luis santana blank presentacion bulgaria 2
TRANSCRIPT
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Water-light interaction:
A novel pathway for multi hallmark
therapy in cancer
Conference on the Physics, Chemistry and Biology of Water 2013
Dr. Luis Santana-Blank
FUNDALASResearch and Development
Caracas Venezuela
Foundation for Interdisciplinary
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30+ years of interest in water-light interactions
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Cancer therapy targets
3X Breast Cancer
Squamous cell carcinoma
A major obstacle for cancer drugs aiming
at single molecular targets to minimizenonspecific toxicity is that clinical responseis often transitory and followed by relapse.
Late Stage Cancer Patients
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Light can stimulate or inhibit (i.e., modulate)cellfunction depending on signal and receptorcharacteristics, which determine biological outcome.
Photobiomodulation uses low-fluence light that cancontrol cellular and tissue energy.
o ATP, GTPo Other high-energy molecules
o Receptors purine and adenine
Effects of light
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One conduit includes absorption by CcO, a key enzymein the respiratory electron transport chain.
Laser photobiomodulation then initiates secondary cell-
signaling resulting in increased energy metabolism.
Effects of light
Cytochrome c oxidase
http://en.wikipedia.org/wiki/Cytochrome_c_oxidase
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Waterprovides pathways for light absorptionand transportation that
can substitute and complement metabolicenergy pathways
through oxygen-dependent and oxygen-independent effects
with critical signaling pathways in primarilyaqueous media
Water
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Wateris a key player in numerous physiologic
mechanisms, including first-contact events in whichcells decide between survival and apoptosis.
Consequently, externally applied light may selectivelytargetWaterto steer biological function.
Water
Figure source: http://astrobob.areavoices.com/tag/water-molecule/
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IPLD Prototype Assessment
Infrared pulsed laser device (IPLD), consisting of a near infrared drive force wave and an ultrasonic carrier wave
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A Phase I trial of an infrared pulsed laser device (IPLD)in patients with advanced neoplasias demonstrated:
The IPLD was clinically safe and improved performance
status and quality of life* Antitumor activity was found in 88.23% of patients with
more than 10 years of follow-up*
Significant modulation of CD4, CD45RA+, CD25, TNF-,
and soluble IL-2 receptor (sIL-2R)**
Published Results
Source: *Phase I trial of an infrared pulsed laser device in patients with advanced neoplasias. Clin Cancer Res. 2002; 8: 3082-3091. **Evaluation of serum
levels of tumor necrosis factor-(TNF-a) and soluble IL-2 receptor (sIL-2R) and CD4. CD8 and natural killer (NK) populations during infrared pulsed laser
device (IPLD) treatment. Clin Exp Immunol. 90: 4348, 1992.
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The phase I clinical trial also showed:
Published Results
Selective activation ofprogrammed cellulardeath (i.e., apoptosis,necrosis, anoikis) and
Cytomorphologicchanges in tumors, not
in peripheral tissues.
Source:Photo-induced cytomorphologic changes in an advanced cancer phase I clinical trial. Lasers Surg Med. 2002;30(1):18-25.
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Source: Microdensitometry of T2-weighted magnetic resonance (MR) images from patients with advanced neoplasias in a phase I clinical
trial of an infrared pulsed laser device (IPLD). Lasers Surg Med. 2004; 34 (5):398-406.
Waterdiffusion changes acted as predicator of tumorresponse
Published Results
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Chondrosarcoma of the posterior fossa with
compression of the brainstem.
Published Results
Source:Phase I trial of an infrared pulsed laser device in patients with advanced neoplasias. Clin Cancer Res. 2002; 8: 3082-3091.
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External electromagnetic energy (light)supplementation can...
Enhance and even substitute for endogenousATP
Power and modulate physiologically reparativemechanisms
Help reestablish homeostasis / homeokinesis,
even when physiologic metabolic pathways havebeen compromised.
Basic Premise
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Proposed Mechanisms
Photo Infrared Pulsed Biomodulation (PIPBM)
Source: Photo-infrared pulsed bio-modulation (PIPBM): a novel mechanism for the enhancement of physiologically reparativeresponses. Photomed Laser Surg. 2005 Aug;23(4):416-24. Review. Photomed Laser Surg. 2005;23(4):416-24
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Proposed Mechanisms
Water Oscillator ParadoxSource: Theoretic, experimental, clinical bases of the water oscillator hypothesis in near-infrared photobiomodulation. Photomed Laser Surg. 2010 Aug;
28 Suppl 1:S41-52
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Proposed
Mechanisms
Photobiomodulation of Aqueous
Interface as Selective Rechargeable
Bio-Batteries in Complex Diseases
Source: Photobiomodulation of Aqueous Interface as Selective Rechargeable Bio-Batteries in Complex Diseases. Photomed Laser Surg. 2012; 30(5):242-9
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Retrospective analysis of published data
1H-NMR relaxation times and correlation times
Microdensitometry of T2 weighted tumorheterogeneities from the phase I trial in patients
Algorithm for tumor characterization
Control Histological and MRI results
Photo-Induced Effects Over the EZ
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Source:Santana-Blank L, et al. Short-Term Bioeffects of an Infrared Pulsed Laser Device on Burned Rat Skin Monitored by Transverse Relaxation
Times (NMR). Lasers in Surgery and Medicine 2000. 27:411- 419.
1H-NMR Relaxation Times
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Source: Rodrguez-Santana E, et al. H-NMR spin-lattice and correlation times of burned soft-tissue after treatment with an
infrared pulsed laser device. Lasers Surg Med. 2003;33(3):190-8.
1H-NMR Correlation Times
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Perkin-Elmer microdensitometer (Wellesley-USA) with 50 per pixel resolution
Transference function connected to IBM PC computer (Yorktown Heights-USA).
Images edited to obtain thresholds and correct background irregularities.
A linear transformation was applied to convert MRIs to 256 intensity levels using
the High-Level Image Processing System (HIPS) software package (IBM).
Microdensitometry
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Results are highlyconsistent with
cytomorphologicresults showing aselective increasein tumor apoptosis.
Histological Results
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Pre-IPLD treatment Post-IPLD treatment
Source: Solid Tumors and Photobiomodulation: A Novel Approach to Induce Physiologically Reparative Homeostasis / Homeokinesis
Journal of Solid Tumors. 2012; 2(6):23-35
Patient with recurrent papillary malignant meningioma. Prior to entering
the phase I trial, the patient received radiotherapy (5220 rads) and
chemotherapy following left orbital exenteration.
Clinical Results
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Left-cheek metastasis of malignant papillary meningioma (R)
Red tones relate to high water content caused by photo-induced cell death.
Blue shades correspond to active tumor areas.
The wide divide is consistent with loss of cellular adhesion due to anoikis
Light blue areas strongly suggests highly ordered water.
White areas suggests fluorescence consistent with the presence of structured
matrices, charge separation and pH differences.
A. T2 Weighted MRI B. Raw Microdensitometry
Photo-Induced Effects Over the EZ
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Algorithm For Tumor Characterization
Algorithm curves from the same patient with papillary malignant meningioma (R).
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Laser photobiomodulation may increase potentialenergy in the EZ, which can then act as a rechargeableelectrolytic bio-battery for the external selective
supplementation of the energy demand required forcellular work, signaling pathways and gene expressionin the presence of injury-induced redox potentials.
EZ structuring may be used as a predicator of tumor
response before measurable tumor volume reduction.
Conclusions
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Thank you
FUNDALAS
Research and DevelopmentCaracas Venezuela
Foundation for Interdisciplinary