Preclinical and Clinical Evidence of Immune Responses Triggered in Oncologic Photodynamic Therapy: Clinical Recommendations

Photodynamic therapy (PDT) is an anticancer strategy utilizing light-mediated activation of a photosensitizer (PS) which has accumulated in tumor and/or surrounding vasculature. Upon activation, the PS mediates tumor destruction through the generation of reactive oxygen species and tumor-associated vasculature damage, generally resulting in high tumor cure rates. In addition, a PDT-induced immune response against the tumor has been documented in several studies. However, some contradictory results have been reported as well. With the aim of improving the understanding and awareness of the immunological events triggered by PDT, this review focuses on the immunological effects post-PDT, described in preclinical and clinical studies. The reviewed preclinical evidence indicates that PDT is able to elicit a local inflammatory response in the treated site, which can develop into systemic antitumor immunity, providing long-term tumor growth control. Nevertheless, this aspect of PDT has barely been explored in clinical studies. It is clear that further understanding of these events can impact the design of more potent PDT treatments. Based on the available preclinical knowledge, recommendations are given to guide future clinical research to gain valuable information on the immune response induced by PDT. Such insights directly obtained from cancer patients can only improve the success of PDT treatment, either alone or in combination with immunomodulatory approaches.

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The antidepressant agomelatine reduces fear long term memory but not acquisition or short term expression of fear memories

European Psychiatry ◽

10.1016/s0924-9338(11)72359-8 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 653-653

Author(s):

L. Diaz-Mataix ◽

E. Mocaër ◽

L. Seguin ◽

J.E. Ledoux

Keyword(s):

Fear Conditioning ◽

Clinical Studies ◽

Conditioned Fear ◽

Fear Learning ◽

Long Term Memory ◽

Onset Of Action ◽

Subsequent Exposure ◽

Preclinical And Clinical Studies ◽

Antidepressant Action

Alterations in fear learning processes may be implicated in mood disorders. Fear learning has been investigated with Pavlovian classical fear conditioning paradigms, consisting of pairing a neutral conditioned stimulus (CS), such as a tone, with an aversive unconditioned stimulus (US), such as a footshock. Upon subsequent exposure, the CS is perceived as aversive and provokes a fear response.The novel antidepressant agomelatine acts as a melatonergic receptor agonist and a 5-HT2C receptor antagonist. Its antidepressant action was demonstrated in preclinical and clinical studies. Agomelatine has also anxiolytic properties. The aim of this study was to determine how acute agomelatine treatment might differentially alter fear circuits by using auditory fear conditioning in the rat.A single pre-training injection of agomelatine (40 mg/kg intraperitoneally) significantly reduced freezing to the fear arousing CS 24 hours after training but not during training or 3 hours after training. This pattern of results is consistent with an effect on the consolidation of the fear memory. A single pre-testing injection of agomelatine had no effect on conditioned fear expression.These effects of agomelatine should be considered in relation to its antidepressant action. Agomelatine achieved a reduction of fear conditioning in a single dose, while classical SSRIs only reduced fear conditioning after chronic treatment. This finding is consistent with clinical studies suggesting a faster onset of action of agomelatine than classical SSRI treatment.

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Glucocorticoids Induce a TH2 ResponseIn Vitro

Developmental Immunology ◽

10.1155/1998/73401 ◽

1998 ◽

Vol 6 (3-4) ◽

pp. 233-243 ◽

Cited By ~ 37

Author(s):

Francisco Ramírez

Keyword(s):

Immune Response ◽

Mixed Lymphocyte Reaction ◽

Cytokine Production ◽

High Concentration ◽

Con A ◽

Immunological Effects ◽

Cytokine Synthesis ◽

Continuous Presence

Purified rat CD4+T cells were activatedin vitro, by the polyclonal mitogen Concanavalin A (Con A) or by mixed lymphocyte reaction (MLR), in the presence or absence of the glucocorticoid dexamethasone (DEX). They were then expanded in IL-2 and subsequently restimulated, this time in the absence of the hormone. The results indicate that the exposure of the cells to DEX in the primary stimulation changed the cytokine synthesis induced by the secondary stimulation. IL-4 production was increased by the pretreatment whereas synthesis of IFN-γwas diminished. Addition of DEX in the second activation suppressed all cytokine production. In brief, the transient presence of glucocorticoids in the culture induces a change in the pattern of cytokine production but the continuous presence causes inhibition of cytokine synthesis. Further studies in which IL-4 was used together with DEX showed that the cytokine potentiated the effect of the hormone.The data here presented suggest that glucocorticoids and the neuroendocrine system may be expected to have long-term immunological effects as well as short-lived immunosuppressive ones. High concentration of glucocorticoids suppress cytokine production but when steroids return to basal levels the immune response is directed in a way that favors Th2-type reactions. Possible implications regarding the immune response to pathogens and autoantigens are discussed.

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Photo activated disinfection in Restorative Dentistry: A technical review

CODS Journal of Dentistry ◽

10.5005/cods-6-1-16 ◽

2014 ◽

Vol 6 (1) ◽

pp. 16-18

Author(s):

BS Deepak ◽

K Mallikarjun Goud ◽

P Nishanth

Keyword(s):

Photodynamic Therapy ◽

Antimicrobial Therapy ◽

Clinical Studies ◽

Current Status ◽

Restorative Dentistry ◽

Pertinent Literature ◽

Technical Review ◽

Recent Developments ◽

Current Stage

Abstract The purpose of this review is to summarize the recent developments regarding photodynamic therapy (PDT) in the field of restorative dentistry. A search of pertinent literature was carried out in PubMed to determine the current applications of photo activated disinfection (PAD) in dentistry. This overview will provide the practitioners, the current status and use of PAD. Within the limitations of the present review, it can be concluded that although PAD cannot replace antimicrobial therapy at its current stage, it may be used as an adjunctive tool in restorative dentistry. Further long-term clinical studies are necessary in establishing a more specific place of the technique in the field of dentistry. How to cite this article Deepak BS, Mallikarjun GK, Nishanth P. Photo activated disinfection in Restorative Dentistry: A technical review. CODS J Dent 2014;6;16-18

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Antidiabetic Properties of Germinated Brown Rice: A Systematic Review

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2012/816501 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 35

Author(s):

Mustapha Umar Imam ◽

Nur Hanisah Azmi ◽

Muhammad Iqbal Bhanger ◽

Norsharina Ismail ◽

Maznah Ismail

Keyword(s):

Clinical Studies ◽

Animal Experiments ◽

Brown Rice ◽

Important Variable ◽

Germinated Brown Rice ◽

Neuroprotective Effects ◽

Preclinical And Clinical Studies ◽

Antidiabetic Effects

Diet is an important variable in the course of type 2 diabetes, which has generated interest in dietary options like germinated brown rice (GBR) for effective management of the disease among rice-consuming populations.In vitrodata and animal experiments show that GBR has potentials as a functional diet for managing this disease, and short-term clinical studies indicate encouraging results. Mechanisms for antidiabetic effects of GBR due to bioactive compounds likeγ-aminobutyric acid (GABA),γ-oryzanol, dietary fibre, phenolics, vitamins, acylated sterylβ-glucoside, and minerals include antihyperglycemia, low insulin index, antioxidative effect, antithrombosis, antihypertensive effect, hypocholesterolemia, and neuroprotective effects. The evidence so far suggests that there may be enormous benefits for diabetics in rice-consuming populations if white rice is replaced with GBR. However, long-term clinical studies are still needed to verify these findings on antidiabetic effects of GBR. Thus, we present a review on the antidiabetic properties of GBR from relevant preclinical and clinical studies, in order to provide detailed information on this subject for researchers to review the potential of GBR in combating this disease.

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Abstract B010: Antitumor cellular immune response elicited by Toca 511 and Toca FC therapy in preclinical and clinical studies

10.1158/1535-7163.targ-17-b010 ◽

2018 ◽

Author(s):

Tiffany T. Montellano ◽

Derek Ostertag ◽

Daniel J. Hogan ◽

Oscar R. Diago ◽

Dawn Gammon ◽

...

Keyword(s):

Immune Response ◽

Clinical Studies ◽

Cellular Immune Response ◽

Preclinical And Clinical Studies ◽

Cellular Immune

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Photodynamic Therapy and Antitumor Immunity

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2012.0173 ◽

2012 ◽

Vol 10 (Suppl_2) ◽

pp. S-40-S-43 ◽

Cited By ~ 30

Author(s):

Sandra O. Gollnick

Keyword(s):

Immune Response ◽

Photodynamic Therapy ◽

Immune System ◽

Antitumor Immunity ◽

Adaptive Immune System ◽

Preclinical Studies ◽

Adaptive Immune ◽

Shed Light ◽

Clinical Strategy

Preclinical studies have shown that local photodynamic therapy (PDT) enhances systemic antitumor immunity. In addition, it has long been known that the long-term efficacy of PDT depends on the presence of an intact adaptive immune system. Years of research in the laboratory have attempted to shed light on the mechanisms of the PDT-enhanced antitumor immune response, suggesting that increased expression of proinflammatory cytokines may play a key role. This overview on the immunologic potential of PDT briefly explores these proposed mechanisms and addresses preliminary results with PDT vaccines in combination with surgery as perhaps a new clinical strategy for cancer treatment outside the laboratory.

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Immune responses to AAV vectors: overcoming barriers to successful gene therapy

Blood ◽

10.1182/blood-2013-01-306647 ◽

2013 ◽

Vol 122 (1) ◽

pp. 23-36 ◽

Cited By ~ 378

Author(s):

Federico Mingozzi ◽

Katherine A. High

Keyword(s):

Gene Therapy ◽

Immune Response ◽

Immune Responses ◽

Clinical Studies ◽

Genetic Diseases ◽

Wild Type Virus ◽

Small Scale ◽

Therapeutic Gene ◽

Positive Results

AbstractGene therapy products for the treatment of genetic diseases are currently in clinical trials, and one of these, an adeno-associated viral (AAV) product, has recently been licensed. AAV vectors have achieved positive results in a number of clinical and preclinical settings, including hematologic disorders such as the hemophilias, Gaucher disease, hemochromatosis, and the porphyrias. Because AAV vectors are administered directly to the patient, the likelihood of a host immune response is high, as shown by human studies. Preexisting and/or recall responses to the wild-type virus from which the vector is engineered, or to the transgene product itself, can interfere with therapeutic efficacy if not identified and managed optimally. Small-scale clinical studies have enabled investigators to dissect the immune responses to the AAV vector capsid and to the transgene product, and to develop strategies to manage these responses to achieve long-term expression of the therapeutic gene. However, a comprehensive understanding of the determinants of immunogenicity of AAV vectors, and of potential associated toxicities, is still lacking. Careful immunosurveillance conducted as part of ongoing clinical studies will provide the basis for understanding the intricacies of the immune response in AAV-mediated gene transfer, facilitating safe and effective therapies for genetic diseases.

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Photonics immunotherapy — A novel strategy for cancer treatment

Journal of Innovative Optical Health Sciences ◽

10.1142/s1793545816300019 ◽

2016 ◽

Vol 09 (01) ◽

pp. 1630001 ◽

Cited By ~ 11

Author(s):

Feifan Zhou ◽

Robert E. Nordquist ◽

Wei R. Chen

Keyword(s):

Immune Response ◽

Cancer Treatment ◽

Antitumor Immunity ◽

Therapeutic Strategy ◽

Tumor Antigens ◽

Local Treatment ◽

Immunological Effects ◽

Novel Strategy

Photonics immunotherapy is a novel cancer treatment strategy that combines local phototherapy and immunotherapy. Phototherapy is a noninvasive or minimally invasive therapeutic strategy for local treatment of cancer, which can destroy tumor cells and release tumor antigens, inducing an in situ antitumor immune response. Immunotherapy, including the use of antibodies, vaccines, immunoadjuvants and cytokines, when combined with phototherapy, could bring a synergistic effect to stimulate a host immune response that effectuates a long-term antitumor immunity. This review will focus on the development of photonics immunotherapy and its systemic antitumor immunological effects.

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