. locomotion: growth factors like insulin-like growth factors 1 and 2 have chemotactic activity for tumor cells.

Question 45

why cant tumor that metastazie last long?

Answer 45

they are vulnerable to the immune system during their trip in the circulation and they may be suppressed at their new site by either the lack of stroma or suppression by the immune cells.
tumor cells my have adhesion molecules whose ligands are expressed preferentially on the endothelial cells of the target organ. thus they may have a preference to where they deposit.
some areas are unfavorable for tumors such as the skeletal muscle and spleen are rare sites of metastasis.

Tumor cells can secrete molecules that act on the stroma that in turn make metastatic site more favorable.

Question 46

describe how tumor cells evade the immune system?

Answer 46

tumors that are heavily invaded by immune cells are more likely to be resolved then ones that are not invaded, this is supported by the success of immunotherapy and cancer increase in immunodeficient people.

Question 47

what are the tumor antigens?

Answer 47

they are acquired mutations in genes of cancer cells (via smoking) are not tolerated by the immune system. The varied mutations may generate new protein sequences called neoantignes.
Other antignes can be derived from infections such as the HPV and EBV (epstein barr viruses) that are recognized by cytotoxic T cells.

Question 48

what stimulates the immune response in tumors?

Answer 48

death of tumor cells which occurs with some frequency as the stresses placed on tumor cells causes them to die and release DAMPS damage associated molecular patterns that are taken up by phagocytes and APC. neoantigens are presented by APCs by MHC1 to CD8+ T-cells which activate and proliferate and kill the tumor cells expressing the same antigen via their own MHC1. Th1 cells may secrete IFN-gamma and activate macrophages.

Question 49

what are some techniques that have evolved in tumors to avoid the immune system?

Answer 49

Mutations to B2-microglobulin that prevent the assembly of functional MHC class I molecules. Other proteins that inhibit CTL function are also made.
One example: PD-L1 which engages with the CTL PD-1 on CTL's which causes them to become unresponsive and lose their ability to kill tumor cells. CTLA4: does the same thing.
Drugs targeting these pathways 
-certain factors may be released that alter the function of immune cells such as macrophages and Th2 lymphocytes that are responsible for suppressing the immune system during wound healing.

Question 50

why don’t all the environmental factors that cause cancer actually lead to cancer?

Answer 50

Do to the cells natural ability to repair its own DNA.

Question 51

Describe xeroderma pigmentosum

Answer 51

an autosomal recessive disorder caused by a defect in DNA repair that is associated with a greatly increased risk for cancers arising in sun exposed skin. UV rays cause cross-linking of pyrimidine residues preventing normal DNA replication.
this would be repaired by the nucleotide excision repair system. loss of this system causes this disease.

Question 52

Describe ataxia telangiectasia?

Answer 52

mutation to ATM that senses DNA damage and directs p53 to initiate DNA damage response.
BRCA1 and BRCA2 account for 50% of cases of familial breast cancer.

Question 53

what are some of the proposed cancer-enabling effects of inflammatory cells and resident stromal cells?

Answer 53

• release of factors that promote proliferation
• Removal of growth suppressors
• enhanced resistance to cell death
• angiogenesis
• invasion and metastasis (macrophages releasing TNF and EGF may directly stimulate tumor cell motility.

Question 54

what are the 3 classes of carcinogens?

Answer 54

1. chemical (direct and indirect)
2. radiation energy
3. microbial products

Question 55

give examples of direct and indirect chemical that cause cancer?

Answer 55

Direct: alkylating agents in chemotherapy drugs (no chemical modification, direct action on cells)
Indirect: polycyclic hydrocarbons that are created from smoke from burning. B-naphthylamine was responsible for bladder cancers in heavily exposed workers in the aniline dye and rubber industries.

Question 56

what are promoters?

Answer 56

they are non-carcinogenic substances that to be effective repeated or sustained exposure to the promoter must follow the application of the mutagenic chemical or initiator.
These initiators force the cell to proliferate including cells that have acquired some mutations allowing them to acquire even more mutations and eventually become neoplastic.

Question 57

Describe radiation carcinogenesis?

Answer 57

double stranded DNA breaks are common in radiation.
carcinogenesis is the ability to damage DNA by forming pyrimidine dimers which are a type of DNA damage is repaired by the nucleotide excision repair pathway. The repair system may become overwhelmed and lead to cancer.

Question 58

Describe HTLV-1?

Answer 58

• HTLV-I causes a T-cell leukemia that is endemic in japan and the caribbean.
• HTLV-I genome encodes a viral protein called Tax, which stimulates proliferation, enhances cell survival and interferes with cell cycle controls, although this proliferation initially is polyclonal the proliferating T cells are at increased risk for secondary mutations that may lead to the outgrowth of a monoclonal leukemia.

Question 59

Describe human papillomavirus?

Answer 59

HPV virus forms E6 and E7 exomes;
E6: degrades p53 and stimulates telomerase (immortality)
E7: this speed cells through the G1-S cell cycle checkpoint. It displaces E2F from RB. It also activates the p21 and p27 CDK inhibitors the bind to Cyclin E and A.

In summary: high-risk HPVs encode oncogenic proteins that inactivate RB and p53, activate cyclin/CDK complexes and combat cellular senescence.

Question 60

Describe epstein-Barr virus?

Answer 60

it causes Burkitt lymphoma infecting B-cells causing tumors. It attackes to the CD21 of Bcells to infect them. I promotes B-cell proliferation by mimicking the affects fo CD40.
LMP1 is one of the oncogenes found in the virus and induces B cell lymphomas.
LMP1 promotes signaling through the NF-kB and JAK/STAT pathways, both of which promote B-cell proliferation and survival.
The cell “borrows” a normal B cell activation pathway to promote its own replication by expanding the pool of infected cells.
Another oncogene called EBNA2 transactivates several host genes: cyclin D and the SRC family of protooncogenes.

The virus could stay in the memory T-cells.

Most cells have the 8:14 translocations.

LMP-1 and EBNA2 are antigenic and can be recognized by cytotoxic T cells thus a competent immune system can deal with this infection.

Question 61

what does EBV cause?

Answer 61

• nasopharyngeal lymphoma
• hodgkin lymphoma
• burkitts lymphoma
• T-cell lymphoma

Question 62

describe the HBV and HCV virus (hepatitis)

Answer 62

This virus causes inflammation in the liver and the ROS released causes DNA damage.
The virus has a random mode of tissue integration and thus can damage tumor suppressor genes.
The NF-kB pathways is activated and apoptosis is blocked allowing mutations to accumulate.
the gene known as HBx can directly or indirectly affect transcription factors like p53.

The full pathways is not yet fully understood.

Overall: increased epithelial cell proliferation on a background of chronic inflammation.

Question 63

describe helicobacter pylori?

Answer 63

similar mechanism as HBV and HCV;
Overall: increased epithelial cell proliferation on a background of chronic inflammation.

H-pylori induced gastric cancers is multifactorial (not well understood), including immunologically mediated chronic inflammation, stimulation of gastric cell proliferation and production of reactive oxygen species that damage DNA. H,pylori pathogenicity genes such as CagA also may contribute by stimulating growth factor pathways.
-it is believed that H-pylori infection leads to polyclonal B cell proliferations and that eventually a monoclonal B-cell tumor (MALT lymphoma) emerges as a result of accumulation of mutations.

Question 64

what are the 5 ways that benign tumors can cause problems?

Answer 64

1. location impingement on adjacent structures
2. functional activity such as hormone
3. bleeding and infections when the tumor ulcerates through adjacent surfaces
4. symptoms that result from rupture or infraction
5. cachexia or wasting.

Question 65

what causes cachexia in tumors?

Answer 65

not known
could be TNF from macrophages suppress appetite and inhibits the action of lipoprotein lipase preventing the release of FFA (free fatty acids).

Question 66

what are paraneoplastic syndromes?

Answer 66

symptoms that occur in patients with cancer and that cannot be realdy explained by local or distant spread of the tumor or by the elaboration of hormones indigenous to the tissue of origin of the tumor are referred to as paraneoplastic syndromes. EXAMPLES:

• Hypercalcemia: could be do to PTH made by tumor cells, osteolytic metastatic disease of bone
• Cushing syndrome do to ectopic production of ACTH by cancer cells
• hypercoagulability.

Question 67

what is staging and grading of cancer?

Answer 67

Grade: degree of differentiation
Stage: spread of the cancer.
N0 is used to indicate an in situ lesion.