Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MEDSCI 708 > Topic 2-Lecture > Flashcards

Topic 2-Lecture Flashcards

1
Q

What is cancer?

A

This condition, also known as a malignant tumour or malignant neoplasm, ios a group of diseases involving abnormal growth with the potential to invade or spread to other parts of the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the six characteristics of cancer?

A

Self-sufficiency in growth signalling
Insensitivity to anti-growth signals
Evasion of apoptosis
Enabling of a limitless replicative potential
Induction and sustainment of angiogenesis
Activation of metastasis and invasion of tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are some of the causes of cancer?

A

Radiation such as Ultraviolet light, sunshine and X-rays, radioactive elements induce DNA damage and chromosome breaks
Chemicals including smoke and tar along with other mutagens
Oncogenic viruses where DNA or cDNA copies of viral oncogenes are inserted into the genome of host target cells
Hereditary where certain oncogenes can be inherited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the different genetic changes which occur in carcinogenesis?

A

Activating mutations in oncogenes such as growth factor receptors which lead to a gain of function
Inactivating mutations in tumour suppressor genes such as p53, these may help facilitate the evasion of apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a carcinoma?

A

A cancer derived from epithelial cells, this group contains many of the common cancers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is Sarcoma?

A

Arising from connective tissue (bone, cartilage, fat, nerve)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are Lymphoma and leukaemia?

A

Cancers derived from hematopoietic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are germ cell tumours?

A

Cancers which arise from pluripotent cells most in the testicle and ovary (seminoma and dysgerminoma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is a blastoma?

A

Cancer derived from immature, precursor cells or embryonic tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the four key treatment options for cancer?

A

Mechanical based methods or surgery
Physics based methods or radiotherapy
Chemical methods or chemotherapy
Biological methods or immunotherapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the features which distinguish immunotherapeutic treatments from the traditional chemotherapeutic approach?

A

Immunotherapy relies on performing single cell kills, uses agents which can migrate to cancer tissues, uses highly specific agents, may provide memory or life-long protections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What process must a cancer go through if it is too survive in an immunologically active environment?

A

The same mutations which cause cancer cells to transform from a normal cell to a cancer cell may generate new immunologically active antigens, this can then lead to either elimination of the cancer by immunological attack or equilibrium where the rate of immunological mediated cell killing equals the cancer cell growth rate.
In the case of an equilibrium, this cancer may then undergo immunoediting, where some clones are generated which are less susceptible to recognition by the immune system, these clones have a selective advantage and over grow the rest of the tumour resulting in a cancer which has evaded the immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How do Cytotoxic Lymphocytes attack cancer?

A

They attach to MHC-I peptide complex, of they recognize the peptide as foreign and become appropriately licenced by surrounding signals then they will kill the cancer cell through either engaging of death receptors such as Fas or through the release of cytotoxic granules containing perforin and granzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How can helper T cells help in the fight against cancer?

A

They can react to the MHC II peptide complex and then secrete cytokines which will help either a cytotoxic T cell response (Th1 helper T cells) or an antibody mediated response (Th2 helper T cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How do antigen presenting cells help in the fight against cancer>?

A

They can present tumour antigens to lymphocytes to activate them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do NK cells help in the fight against cancer?

A

Directly killing tumour cells after activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How do NKT help in the fight against cancer?

A

Use of TRAIL/perforin-tumour cell lysis and IFN-gamma angiogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do macrophages help in the fight against cancer?

A

Antigen presenting and cytokine stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How does IFN-alpha help in the immune response to cancer?

A

Upregulating MHC class I, tumour antigens and adhesion molecules; promoting activity of B and T cells, macrophages and DCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does IFN-gamma help in the immune response to cancer?

A

Activation of NK cells and macrophages and promotion of B cell differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does IL-2 help in the immune response to cancer?

A

It is a T cell growth factor that binds to a specific tripartite receptor on T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does IL-12 help in the immune response to cancer?

A

Promotes NK and T cell activity and acts as growth factor for B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How does GM-CSF help in the immune response to cancer?

A

This reconstitutes antigen presenting cells

24
Q

What are the four mechanisms through which antibodies can kill cancer cells?

A

Antibody-dependnet cell mediated cytotoxicity
Complement dependent cytotoxicity
Interfering with cell signalling by binding to surface receptors inducing cell death
Through carrying a drug such as a anti-microtubule agent

25
Q

What are the mechanisms through which cancer can evade the immune system?

A

They can alter their characteristics as a result of their genetic instability and high mutation rate
Suppression of the immune system via dysregulation
Outpacing the immune system by proliferating faster than the immune system has the capacity to respond to

26
Q

What are the 6 key defence systems of cancer cells from the immune system?

A

Alteration of MHC I and tumour antigen expression
Dysregulated co-stimulatory molecules
Changes in T cell signal transduction molecules
Production of immunosuppressive cytokines
Induction of immunosuppressive cells
Production of other suppressive factors

27
Q

How do cancer cells lose or down regulate MHC?

A

There may be total loss through loss of the beta2 microglobulin
There may be haplotype loss with loss of heterozygosity in chromosome 6
There may be HLA allelic loss by mutatiosn in the HLA genes
There may be locus downregulation of HLA-A,B,C

28
Q

What are some examples of tumour antigens?

A

Mutated self antigens
Viral antigens
Oncofetalproteins
Autoantigens

29
Q

What immunosuppressive cells can be produced by tumour cells?

A

IL-10 which inhibits antigen presentation and IL-12 production
VEGF this avoids immune recognition, inhibiting the effector function preventing T cell activation and cytokine production
TGF-beta which induces overproduction of IL-10 and suppresses activation of immune cells

30
Q

What are the immunosuppressive cells which are induced by tumours to help defend themselves from the immune system?

A

Regulatory T cells which is a subpopulation of T cells that modulate the immune system and maintain tolerance to self-antigens
CD4+CD25+FoxP3+ T Cells which confer immunological tolerance to self-antigens and inhibition of T cell proliferation
Gr1+CD11b+ myeloid cells which accumulate in spleens, lymph nodes and blood of tumour bearing mice they inhibit antibody production, CTL generation, T cell function, lymphocyte proliferation and CD3 zeta chain expression

31
Q

What suppressive factors are produced by tumours?

A

IDO which is expressed by most tumour tissues and splenic DC subsets leading to blockage of proliferation of T cells
Ganglioside which suppresses the function of cytotoxic T cells and dendritic cells
Prostaglandin E2 which will inhibit DC maturation, T cell activation and cytokine production

32
Q

What immune defects in T cells can help a tumour develop?

A

There may be alterations in signal transduction molecules in immune cells such as loss of the CD3 zeta chain from the TCR-CD3 complex preventing T cell activation

33
Q

What malfunctions of the dendritic cell system can allow a tumour to develop?

A

Tumour-mediated inhibition of DC generation, differentiation and maturation
Functional impairment of DCs through a lack of expression of co-stimulatory molecules
Induction of DC apoptosis by tumours

34
Q

What is cancer immunotherapy?

A

Strategies to improve the cancer-associated immune response by either boosting components of the immune system that produce an effective immune response or by inhibiting components that suppress the immune response

35
Q

What immunotherapy strategies focus on supplementing the missing or insufficient immune elements?

A

Injection of cytotoxic T cells
DC vaccine
Injection of activated NK cells
Use of tumour associated antigen vaccination
Treatment with effector cytokines IL-2, IFN-alpha and IL-12

36
Q

What immunotherapy strategies focus on blocking the suppressive immune mechanisms of the cancer cells?

A

Blocking the function of regulatory T cells
Blocking of the pathway used by Dysfunctional dendritic cells
Blocking the potential common cytokine signalling of suppressive cytokines
Blocking the function of other suppressive factors

37
Q

What are the current cancer immunotherapies in clinic and clinical trials?

A 
Antibody therapy
Cytokine therapy
Adoptive therapy
Vaccination
Combinational Therapy
38
Q

What is antibody therapy?

A

This is now one of the successful and important strategies for the treatment of cancer with its fundamental basis being observations of antigen expression by tumour cells, it has gone through generational development with technical development from antibody chimerization to humanization

39
Q

What is Rituximab?

A

The first FDA approved antibody used in the treatment of B-cell non-hodgkin lymphoma

40
Q

What are the mechanisms of action of rituximab (anti CD20)?

A

In CDC the C1 component of the complement cascade binds to the Fc region of the antibody activating complement resulting in the eventual formation of the membrane attack complex
In antibody dependent cellular cytotoxicity effector cells bind to the FC portion of the antibody via Fcgamma receptors leading to the release of perforin
In direct cytotoxicity the antibody may induce internal signalling within the tumour cell leading to anti-proliferative effects or cell death which may involve apoptosis or other cell death pathways

41
Q

What is Bevacizumab?

A

A mab approved for the treatment of cancers, it binds to VEGF preventing it from interacting with receptors and thus blocking tumour angiogenesis

42
Q

What is Herceptin/trastuzumab?

A

An antibody approved for the treatment of HER2+ breast cancer which acts through antibody dependent cellular cytoxicity and direct cytotoxicity where it can lead to the internalization of HER2, disruption of dimerization, and inhibition of Akt activity and angiogenesis

43
Q

How do antibody drug conjugates work?

A

They bind to a receptor and become internalized and transported to the lysosome where the linker between the antibody and the bound drug can be broken allowing the drug to be delivered in high doses to cancer cells
Trastuzumab was the first approved version of these which consisted of an antibody against the HER-2 receptor linked to the cytotoxic agent mertansine

44
Q

What are two recently approved drugs which target immune checkpoints for the treatment of cancer?

A

Anti CTLA-4 (Ipilimumab) which blocks a receptor which typically confers inhibitory signals to T cells
Anti-PD1 (Programmed death protein-1) known as Keytruda, this blocks a cell surface receptor found on T cells and pro B cells binding the two ligands PD-1L and PD-2L

45
Q

What have been the milestones in the development of active immunotherapy?

A

In 1893 William Coley uses live bacteria as an immune stimulant to treat cancer
1949 Sir Mac Burnet publishes the theory of acquired immune tolerance
1957 there is the discover of tumour specific antigens by George Klein
1967 Burnet proposes the theory of immunosurveillance
1973 there is the discovery of dendritic cells by Ralph Steinman
1991 Discovery of first molecular defined tumour antigens recognized by human T cells
1992 IL-2 is approved as an anti-cancer therapy
1997 first approval of monoclonal antibody as anti-cancer therapy
1998 First report of complete/partial regressions with therapeutic cancer vaccine
2010 First approval of therapeutic cancer vaccine

46
Q

What are the two FDA approved, cytokine based cancer treatments?

A

High bolus dose of IL-2 for metastatic melanoma and renal cell carcinoma
IFN-alpha for the adjuvant therapy of stage III melanoma

47
Q

What cytokine based cancer treatments are currently in clinical trial?

A

Cytokines like GM-CSF, IL-7, IL-12, IL-15, IL-18 and IL-21 and have entered clinical trials for patients with advanced cancer

48
Q

What is adoptive cell transfer immunotherapy?

A

This refers to stimulating immune cells by exposing them to tumour cells or antigens in the lab and the injecting expanded populations of the treated immune cells into each patient

49
Q

What is the difference between an autologous and allogenic adoptive cell transfer treatment?

A

In autologous treatments the patient is both donor and recipient
In allogenic treatment the cells raised up against the antigen are acquired from a donor

50
Q

How is engineered adoptive T cell immunotherapy performed?

A

Some tumour cells can produce the immunosuppressant TBF-Beta to prevent CTL attack
To overcome this specific CTL can be made resistant to the effects of TGFbeta via transgene expression of a dominant-negative TGFbeta type II receptor
Alternatively specific T cells can be modified to produce IL-12 to overcome the inhibitory effect from IL-10
Some tumours can produce FasL in the counter attack, so siRNA can be used to knock down the Fas Receptor in specific CTL which allows a significant reduction of the CTL to this effect

51
Q

How does Chimeric antigen receptor T cell therapy?

A

Use of CTLS which have been modified through the use of viral vectors to express an MHC independent receptor of tumour cell antigen that will provide all the known costimulatory molecules in receptors

52
Q

How are cells used in CAR T cell therapy prepared?

A

Lymphocytes are prepared form the patient or donor and then grown in culture they are then placed in a retronectin-coated culture bag and provided with IL-2 and a CAR, viral transduction then results in CAR expressing T cells which are given cytokine support to allow them to proliferate, subjected to preparative chemotherapy allowing infused CAR-modified T cells

53
Q

What are the different approaches of antitumour vaccination?

A

A vector encoding immunostimulatory cytokines might be transfected into tumour cells allowing DCs to become activated and being able to stimulate CTLs
Alternatively Tumour Lysate might be added with a viral vector and peptides to a DC leading to the production of DCs loaded with tumour peptide to stimulate CTLs
Finally a viral vector, peptides an plasmid DNA may be directly injected into the patient leading to local tumour antigen expression by DCs and stimulate CTL

54
Q

What is Provenge?

A

The first FDA approved therapeutic cancer cell vaccine

55
Q

What is the role of personalized medicine in cancer immunotherapy?

A

By increasing our knowledge of cancer biology we can classify cancers into more and more specific types, this allows for people to be better screened and the most appropriate treatment to be selected for them saving both time and money in comparison to the previously used hit and miss approach

MEDSCI 708 (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions