neoplasia Flashcards
Anaplasia
- is a condition of cells with poor cellular differentiation, losing the morphological characteristics of mature cells and their orientation with respect to each other and to endothelial cells
- term used to describe loss of cellular differentiation and reversion to more primitive cellular morphological features
- often indicates irreversible progression to neoplasia
Neoplasia
- is a “process of new growth” in which normal cells undergo irreversible genetic changes, which render them unresponsive to oridnary controls on growth exerted from within the transformed cell or by the surrounding “normal” cells
- if they expand past their normal anatomic boundaries they can create a macroscopically (grossly) or microscopically detectable neoplasm
- Uncontrolled purposeless cell proliferation, continues without the inciting cause, forms from a single mutated cell.
- Neoplastic cells exhibit altered differentiation & ↑ rate of growth
- rate of growth exceeds normal for the tissue
- tumours classified as “benign or malignant” (Ultimately should be able to tell prognosis by looking at it)
viruses that cause cancers and tumours in domestic animals
- retroviruses
- papillomavirus
Cancer
- while the terms “neoplasm” and “tumor” may refer to either benign or malignant growths
- the term “cancer” always refers to a malignant growth
- a malignant neoplasm
- Like “crab”, crab claws are supposed to refer to malignant tumor
Gross Lesions
-important to note that a gross lesion descirbed as a “tumour” or a “mass” may be a neoplasm or a non-neoplastic lesion like a granuloma
Benign Tumours
- “harmless”
- do not invade the surrounding tissue or spread to new anatomic locations within the body
- thus these tumors are usually curable and are rarely responsible for the death of an animal
Malignant Tumors
- “harmful”
- if left untreated, invade locally, and spread by metastasis (“change of place”)
- ultimately kill the animal by interferring with ciritcal body functions
“Tumour”
- non-specific term for swelling, but popular use= neoplasm
Oncogenesis/tumourogenesis
- Process of development of neoplasm
Tissues Grow/Maintain by
- cell proliferation
- cell differentiation
- Differentiation: process of maturing of normal cells
Totipotent Cells
- such as those in the ovum
- they have the capacity to form every adult cell type in the body
Fully Differentiated Cell
(Normal Process)
- expresses small % of genetic information of fertilized ovum
- Differentiation involves restriction of genome expression
Normal Cell Proliferation
(Cell Cycle)
- cell in its resting phase is kicked into the cell cycle following release of Growth Factor
- binding of that growth factor to the receptor on the cell surface
- then transduction and translation of cell cycle proteins
- which then allows the cell to replicate in a CONTROLLED manner
Tumour Suppressor Genes
ex: p53
- tumor suppressor genes act as checkpoints during that cell cycle
- If the cell seems damaged, either allows that cell to be repaired or the cell will die through apoptosis to prevent your defective genetic material from being passed on to the next generation
- P53 is a really good example of a tumor suppressor gene “defender of DNA integrity”
Tumour Nomenclature
- Most tumours consist of a single cell type; name reflects cell type (mesenchymal/ epithelial) from which it arises
- Prefix adeno- = glandular tumour e.g. pituitary adenoma, mammary adenocarcinoma
- Suffix -oma = benign neoplasm e.g. fibroma, histiocytoma, lipoma, haemangioma. Exceptions:
- Carcinoma = malignant tumour of epithelial origin e.g. squamous cell carcinoma (tumour of squamous epithelial cells), gastric adenocarcinoma (gastric glands)
-
Sarcoma = malignancy of mesenchymal origin
e. g. fibrosarcoma (fibrous connective tissue)
osteosarcoma (bone)
chondrosarcoma (cartilage)
haemangiosarcoma (blood vessels)
histiosarcoma
lymphosarcoma
-these cells will grow in a different pattern compared to epithelial cell tumors
Epithelial
(Neoplasia)
- cells are forming clusters–> epithelial cells: squamous cell carcinoma
- they have intercellular adhesion molecules
- Derived mostly from ectoderm & endoderm germ layers, but also mesoderm.
- Cells cover or line the surfaces of the body or organs.
- Apical basal polarity, cell to cell tight junctions.- when there is epithelial cells metastasizing you have to break down the junctions between the cells
- High density with little intercellular substance
- Separated from connective by a basement membrane: always lying on a basement membrane, but when they become malignant they break through B and invade surrounding tissue
Fundamentals to Neoplasia Development
- loss of control of cell proliferation
- loss of normal cell differentiation (i.e. cells are anaplastic)
- Anaplasia: lack of differentiation
- Become less and less differentiated, become less and less like the cell that they started from
- as the tumor acquires more genetic differentiations, it will be hard to tell the cell the tumor started from (ex: hepatocyte in the liver vs. tumor cell it becomes in the liver, etc.)
- well differentiated tumor (benign tumor) - it will look morphologically like a hepatocyte
- as the tumor acquires genetic mutations and becomes less differentiated, it will become more and more difficult for us to tell that the tumor comes from the hepatocyte. They wont look like hepatocytes or express the correct proteins
- tumor is poorly differentiated
Mesenchymal Cell
Neoplasia
- “streaming” or forming streams (ex: fibrosarcoma)
- Derived from the mesoderm
- Connective tissues
- No polarity, loosely attached to each other
- Produce & are separated by extracellular matrix.- if a tumor has streaming cells you are looking at what they are producing
Bone: osteosarcoma
Collagen: fibrosarcoma
WIthin Mesenchymal Derived Tumors:
Lymphoid & haematopoetic tumours
(round cell tumours)
- although they are mesenchymal in origin they are going to look different
- going to look like sheets of cells
- supported by the tissue of whatever stroma they are already growin in
Derived from the mesoderm, form sheets of round cells
Dif dx for round cell cutaneous tumours: mast cell tumour, histiocytoma, plasmacytoma, lymphoma.
Clonal Evolution Model of Cancer
- get a normal cell and a genetic mutation that leads to loss of control of differentiation and proliferation
- get clonal expansion of that cell until you get a clinically identifiable tumor which generally is going to consist of 10^9 cells
- it is quite possible for tumors to be growing that you can’t detect physically at any point in time
- mutation is likely going to occur in either the proto-oncogenes or in the tumor suppressor genes!
- that is going to affect your cell cycle
-this will affect the homeostatic cell proliferation and differentiation of your cell
-homeostasis depends on dynamic equilibrium between growth-promoting factors and growth-inhibiting factors
-A mutation in either sets of these genes could lead to a loss in control of proliferation and differentiation
Proto-Oncogenes
- Proto-oncogenes- normal gene which encodes proteins (GFs) that function to stimulate cell division, inhibit cell differentiation & halt cell death
- BUT genetic mutation oncogenes overexpression of GFs etc uncontrolled cell proliferation
- Oncogenes: SRC, RAS, MYC, hTERT & Her-2/neu
Tumor Supressor Genes
Tumour suppressor genes control the checkpoints during the cell cycle
- p53: important tumour suppressor gene- ‘defender of DNA integrity’- if it detects DNA damage it either arrests the cell cycle, allowing cell to repair or causes cell apoptosis
- Rb: alters activity of transciption factors & therefore controls cell division
- APC: controls availability of a TF
In a normal cell you have a dynamic equilibrium between growth promoting (proto-oncogenes) & growth inhibiting factors (tumour suppressor genes)- mutation in either disrupts the balance
MYC
(oncogenes)
- example of a possible oncogene
- The MYC protein is a transcription facotr and controls the expression of several genes
- cMYC is upregulated in feline leukemia virus
SRC
(oncogene)
Src was the first oncogene ever discovered
The Src protein is a tyrosine kinase which regulates cell activity
HER-2/neu
(oncogenes)
- HER-2/neu encodes for a cell surface receptor that can stimulate cell division
- THe HER-2/neu gene is amplified in up to 30% of human breast cancers
Proto-oncogene abnormalities
- Lung Tumours (dog)
- Mammary Carcinomas (dog, cat)
- Malignant plasmacytoma (dog)
- Malignant melanoma (dog)
- Leukaemia (cat)
Tumour Supressor Gene (p53) abnormalities
- Thyroid carcinoma (dog)
- Lymphoid Tumours (dog)
- Osteosarcoma (dog)
- Mammary Tumours (dog)
- Colorectal Tumours (dog)
How does that mutation or genetic injury occur?
(Molecular Basis of Cancer)
- Genetic injury required for tumour development, which may be:
- Inherited in germ cell line
- or Acquired in somatic cells (i.e. effects of environmental agents)-likely more the case in older age?
- Carcinogenesis: multistep process (initiation and promotion steps occur)
- attributes of malignancy acquired in step-wise fashion (tumour progression)
- i.e. accumulation of successive mutations
Initiation
(first step of Carcinogenesis)
Initiation= introduction of irreversible genetic change into cells by action of mutagenic initiator (e.g. chemical/ physical carcinogens that damage DNA)
- Initiated cells appear morphologically normal, may remain quiescent for years
- But have mutations which give them growth advantage, e.g. respond more quickly/vigorously to mitogenic signals or are resistant to apoptosis-inducing stimuli
Promotion
(Second step Carcinogenesis)
Promotion= exposure to certain stimuli (promoting agents /promoters), most of which drive proliferation
Initiated cells grow more rapidly & in less controlled way
may lead to development of pre-neoplastic lesion/ benign tumour
Promoters are non-mutagenic: (non-genetic) & effects can be reversible
Progression
(third step oncogenesis)
Progression- includes conversion of benign tumour increasingly malignant, ultimately metastatic one
Malignant conversion = irreversible
Complex, poorly understood process; selecting for increasingly malignant clones
Increasing tumour cell heterogeneity (diversity) occurs with progression
Every tumor behaves differently:
Ex: mast cell tumors can behave in different ways.
Benign, medium size, or malignant.
Ex: sebaceous glands: will get benign, but they will never really become malignant.
It is hard to tell, there are a lot of grey areas
can’t always tell if it is malignant or benign right off the bat
Process of Carcinogenesis
Tumor Growth/ Progression
Depends on:
- Rate of division*
- Proportion of cells replicating*
- Rate of cell death
- Rate of differentiation
*Implications for treatment: classical treatments target cells which are rapidly synthesizing DNA
- these will help decide what treatment to use
- will also tell us how invasive we think that tumor may be
How do we look for rate of division in a tumor?
- look for mitotic figures (mitotic index)
- when you look at any tumor, looking at how many of those cells are dividing
- give mitotic rate to a tumor: look at 10 fields in high power, count the mitotic figures in those ten fields and give an estimate of the number of mitotic figures in each of those high power fields
- might be looking at 3 mitoses in 10 fields in a slow growing tumor and up to 70-100 in a really nasty tumor
- Part of tumor progression!
- mitoses are more likely to be seen in malignant neoplasms
How can we note the proportion of cells replicating?
- if a cell is replicating it means it is out of that resting phase and has entered the cell cycle
- stain it,
look for DNA replication
- or look for proteins that are specifically expressed in the cell cycle not in the resting phase KI-67 (expressed by all cells that arent in the resting or dormant phase)
- gives us additional information on the prognoses
- in mast cell tumors we can use the KI-67 that has been related to the grade of the tumor
How do we look for rate of cell death in a tumor?
Rate of cell death:
- look for how many apoptotic cells there are
- by eye or look for certain protein expression related to apoptosis
How do we look for Rate of Differentiation in a tumour?
ex: do they look like hepatocytes or don’t resemble the cell they are originating from
Hereditary Genetic Damage and Neoplasia
Characteristics:
- Develop tumour at a young age
- Poss bilateral tumours in paired organs (ex: uterus) , or multiple primary tumours.
- Family history
- Usually autosomal dominant.If recessive, affected gene inherited from both parents
- Examples of tumours in young animals: haematopoietic (stem cells that give rise to blood cells) , brain, skin, MCT (dogs), lymphoid (cats)
- Also breed specific tumours:
- Boxers, Bermese Mountain Dogs, Retrievers, GSD & Daschund= ↑ susceptible to certain types
- certain tumors are going to be seen in certain breeds
- Tends to also be hereditary if you see multiple tumors on multiple organs
Age
Age-
most tumours ↑ incidence with age:
Due to:
- accumulation of genetic damage,
- ↓ Immune function
- Lag between transformation & clinically detectable tumour (slow growth)
Acquired Genetic Damage
(Mutagenic Initiators and Neoplasia)
- Chemicals-
- naturally occurring (moldy grains, peanuts- predispose to Aflatoxin B1 in cattle and lead to liver cancer), toxin in bracken fern (lead to bladder cancer in cattle–> multistep porcess, bovine infected with papillomavirus causing the benign growth in GI tract and when that animal eats Bracken (toxins) that animal is exposed you get additional mutations and malignant tumor within GI tract - carcinomas) Note: most of these pro-carcinogens are not active right away, they usually get metabolically activated, like in the liver (may also be excreted rather than metabolically activated)
- alkylating agents,
- polycyclic aromatics HCs,
- aromatic amines & azo dyes,
- asbestos.
- Most require metabolic activation in vivo ultimate carcinogen- therefore its possible for pro-carcinogen to be detoxified & excreted before neoplasm occurs in some cases
- Radiation- Mutations caused by direct (radiant energy) or indirect (free radicals) effects
- E.g. UV rays (UVB) Squamous cell carcinoma in white cats ears & Hereford cattle eyelids. non-pigmented areas lack melanin to protect nucleus from damage!
- Ionizing radiation: radioisotopes (e.g. Radon), radiographs, radiation therapy (shorter λ)
- Hormones: e.g . steroid hormones, GH
- Immunological factors: Immunosuppression has a role in genesis of certain tumours (e.g. FeLV)- cell that is transformed is T-cell? Also have an increased instance of tumors in FIV animals
- Chronic inflammation/irritation: often associated with tumour development, especially in skin and other epithelial surfaces. Cells are continually replicating in response to the chronic irritation and therefore have an increased risk of acquiring a mutation during that replication. Possibly related to resultant hyperplasia
- Bacteria, parasites: e.g. Spirocerca sp .,
- Viruses- Variety of DNA & RNA viruses, usually occur in young animals. May affect relatively large
- numbers of animals in group/herd (e.g. viral papillomas, FeLV, FIV)
- retroviruses
- May integrate their genome host cellular DNA, interferes with normal cell replication
- May cause immunosuppression, allows tumours to develop e.g. FeLV- cats, HIV- humans
- May stimulate cell proliferation
Chemical Carcinogenesis
Hormonal Carciogenesis
- some tumours are influenced by hormones
- spayed bitches- reduced incidence of (malignant) mammary tumours, mammary epithelial cells have receptors for GH
- castration of dogs-regression of perianal tumours
Tumour Angiogenesis
Tumours (benign & malignant) cannot enlarge (beyond 1-2mm) without becoming vascularised
Required for: metabolism by tumour cells, sustained growth & metastasis of malignant tumours
-both malignant and benign tumors need this vascularization!!
- Tumor releases growth factors to stimulate angiogenesis and growth of host enotelial cells
- Tumours induce host vessels to supply branches by production of “tumour angiogenesis factors”
- Tumour lymphangiogenesis similar- essential for lymphatic spread of tumours
- *tumour vessels (especially malignant) are tortuous, irregular, leaky, less efficient than host vessels**, especially in faster growing tumour, vessels don’t get chance to form properly & you get disruption of blood delivery to neoplastic cells extensive necrosis due to hypoxia
- less likely to support the tumor with blood supply
- will see areas of necrosis where tumor has outgrown its blood supply
- research is looking to target these endotehlial cells of the vessels in tumors to try and prevent them from growing . sometimes use the density of these vessels for the diagnostics of these tumors –> not so much in vet med world though
Other Factors in Aetiology of Neoplasia
Other factors in aetiology of neoplasia
Hormones- some tumours are influenced by hormones
- Spayed bitches - ↓ incidence of (malignant) mammary tumours
- Castration of dogs - regression of perianal tumours
Immunological factors Immunosuppression has role in genesis of certain tumours (e.g. FeLV)
Chronic inflammation/irritation- Often associated with tumour development, esp in skin & other
epithelial surfaces. Possibly related to resultant hyperplasia
Other features of Tumours
- Can get Metaplasia (to cartilage and bone) of connective tissue stroma in some tumours
- e.g. mixed mammary tumours
- Occurs from changes in the environment or oxygenicity of the tissues which can definitely occur in tumors, they have developed from that same tissue!
- Therefore you can get some areas of bone and cartilage formation in the tumor where the tumor is originating from the epithelial cells
Immunohistochemistry
Used diagnostically to help identify tumour cells histologically- Look for the proteins which the specific cell types express i.e.
- Epithelial cells always express keratin
- Mesenchymal cells always express vimentin
Relies on Ab-Ag binding to identify antigens within tissue, colour brown if present
Can narrow search & test for further proteins of specific cells e.g. endothelial cells express VWF, CD31
want to use KI 67 when identifying a tumor, it will help us look at vimentin or keratin to differentiate the cancerous tissue present
using antibodies to detect antigen within the tissue to help work out the origin of that tumor
Haemangioma
Haemangioma- benign tumour of vascular endothelium
Tumor of endothelial cells, but they still know what they are doing and form vessels!
-weird naming
Haemangiosarcoma
Haemangiosarcoma- malignant tumour of vascular endothelium
-less differentiated, can only see some blood vessels, not really
-
Lymphoma, Lymphosarcoma
Lymphoma, lymphosarcoma (leukosis)- malignant tumours of lymphoid tissue
- Leukaemia - used when malignant lymphoid cells are circulating in the blood
Myeloma, Plasma Cell Tumour
Myeloma, plasma cell tumour or plasmacytoma- all= plasma cell tumours
Melanoma, Melanocytoma
Melanoma, melanocytoma= tumours of melanocytes (can also be melanotic or amelanotic)
melanocytes: pigment producing cells
- dont all produce melanin?
Sarcoid
low grade fibrosarcoma, in skin of horses & cats, viral involvement
Granuloma
Not neoplastic, chronic inflammatory reaction
Tumour Histology
(Benign or Malignant)
- Cell and nuclear characteristics
- Mitotic Index: how many cells are prolferating
- Signs of invasion or metastasis: Look in blood vessels or lymphatics for signs of metastasis, look around surrounding tissue
- margins (if excision biopsy): What kind of tumor free margins are there surrounding that tumor. If its benign tumor is there a capsule around it?
- Other features: connective tissue, ground substance, vascularity, necrosis (classically point to quickly growing tumor and it bein gmore malignant), ulceration, etc. -help us to determine what kind of tumor it is. ex: mesenchymal tumor, is it producing collagen, is it made of fibroblasts, is it producing bone, is it made of osteoclasts?
B vs. M
Cell and Nuclear Characteristics
Cell and nuclear characteristics
Look for nuclear to cytoplasmic ratio, appearance of nucleus, pattern of chromatin
- Benign tumours- uniform cell appearances
- Malignant- non uniform: variable cellular & nuclear size & shape & possibly multinucleated
B vs. M
Mitotic Index
Mitotic index = count of mitoses per 10 HP fields
Mitosis occurs in both but mitotic figures appear abnormal in malignant tumours
Exception: cutaneous histiocytoma- benign but ↑ mitotic rate- regress naturally
B vs. M
(SIgns of Invasion/ Margins)
- Benign tumours: Grow by expansion, may have rim of connective tissue (capsule), Don’t invade underlying/ adjacent tissue & ‘shell out’ easily at surgery
Malignant Tumours: Invasive & infiltrative, lacking defined border/ capsule.
Surgery requires removal of wide margin of surrounding tissue if possible
Metastasis
Metastasis = Single most important feature distinguishing benign from malignant tumours
- malignant can, benign cannot
- effects of metastases can alert the clinician that there is a primary tumor at all
Metastases (secondary malignant growths) may be presenting sign e.g. hepatopathy, bone pain & fractures, lymphadenopathy, ascites/pleural/pericardial effusion
-ex: could have a primary lung tumor that has metasticized to the bone and there is a break if the animal jumps
-sometimes there really isnt much of the normal tissue left
Tumour cells within blood vessels indicates metastatic potential- must evade host defences whilst travelling through vessels & set up specific factors to proliferate in new tissue- so metastasizing= v. rare
Routes of Metastasis
*Tumors are going to go the easiest route
- Local Invasion
- Intra-vascular – blood (haematogenous)/ lymphatic (offers ↓ resistance & ↓ pressure)
- Serosal/ transcoelemic spread- coelomic surfaces ideal e.g. peritoneum, pleura, pericardial sac etc
- often with protein-rich exudate, cells can be detected in fluid aspirates
- Examples: carcinomas of pancreas (partrick swayze), lung, kidney, ovarian cancer
- Intra-organ spread/ seeding- uncommon, may occur via airways in lungs or local blood/lymph drainage
(liver, kidneys)
Metastatic Cascade
*metastasis via vessels
- Primary tumour forms,
- Detachment and Migration of Malignant Cells: cadherins which usually join cells together= down regulated by neoplastic cells (in contact inhibition) .Need to then secrete proteins to allow them to move trhough the matrix of that tumor
- move through the surrounding mesenchyme by releasing cytokines- Then need to adhere to vessel wall and secrete proteins to allow them to go through that vessel wall
- Go into blood supply and avoid host immune responses and platelet clumping
- Need to get out of that blood vessel and find an environment that is actually going to give them the right growth signals and cytokines they need to proliferate and grow a new tumor –> migrate to organs preferentially & cause secondary tumours (specific tumours metastasize to specific areas)
- not efficient or well understood, but unfortunately it happens
- E.g. bone: mammary, thyroid, prostate, ovary, lung, melanoma
- Brain: melanoma
DIfferent types of tumors like to metasticize to certain places!!!
-ex: mammary tumors like to metasticize to the lung
Other Features of Tumours
connective tissue, ground substance, vascularity, necrosis, ulceration etc
Metaplasia in tumours
- e.g. mixed mammary tumours- glandular tissue is converted bone/ cartilage
Metaplasia of connective tissue stroma in some tumours to cartilage or bone
Multiple Tumors in one Organ/Tissue
- metastatic shower
- OR intra-organ spread
- OR more than one type of primary tumor in the organ
- (e.g. mammary tumors , elderly unspayed bitches or testicular tumors, elderly dogs)
- Or multiple spontaneous primary tumors of the same type within the organ or tissue (unusual)- ? liver tumors
When looking at a tumor and lesions, always ask:
- what cells are in that organ?
- What cells could transform?
- What does this tumor look like?
- Has it metastasized from another organ?
Benign Characteristics
KNOW
- rsemble normal tissue/cell
- Uniform cell and nuclear size/shape
- Grow by expansion
- Ofen encapsulated
- Often slow growth
- Usually low numbers of mitoses
- DO not spread
- May ulcerate on body surface, may cause pressure on other organs
- Endocrine tumours may or may not be functional
- Usually amenable to surgery
Malignant Characteristics
KNOW
- May look different to normal tissue/cell
- Often variable cell and nuclear size/shape/number
- Grow by invasion
- USually no capsule
- OFten fast growth
- Often high numbers of mitoses
- Spread (local invasion, metastasis)
- Necrosis centrally, ulcerate
- May be functional; secretions may be inappropriate (paraneoplastic effects)
- Often hard to completely remove surgically
Tumor Nomenclature: What do you need to get across?
When you get something in the lab:
- describe where it is and what cell layers it is orignating in or expanding to
- describe what the cells look like: shape of the cells, nucleus, mitotic figures, any necrosis
- by the end of that you should be able to give it to someone and they will know what kind of tumor it is
with naming: really just want to get where it is coming from and whether it is benign or malignant
Effects of Tumor on the Host
- Direct effect on tissue/organ – replacement of functioning cells, compression, invasion, organ rupture, embolus formation (infarction), ulceration, haemorrhage… could see clinical signs as a result: vomiting, blood in feces, or may bleed out and die from haemorhaggic shock
- E.g. abdominal haemorrhage from ruptured tumour in liver/ spleen (haemangiosarcoma)–> German Shepherd Dogs
- Cachexia – inappetance & loss of muscle and fat due to ↑ levels of certain inflammatory cytokines (particularly TNF & IL-6)
- tumor necrosis factors released by some tumors that can lead to cachexia
- Indirect/ paraneoplastic effects – usually due to production of abnormal tumour products that aren’t produced by those cells in normal tissues
- May be due to altered differentiation - expression of usually latent gene
- e.g. active substance inappropriately produced by tumour cells or ectopic receptor production
Paraneoplastic Effects of Tumours
- “systemic complications that are remote from the primary tumour”
Just know one so you can give example of a paraneoplastic effect!
- Affecting blood: Anaemia, thrombocytopenia, disseminated intravascular coagulation
- Affecting skeleton:
-
Hypercalcaemia of malignancy –Parathyroid hormone analogue produced by certain tumour cells
- going to see the osteoclastic resoprtion of bone
- (e.g. anal sac carcinomas/ lymphomas Ca deposited in tissues- e.g. lung alveoli )
- will see mineralized tissue within alveolar walls - Hypertrophic osteopathy, symmetrical lameness & extensive periosteal newbone in distal limbs (clinical signs)
- Associated with space-occupying thoracic lesions
- mechanisms unknown
* Neurologic effects:- Related to metabolic effects e.g. hypercalcaemia, hypoglycaemia seizures
- Myasthenia gravis: immune mediated response to thymoma
- Blocks NMJs
* GIT: GI ulceration, abdominal pain, vomiting, haemorrhage/ melaena (due to bioactive mediators)
Immune Responses and Tumors
Does the immune system recognise tumour cells as foreign?
- Tumors are good at masking themselves and hiding from our immune system
- Various molecules expressed on tumour cell surface = tumour antigens (Ags), may be:
- Newly-expressed molecules e.g. viral proteins (if due to a papillomavirus or retrovirus)
- Altered cell products (from cells that are less differentiated, will express proteins that may be more associated with angiogenesis? so might get some embryological proteins expressed. or they are so poorly differentiated that they are just expressing something completely different)
- Re-expressed molecules e.g. embryonic/ oncofetal Ags e.g. Carcinoembryonic Ag, α-fetoprotein
- Presence of lymphos around many tumour types suggests immunosurveillance, may ↑ prognosis
- Immunosuppressive diseases associated with ↑ malignancies (proving that the immune response does have a role in tumor growth)
- can start to get cell mediated immunity towards tumor cells!
- Anti-tumour effector mechanisms: NK cells, Cell-mediated immunity (CTLs) & Humoral response (complement)
Evasion of Immune System by Tumours
variety of mechanisms:
- Failure to display antigenic (or costimulatory) molecules by tumour cell –> lack of T cell recognition, not recognized
- Antigen masked by tumour celll–>lack of T cell recognition
- Tolerance - express proteins that are normal-hard to detect that it is different , tumour antigen (or costimulatory) molecule shared with normal tissue–> Lack of recognition of tumour or recognition but lack of activation of T lymphocyte
- Immunosuppression by tumour cells or their products–> Lack of response by IS or apoptosis of T cells
General Functions of the Skin
Enclosing Barrier:
- water, electrolytes, macromolecules IN
- Microbes, chemicals OUT
- physical protection
- UV protection
- allows movement
Leukamia
Leukemia is a malignancy (cancer) of blood cells. Inleukemia, abnormal blood cells are produced in the bone marrow. Usually, leukemia involves the production of abnormal white blood cells – the cells responsible for fighting infection
