Download Viruses Associated with Human Cancer

CANCER AND
MICROORGANISMS
■ Generally, there are three
etiological causes of cancer:
■ 1-chemical
■ 2-physical
■ 3-biological
Common Pathophysiological Mechanism of Cancer
Disease
■ “Cancer reparative trap”
Helicobacter-pylori and Gastric
cancer
it has been increasingly considered as the ■
strongest known risk factor for gastric
adenocarcinoma. On the other hand, it is
associated with a reduced risk of
developing esophageal adenocarcinoma.
What is Helicobacter pylori?
■ It is a spiral shaped bacterium that grows in the
mucus layer of the stomach .
Types of Helicobacter-pylori
■ CAG +ve
■ CAG-ve
■ A Meta-analysis conducted all over the world showed that
individuals infected with (cagA +ve) Helicobacter pylori had
twice risk of developing non cardia gastric cancer than those
who were infected with –ve (cagA) Helicobacter pylori .
Chlamydophila pneumoniae and lung cancer
■ Lung cancer is the leading cause of death
■ Chlamydophila pneumoniae is a Gram-negative bacillus and an
intracellular parasite that causes respiratory infection in more than
50% of adults.
■ A relationship between Chlamydophila pneumoniae and lung
cancer was examined.
■
Chlamydophila pneumoniae infection has been implicated in
several chronic lung diseases by direct antigen detection an
elevation in its antibody have been observed in lung cancer.
chlamydophila pneumoniae and
lung cancer
60%
50%
40%
30%
20%
10%
0%
male
females
Streptococcus bovis and
colorectal cancer
■ Colorectal cancer (CRC) is a common malignancy in
developed countries and is the 3rd most common cancer
in the United States .
■ Streptococcus bovis is a normal inhabitant of the human
gastrointestinal tract
■ 45 cases of streptococcus bovis infection were studied.
39% of adult patients who went through the colonoscopy
present colonic neoplasia. invasive cancer was present in
32% of the patients.
Patients with streptococcus
bovis
Chart Title
45
40
35
30
25
20
15
10
5
0
patients with
streptococcus bovis
patient with neoplasia
patient with invasive patients
.
VIRUSES
ASSOCIATED WITH
HUMAN CANCER
A brief glimpse of the history of
correlating viruses and cancer
■ Classical times: Cancer is due to infection;
The incidence of cancer in married couple.
■ Today, viruses are accepted as causes of
human cancers, and it’s estimated that
between 15 and 20% of all human cancers
may be caused by viruses
Features of Oncogenic
Viruses
■ ability to infect, but not kill, their host cell
■ the tendency to establish long-term persistent
infections
■ have evolved strategies for evading the host
immune response
Viruses as competent sole
carcinogenic agents?
■ Viruses contribute with many other co-factors in
carcinogenesis
■ are not sufficient to cause it on their own
■ patients only develop cancer many years after the initial
infection with the virus
■ co-factors include host immunity and chronic inflammation,
and additional host cellular mutations
Criteria to linking viruses to
cancer
– All patients with the same cancer have been
infected with the same virus
– The virus is present in the tumour cells
– The viral genes are able to promote cancerous
growth in the laboratory
Mechanism
■
■
■
■
Infection
Replication
Latency
Activate oncogenes or suppress
“Tumor suppressor Genes”
Prevention of Cancer by
microorganisms
Probiotics
1. What are probiotics ?
Probiotics (a term derived from the Greek meaning
“ for life “) live organisms that when ingested in
adequate amounts exert a health benefits on the
host. Probiotics can be supplied through foods,
beverages, and dietary supplements.
Studying the role of probiotics in
cancer prevention :
1. In vitro studies
2. In vivo studies in laboratory animals
3. Epidemiological studies
4. Studies in human volunteers
2. Mechanisms by which lactic acid bacteria
inhibit colon cancer
1. Enhancing the host’s immune response.
2. Binding and degrading potential carcinogens.
3. Alteration of the metabolic activities of
intestinal microflora.
4.Alteration of physicochemical conditions in
the colon.
5. Effects on physiology of the host.
BACTERIA IN
CANCER THERAPY
Background
■ the American physician William Coley noticed that
one of his patients suffering from neck cancer
began to recover following an infection with
erysipelas
■ He developed a safer vaccine composed of two
killed bacterial species, S. pyogenes and Serratia
marcescens to simulate an infection with the
accompanying fever without the risk of an actual
infection to use it for cancer treatment.
■ How can scientists develop Bacteria
attacking cancer cells?
- Passive targeting ; accumulate in tumors
because their vasculature is defective and the
preference for hypoxia environment of the
bacteria
- Specific targeting ; Bacteria would be engineered
to specifically recognize ,invade and destroy the
targeted tumor cells and leave healthy tissue
alone.
“Tumoricidal
agent”
■ Bacteria as tumoricidal agents
The use of live, attenuated or genetically- 
modified, nonpathogenic bacteria has begun to
emerge as potential antitumor agent in which
those species were able to proliferate,infect and
lyse the tumors, thus resulting in tumors
regression .
■ Bacteria as vector for gene therapy
Bacteria can be genetically modified to
deliver a therapeutic gene to the tumor
cells.
Once the bacteria becomes within the
target tissue, gene expression will occur
producing the required protein that
destroys the cancers.
■ Bacteria as immunotherapeutic agents
Bacteria can be used to enhance the recognition of
tumor cells by the immune system and the
antigenicity of the tumors. Bacteria selectively
invade the cancer tissues and present bacterial
antigens thus being targets for the host immune
system. The host immune system then destroys the
bacteria infected tumor cells which would have
otherwise evaded the attack.
Virus in cancer
therapy
■ Stimulation of immune
responses (CTLs)
Viral vectors can elicit cytotoxic T
lymphocytes (CTL) that are crucial
for control of intracellular
pathogens and cancer.
■ Gene-directed enzyme prodrug therapy
(GDEPT-mediated therapy)
A non-toxic prodrug is converted into a
toxic drug inside of tumor cells which
were transformed with a gene construct
encoding the enzyme needed for the
prodrug-drug conversion.