ABC super-family of ATP-dependent
transporters
Proteins in this family are related to each other by having very similar amino
acid sequences within the same regions. These regions are involved in binding
ATP and releasing its chemical energy which is used to transport some substance
across a membrane.
amino acid
Amino acids are the components of proteins. There are 20 different amino acids.
The composition and the arrangement of amino acids in a protein make each
protein unique.
angiogenesis
Angiogenesis is the process of new blood vessel growth. In people without
cancer it only occurs during wound healing, inflammation and during pregnancy.
When a tumour gets to 1-2mm diameter in size, it begins to exhaust the local
supply of oxygen and nutrients and needs to recruit blood vessels to maintain
its growth.
angiostatin
Angiostatin and endostatin are anti-angiogenic compounds developed by
Professor J Folkman's research team, Harvard Medical School, U.S.A.
animal models
Animal models are an essential part of translating the results of laboratory
studies on cultured cells into clinical practice. Once the relationships have
been determined and understood at the molecular and cellular levels, these
relationships are investigated in animals. This provides information which
is essential to performing a clinical trial. The use of animals in research
is strictly controlled by legislation and closely monitored by institutional
animal ethics committees.
anthracyclines
The anthracyclines are a family of related antibiotic drugs isolated from
yeast and used in chematherapy to treat cancer. The most commonly used members
are Doxorubicin, Daurnorubicin, Epirubicin and Idarubicin.
bFGF
Basic Fibroblast Growth Factor is a cytokine (cellular growth hormone) which
stimulates the growth of many cells including fibroblasts.
basement
membrane The basement membrane is a barrier layer made up mainly of proteins,
lipids and carbohydrates. It holds endothelial cells in place to form the
walls of blood vessels.
Bill Walsh
Our inspiration.
biochemistry
Biochemistry is the study of how molecules interact in living systems.
chemotherapy
Chemotherapy is a major form of cancer treatment using chemical drugs
which preferentially kill cancer cells.
chlorambucil
Chlorambucil belongs to the alkylating agent class of chemotherapeutic drugs
which disrupt DNA synthesis by chemically modifying it. Cells die when they
cannot replicate their DNA.
chromosome
chromosome DNA, which is the chemical that contains the genetic information
to make a living organism, is packaged into structures called chromosomes.
Each normal human cell has 46 chromosomes.
cisplatin
Cisplatin is a synthetic chemotherapeutic drug which disrupts DNA synthesis
by chemically modifying it. Cells die when they cannot replicate their DNA.
cultured cancer cells
Many types of cancer cells can be grown continually in the laboratory. These
cultures of cancer cells have provided valuable information on how cancers
grow and how they respond to various chemotherapeutic drugs.
cytoplasm
The cytoplasm is the cellular compartment surrounding the nucleus and surrounded
by the plasma membrane.
DNA
This is the macromolecule that contains the genetic code or instructions (genes)
for making proteins and for producing the next cell generation. It is found
in the nucleus of cells.
drug resistance
Drug resistance is when cancer cells become resistant to the killing effects
of a chemotherapeutic drug. Drug resistance can be an inherent property of
a cancer or it can develop during chemotherapy or radiotherapy. Clinical drug
resistance involves simultaneous resistance to a broad range of chemotherapeutic
drugs. Cultured cancer cells can be made resistant in the laboratory by drug
treatment and the resistant sublines are usually cross resistant to other
drugs.
drugs
Drugs refers to any chemical used to treat cancer.
efflux
Efflux in the context of cellular transport means actively transported out
of a cellular compartment.
endostatin
Angiostatin and endostatin are anti-angiogenic compounds developed by Professor
J Folkman's research team, Harvard Medical School, U.S.A.
endothelial cells
These are cells that line the inside of all blood vessels where they play
a role in maintaining the structure of the blood vessel and they are involved
in determining which compounds are transported in and out of the blood and
the surrounding tissue.
enzyme
An enzyme is a protein that participates in a chemical reaction. It catalyses
to conversion of one chemical to another.
epirubicin
Epirubicin is a member of the anthracycline family of chemotherapeutic drugs
used to treat cancer. It is reported to kill cancer cells in a variety of
ways, by chemically modifying DNA and preventing its replication, by inhibiting
topoisomerase II, an enzyme involved in DNA replication and by disrupting
the cell membrane.
extended-multidrug resistance
Multidrug resistance describes the combined resistance to chemotherapeutic
drugs that are "natural product" drugs, ie. drugs which are isolated from
plants, yeast, fungi and bacteria. Extended-multidrug resistance is term coined
by our research group to describe a broader drug resistance which includes
synthetic drugs as well as the "natural product" drugs.
extracellular matrix
The extracellular matrix is mainly made up of proteins, oligosaccharides and
lipids and it fills the space between cells.
fractionated radiation
Radiotherapy treatment is given as a course of many low dose treatments spread
over time. This is fractionated radiation. It reduces the unwanted side effects
associated with high dose treatment and it increases the effectiveness against
the cancer.
Gy
Gy is a unit measure of radiation.
heparanase
There are many different enzymes required to break down the mixture of proteins
and oligosaccharides that are the structural components of the extracellular
space. Heparanase is one such enzyme which breaks down the oligosaccharides.
inherently resistant
Some cancers are more resistant to treatment with chemotherapeutic drugs than
others even before exposure to chemotherapy.
leukaemia
Cancer of the blood cells
lipophilic
Compounds that dissolve in organic solvents more easily than in water are
described as lipophilic (liking lipid) or hydrophobic (not liking water).
lymphatic system
The lymphatic system conists of a network of capillary like vessels which
collects fluid from the intracellular space and return it to the blood supply.
MDR1 gene
The MDR1 gene is a stretch of DNA on chromosome 7 which codes for P-glycoprotein,
the multidrug resistance transport protein.
metalloproteinases (MMPs)
This is a family of enzymes, the members of which are involved in specifically
cleaving proteins into smaller fragments. They are involved in the breakdown
of tissue associated with the spread of cancer and the development of new
blood vessels.
metastasis
The spread of cancer from one tissue to another is called metastasis.
methotrexate
Methotrexate is a drug used in the chemotherapeutic treatment of cancer. It
kills cancer cells by inhibiting the production of precursor bases required
for the synthesis of DNA.
molecular biology
Moleular biology is the study of how life works at the molecular level. It
focuses on how the molecules of DNA contain the instructions for making proteins
and how these proteins go to make up an organism.
molecular weight
The molecular weight of a substance is the sum of all its atomic components
and is an indication of its molecular size.
monosodiumglutamate
(MSG) This is a commonly used food additive as well as an important amino
acid.
MRP1
Multidrug resistance protein, which used to be known as multidrug resistance-associated
protein is abbreviated MRP. Several related proteins have been identified
so the original member of this family is now abbreviated as MRP1. MRP1 is
a protein that belongs to the ABC superfamily of transport proteins and it
causes resistance to many chemotherapy drugs.
natural product drugs
Drugs that have been isolated from organisms such as plants, bacteria, fungi
and yeast are known as natural product drugs. Examples are: doxorubicin, daunorubicin,
epirubicin, idarubicin, vinblastine, vincristine, navelbine, etoposide and
taxol.
neurotoxicity
Neurotoxicity is chemical damage to nerves and nerve cells.
nucleotide binding domain
This is a region in a protein, called a domain, that binds a nucleotide. All
members of the ABC super family of transport proteins have a nucleotide binding
domain.
nucleus
The nucleus is the organ within a cell that contains the genetic information
in the form of DNA.
P-glycoprotein
The protein made from the MDR1 gene on human chromosome 7, is P-glycoprotein.
P-glycoprotein belongs to the ABC superfamily of transport proteins and it
causes resistance to many chemotherapy drugs and for this reason it is known
as the multidrug resistance efflux pump. P-glycoprotein actively transports
drugs out of resistant cancer cells.
pharmacokinetics
This is the time dependent change in concentration of a drug in a compartment
or compartments of the body such as the blood or liver.
phenotype
The phenotype of a cell is made up of those molecular and cellular characteristics
that distinguish it from other cells.
PI88
This is a synthetic, highly sulphated oligosaccharide that is an inhibitor
of the heparanase enzyme and has anti-angiogenic and anti-metastatic properties.
It was developed by Professor Chris Parish and his team at the Australian
National University and is now being tested and further developed by the Australian
company, Progen.
proteins
Proteins are made up of amino acids. The sequence of the amino acids and the
amino acid composition is what makes each protein unique. The sequence of
the amino acids in a protein is determined by the base sequence of the gene
that codes for the protein. There are generally 20 different amino acids found
in proteins and it has been estimated that there are 100,000 different proteins
in humans.
radiation resistance
Some cancers and cancer cells become more resistant to radiotherapy and require
higher levels to kill them. This is known as radiation resistance.
radiotherapy
Radiotherapy is one of the major forms of treatment for cancer. It involves
using radiation or a beam of energy, to preferentially kill cancer cells.
selection of drug resistance
Treating a population of cells with a drug and causing the cells to adapt
and become resistant to the drug.
side effects
The side effects of cancer treatments are the other activities the treatment
has on the normal non-cancerous tissues.
small cell lung cancer
This is a type of lung cancer which arrises in a specific class of cells in
the lung. A characteristic of these cells is their relative small size.
subline
A subline is a subdivision of a cell line. A culture of cells treated with
a chemotherapeutic drug or with radiation that have altered properties compared
to that of the original cell line, is called a subline of the original cell
line.
taxol
Taxol, also known as paclitaxel, is a drug used in the chemotherapeutic treatment
of cancer. It is a natural product drug which was originally isolated from
the bark of the Pacific yew tree.
thalidomide
Thalidomide is a drug that inhibits the development of blood vessels. When
taken during pregnancy, it can inhibit the proper development of the foetal
limbs. It has recently been shown to inhibit the development of blood vessels
associated with cancers and to reduce their growth.
tight junction
Tight junctions are formed between two cells such as endothelial cells when
their outer membranes become closely associated.
translational research
Translational research promotes the ideas generated by laboratory-based
research into clinical use.
transmembrane domain
The part of a protein associated with and passing through a cellular membrane
is known as the transmembrane domain.
Vinblastine
Vinblastine is a drug used in the chemotherapeutic treatment of cancer.
It is a natural product drug belonging to the Vinka alkaloid family.
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