Low-doses of sequential-kinetic-activated interferon-γ enhance the ex vivo cytotoxicity of peripheral blood natural killer cells from patients with early-stage colorectal cancer. A preliminary study

Radice, Elisabetta; Miranda, Vincenzo; Bellone, Graziella

doi:10.1016/j.intimp.2013.12.011

Cited by 36 publications

(26 citation statements)

References 44 publications

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“…Moreover, many clinical trials have tested highly diluted SKA drugs in various pathologies. Significant effectiveness has been reported in supportive therapy and pain relief in cancer patients [Rajendran, 2004;Sunila et al, 2009;Radice et al, 2014]. In addition, a reduction of symptoms and an improved quality of life have been observed in patients with psoriasis or vitiligo [Witt et al, 2009;Roberti et al, 2014;Barygina et al, 2015] or in immune system imbalances [Kho et al, 2012].…”

Section: Discussionmentioning

confidence: 99%

“…The same doses of IL-12 also promote inhibition of the proliferation of lung adenocarcinoma cells in vitro [D'Amico et al, 2012]. Also, these highly diluted forms have been obtained via a sequential kinetic activation (SKA) technique and these cytokines have shown capability to exert immunomodulatory action in colon cancer as well [Radice et al, 2014;Roberti et al, 2014]. Lastly, these highly diluted SKA cytokines have been demonstrated to have a significant beneficial effect in skin diseases both in patients and in cultured cells [Barygina et al, 2015;Radice et al, 2015].…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of the Nonneuronal Cholinergic System by Highly Diluted Acetylcholine in Keratinocytes

Uberti¹,

Bardelli²,

Morsanuto³

et al. 2016

Cells Tissues Organs

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The physiological effects of acetylcholine on keratinocytes depend on the presence of nicotinic and muscarinic receptors. The role of nonneuronal acetylcholine in keratinocytes could have important clinical implications for patients with various skin disorders such as nonhealing wounds. In order to evaluate the efficacy of highly diluted acetylcholine solutions obtained by sequential kinetic activation, we aimed to investigate the effects of these solutions on normal human keratinocytes. Two different concentrations (10 fg/mL and 1 pg/mL) and formulations (kinetically activated and nonkinetically activated) of acetylcholine were used to verify keratinocyte viability, proliferation, and migration and the intracellular pathways involved using MTT, crystal violet, wound healing, and Western blot compared to 147 ng/mL acetylcholine. The activated formulations (1 pg/mL and 10 fg/mL) revealed a significant capacity to increase migration, cell viability, and cell proliferation compared to 147 ng/mL acetylcholine, and these effects were more evident after a single administration. Sequential kinetic activation resulted in a statistically significant decrease in reactive oxygen species production accompanied by an increase in mitochondrial membrane potential and a decrease in oxygen consumption compared to 147 ng/mL acetylcholine. The M1 muscarinic receptor was involved in these effects. Finally, the involvement of ERK/mitogen-activated protein kinases (MAPK) and KI67 confirmed the effectiveness of the single treatment on cell proliferation. The intracellular pathways of calcium were investigated as well. Our results indicate for the first time that highly diluted and kinetically activated acetylcholine seems to play an active role in an in vitro model of wound healing. Moreover, the administration of acetylcholine within the physiological range may not only be effective but is also likely to be safe.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stimulation of the Nonneuronal Cholinergic System by Highly Diluted Acetylcholine in Keratinocytes

Uberti¹,

Bardelli²,

Morsanuto³

et al. 2016

Cells Tissues Organs

View full text Add to dashboard Cite

show abstract

“…A possible answer can be found in the LDM approach. The availability of low dose SKA signaling molecules (cytokines, growth factors, hormones, and neuropeptides) makes it possible to use lower doses of activated molecules (active range between picomoles and femtomeoles) (18)(19)(20)(21)(22) with therapeutic outcomes comparable to those induced by high doses but without the side effects.…”

Section: Ldm: a New Instrument For Treatment Of Skin Diseasesmentioning

confidence: 99%

Skin as a Psychoneuroendocrine Immunology Microcosm: The New Frontier of Low Dose Therapy With Cytokines and Growth Factors in the Systemic Treatment of Chronic Autoimmune Inflammatory Diseases in Dermatology

Lotti

Rivkina

Fioranelli

2016

Jentashapir J Health Res

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In recent years, the central role of signaling molecules, such as hormones, cytokines and growth factors, has become evident in both physiological and pathological processes; these signaling molecules are the main regulating effectors of whole body biological functions, in accordance with the guiding principle of psychoneuroendocrine immunology (PNEI). Low dose medicine (LDM) represents an innovative medical approach in which the latest evidence in the fields of molecular biology, PNEI and nano-concentration pharmacology are merged. LDM suggests the use of low-doses of activated biological molecules in order to manage PNEI homeostasis, and this approach represents a new opportunity for the development of therapeutic strategies based on immune balancing interventions. Scientific evidence regarding the efficacy and safety of the LDM approach in the treatment of psoriasis vulgaris, and positive preliminary data regarding the oral administration of low dose activated cytokines for vitiligo and atopic dermatitis treatment, support the LDM-based therapeutic approach for many dermatological diseases.Keywords: Psycho-Neuro-Endocrine-Immunology, Low Dose Medicine, Signaling Molecules, Sequential Kinetic Activation, Psoriasis Vulgaris, Dermatologic Diseases ContextIn recent years, a unified vision of the biological functions of the body has been theorized, in accordance with the guiding principles of psychoneuroendocrine immunology (PNEI) (1-4). The PNEI approach represents a paradigm shift from a strictly biomedical view of health and disease to an interdisciplinary view. The main unifying PNEI element is identified in the bi-directional crosstalk (5) between the psychoneuroendocrine systems and the immune system, which is mediated by a complex network of signaling (messenger) molecules (cytokines, hormones, growth factors, neuropeptides) that are the vehicles for the biological information necessary for the complex and efficient regulation of cellular responses to stimuli.The signaling molecules play a decisive role in determining a person's state of health or disease, and it is compelling to consider diseases as expressions of the change in concentrations (both in excess or in defect) of these substances. In order to test the hypothesis that messenger molecules can be used for therapeutic purposes, research in the medical world is increasingly directed toward the study of the messenger molecules, which determine the fate of many pathological conditions in a positive (healing) or negative (disease) way.The multi-system axes, such as the gut-brain-axis and the skin-gut-axis, are controlled and managed by a continuous information exchange driven by cytokines, neuropeptides, neuro-hormones and other signaling molecules, in order to maintain PNEI homeostasis.In summary, altered cross-talk caused by the imbalance between specific signaling molecules is a fundamental requisite for the onset of inflammatory, allergic and autoimmune diseases (6, 7). Preserving and/or restoring the physiological signaling, based on messe...

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“…Since 2009 new publications [27][28][29][30] followed the paper published by Gariboldi, et al (Table 1) extending available data regarding LDM therapeutic design, efficacy and safety. The research works described in this review can be classified on the basis of the previously described therapeutic approach (Table 2).…”

Section: Scientific Literature Supports Ldm Approachmentioning

confidence: 99%

The History of Low Dose Medicine Research Review of Preclinical and Clinical Studies with Low Dose SKA Cytokines Since 2009

Mg¹

2014

Interdiscip J Microinflammation

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Since the second half of the 80s the development of the Psycho-Neuro-Endocrine-Immunology concepts resulted in a change of perspective, from a separatist point of view to an unifying one, relating to the interpretation of the biological functions of the body. A key point was the recognition of the importance of continuous cross-talk between cells, organs and systems in both physiological and pathological conditions based on the fine regulation of the levels of a large number of messenger molecules.Interpreting the pathological phenomenon as an imbalance in intercellular signaling, the administration of low physiological doses of messenger molecules (which act as homeostatic modulating agents) can be considered an intriguing and innovative approach in order to restore the correct intracellular signaling and consequently to restore healthy conditions; these concepts are the milestones of Low Dose Medicine.

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Low-doses of sequential-kinetic-activated interferon-γ enhance the ex vivo cytotoxicity of peripheral blood natural killer cells from patients with early-stage colorectal cancer. A preliminary study

Cited by 36 publications

References 44 publications

Stimulation of the Nonneuronal Cholinergic System by Highly Diluted Acetylcholine in Keratinocytes

Stimulation of the Nonneuronal Cholinergic System by Highly Diluted Acetylcholine in Keratinocytes

Skin as a Psychoneuroendocrine Immunology Microcosm: The New Frontier of Low Dose Therapy With Cytokines and Growth Factors in the Systemic Treatment of Chronic Autoimmune Inflammatory Diseases in Dermatology

The History of Low Dose Medicine Research Review of Preclinical and Clinical Studies with Low Dose SKA Cytokines Since 2009

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