Transcript بسم الله النور

Photobiomodulation
In radiodermatitis , indications and pitfalls
Nasrin Zand, MD
Dermatologist, Assistant Professor of Dermatology,
Medical Laser Research Center
(MLRC), ACECR
Photobiomodulation
Promoting wound healing and tissue repair
Inflammation reduction
Pain relief

Increase cell proliferation (DNA&
mRNA synthesis, mitosis and cell
proliferation





Epidermal cells (re-epithelialization)
and migration
Endothelial cells (neovascularization)
Fibroblasts proliferation and migration
and secretion of collagen type III.
Increased protein and GF : KGF,
EGF, PDGF, VEGF,…
Improved blood supply
Endothelial cell proliferation ↑

VEGF ↑

Release of NO into endothelium of
blood vessels
→Angiogenesis↑

PBM effects on RD
Ulceration, promoting wound healing
Inflammation
Fibrosis reduction
PBM
oxidant/antio
xidant
balance
downregulati
on of TGF-β
inhibition of
excessive
fibroblast
proliferation
Author
Sample
size
Device
Wave
length
Power
(mW)
Energy
density
(J/cm2)
Laser
schedule
Evaluation
Results
Schindl
1999
3
HeNe
LD
632.8
30
30
3/wk
until
wound closure
Weekly
36 m.
follow-up
Improved
wound
healing
DeLand
2007
47
LED
590
NA
0.15
Daily after each
RT
session
Baseline,
weekly
during RT and
2–6 wks after
the end of RT
No reduced
incidence
of RD grade
Baseline,
weekly
during RT and
2–6 weeks
after
the end of RT
No reduced
incidence
of RD grade
Baseline,
fraction
20 of RT and
at
the end of RT
Significantly
less
severe skin
toxicity
in LLLT
group
Fife
2010
33
LED
590
NA
NA
Censabella
2016
79
LD
808–905
60
4
Daily before
and after
each RT session
+7
additional daily
TX after the
end of RT
2 times/week
after the
RT session
starting at
fraction 20 of
RT
Can aggressiveness of cancer cells
increased by PBM?
Can we be sure about safety of
PBM in RD?
LLLT as non-ionizing irradiation
is not able to induce damage to cells DNA
However
it can modify cell behavior.
It is not surprising that cancer
is generally considered
As a relative if not absolute contraindication
to phototherapy.
Caution is generally suggested
even in treating areas remote to the neoplasm.
Photobiomodulation
In vitro studies
PBM : 660 nm, energy density: 1J/cm2
tongue SCC cells (in vitro)
mitotic rate↑
invasive potential ↑
PBM : 660 nm, energy density: 1J/cm2
human breast carcinoma (in vitro)
melanoma cell lines
mitotic rate↑
invasive potential ↑
Dysplastic cell line DOK
All the employed periods, wave
lengths and doses
Enhanced cell viabilty
Higher expression of specific proteins related to
cancer invasion and progression, such as pAkt,
Hsp90, pS6ser240/244 and Cyclin D1.
Cancer cell line SCC25
Red and NIR (660-780nm)
Marked growth stimulation
at some fluences
Cancer cell line SCC9
RED (660nm)
NIR (780nm)
Pronounced inhibition
of growth
Enhanced
cell viability
PBM : 805 nm, energy density: 4 and 20 J/cm2
Gingival SCC
mitotic rate↓
PBM : 808 nm, energy density: 5.85 and 7.8 J/cm2
Human hepatoma cell line
mitotic rate↓
PBM : 805 nm, energy density: 5-20 J/cm2
glioblastoma/astrocytoma cells
mitotic rate: slightly decreased
LLLT
can induce
either proliferation or growth inhibition
depending on
the parameters employed
and also on the cell line studied.
Photobiomodulation
In vivo studies
660 nm, 30mW, 424 mW/cm2, 56.4 J/cm2, 133 s, 4 J
Chemically induced SCC in hamster cheek pouch
Tumor growth↑
UV-induced skin tumors in mouse model
PBM: 670 nm
twice a day, 5 J/cm2, 37 days
UV-induced skin tumors in mouse model
Small but significant reduction in tumor
area in the PBM group
Stimulation of the growth of human tumor by
low-power laser irradiation.(2001)

PBM: 633nm, 3.5 J/cm2 , thrice/wk for 2 wks.

Model : human gastric adenocarcinoma transplanted into
immunodeficient athymic nude mice→ acceleration of
tumor growth

This suggests that LLLT is indeed capable of activating
tumor growth under conditions that exclude immune
resistance.
Laser Therapy Inhibits Tumor Growth in Mice by Promoting
Immune Surveillance and Vessel Normalization
2016 Ottaviani


B16F10 melanoma and oral carcinogenesis in mouse
660 nm, fluence :3 J/cm2 power :100mW, irradiance: 50mW/cm2,
fluence :3 J/cm2, time 60 s, CW

800 nm, fluence, 6: J/cm2, power: 1W, irradiance 200m:W/cm2, time
30 s, CW

970 nm, fluence :6 J/cm2, power: 2.5 W, irradiance 200 mW/cm2,
time 30 s, CW

The same protocols were applied in vivo, once a day for 4 days.

Invitro: significant increase in cell metabolism
(ATP Production Assay)

In vivo:



Tumor progression ↓
Number of neoplastic cells infiltrating and invading
of surrounding tissues ↓
The effect of laser light on cancer cell growth is
different in cell culture and in vivo

Inhibition of tumor growth and invasion without
directly affecting tumor cell proliferation

Improvement of perfusion and maturation of
tumor vessels


Highly angiogenic macrophages within the tumor
mass ↓ → promoting vessel normalization
Recruitment of immune cells around tumor
masses. in particular T lymphocytes and dendritic
cells→ IFNs 1.

Activation of dermal DCs to effectively migrate
to draining lymph nodes and to induce antigenspecific CD8+ and CD4+ T cell responses

Thus, while laser light seems to increase the
proliferation of cultured cells, the net effect in
vivo is a reduction of tumor growth and tumor
cell infiltration in surrounding tissues.
ATP signaling
↓
Release of NO from cytochromes oxidase
↓
Modulation of apoptosis in cancer
Modulation of ATP signaling
↓
Tumor cell suicide
Karu 2010
The potential therapeutic
Effect of PBM in lung cancer.
Abrahamse 2013
5 year
Survival rate
LLLT
+
LLLT
-
Grade 2
100%
85.71%
Grade 3
94.44%
78.94%
Mikhailov 2000
PBM prior to RT
Normal human lymphoblasts and leukemia cells
Different response of normal versus malignant cells
PBM does not confer protection and may even
sensitize cancer cells to RT induced killing
However some other studies….
660 nm, 30mW, 424 mW/cm2, 56.4 J/cm2, 133 s, 4 J
Chemically induced SCC in hamster cheek pouch
Tumor growth↑
Perhaps we will one day see
phototherapy used for cancer management.
The future is bright.
Stay tuned!
Lanzafame