MITOTIC INHIBITION

ID

STUDENTS NAME

USTHBI4-

NG PHNG DUNG

USTHBI4059

NGUYN THI MINH HI

USTHBI4-

KHC THI HNG

USTHBI4-

PHAM MY LINH

USTHBI4-

TRN THANH TU

Contents
Brief information about Mitosis
Mechanism of mitotic inhibition
Application of some mitotic inhibitors
Taxanes
Paclitaxel
Docetaxel

Angiogenesis inhibition
Telomerase inhibition

 Mitosis : a part of cell

cycle which chromosomes
are separated into 2
identical sets.
Occur : Cell nucleus.
Cytokinesis : Cytoplasm,
organelles and cell
membrane are divided into
new cells with same
components.

Telophase
Cell membrane
completes
constriction
Nuclear envelope
reforms

Anaphase
Sister
chromatids are
separate.
Chromosomes
are pulled to
opposite poles.

Prophase
Chromosomes condense
Nuclear envelope disappears
Chromosomes connect to
microtubules

Metaphase
All chromosome are
aligned at metaphase

Mitotic Inhibition
Mitotic inhibitors: drugs that
inhibits Mitosis or cell division.
Mechanism of mitotic
inhibitors:
Inhibition of polymeration
process of microtubules
(structures that pull the cell
apart when it divides)
Stopping nutrient supply
Making chromosomes are
abnormal (shorten).

Roles of Microtubules
Functi
on

Microtubules provide
the structure and
machinery for
chromosome
segregation during
mitosis

Inhibitors inhibits the

Polymerization Process

Interruption of
nutrient supply
Using inhibitors to cut off
the nutrient (e.g. blood)
supplied to growth phases
(G1, G2)

Taxan
es

Natural agent : from the

genusTaxus(yews)

Mechanism of action:
Inhibiting microtubule
polymerization
Disrupting
themicrotubulefunction
Preventing cells from
enteringmitosis.
Stimulatingapoptosis, or
Side effects:
programmed cell death.
- Bone Marrow Suppression
- Nausea and Vomiting
- Hair Loss
- Peripherial Neuropathy
- Peripherial Neuropathy

Paclitaxel
Used to treatlung
cancer,ovarian cancer,breast
cancer, and advanced forms
ofKaposi's sarcoma.

Docetaxel
used to treat breast, ovarian, andnon-small cell
lung cancer

Vinca
alkaloi
ds

from the periwinkle plantCatharanthus

roseus(basionymVinca rosea) and
othervincaplants.

Mechanism: bind totubulinat the

forming end of microtubules anddisrupt
spindle assembly.

Side effects: nausea, vomiting,

fatigue, headache, dizziness, peripheral
neuropathy, hoarseness, ataxia,
dysphagia, urinary retention,
constipation, diarrhea, bone marrow
suppression, alopecia and phlebitis at
the infusion site.

Including:

Vinblastine: used to

treatleukaemia,Hodgkin's lymphoma, non-small

cell lung cancer, breast cancer andtesticular
cancer .

Targeting Angiogenesis in
Cancer Therapy

Angiogen
esis is the
physiological
process through
which new blood
vessels form
from pre-existing
vessels.

Blood vessels are composed of three main cell types

VEGF and
FGF

PDGF

PDGF and
FGF

Angiogenesis was mainly regulated by three angiokinase

Three
signaling molecules
pathways
Vascular endothelial growth factor (VEGF)
Platelet-derived growth factor (PDGF)
Fibroblast growth factor (FGF)

Activate the receptor tyrosine kinases

on endothelial cells, pericytes and
smooth muscle cells to initiate
important pro-angiogenic signaling

 Tumors need a
blood supply to
provide the
oxygen and
other essential
nutrients they
require in order
to grow beyond
a certain size.
Angiogenesis is
also required for
the spread of a
tumor, or
metastasis.

Tumors cannot grow beyond a certain size or spread without a blood

supply, scientists are trying to find ways to block tumor angiogenesis.

Some kind of Angiogenesis

Inhibitors were used to treat Cancer
in Human
Origin

Mechani
sm

Cancer

How to
use?

Bevacizum
ab
(Avastin)
Sorafenib
(Nexavar)

Recombinant
humanize
monoclonal
antibody

Inhibiting VEGF-A

Colorectal
cancer,kidney
cancer, andlung
cancer.

Injected into vein

Small
molecularinhibitor
(C21H16ClF3N4O3)

Sorafenibis a
Kinase
Inhibitor(VEGFR
andPDGFR)

Kidney cancer,liver
cancer, andthyroid
cancer

A pill was taken by

mouth

Ramuciru
mab
(Cyramza)

Fully
humanmonoclonal
antibody(IgG1)

Binding to VEGFR2 Stomach cancer

it works as a
receptor antagonist

Injected into a vein

Side effects of Angiogenesis Inhibitors

High blood pressure

A rash, dry, itchy skin
Diarrhea
Fatigue
Low blood counts
Problems with wound healing or cuts re-opening
Rarely, angiogenesis inhibitors may cause serious
bleeding, heart attacks, heart failure, or blood clots.

Telomerase Inhibition

What is the Telomerase?

Telomere: The sequences of
DNA extending at the ends
of chromosomes.
Telomerase: a
ribonucleoprotein that
maintains the lengths of
chromosomal ends.
2 major components of the
telomerase holoenzyme:
Telomerase reverse
transcriptase (TERT) protein
subunit
Telomerase RNA (TR)
component

Telomerase in Cancer
Therapy
Telomerase is expressed in germline,
embryonic stem cells and most somatic
stem cells, barely detectable in the great
majority of adult somatic cells
In actively dividing somatic cells, the
telomeres shorten with each cell replication.
Telomerase is overexpressing in human
cancer cells (approximately 90% compare
with normal cells)
Analysis of telomerase activity has potential
as a diagnostic marker of cancer

Targeting Telomerase in Cancer

Therapy

Inhibition telomerase activity can leads to:

a marked reduction in cellular

viability
induces apoptosis of cancer
cells

Relative low risks

The inducing of some effective drug