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PHUONG 20101141
Script for presentation Chapter 10: Growth factor.
Slide 1: COVER PAGE
Hello everyone. My name is PHUONG, an undergraduate student
in Department of Bio and Brain Engineering. Today, I will make a presentation about chapter
10 of Growth factors. This chapter is divided into 2 parts.
The first part presented by me will concentrate on the haematopoietic growth factors including
the description several types of them and their applications.
Slide 2: CONTENT
This is the main content of the first part. First of all, I will briefly introduce various
type of growth factor. Secondly, haematopoetic growth factors will be clearly presented and
their clinical application will be emphasized. ----------------------------------------------------------------------------------------------------
Slide 3: INTRODUCTION In eukaryotic cells, growth factors play critical
roles in modulating the differentiation, growth and division of cells.
Looking at the table, we can see a wide range of polypeptide growth factors performing in
many important cell types namely interleukins, interferons gamma, colony-stimulating factors,
Because growth factors can promote acellerated cellular growth, differentiation and division,
they are good potential target applied in pharmaceutical industry.
We can name some common products like leukine produced by Berlex Labs to recover neutrophil
after bone marrow transplantation or Neuplasta to treat neutropenia.
Slide 4: Haematopoietic growth factor
In our body, blood cells are derived from a single cell type, i.e. the stem cell.
The production of many mature blood cells begins when a fraction of the stem cells differentiates,
forming a specific cell type termed colony-forming unit). These cells, in turn, differentiate
to yield CFU-GEMM cells, a mixed CFU that has the potential to differentiate into a
range of mature blood cell types, including granulocytes, monocytes, erythrocytes, platelets,
eosinophils and basophils. The normal haemopoiesis occurs when small
fraction of stem cells undergo differentiation at any given time while the remainder keep
self-renewing.
Then, Haematopoietic growth factors play important role in haemopoiesis. They help to Balance
correctly between stem cell self-renewal and differentiation and also regulate the process
of differentiation.
A group of cytokines termed ‘haemopoietic growth factors including :
+ interleukins, which primarily affect production and differentiation of lymphocytes;
+ CSFs, which play a major role in the differentiation of stem-derived cells into neutrophils, macrophages,
megakaryocytes, eosinophils and basophils; + EPO or erythropoietin , which is essential
in the production of red blood cells; + TPO or throbopoietin , which is important
in the production of platelets. ----------------------------------------------------------------------------------------------------
Slide 5: INTERLEUKINS
There are 3 main colony stimulating factors belong to interleukin family.
They are: Granulocyte CSF, Macrophage CSF, and Granulocytes Macrophage CSF.
The table generally summarizes some properties of them in terms of molecular mass, the cells
type that they are produced from and also their target during biological activities.
Slide 6: GRANULOCYTE CSF Granulocyte colony-stimulating factor performs
biological activities. For example, they are: • Functioning as a growth and differentiation
factor for neutrophils and their precursor cells.
• Activating mature neutrophils, which ingest and kill bacteria.
• Stimulating growth/differentiation of various other haemopoietic progenitor cells.
• Promoting proliferation and migration of endothelial cells
Slide 7: MACROPHAGE CSF The second factor of interleukin family is
MACROPHAGE colony stimulating factor. The biologically active form of this is a homodimer,
which • Existing as integral cell surface proteins
• Being released from producer cell by proteolytic cleavage, which helps cytokine become soluble.
Slide 8: GRANULOCYTE MACROPHAGE CSF The third factor, granulocyte macrophage Colony
stimulating factor is essential in physiological roles, such as
• Proliferation/differentiation factor of haemopoietic progenitor cells, particularly
those yielding neutrophils and macrophages. • Promoting haemopoiesis.
• Activation of mature haemopoietic cells. This biological activity will lead to
Enhanced phagocytic activity. Enhanced microbiocidal activity.
Augmented anti-tumor activity. Enhanced leukocyte chemotaxis.
Slide 9: CLINICAL APPLICATION OF CSF
All three colony stimulating factors types are useful in the treatment of infectious
diseases, some forms of cancer and the management of bone marrow transplants because they stimulate
the differentiation/activation of white blood cell types most affected by such conditions.
Granulocyte Colony Stimulating factor and Granulocyte Macrophage colony stimulating
factor is used for treating neutropenia & accelerating neutrophil recovery after bone marrow transplantation.
For example, in reality, Granulocyte colony-stimulating factor and granulocyte macrophage Colony stimulating
factor are applied for treating neutropenia, a disease that decrease in blood neutrophil
below 1.5 billion cells per litre. This disease is caused by serious infections or Chemotherapeutic
agents in cancer patients. The product name is NEUPOGEN - a recombinant
Granulocyte colony-stimulating factor Neupogen (filgrastim) is produced in engineered
E.coli. Compared to the native human one, it has
➢ Additional methionine residue at N-terminal end.
➢ Absence of glycolysation. Daily infusion for several days and can be
used in conjunction with cancer therapy prophylactically (to prevent neutropenia onset) or therapeutically
(to reverse established neutropenia) to accelerate neutrophil count recovery or reduce the median
number of days of severe neutropenia.
However, there can be some Side effects such as bone and muscle pain, splenic rupture,
adult respiratory distress syndrome. ----------------------------------------------------------------------------------------------------
Slide 10: Erythropoietin
The erythroid precursor cells, BFU-E (burst forming unit-erythroid), display EPO receptors
on their surface. The growth and differentiation of these cells into CFU-Es (where E stands
for erythroid) require the presence of not only EPO, but also IL-3 and/or granulocyte
macrophage Colony stimulating factor. 1. EPO structures
• An atypical cytokine, endocrine hormone. • Encoded by a single copy gene located
on human chromosome 7. • A glycoprotein with 3 Nitrogen-linked
and 1 Oxygen-linked glycosylation sites. • Synthesized by kidney cells or liver (foetus).
In general, EPO production is regulated by the Oxygen demand of producer cells.
2. EPO biological functions: Stimulating erythropoiesis and promoting erythroid differentiation (although
it is still an unclear evidence) • Increasing the number of committed cells
capable of differentiating into erythrocytes. • Accelerating the rate of differentiation
of such precursors. • Increasing the rate of Hemoglobin synthesis
in developing cells. 3. EPO receptors coupled with JAK2 kinase
to generate EPO signal transduction ----------------------------------------------------------------------------------------------------
Slide 11: Therapeutic applications of erythropoietin
Erythropoietin is a therapeutic target to treat anemia.
The product name Neorecormon (or also called epoetin beta) is a recombinant human EPO for
medical use. • It is Produced by recombinant DNA technology
in a CHO cell line. • Doctors will prescribe Neorecormon with
once or several times weekly administration • Treatment and prevention of anaemia with
increased haemocrit values • However, there are some side effects such
as increasing blood pressure, respiratory infections or increase the number of platelet.
Slide 12: Therapeutic applications of erythropoietin (cont)
Here is the diagram clearly illustrate several steps in the production of the EPO-based product
‘Neorecormon’. You can look through it. ----------------------------------------------------------------------------------------------------
Slide 13: Chronic disease and cancer therapy
As we discuss in the previous 2 slides, Erythropoietin is a therapeutic target to treat anemia. So
we will investigate the cause of anemia and how therapeutic Erythropoietin drug do effect?
First of all, there are some factor causimh anemia.
Factors causing anaemia: • Severe and chronic infection induces anaemia
and this is becoming worse when we use drug to treat infection.
• Also, Various malignancies will decrease EPO levels, which can lead to anaemia.
• Last but not least, Chemotherapeutic agents will reduce stem cell population, making anaemia
severe So, what Effects of Administration of EPO
can have ?: • Improving haematocrit levels.
• Decreasing transfusion requirements. • Enhancing the sense of well-being and
overall quality of life. • The success rate of EPO in alleviating
cancer-associated anaemia has ranged from 32%-85%
Slide 14: Thrombopoietin Another important haemopoietic growth factor
is Thrombopoietin
Human Thrombopoietin is a 332 amino acid, 60 kDa glycoprotein, containing six potential
Nitrogen-linked glycosylation sites. These are all localized towards the Carbon-terminus
of the molecule. The Nitrogen-terminal half exhibits a high degree of amino acid homology
with EPO and represents the biologically active domain of the molecule.
Thrombopoietin is the haemopoietic growth factor that regulates platelet production.
This molecule may, therefore, represent an important future therapeutic agent in combating
thrombocytopenia, a condition characterized by reduced blood platelet levels.
The most likely initial Thrombopoietin therapeutic target is thrombocytopenia induced by cancer
chemo- therapyor radio- therapy.
That is the end of my presentation. Thank you.
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