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DR Mushiri Lecture 6
DR Mushiri Lecture 6
LECTURE 6
Cancer
• Derived from Greek word for crab, karkinoma
• Malignant tumor
• Tumor
• Also referred to as a neoplasm—
new growth
More than 200 types
Benign vs. Malignant Tumors
Benign Malignant
Grow slowly Grow rapidly
Well-defined capsule Not encapsulated
Not invasive Invasive
Well differentiated Poorly differentiated
Low mitotic index High mitotic index
Do not metastasize Can spread distantly
(metastasis)
• Almost any mammalian organ and cell type can succumb to oncogenic
transformation, giving rise to a bewildering array of clinical outcomes.
• The causes of cancer are many and varied, and include genetic
predisposition, environmental influences, infectious agents and ageing.
These transform normal cells into cancerous ones by derailing a wide
spectrum of regulatory and downstream effector pathways. It is just
this complexity that has hampered the development of effective and
specific cancer therapies.
• Any attempt to provide a comprehensive overview of cancer-related
knowledge would be futile — therefore the next two lectures will focus
on topics undergoing particularly rapid progress.
Properties of cancer cells
And growing
And growing
And growing
Cancer Incidence and Death Rate
Early detection is the key!
Cancer: Benign
Malignant tumors: high rate of division, properties may vary compared to cells of origin. Most
malignant cells become metastatic
Invade surrounding tissue and establishment of secondary areas of growth: Metastasis
Apoptosis
• Apoptosis is a tightly regulated form of cell death,
also called the programmed cell
death. Morphologically, it is characterized by
chromatin condensation and cell shrinkage in the
early stage. Then the nucleus and cytoplasm
fragment, forming membrane-bound apoptotic
bodies which can be engulfed by phagocytes. In
contrast, cells undergo another form of cell death,
necrosis, swell and rupture. The released
intracellular contents can damage surrounding
cells and often cause inflammation.
Classification and Nomenclature
• Malignant tumors
• Named according to the tissues from which they arise
• Malignant epithelial tumors are referred to as
carcinomas
• Adenocarcinoma (from glandular epithelium)
NODES
METASTASIS
Tumor Markers
• Tumor cell markers (biologic markers) are
substances produced by cancer cells or that are
found on plasma cell membranes, in the blood,
CSF, or urine
• Hormones (Epi – in blood, adrenal medullary
tumor)
• Enzymes
• Genes
• Antigens (PSA – in blood, prostate cancer)
• Antibodies
Hallmarks of Cancer
Viruses and Cancer
• Implicated
• Hepatitis B and C viruses
• Infection
• Risk increases when the absolute neutrophil and
lymphocyte counts fall
Cancer Treatment
• Ionizing radiation
• Eradicate cancer without excessive toxicity
• Avoid damage to normal structures
• Ionizing radiation damages the cancer cell’s DNA
• Surgery
• Biopsy and lymph node sampling
• Sentinel nodes
• Debulking surgery –remove most of tumor
• Palliative surgery – relief of symptoms
• Hormone therapy
• Receptor activation or blockage
• Interferes with cellular growth and signaling
DISCUSSION ABOUT PICTURE
Side Effects of Cancer Treatment
• Gastrointestinal tract
• Bone marrow
• Hair and skin
• Reproductive tract
Fast Facts About Cancer
Percentage of
Cancers
Attributable to
Risk Factor
• 18% of cancers
globally
(>2 million cases/year)
• 26% of cancers in
LMICs
• 40% of cancers in
Africa
10
S. Korea
China
Cancer of the liver cause ~1% of all deaths worldwide (~100 deaths per
million people per year) and 9% of all deaths from cancer.
Impact of Socioeconomic
Status on Cancer Burden
Overall (non-adjusted) Cancer Incidence Rates
(Per 100K, Both Genders; All Cancers Except Non-Melanoma Skin)
1500 15
12.9 64%
1000
10 7.5 57%
5
500
5.7 7.4
0
0 2010 2030
Ages < Ages Ages Ages Ages
20 20-49 50-64 65-74 75+ Data derived from GLOBOCAN
2008
Data from SEER 2010
Breast Cancer Kills Men,Too.
Risk factors for male • Less than 1% of all new breast cancer
cases occur in men.
breast cancer
Testicular abnormalities: cryptorchidia, congential
inguinal hernia, orchiectomy, orchitis, testicular • Men with a BRCA1 mutation have a 1%
trauma
risk of developing breast cancer by age
Hormonal alterations: 70; BRCA2 mutations confer a 6% risk.
Infertility, Klinefelter’s syndrome, obesity, cirrhosis
(and heavy alcohol intake)
Family history of breast cancer, mutations in • Breast cancer prognosis, even in stage I
BRCA1/2, CHEK2, PTEN cases, is worse in men than in women.
Benign breast lesions:
Nipple discharge, breast cysts, breast trauma
Exposure to radiation or high temperatures • Treatment for male breast cancer has
usually been a mastectomy, which may be
Old age followed by radiation, hormone therapy
(such as with tamoxifen), or
Jewish descent chemotherapy.
Types of Breast Cancer Ductal carcinoma in situ
(DCIS) is the most common
type of non-invasive breast
DCIS: Ductal Carcinoma In Situ cancer.
LCIS: Lobular Carcinoma In Situ
IDC: Invasive Ductal Carcinoma
ILC: Invasive Lobular Carcinoma
Inflammatory Breast Cancer
Male Breast Cancer
Recurrent and Metastatic Cancer
In inflammatory breast cancer, cancer cells invade local lymphatic ducts, impairing drainage
and causing edematous swelling of the breast.
Peau d’orange: The skin of the breast is tethered by the suspensory ligament of Cooper,
which, with the accumulation of fluid, can cause the breast to take on a dimpled appearance
similar to an orange.
Inflammatory Breast Cancer
Inflammatory breast cancer (IBC) accounts for between 1 percent and 6
percent of all breast cancer cases in the United States.
The 5-year survival rate for patients with IBC is between 25-50 percent,
significantly lower than the survival rate for patients with non-IBC breast
cancer.
IBC has a high risk of recurrence and is the most aggressive kind of breast
cancer. IBC is more likely to have metastasized at the time of diagnosis than
other breast cancer types.
Men can develop the disease, but at an older age. Black women are slightly
more likely than are white women to have IBC.
Risk Factors
• The most significant risk factors for
breast cancer include gender (being
female) and age (growing older).
Other factors:
• Personal history of endometrium, ovary or colon cancer
• Alcohol consumption
• Height (tall)
• High socioeconomic status
• Jewish heritage
Breast Cancer Screening and Prevention
Surveillance
Mammography
Sonogram
MRI
Clinical and self breast exam
Risk Avoidance
Diet and Exercise
Chemoprevention
Tamoxifen
Raloxifene
Prophylactic Surgery
Bilateral Prophylactic Mastectomy
Oophorectomy
Mammograms:
for low-income women and the uninsured.
Mammograms are usually covered by health insurance for women in the
recommended age bracket. While some insurance plans have no out-of-
pocket expenses required, others charge a $10-$35 co-pay.
The Centers for Disease Control and Prevention (CDC) coordinates the
National Breast and Cervical Cancer Early Detection Program to provide
screening services, including clinical breast exams and mammograms, to
low-income, uninsured women throughout the United States. Visit the
CDC website to find contact information for local programs
Financial hardships,
The Breast Cancer occupational changes
Experience
Mental and emotional changes
such as “chemobrain,” depression
and fear of recurrence Changes in relationships with
family and friends
Positive lifestyle changes such
as increased exercise, healthier
eating, stress reduction
Complementary medicine can improve quality of life for
breast cancer patients:
• Acupuncture • Spirituality & Prayer
• Meditation • Reiki
• Aromatherapy • Support Groups
• Guided Imagery • Tai Chi
• Hypnosis • Shiatsu
• Journaling • Yoga
• Chiropractic Therapy • Music Therapy
• Massage • Progressive Muscle
Relaxation
Screening
• Mammogram. A mammogram is an X-ray of the breast. Mammograms are the
best method to detect breast cancer early when it is easier to treat and before it
is big enough to feel or cause symptoms. Having regular mammograms can lower
the risk of dying from breast cancer. If you are age 50 to 74 years, be sure to have
a screening mammogram every two years. If you are age 40–49 years, talk to your
doctor about when and how often you should have a screening mammogram.
• http://www.cdc.gov/cancer/breast/basic_info/screening.htm
What are the pressures behind?
Prostate Cancer
• The average lifetime chance that a man will develop lung cancer is about 1 in 13. For a woman it
is 1 in 16. These numbers include both smokers and non-smokers. For smokers the risk is much
higher, while for non-smokers the risk is lower.
• http://www.cancer.org/Cancer/LungCancer-SmallCell/OverviewGuide/lung-cancer-small-cell-overview-what-causes
LASERS IN CANCER
• X-rays
• How lasers work
• Medical applications of lasers
• Applications of high power lasers
• Medical imaging techniques
• CAT (computed axial tomography) scans
• MRI’s
Modern physics ideas are strange!
• Electromagnetic waves sometimes behave like
particles- photons –discreet (quantized) packets of
energy E = hf = hc/l
• Electrons sometimes behave as waves – matter waves
that can only exist in allowed orbits
• Electrons have a wavelength and can experience diffraction!
A
A
A
The Photon Concept
• a beam of light waves also behaves like a beam of
light particles called PHOTONS
• Photons are little packets of electro-magnetic energy
• The energy is proportional to the frequency or
inversely proportional to the wavelength
• Ephoton = h f, but c = f l so Ephoton = h c/l,
• where h is a constant called Planck’s constant, and c is
the speed of light
• blue photons have more energy than red photons
• Energy is absorbed or emitted in discreet amounts
sodium absorption line
The uncertainty principle
E = hf
hc
=
l
X-ray machines
X-ray tube
How are x-rays produced?
x-ray
tube copper
target
laser
cutting
tools
Laser Fusion Energy
fuel pellet
1 mm diameter
Laser spiking:
ØIn glass, the linewidth is larger than in YAG, and hence in glass the
Laser threshold is higher
•Laser medium is mixture of Helium and Neon gases in the ratio 10:1
•Medium excited by large electric discharge, flash pump or continuous
high power pump
•In gas, atoms characterized by sharp energy levels compared to solids
•Actual lasing atoms are the Neon atoms
Pumping action:
Electric discharge is passed through the gas
Electrons are accelerated, collide with He and He atoms and excite them
to higher energy levels
•Helium atom accumulates at levels F2 and F3
•Levels E4 and E6 of neon atoms have almost same energy as
F2 and F3
•Excited Helium ions collide with Neon atoms and excite them to
E4 and E6
Transitions:
üTransition between E6 and E3 produce 6328 A line output
üFrom E3 to E2 spontaneous emission takes place – 6000 A
üE2 – metastable state – tends to collect atoms
üFrom E2 atoms relax back to ground level
(Energy levels of helium and neon - diagram)
Difficulties:
Gain at 3.39 µm is much higher than that at 0.6328 and hence
Oscillations will tend to occur at 3.39 µm
This prevents further build up of population in E6 difficult
Carbon dioxide
Hydrogen
Nitrogen
Helium
(proportions vary according to a specific laser)
•Electron impact excites vibrational motion of the nitrogen.
•Collision energy transfer between the nitrogen and the CO2 molecule
causes vibrational excitation of the carbon dioxide
•Excite with sufficient efficiency to lead to the desired population inversion
necessary for laser operation.
•Laser transition occurs at 10.6µm
•CO2 laser……
One of the most widely used tunable lasers in the visible region
DYE – organic substances dissolved in solvents (water, ethyl alcohol,
Methanol ethyl glycol etc)
- Exhibit strong and broad absorption and fluorescent spectra
- Can be made tunable
- Tunability from 0.3 µm to 1.2 µm
States….
So – Ground state
S1 – first excited singlet state
T1, T2 – excited triplet states of the dye molecule
Working….
•Each state consists of a large number of closely spaced
Vibrational and rotational sublevels
•Dye molecules are excited by radiation
•Molecules are excited to various sublevels of state S1
•From there they relax quickly to the lowest level V2 of S1
•Molecules from V2 emit spontaneously and de-excite to
different sublevels of So
•Thus emitting a fluorescent spectrum
•Molecules from S1 can also make a nonradiative relaxation to T1
•This is called intersystem crossing
•Experimental dye lasers use flash lamps, pulsed lasers or continuous
lasers as pumping sources
•Pump lasers include Nitrogen Lasers, Argon Lasers, Krypton Lasers,
YAG laser
Pump Tuning Avg. Output Peak output Pulse
range (nm) Power (W) Power (W) duration (ns)
Nitrogen 350-1000 0.1 – 1 10000 1 – 10
laser
Flashlamp 400-960 0.1 – 100 100000 102 -105
Advantages:
•Capability of direct modulation into Gigahertz region
•Small size and low cost
•Capability of Monolithic integration with electronic circuitry
•Direct Pumping with electronic circuitry
•Compatibility with optical fibers
vBasic mechanism of light emission from a semiconductor
vHomojunction and Heterojunction lasers
vThreshold current density
vCarrier and Photon confinement