Transplantation of tissues and organs (Chapter 15)

1
Transplantation of tissues and organs(Chapter 15)

• History of Organ Transplantation
• 1812 The first successful blood transfusion
• 1954 First successful living sibling kidney
  transplant by Dr. Joseph Murray, Boston
• 1967 First successful liver transplant by Dr.
  Starzl, Denver
• 1967 First Successful Heart Transplant by Dr.
  Christiaan Barnard, South Africa
• 1983 FDA approves Cyclosporine, the most
  successful anti-rejection medication developed
  to date
• 1992 Baboon liver transplanted into man dying
  of liver failure
• 2005 The world's first face transplant on a
  living human carried out by Dr. Jean- Michel
  Dubernard, a plastic surgeon in France. Isabelle
  Dinoir underwent surgery to replace her
  original face that had been ravaged by her dog.

2
Immune responses against transplanted tissues

• Immune responses against transplanted tissue or
  organs are caused by genetic differences between
  donor and recipient, most often in the HLA
  molecules.
• During transplantations, the HLA molecules
  represent antigens against which the immune
  response is directed.
• These antigens that vary between members of the
  same species are called alloantigens, and the
  immune responses they induce are called
  alloreactions.
• Immunogenetics studies genetics of alloantigens.
• Blood transfusion is the most widespread kind of
  transplantation in clinical medicine
• Graft the transplanted organ

3
Matching donor and recipient for HLA class I and
II molecules improves the outcome of
transplantation

• The major cause of graft rejections are the
  differences in the HLA class I and II molecules
  within the populations.
• Only in the case of identical twins, the HLA
  class I and II molecules are identical, and there
  is no risk of alloreactivity during
  transplantations.
• During transplantations, the donor and recipients
  are analyzed for HLA class I and II compatibility
  (by serological assays based on monoclonal
  antibodies).
• The immunogenetic differences (in the HLA class I
  and II molecules) are much smaller within a
  family than within the whole populations ?
  clinical outcomes are better between relatives
  (siblings) than between unrelated people.

4
Alloreactions during transplantations
Transplant rejection and graft-versus-host
reaction are immune responses caused by genetic
differences between transplant donors and
recipients
5
Sources of transplanted organs (grafts)

• Autografts Tissues transplanted from one site to
  another on the same person (skin transplantations
  in burn patients).
• Isografts Transplantation between genetically
  identical individuals (twins).
• Allografts Transplantations between two
  genetically different individuals.
• Xenografts Transplantations between two
  different species (humans and monkeys or pigs
  not routinely used raise many scientific and
  ethical issues).

6
In blood transfusions, donors and recipients are
matched for the A, B, O system of blood group
antigens

• The first blood transfusion was performed in
  1812.
• Today, the blood transfusion is the most common
  clinical transplantation procedure.
• There are no HLA molecules on erythrocytes
• However, the major immunogenetic barrier to
  transfusion with red blood cells arises from
  structural variety in the carbohydrates present
  on the erythrocyte surface.
• The resulting differences in these carbohydrates
  are the molecular basis for the A, B, O blood
  group system.
• The antigens in the ABO system are glycoproteins
  with their sugar residues exposed at the
  erythrocyte surface. The terminal sugar
  determines whether the antigen is A or B.
• The critical principle is that people usually
  have antibodies against those erythrocyte
  antigens that they lack.
• Why do we have antibodies against erythrocyte
  antigens that we lack? Bacteria living in our
  intestine express antigens similar to those on A
  and B. We synthesize antibodies against these if
  we do not have the corresponding antigens that
  is, if our immune system sees them as "foreign"
  rather than "self".

7
Structure of the A, B, O blood group antigens
8
ABO blood grouping system

• Blood group AIf you belong to the blood group A,
  you have A antigens on the surface of your red
  blood cells and B antibodies in your blood
  plasma. 
• Blood group BIf you belong to the blood group B,
  you have B antigens on the surface of your red
  blood cells and A antibodies in your blood
  plasma.   
• Blood group ABIf you belong to the blood group
  AB, you have both A and B antigens on the surface
  of your red blood cells and no A or B antibodies
  at all in your blood plasma.People with type AB
  blood are called universal recipients. This means
  they can get any type of blood.
• Blood group 0If you belong to the blood group 0
  (null), you have neither A or B antigens on the
  surface of your red blood cells but you have both
  A and B antibodies in your blood plasma. About
  40 the population has type O blood. People with
  this blood type are called universal donors. Type
  O blood is used for emergencies when there's no
  time to test a person's blood type.

9
Donors and recipients for blood transfusions must
be matched for the A, B, 0 system of blood group
antigens
YES
NO
NO
NO
NO
NO
YES
YES
YES
YES
NO
NO
YES
YES
YES
YES
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10
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Ethnic Distribution of ABO Blood Types
PEOPLE GROUP O () A () B () AB ()
Asian 40 28 27 5
Austrians 36 44 13 6
Blackfoot (N. Am. Indian) 17 82 0 1
Bororo (Brazil) 100 0 0 0
Brazilians 47 41 9 3
Czechs 30 44 18 9
Danes 41 44 11 4
Egyptians 33 36 24 8
English 47 42 9 3
French 43 47 7 3
Germans 41 43 11 5
Japanese 30 38 22 10
Malaysians 62 18 20 0
Mayas 98 1 1 1
Norwegians 39 50 8 4
Persians 38 33 22 7
Peru (Indians) 100 0 0 0
Russians 33 36 23 8
Spanish 38 47 10 5
USA 45 30 20 5
Vietnamese 42 22 30 5
Mean 43.91 34.80 16.55 5.14
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12
Types of graft rejections

• Hyper-acute Caused by presence of pre-existing
  antibodies that bind to the cells/tissues of the
  transplanted organ comparable to type III
  hyper-sensitivity reactions, in which complement
  is activated within blood vessel walls, causing
  blood clotting and hemorrhage. Occurs
  immediately, before the patient leaves the
  operating room. Can be prevented by careful
  cross-matching between the donor and the
  recipient. Example Blood group antibodies A, B,
  O reactions against the graft.
• Acute Caused by alloreactive T cells that
  recognize the donors HLA-derived antigens,
  migrate to the transplanted organ and destroy it.
  Occurs days after transplantation. Can be
  prevented by matching the donor and recipient for
  HLA class I and II molecules, and by
  immunosuppressive drugs.
• Chronic Mediated by alloreactive T cells that
  induce production of anti-HLA alloantibodies by
  activated naive B cells. Occurs months or years
  after transplantation.

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Hyperacute Rejections Antibodies against A, B, O
or HLA antigens can cause hyper-acute rejection
of transplanted organs

• A, B, O antigens are expressed also on the
  endothelial cells of blood vessels this is an
  important factor during transplantations of solid
  organs, such as kidneys.
• For example, if a recipient of group O were to
  receive a kidney from a donor type A, the anti-A
  antibodies in the recipient would quickly bind to
  the blood vessel walls in the donated kidney.
  This would result in an immediate activation of
  the complement and rejection of the graft
  (donated organ).
• This type of reaction is called hyper-acute
  rejection, and occurs immediately before the
  patient leaves the operating room. It is directly
  comparable to type III hypersensitivity
  reactions.
• To avoid the hyper-acute rejections, patients and
  donors are carefully cross-matched.

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Hyper-acute rejection is caused by preexisting
antibodies binding to the graft
15
Acute Rejections Caused by effector T cells
responding to HLA differences between donor and
recipient

• Most transplantations are made across some HLA
  class I and II differences.
• In this situation, the recipient T cells react
  against the donors HLA class I and II molecules
  that are not shared by the recipient.
• CD8 cells respond to HLA class I differences,
  while CD4 cells respond to HLA class II
  differences.
• These alloreactive T cells can attack the donated
  organ and destroy it, causing acute rejection.
• This acute rejection occurs days after the
  transplantation and can be prevented by
  immunosuppressive drugs or anti-T cell
  antibodies.
• The acute rejection mediated by T cells is
  directly comparable to type IV hyper-sensitivity
  reactions.

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Chronic Rejections Mediated by alloreactive T
cells that induce production of antibodies

• Chronic rejections occur months or years after
  the transplantation.
• They are caused by alloreactive T cells that
  induce activation of naive B cells specific for
  the allergenic HLA antigens, and production of
  anti-HLA alloantibodies.
• This type of rejection is responsible for more
  than half of all kidney and heart transplants
  within 10 years after transplantation.
• Now that there are treatments for acute
  rejection, chronic rejection is the major cause
  of graft loss. Most recipients must take
  immunosuppressive drugs for the rest of their
  lives, and even that may not be enough to combat
  chronic rejection.

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Immunosuppressive drugs

• Used in clinical transplantations to suppress
  alloreactions that would otherwise lead to
  transplant rejection.
• Because of their immunosuppressive properties,
  these drugs are associated with increased
  susceptibility to infections.
• Generally used in combinations so that their
  immunosuppressive effects are additive while
  their toxic effects are not.
• 1. Corticosteroids
• 2. Cytotoxic drugs
• 3. Drugs inhibiting T cell activation

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• Corticosteroids
• Potent immunosuppressive drugs that inhibit
  inflammation and leukocyte activation.
• The mechanism consists of inhibiting
  transcription factor NFkB that induces synthesis
  of many of the pro-inflammatory proteins.
• Have many serious side effects such as increased
  glucose (diabetes), increased susceptibility to
  infections, and adverse neuro-developmental
  effects.

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Cytotoxic drugs

• Interfere with DNA replication, thus killing
  proliferating cells.
• Azathioprine and cyclophosphamide are the most
  commonly used cytotoxic drugs for immune
  suppression. Side effects include nausea and
  vomiting, hair loss, low blood cell counts, and
  fetal damage or death.
• Cytotoxic drugs are usually given at high doses
  with a transplant to block acute rejection and
  then at lower doses with corticosteroids for
  maintenance.

20
Drugs inhibiting T cell activation

• Selective drugs that specifically inhibit T cell
  activation first introduced in 1970s, greatly
  improving outcomes of transplantations.
• Disrupt signal transduction from the T cell
  receptor in activated T cells.
• Represented by cyclosporin and tacrolimus, which
  inhibits signal transduction in activated T
  cells, thus inhibiting IL-2 synthesis that is
  essential for T cell proliferation and
  differentiation.
• Cyclosporin A is derived from the Norwegian soil
  fungus Tolypodcladium inflatum. Tacrolimus (FK
  506) comes from the Japanese filamentous
  bacterium Streptomyces tsukabaensis rapamycin, a
  closely related drug also from Streptomyces is
  currently in clinical trials as an
  immunosuppressant.
• Cyclosporin A and tacrolimus are usually
  administered in high doses with a transplant to
  block acute rejection and then at lower doses for
  maintenance.

21
Immunological effects of cyclosporin
A major advantage of this class of drugs is that
they do not target proliferating cells, and
therefore do not interfere with hematopoiesis (do
not cause anemia).
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Patients needing a transplant outnumber the
available organs

• The success rates of transplant surgery have
  improved remarkably, but growing shortages exist
  in the supply of organs and tissues available for
  transplantation. Many Americans who need
  transplants cannot get them because of these
  shortages.
• 18 people die awaiting an organ transplant in the
  United States every day.
• The number of people in the U.S. waiting for an
  organ transplant is over 100,000.
• An estimated 14,000 people who die each year meet
  the criteria for organ donation, but less than
  half of that number become actual organ donors.
• By signing a Uniform Donor Card, an individual
  indicates his or her wish to be a donor.

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Manipulations of the Immune Response(Chapter 16)

• Insufficient or misdirected and exaggerated
  immune responses result in different
  immunodeficiency and autoimmune diseases.
• Immune system can be manipulated to the benefit
  of patients
• The main types of manipulations of the immune
  system involve
• 1. Vaccination
• 2. Inhibition of inflammation
• 3. Immuno-suppression during organ
  transplantation
• 4. Manipulations during cancer

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Cancer and its interaction with the immune system

• Cancer is a diverse collection of
  life-threatening diseases that are caused by
  abnormal and invasive cell proliferation.
• Cancer cells are very similar to normal cells,
  and the immune system is unable to attack them
  early and effectively.
• Cancer results from mutations (changes in DNA)
  that control cell growth.
• The branch of medicine that deals with cancer is
  called oncology.

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Cancer Cells are Different

• Escape normal intercellular communication
• Allow for rapid growth
• Increased mobility of cells
• Invade tissues
• Metastasis
• Evade the immune system

26
During oncogenesis, some of the antigens on the
cancer cell surface change tumor antigens. Some
of these tumor antigens are shed from the cancer
cells. These shed antigens prompt action from
cytotoxic T cells, NK cells, and macrophages.
According to the theory of immune surveillance,
patrolling cells of the immune system provide
continuous surveillance, catching and eliminating
cells that undergo malignant transformation.
Tumors develop when this immune surveillance
breaks down or is overwhelmed.
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Evidence for Tumor Immunity

• The high frequency of cancers in immunosuppressed
  patients
• Extremes of age
• Primary and secondary immunodeficiency
• Immunosuppressive drugs
• Tumors that are infiltrated by T cells and
  monocytes have an improved prognosis
• Spontaneous regression occurs
• Melanoma, breast, lung cancers
• Human tumors are immunogenic
• Tumors antigens have been defined
• Tumor specific T cells and antibodies are found
  in cancer patients

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Experimental Evidence for Tumor Antigens and
Immune Response
4. No tumor growth
2. Excise tumor
3. Re-challenge with same tumor
1. Inject Tumor
1. Inject Tumor
2. Excise tumor
3. Re-challenge with different tumor
4. Tumor grows
29
Nude mice cannot reject tumors and have been thus
used to test new anti-cancer therapies

• The nude mice have a dysfunctional immune system,
  and can only live in a sterile environment.
• They cannot reject any transplanted tissue,
  including tumors.
• Nude mice are very useful in cancer research
  because injected human cancer cells can grow into
  tumors allowing new ways to test cancer
  therapies.

Nude mouse with transplanted rabbit skin
30
Tumors Benign vs. malignant

• Mass of abnormally proliferating cells is called
  tumor ( swelling) or neoplasm ( new growth).
• Benign Encapsulated tumors, localized and
  limited in size
• Tumors
• Malignant Invasive tumors, invading adjacent
  tissues

Adenoma benign tumor of glandular tissue
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Classification of tumors

• Tumors Primary the site of cancer origin
• Secondary the new tumors formed by metastasis
  (cancer cells are carried by blood or lymph
  to distant places)
• Solid tumors Carcinomas - cancers of epithelial
  cells (stomach, lung, breast prostate) 90
  of all cancers
• Sarcomas - cancers of all other cell types
  (bones, muscles) very rare
• Immune system cancers Leukemias cancers of
  blood cells
• Lymphomas cancers of lymphoid tissues
• Myelomas cancers of bone marrow

8 of all cancers
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Ten Most Frequent Cancers in the United States

1. Breast
2. Prostate
3. Lung
4. Colon/rectum
5. Lymphomas
6. Bladder
7. Uterus
8. Skin
9. Kidney
10. Leukemias

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A cancer arises from a single cell that has
accumulated multiple mutations

• The proper division of cells is controlled by
  many mechanisms and multiple checkpoints ? the
  control of cell division is never dependent on
  only one protein cell must accumulate multiple
  mutations in order to undergo malignant
  transformation.
• Cell division and malignant transformation are
  controlled by two classes of genes
  proto-oncogenes and tumor suppressor genes.
• Proto-oncogenes are genes that regulate cell
  division and proliferation. The mutant forms of
  proto-oncogenes that contribute to malignant
  transformation are called oncogenes.
• Tumor suppressor genes encode proteins that
  prevent malignant transformation. Loss of these
  proteins results in malignant transformations and
  cancer. One of the most important tumor
  suppressor genes is p53, loss of which is
  responsible for 50 of human cancers.

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Proto-Oncogenes and Normal Cell Growth
Normal Growth-Control Pathway
Oncogenes are related to normal genes called
proto-oncogenes that encode components of the
cells normal growth-control pathway. Some of
these components are growth factors, receptors,
signaling enzymes, and transcription factors.
Growth factors bind to receptors on the cell
surface, which activate signaling enzymes inside
the cell that, in turn, activate transcription
factors inside the cells nucleus. The activated
transcription factors turn on the genes
required for cell growth and proliferation.
Growth factor
Receptor
Signaling enzymes
Transcriptionfactors
DNA
Cell nucleus
Cell proliferation
35
p53 Tumor Suppressor Protein Triggers Cell Suicide
p53 protein
Cell suicide (Apoptosis)
Normal cell
Excessive DNA damage
Normal cell
Cell suicide (Apoptosis)
Excessive DNA damage
One particular tumor suppressor gene codes for a
protein called p53 that can trigger apoptosis.
In cells that have undergone DNA damage, the p53
protein acts like a brake pedal to halt cell
growth and division. If the damage cannot be
repaired, the p53 protein eventually initiates
cell suicide, thereby preventing the genetically
damaged cell from growing out of control.
36
NFkB-dependent genes are involved in different
aspects of oncogenesis

• Recent evidence has accumulated from a large
  variety of human malignancies indicating a role
  for NFkB in promoting oncogenic conversion and in
  facilitating later stage tumor properties such as
  metastasis.

Oncogene 25 6817, 2006
37
Constitutive NFkB activation in human cancers
Oncogene 25 6817, 2006
38
Exposure to chemicals, radiation, and viruses can
facilitate the progression to cancer

• The number of mutations in the body can be
  increased by mutagens, chemical and physical
  agents that damage DNA. Mutagens that are known
  to increase the risk of cancer are called
  carcinogens.
• Physical carcinogens (UV light, radiation)
  usually induce extensive DNA mutations DNA
  breaks and chromosome translocations.
• Chemical carcinogens (asbestos, benzene, estrogen
  therapy, tobacco products) usually induce single
  nucleotide substitution in the proto-oncogenes
  and tumor suppressor genes.
• Oncogenic viruses and bacteria Certain viruses
  and bacteria can also induce malignant
  transformation viruses are associated with 15
  of all human cancers. Some oncogenic viruses -
  Papilloma virus, Epstein-Barr virus - bind to
  p53, thus inactivating it and enabling the
  virus-infected cell to proliferate. Bacterium
  Helicobacter pylori is associated with
  pathogenesis of stomach inflammation, ulcers, and
  cancer.

39
Vaccine against HPV now available in the US
40
Cancer therapies

• Surgery
• Chemotherapy
• Radiation therapy
• Immunotherapy
• Types of immunotherapies include
• Cancer vaccines (active specific immunotherapies)
  
• Monoclonal antibody therapy (passive specific
  immunotherapies)
• Nonspecific immunotherapies (cytokines)

Classical New, emerging
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Immunotherapies

• Cancer vaccines (Active Specific Immunotherapy)
• Contain cancer cells, parts of the cancer cells,
  or pure tumor-associated antigens (antigens
  expressed only on tumor cells but not on healthy
  cells).
• Induce production of tumor-specific antibodies
  and stimulate killer CD8 T cells to attack the
  cancer cells.
• So far used only in clinical trials not approved
  for general use.
• Monoclonal Antibody Therapy (Passive Specific
  Immunotherapy)
• Monoclonal antibody therapy is a passive
  immunotherapy because the antibodies against the
  tumor-associated antigens are produced outside
  the body (in the lab) rather than by the immune
  system. This type of therapy can be effective
  even if the immune system is weakened.
• Approved for treatment of certain cancers (breast
  cancer, leukemias).
• Nonspecific Immunotherapies (Cytokines)
• Stimulate the immune system in a very general
  way.
• Interleukin-2 (IL-2) Stimulates the ability of
  NK cells to kill the cancer cells. Used to treat
  melanomas and kidney cancers.
• Interferons Slow the growth of cancer cells
  stimulate the cancer killing ability of NK cells.
  Used to treat leukemias, lymphomas and melanoma.

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Monoclonal antibodies (MAbs)

• Monoclonal antibodies are the most widely used
  immunotherapy.
• The first MAbs were made entirely from mouse
  cells. One problem with this is that the human
  immune system will see these antibodies as
  foreign and then will mount a response against
  them. This can cause allergic-type reactions.
• Over time, researchers have learned how to
  replace some parts of these mouse antibody
  proteins with human parts. Depending on how much
  of the MAb is human, these are called chimeric or
  humanized antibodies they are likely to be safer
  and more effective than older MAbs.

Chimeric Antibodies The variable regions of a
mouse antibody are expressed along with human
constant regions. This provides the antibody with
human effector functions. Humanized Antibodies
Only the HVR (CDR) regions from the rodent
antibody V-regions are combined with framework
regions from human V-regions. The idea is that
these antibodies should be more human-like than
chimeric and thus have fewer allergic responses.
42
43
Monoclonal antibodies used to treat cancer
MAb name Trade name Used to treat Approved in
rituximab Rituxan chronic lymphocytic leukemia 1997
trastuzumab Herceptin Breast, stomach cancer 1998
gemtuzumab Mylotarg acute myelogenous leukemia 2000
alemtuzumab Campath chronic lymphocytic leukemia 2001
ibritumomab tiuxetan Zevalin non-Hodgkin lymphoma 2002
tositumomab Bexxar non-Hodgkin lymphoma 2003
cetuximab Erbitux Colorectal, head neck cancers 2004
bevacizumab Avastin colorectal, lung, breast cancer 2004
panitumumab Vectibix colorectal cancer 2006
ofatumumab Arzerra chronic lymphocytic leukemia (CLL) 2009
denosumab Xgeva cancer spread to bone 2010
ipilimumab Yervoy melanoma 2011
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44
Immunotherapy
Radioisotope
Herceptin
Growth factor
Herceptin blocks receptor
Antibody
Antigen
Breast cancer cell
Lymphoma cell
Lymphoma cell destroyed
Growth slows
A new approach to cancer therapy uses antibodies
that have been specially made to recognize
specific cancers. When coupled with natural
toxins, drugs, or radioactive substances, the
antibodies seek out their target cancer cells and
deliver their lethal load.
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45
HPV Antibodies (Vaccines) Prevent Infection and
Cervical Cancer

• Human papillomavirus (HPV) is the most common
  sexually transmitted virus in the United States.
  At least 70 percent of sexually active persons
  will be infected with HPV at some time in their
  lives. HPV infects both men and women.
• Over 99 percent of cervical cancer cases are
  linked to long-term infections with high-risk
  HPV.
• The vaccination protects a person from future
  infection by the high-risk HPV
• After the vaccination, if an exposure occurs,
  the vaccinated persons antibodies against the
  HPV opsonize the virus and prevent it from
  attachment to the host epithelial cells..

Papillomavirus
Antibodies
45
46
Cellular immunotherapy
46
47
Cancer Immunotherapy Dendritic Cells That
Attack Cancer
By modifying dendritic cells, researchers are
able to activate T cells that attack the cancer
cells. Because a tumor antigen alone is not
enough to result in a strong immune response,
cytokines are first fused to a tumor antigen with
the hope that this will send a strong antigenic
signal. Next, the patient's dendritic cells are
isolated and grown in the incubator to let them
take up this fused cytokine-tumor antigen. This
enables the dendritic cells to mature and
eventually display the same tumor antigens as
appear on the patient's cancer cells. When these
special mature dendritic cells are given back to
the patient, they present their newly acquired
tumor antigens to the T cells that can respond
and attack the patient's cancer cells.
Dendrion FDA approval for prostate cancer
treatment
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48
Cancer and diet

• Almost 25 centuries ago, Hippocrates remarked
  Let food be the medicine and medicine be the
  food.
• About 1/3 of the cancer deaths in the US each
  year are due to nutrition factors, including
  obesity. (ACS)
• For most Americans who do not smoke, dietary
  choices and physical activity become the most
  important determinants of cancer risk. (ACS)
• Populations with higher consumptions of fruits
  and vegetables have lower incidence of
  gastrointestinal and respiratory tract cancers.
• Consumption of meat, especially red meat, has
  been associated with increased cancer risk at
  several sites, most notably colon and prostate.
  (ACS)

49
Cancer and diet Broccoli

• Broccoli contains certain chemicals that may
  reduce the risk of colorectal, breast, prostate
  and other cancers. Broccoli belongs to the
  cabbage and mustard families, which also includes
  cauliflower, radishes, and brussels sprouts.
• Broccoli is a good source of many phytochemicals
  (chemicals from plants) that may have anti-cancer
  properties. For example, broccoli contains
  several compounds called isothiocyanates,
  including sulforaphane and indole-3-carbinol
  (I3C), which have been suggested as possible
  anti-cancer agents in recent years. Early studies
  have shown these substances may act as
  antioxidants and may boost detoxifying enzymes in
  the body. Some studies have also suggested they
  may alter body estrogen levels, which might
  affect breast cancer risk.

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Cancer and spices

• Most agents derived from spices have antioxidant
  and anti-inflammatory activities. The antioxidant
  activities of these dietary spices suggest that,
  besides imparting flavor to foods, they possess
  potential health benefits.
• Recent research has also shown that many spices
  (curcumin - curry, garlic, capsaicin - hot chili
  pepper) inhibit activation of the transcription
  factor NFkB, which regulates transcription of
  anti-apoptotic ( pro-survival) genes. Thus,
  these spices can induce apoptosis, and have
  anti-tumor properties.

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Mechanism of NFkB inhibition in cancer

• Curcumin (curry)
• Capsaicin (hot chili peppers)
• Garlic

Anti-apoptotic (pro-survival) genes, cell growth
regulating genes