EX2: Cancer Flashcards
(156 cards)
1
Q
Define neoplasm.
A
Abnormal mass of tissue produced when cells divide more than they should or do not die when they should.
2
Q
what does a neoplasm lack
A
normal regulatory controls or cell growth and division
3
Q
Define neoplasia.
A
Process of formation of an abnormal growth.
4
Q
Define proliferation.
A
The process by which cells divide and reproduce.
5
Q
when do cells proliferate
A
continuously or in response to body needs
6
Q
What are the two ways by which cells proliferate?
A
Meiosis and Mitosis
7
Q
What mediates cell proliferation?
A
Gene expression, growth factors, and signaling molecules.
8
Q
What is the specific kinase that regulates cell division? when does it change?
A
mTOR, which also changes depending on local nutrition.
9
Q
Define differentiation.
A
The process by which cells are transformed into different and more specialized cells.
10
Q
What causes a cell to be differentiated? What influences this?
A
Gene expression, which is heavily influenced by growth factors and other stimuli (such as tissue environment)
11
Q
what do we all start from
A
a single cell
12
Q
As a cell becomes MORE specialized, is it more or less likely to undergo mitosis (divide)?
A
Less likely!
Important!!!!!!!!
13
Q
what are stem cells
A
highly undifferentiated cells that have the potential to divide into multiple types of progenitor cells, which eventually become fully differentiated cells
Highly undifferentiated cells with SELF-RENEWAL
14
Q
what do stem cells have the have the potential to do?
A
They have the potential to divide into multiple types of progenitor cells, which will eventually become fully differentiated cells.
15
Q
What is a progenitor/parent cell? Why is it distinct from a stem cell?
A
It is still a cell that can divide, BUT parent cells has a limited range (or one type) of cell it can differentiate into.
16
Q
What are the 5 types of stem cells from most undifferentiated to most differentiated?
A
Totipotent: give rise to ALL CELL TYPES - aka total range- including placenta
Pluripotent: give rise to all adult organism cell types (PLENTY)
Multipotent: give rise to MULTIPLE, but not all, cell types
Oligopotent: give rise to a FEW cell types (Oligo means few/scanty)
Unipotent: give rise to ONE cell type
17
Q
What are most progenitor cells in terms of stem cell ranking?
A
Oligopotent or unipotent.
18
Q
path of cellular differentiation
A
stem cell -> stem cell OR
-> progenitor cell ->daughter cell-> fully differentiated cell
19
Q
Define carcinogenesis.
A
Origin and development of cancerous neoplasms
20
Q
What kind of cells are most susceptible to neoplasia?
A
Rapidly dividing, labile cells
(carcinogenesis)
21
Q
what kind of cells are less prone to neoplasia?
A
permanent, undividing cells
22
Q
What percentage of genetic defects or mutations that lead to cancers develop post birth?
A
95%
23
Q
Define oncogenesis.
A
The mechanism by which normal cells BECOME cancer cells.
24
Q
What is monoclonal origin?
A
The concept of cancer originating from a single cell with genetic mutations.
25
mutations in what kind of genes can lead to cancer
genes that control cell growth and replication
26
What 3 genes are responsible for making sure our cells do NOT develop into cancer?
Mutator genes
Protooncogenes
Tumor suppressor genes.
so mutations in these genes can lead to cancer
27
Define mutator genes and give examples
They help repair mutated DNA and protect our genome.
The repair typically happens AFTER environmental insult
chemicals, radiation, viruses, inherited deficits
28
what is required for mutator genes to produce cancerous neoplasms
requires failure of MULTIPLE mutator genes to produce cancerous neoplasms
29
what happens from a failure of mutator genes to repair DNA
accumulation of other genetic mutations
30
Define protooncogenes.
Promote cell growth and development.
Specifically, they are normal genes that code for the proteins that regulate cell growth and differentiation, AND they have potential to become oncogenes through 3 methods
31
Define tumor suppressor gene.
regulate cell division and apoptosis to ensure the optimal number of cells
32
what does failure of the tumor suppressor gene mean
unrestricted growth and division of cell
two-hit hypothesis for failure
33
Does a single gene mutation usually cause cancer?
No!
34
What is RB gene
RB Gene (Rb protein) is the first tumor suppressor gene ever discovered.
Associated with retinoblastoma and other cancers.
35
what is TP53 gene
TP53 (p53 protein) is found on chromosome 17.
It is often implicated in many colon, lung, and breast cancers.
Regulates apoptosis of CANCER cells post chemo/radiation.
36
what is BCL2 gene-what cancer is it associated with
BCL2 gene (Bcl-2 protein) regulates apoptosis.
Mutation here results in a POORER response to cancer therapy.
Often associated with leukemia and other cancers.
37
What is the two-hit hypothesis?
Example: Retinoblastoma.
Even if a child carries the susceptibility gene for retinoblastoma, that is only 1 of the 2 chromosomes.
The susceptible child needs just 1 mutation to get retinoblastoma.
However, for someone not born with the gene, they need 2 individual mutations to get retinoblastoma, hence two-hit.
Note: See slide 19 for a visual.
38
what is point mutation
type of protooncogene turning to oncogene method
damage of a single nucleotide base pair
- usually spontaneous or from environmental influences
39
what are chromosomal translocations? what do they result in and what can they create?
type of protooncogene turning to oncogene method
chromosome breaks, relocates, and unites with another chromosome.
often results in overproduction of proteins associated with gene
can create new "chimeric" genes- philadelphia chromosome
40
what is gene amplification and what does it lead to
type of protooncogene turning to oncogene method
accelerating replication of genes, leading to overproduction of proteins associated with that gene.
41
through what three methods can protooncogenes become oncogenes
point mutation, chromosomal translocations, gene amplification
42
Define oncogenes. What do they encode and what do they disturb?
Genes that promote UNregulated cell growth and development, inhibit cell death.
They encode growth factors to promote cell division.
Disturbing cell surface receptors and cell-to-cell communication.
Encoding proteins to alter cell cycle, restrict apoptosis, and impact differentiation.
43
what are the two ways to name an oncogene?
Viral onc = denoted with v, ex; v-src
Cellular onc = denoted with c, like c-neu
44
What are some general types of genetic mutations for chromosomes?
Duplication, Inversion, Deletion, Insertion, Translocation.
See slide 22 for visual.
45
What two events are required for cancer to develop and then progress?
Initiating event
Promoting event
46
Define initiating event and what cells are most susceptible.
Initiating events are the event that causes a mutation in a cell. This is usually caused by a carcinogenic agent or a sporadic mutation.
The cells most susceptible are the ones actively synthesizing.
47
Define promoting event and a common cause.
It is the event that causes the cell to actively grow and reproduce more. (expansion of g+r)
Most commonly caused by chronic inflammation.
Also, complete carcinogens can do both initiation and promotion of neoplastic transformation.
48
define immunologic response as a host factor
functional immunity allows for destruction of abnormal "self" cells
49
(immuno response) many cancer cells express what
abnormal HLA-1 surface antigens that can be recognized by the body
50
what does impaired immunity cause
less ability to destroy tumor cells
51
what type of patient has higher rates of cancer?
many immunosuppressed patients such as HIV/ AIDS patients
52
Define Progression in terms of cancer.
Extension of promotion phase.
Important:
Cell no longer requires the promoter to be present AND
Cell acquires ability to invade tissue, metastasize, and grow autonomously.
53
What are the host factors that affect cancer susceptibility?
Immunologic response
Age
Chronic Inflammation
Genetic Predisposition
Genetic Disease
Hormones
54
why is age a host factor
increasing age increases incidence of cancer
Older people have accumulated more mutations/DNA damage.
Increased methylation of genes, which turns them OFF.
Weaker immune responses overall.
55
Why does having chronic inflammation increase your rates of neoplasia
During chronic inflammation, we have higher numbers of phagocytes floating around producing free radicals to destroy invaders but they can also damage other healthy cells while protecting us.
Inflammation also = cell proliferation, increased growth factor,
more angiogenesis,
increased nutrients and oxygen,
increased ability to grow and spread due to tissue remodeling.
56
what is genetic predisposition? does it mean someone will for sure get cancer?
genetic predisposition means its possible to see familial tendencies for cancer
does NOT mean someone is guaranteed to get cancer!
57
what is genetic predisposition due to?
inherited factors that increase the likelihood of neoplasia
- inefficient breakdown and disposal of carcinogens
- altered ability for DNA repair
-impaired cell proliferation and differentiation
58
what are carcinogens
substance, agent, organism capable of causing cancer
59
what are BRCA genes and what is the genetic predisposition of them?
BRCA-1 and BRCA-2 genes are tumor suppressor genes. They are inherited mutations that greatly increase the risk of multiple cancers
** especially breast and ovarian
60
what are the risks of the general population to get breast/ovarian cancer and the risks of getting breast/ovarian cancer with BRCA 1, 2 genes?
general population: 12% of women will get breast cancer and 1.4% will get ovarian cancer
BRCA-1: 55-65% will get breast cancer and 39% will get ovarian cancer
BRCA-2: 45% will get breast cancer and 11-17% will get ovarian cancer
61
Which of the two BRCA genes results in higher incidences of breast/ovarian cancer?
BRCA1,
which has a 55-65% breast cancer rate, 39% ovarian.
62
what are benign tumors? can they turn into malignant tumors?
increased abnormal cell growth but no ability to invade other tissues or spread (metastisize) to other areas
-some but not all can progress to malignant tumors
63
how are genetic diseases a host factor risk for cancer
certain inherited conditions are known to manifest with neoplasia
-not all neoplasms are necessarily cancerous
- increased or unregulated cell growth in the disease= higher cancer risk
64
What are some common genetic diseases associated with cancer?
Multiple endocrine neoplasia (MEN)
Familial adenomatous polyposis of the colon
Neurofibromatosis
AKA all of these disease involve either tumor growth (benign initially) or cell growth in general.
65
what are hormones and how do they cause cancer? what are the male and female organs targeted?
Hormones are signals sent to many normal tissues that promote cell replication.
Specifically, the sex organs receive these signals and are signaled to grow, but they can sometimes grow uncontrollably.
women- breast, uterus, endometrium
male- prostate, testes
66
how is the knowledge of hormones used to treat cancers?
some cancer treatments involve starving cancer cells of hormones by inhibiting that hormone's production.
this therefore will stop the hormone from telling the cells in the organ to grow, inhibiting replication and metastasis
67
what does ionizing radiation do
directly kills cells; causes reactive oxygen molecules that interrupt cell membranes and allow radiation to damage cell DNA.
68
How does cancer causing risk vary with ionizing radiation
Risk varies with intensity of radiation, duration & number of exposures, area of exposure, age of exposure, AKA if you get a lot of radiation.
- massive radiation exposure strongly linked to cancer
( cancer rate in atomic bomb survivors from hiroshima and nagasaki was 30x the normal rate)
69
is everyday radiation exposure linked to causing cancer?
cancer is more difficult to isolate as a cause in "everyday" exposures to radiation due to multiple other possible etiologies
70
What is UV radiation most commonly associated with? Why?
Skin cancer.
UV radiation does not penetrate deep into skin.
71
what does UV radiation and your risk of cancer depend on
- site and skin type
(less melanin- higher rates skin cancer)
- intensity of UV radiation exposure
(australia vs US southwest and tanning beds vs natural light)
72
Having more of this can help prevent skin cancer.
Melanin
73
what are chemical agents dependent upon in their risk of causing cancer
heavily influences by individual susceptibility, specific agent exposed to, duration, and frequency of exposure
74
What are some of the most common chemical agents that cause cancer?
Tobacco
Alcohol
Diet (Benzene, Polycyclic aromatic hydrocarbons (PAHS), and high-fat diets)
* also need to consider occupational and industrial exposure
75
What are the two types of chemical agents?
Direct and indirect.
Indirect means it becomes metabolized by the body into a direct carcinogen.
76
How does alcohol affect cancer susceptibility?
Modifies our ability to metabolize carcinogens in the liver and esophagus.
It also has toxic metabolites itself that can lead to DNA mutations.
77
How much of all cancer deaths is tobacco linked to in the US?
30%!!!!!!!!!!!!!!!
78
What are benzenes often found in? What about PAHs?
Benzenes are often found in preservatives in foods and soft drinks.
PAHs, or polycyclic aromatic hydrocarbons, are found in food fried in fat (oil) that has been reused multiple times or smoked/broiled meats.
79
what diet has a possible link to cancer
high fat diets
80
what percent of human cancers are associated with viral infections? what does the virus do?
up to 15%
the viruses alter DNA content and expression
81
Name some viruses associated with cancers.
Human papillomavirus (HPV): Cervical, Anogential, oropharyngeal
Hep B & C (HBV, HCV): Hepatocellular carcinoma
Epstein-Barr Virus (EBV): Lymphoma, Nasopharyngeal cancer
Human Herpesvirus-8 (HHV-8): Kaposi's sarcoma
HTLV-1: T-cell leukemia
82
Name some bacteria associated with cancers.
Schistosomiasis - bladder
Heliobacter pylori - gastric
83
what is a benign neoplasia
it resembles the tissue or origin (well-differentiated) and is localized
84
how do benign neoplasias occur? are they fast or slow growing?
- loss of control of cell proliferation
- typically slower rate of growth than most malignant cells
- may actually stop growing or regress spontaneously
85
what can benign neoplasias cause? what may they produce? and what do they tend to have?
can cause compression of nearby structures
- may affect normal tissue structure and/or function
may produce abnormal levels of hormones
tend to have more clearly defined margins
- often enclosed in a fibrous capsule
86
What are some key differences between a benign neoplasia and a malignant neoplasia?
Benign is well-differentiated (aka it resembles the tissue it originated from). Also localized.
Benign grow slow, usually cause compression rather than invasion, do not spread.
Usually has defined margins, unlike a malignant neoplasia.
87
what is a malignant neoplasm and where does it spread to
cells are often less differentiated (anaplastic); have atypical cellular structure
ultimately spreads to distant sites in the body by hematologic or lymphatic spread
88
do malignant neoplasms grow slowly or fast? what can they compress? what are their margins?
- tend to grow more rapidly
- compress local tissues; depriving local cells of nutrients
- they have irregular margins due to invasion of local tissues by cellular processes
89
What kind of cancer starts out disseminated?
Hematologic cancers.
90
What is anaplasia? What does high degree of anaplasia imply?
Loss of cell differentiation and therfore cell function.
Higher degree = more aggressive neoplasm.
A less differentiated cell = more like to replicate, more likely to be cancerous.
91
If I have a malignant neoplasm under my microscope, name some more key features that make it cancer rather than a benign tumor.
Large, variable sized nuclei, usually much bigger than the cytoplasm. (This is because it is actively replicating)
Loss of normal cell features, disorganized appearance.
92
If I was looking at some tissues under a microscope, what are some key features I look for to determine if it is benign or malignant neoplastic tissue?
The edges and the shape of the cells. Benign will look more rounded, well-defined. Malignant large with variably shaped nuclei.
Malignant will look jagged, out of place, disorganized, and spreading. (loss of normal specialized cell features)
See slide 48 for a visual.
93
what normal cellular characteristics are lost in a cancer cell
- do not function like normal tissue
- loss of cell-cell communication and CONTACT INHIBITION
- increased energy expenditure
- loss of COHESIVENESS and ADHESIVENESS
- secretion of enzymes to degrade surrounding tissue
- secretion of excessive growth factors
- presentation of abnormal tissue antigens
94
What are the 4 grades of tissue anaplasia? What is the degree I hope my neoplasm is?
Grade 1-4.
- Grade 1 means well-differentiated, which is ideal.
- Grade 2 is moderately differentiated
- Grade 3- moderately differentiated
- Grade 4 is poor differentiation, aka what we DONT want.
95
What are the environmental factors that cause cancer?
Ionizing radiation
UV radiation
Chemical agents
Viruses and bacteria
96
How do I name a benign tumor?
nomenclature of neoplasia varies depending on the neoplasia
"Cell type" + "-oma"
97
what is an adenoma
benign tumor of glandular epithelial origin
98
what is a papilloma
benign tumor with fingerlike projections
99
what is an epithelioma
benign tumor of squamous epithelium
100
How do I name a malignant tumor?
cell type + (origin tissue type) + -oma
origin tissue type refers to carcin and sarc.
101
what does "-carcin-" mean
malignant epithelial cells
102
what does "-sarc-" mean
malignant connective tissue
103
what is an adenocarcinoma
malignant tumor of glandular epithelial cells
104
what is a chondrosarcoma
malignant tumor of chondrocytes (cartilaginous tissue)
105
What are some exceptions to malignant tumor naming?
Lymphoma
Leukemia
106
what is a lymphoma
malignant cancer of the lymphocytes
doesnt follow malignant naming
107
what is leukemia
malignant cancer of the blood-forming bone marrow, specifically leukocyte progenitors
does not follow malignant naming
108
what is the evolution of carcinoma
Early:
- normal epithelium (3p21-9p21 LOH)
-hyperplasia (telomerase dysregulation)
- squamous metaplasia (p16INK4a methylation)
Intermediate:
- dysplasia (8p22-24 LOH, FHIT inactivation)
Late
(TP53 inactivation, 5q22 LOH)
- carcinoma in situ
- invasive carcinoma
109
What are the 3 types of plasia?
Hyperplasia
Metaplasia
Dysplasia
110
What is hyperplasia?
It simply means an increased number of cells in a given area.
- The cells generally appear normal or near normal on microscopy
- may be physiologic or due to carcinogenic stimuli
-can be REVERSIBLE
111
What is metaplasia?
Replacement of a differentiated cell type by another differentiated cell type.
May be physiologic or due to exposure to carcinogenic stimuli
Example:
- Cervix goes from glandular epithelium to squamous epithelium.
- Esophagus goes from squamous to columnar.
can be REVERSIBLE
112
What is dysplasia?
Increasing degree of disorganized cell growth or maturation
Often considered a precursor to cancer
may still be reversible (sometimes)
113
What types of plasia are reversible?
All of them, but dysplasia is not always reversible.
114
What is carcinoma-in-situ?
A carcinoma confined to an epithelium that HAS NOT penetrated basement membrane.
*As a result, the prognosis is often better than invasive carcinomas.
115
What is invasive carcinoma?
Carcinoma that has invaded beyond the basement membrane and now has the potential to spread to other tissues.
116
What is the transition that causes a carcinoma-in-situ to become invasive?
EMT
Epithelial-mesenchymal-transition, aka breaking past the basement membrane.
117
describe the process/steps of carcinoma in situ--> tumor cells
1- carcinoma in situ cell becomes capable of invasion of basement membrane
2- tumor cells undergo epithelial- mesenchymal transition (EMT), traverse the basement membrane and invade through extracellular matrix (release of proteolytic enzymes)
3- repeated binding to and dissolution of extracellular matrix
4- tumor cells metastasize by way of blood vessels or lymphatics (intravasation)
5- survival in blood and extravasation
6- micrometastases
7- metastases
118
What are some ways cancer spreads?
Direct extension
Seeding
Metastasis
119
Define direct extension of cancer.
Localized growth of a cancer
- epitheleal cancers- penetrating basement membrane is first step
- production of enzymes to degrade local tissues
120
Define seeding for cancers.
It is a method of direct extension where cancer cells are shed into a body cavity or along a path/ track
Most often see in the peritoneal cavity, in biopsies
121
Define metastasis.
Development of a secondary neoplasm distant from the primary neoplasm.
- location of metastasis varies with cancer type
122
what type of cancers is more typically associated with lymphatic spread?
carcinomas
123
what type of cancers are typically associated with hematologic spread?
sarcomas
124
what is the difference of sarcoma v carcinoma?
Sarcomas = connective tissue, which is often vascularized and therefore nearby a blood vessel.
Carcinoma is epithelium, which can be either but usually lymph.
125
What is the TNM classification system in general?
Classifying the primary tumor itself (T)
Classifying if it has spread to regional lymph nodes (N)
Classifying if it has metastasized and how much - distant metastasis(M)
126
what are the classifications and their descriptions of primary tumor (T) in the tumor classification system
TX- primary tumor cannot be evaluated
T0- no evidence of primary tumor
Tis- carcinoma in situ
T1, T2, T3, T4- size or extent of primary tumor
127
what are the classifications and their descriptions of regional lymph nodes (N) in the tumor classification system
NX- regional lymph nodes cannot be evaluaed
N0- no regional lymph node involvement
N1,N2,N3- involvement of regional lymph nodes (number or extent of spread)
128
what are the classifications and their descriptions of distant metastasis (M) in the tumor classification system
MX- distant metastasis cannot be evaluated
M0- no distant metastasis
M1- distant metastasis present
129
What are some common local manifestations of cancer?
Initial manifestations often depend on site involved
- Loss of normal parenchymal tissue.
- Interruption of tissue integrity, which commonly leads to ulcerations, bleeding, necrosis, impaired wound healing.
- Compression of local structures.
- Local palpable mass or asymmetrical enlargement of the involved area
130
What are some more systemic manifestations of cancer?
Pain (due to compression or destruction)
Fever (due to release of pyrogens)
Pruritis (cytokines?)
Jaundice (excess bilirubin)
Infection (impaired immune function)
Pathologic fractures (extremely weakened bone breaks under low stress)
131
How does cancer cause pain?
Compression, infiltration, and destruction of local tissue/structures
- Metastatic cancers lead to a higher incidence of pain
- Often the most painful cancers are bone, testicular, and muscular.
An organ will cause more diffuse and referred pain.
132
what does compression or infiltration of organ by neoplasia cause?
diffuse, poorly localized, or referred pain
if a pt can localize one spot of pain we are less worried about cancer
133
How does cancer cause fever? what cancers are usually associated with fevers? % of unknown fever origins that are cancer?
Releasing pyrogens from cancer cells, along with cytokines from the inflammatory response.
Cancers often associated with fever are lymphoma and leukemia.
up to 7-25% of unknown fever origins are cancer ):
134
How does cancer theoretically cause pruritis? what cancers is it usually associated with?
poorly understood; believed to be due to cytokines and in some cases due to cholestasis
-most associated with leukemia, lymphoma, liver cancer
- may be associated with any cancer that causes bile duct obstruction/cholecystitis
Note: Bile salts build up, which cause cause peripheral nerve fiber irritation.
135
What is jaundice? How does cancer cause it?
Jaundice is excess bilirubin, which appears physically as a yellowing of the skin, eyes, and mucous membranes.
Associated with cancers that cause bile duct obstruction, such as:
- liver,
- gallbladder,
- bile duct,
- pancreatic cancer,
along with metastatic cancers.
136
why may infections be caused by cancer?
due to impaired immune system function, inadequate resources to fight infection, treatment of cancer
137
What cancers tend to affect the immune system/bone marrow directly?
Leukemia, Myeloma, Lymphoma, aka any cancer related to bone marrow/lymph.
138
How does cancer cause pathologic fractures? What is often a warning of it?
- invaseive cancer weakens the bone matrix leading to decreased structural stability and increased fractures
- cancer can leech calcium out of bones, weakening them, due to HYPERcalcemia!
139
what types of cancers can be associated with pathologic fractures?
primary bone cancer, lymphoma, myeloma
140
what cancers are the bones a common site of metastasis for? and what bones in particular
- breast
- kindey
- lung
- prostate
- thyroid
- axial skeleton (spine!!, rubs, skull)
- pelvis
- proximal extremities (femur, humerus)
141
What are the 4 hematologic manifestations of cancer?
Hemorrhage
Anemia
Leukocytosis
Leukopenia
142
What causes a hemorrhage? What kind of cancers usually cause hemorrhages?
- hemorrhages are due to erosion of local blood vessels
- often seen in highly vascularized tissue
- lung cancer, GI tract, GU tract
143
What kind of cancers usually cause anemia? what is anemia?
- anemia is decreased production of RBC
- Cancers that cause blood loss (hemorrhage) (microscopic or gross, highly vascular tissue)
-Lymphoma, myeloma, leukemia
- Metastases to bone marrow (which directly impacts RBC production)
144
what is leukocytosis and what does it result in? what cancers are associated with it?
-over proliferation of leukocytes and leukocyte progenitors
- resulting WBC are often immature and dysfunctional
- classically associated with leukemia; may also see with thymoma
AML, CML, CLL
Acute myeloid leukemia
Chronic myeloid leukemia
Chronic lymphocytic leukemia
145
what is leukopenia and what cancers is it seen in?
- decreased production of leukocytes
- often seen in cancers involving bone marrow due to "overcrowding" of functional marrow space with dysplastic cells
- lymphoma, myeloma, leukemia, and metastases to bone marrow
Acute myelomonocytic leukemia
Monocytic leukemia
AKA leukemias that kill monocytes
146
what does a chronic myeloid leukemia smear show that a normal peripheral smear doesn't?
immature granulocytes that are larger than normal
147
What is cachexia-anorexia syndrome? What kind of cancers typically cause it?
- Weight loss, wasting of body fat & muscle, loss of appetite, and weakness.
- Common manifestation of most solid tumors and high incidence with upper GI and pancreatic tumors.
148
What causes the anorexic state in cachexia-anorexia?
Suppression of satiety in the hypothalamus, often by TNF-alpha, IL-1, and IL-6
(due to tumor releasing inflammatory mediators.)
149
What causes the cachexic (loss of body weight/muscle mass/ weakness) state in cachexia-anorexia?
- Suppression of lipoprotein lipase which allows release of fatty acids to be used by tissues
- increased metabolic needs from cancer lesions ( they steal nutrients)
- Abnormal metabolism of amino acids also leads to an increased depletion of muscles.
- They also may have IMPAIRED nutrient absorption.
AKA cancer steals nutrients and people with cancer can't metabolize nutrients well in general.
150
What is paraneoplastic syndrome?
Manifestations of cancer in sites/areas that are NOT directly affected by the disease.
151
What are some causes of paraneoplastic syndrome?
- Secretion of hormones
- Cytokines and inflammatory response
- Most common in lymphoma or lung/breast/ovarian cancer.
- Varies widely depending on the cancer.
- may be the FIRST sign of cancer!
152
What is one of the most common symptoms of paraneoplastic syndrome?
Hypercalcemia, usually caused by an excess production of a PTH- like molecule
10-20% of all cancer patients (common)
153
What are some other common manifestations of paraneoplastic syndrome?
General: Fever, night sweats, anorexia-cachexia
Dermatologic: Itching, flushing, pigmented skin lesions, herpes zoster.
GI: watery diarrhea
Endocrine: Cushing's, abnormal glucose metabolism, SIADH
Hematologic: thrombocytopenia, pro-coagulant status, anemia
Renal: Glomerulonephritis, impaired renal function
Neurologic: Neuropathy, weakness, myasthenia gravis
Note: SIADH stands for syndrome of inappropriate secretion of anti-diuretic hormone
Pro-coagulant status is usually due to increased platelet count, which is a result of inflammation.
154
What causes almost half of all deaths when a patient has cancer?
- Infections, such as pneumonia, or peritonitis, or sepsis.
- 47%
155
What causes almost a quarter of all deaths when a patient has cancer?
Organ insufficiency/failure
156
What are the 5 causes of death in cancer patients?
- Metastases = very poor prognoses (increased metastases- decreased survival)
- Infection
- Organ insufficiency/failure
- Infarction of major organs
- Hemorrhage
