Luis Santana Blank Presentacion Bulgaria 2

8/13/2019 Luis Santana Blank Presentacion Bulgaria 2

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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

Luis Santana Blank Presentacion Bulgaria 2

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