FUNDALAS Foundation for Interdisciplinary Research and Development Caracas Venezuela

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

30+ years of interest in water-light interactions

Cancer therapy targets

A major obstacle for cancer drugs aiming at single molecular targets to minimize nonspecific toxicity is that clinical response is often transitory and followed by relapse.

Squamous cell carcinoma

3X Breast Cancer

Late Stage Cancer Patients

Effects of light
Light can stimulate or inhibit (i.e., modulate) cell function depending on signal and receptor characteristics, which determine biological outcome.

Photobiomodulation uses low-fluence light that can control cellular and tissue energy.
o ATP, GTP o Other high-energy molecules o Receptors purine and adenine

Effects of light
One conduit includes absorption by CcO, a key enzyme in the respiratory electron transport chain. Laser photobiomodulation then initiates secondary cellsignaling resulting in increased energy metabolism.

Cytochrome c oxidase
http://en.wikipedia.org/wiki/Cytochrome_c_oxidase

Water
Water provides pathways for light absorption and transportation that can substitute and complement metabolic energy pathways through oxygen-dependent and oxygenindependent effects with critical signaling pathways in primarily aqueous media

Water
Water is a key player in numerous physiologic mechanisms, including first-contact events in which cells decide between survival and apoptosis.

Consequently, externally applied light may selectively target Water to steer biological function.
Figure source: http://astrobob.areavoices.com/tag/water-molecule/

IPLD Prototype Assessment

Infrared pulsed laser device (IPLD), consisting of a near infrared drive force wave and an ultrasonic carrier wave

Published Results
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)**

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.

Published Results
The phase I clinical trial also showed:
Selective activation of programmed cellular death (i.e., apoptosis, necrosis, anoikis) and Cytomorphologic changes 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.

Published Results

Water diffusion changes acted as predicator of tumor response

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.

Published Results

Chondrosarcoma of the posterior fossa with compression of the brainstem.

Source:Phase I trial of an infrared pulsed laser device in patients with advanced neoplasias. Clin Cancer Res. 2002; 8: 3082-3091.

Basic Premise
External electromagnetic energy (light) supplementation can...
Enhance and even substitute for endogenous ATP Power and modulate physiologically reparative mechanisms Help reestablish homeostasis / homeokinesis, even when physiologic metabolic pathways have been compromised.

Proposed Mechanisms

Photo Infrared Pulsed Biomodulation (PIPBM)

Source: Photo-infrared pulsed bio-modulation (PIPBM): a novel mechanism for the enhancement of physiologically reparative responses. Photomed Laser Surg. 2005 Aug;23(4):416-24. Review. Photomed Laser Surg. 2005;23(4):416-24

Proposed Mechanisms

Water Oscillator Paradox

Source: Theoretic, experimental, clinical bases of the water oscillator hypothesis in near-infrared photobiomodulation. Photomed Laser Surg. 2010 Aug; 28 Suppl 1:S41-52

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

Photo-Induced Effects Over the EZ

Retrospective analysis of published data
1H-NMR relaxation times and correlation times Microdensitometry of T2 weighted tumor heterogeneities from the phase I trial in patients Algorithm for tumor characterization Control Histological and MRI results

1H-NMR

Relaxation Times

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.
Source:

1H-NMR

Correlation Times

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.

Microdensitometry

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).

Histological Results

Results are highly consistent with cytomorphologic results showing a selective increase in tumor apoptosis.

Clinical Results

Pre-IPLD treatment

Post-IPLD treatment

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.
Source: Solid Tumors and Photobiomodulation: A Novel Approach to Induce Physiologically Reparative Homeostasis / Homeokinesis Journal of Solid Tumors. 2012; 2(6):23-35

Photo-Induced Effects Over the EZ

Left-cheek metastasis of malignant papillary meningioma (R) A. T2 Weighted MRI B. Raw Microdensitometry

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.

Algorithm For Tumor Characterization

Algorithm curves from the same patient with papillary malignant meningioma (R).

Conclusions
Laser photobiomodulation may increase potential energy in the EZ, which can then act as a rechargeable electrolytic bio-battery for the external selective supplementation of the energy demand required for cellular work, signaling pathways and gene expression in the presence of injury-induced redox potentials. EZ structuring may be used as a predicator of tumor response before measurable tumor volume reduction.

FUNDALAS Foundation for Interdisciplinary Research and Development Caracas Venezuela

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