scholarly journals Diffuse Optical Spectroscopy Monitoring of Experimental Tumor Oxygenation after Red and Blue Light Photodynamic Therapy

Photonics ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 19
Author(s):  
Anna Orlova ◽  
Yulia Perevalova ◽  
Ksenia Pavlova ◽  
Natalia Orlinskaya ◽  
Aleksandr Khilov ◽  
...  

Photodynamic therapy (PDT) is an effective technique for cancer treatment based on photoactivation of photosensitizer accumulated in pathological tissues resulting in singlet oxygen production. Employment of red (660 nm) or blue (405 nm) light differing in typical penetration depth within the tissue for PDT performance provides wide opportunities for improving PDT protocols. Oxygenation dynamics in the treated area can be monitored using diffuse optical spectroscopy (DOS) which allows evaluating tumor response to treatment. In this study, we report on monitoring oxygenation dynamics in experimental tumors after PDT treatment with chlorin-based photosensitizers using red or blue light. The untreated and red light PDT groups demonstrate a gradual decrease in tumor oxygen saturation during the 7-day observation period, however, the reason is different: in the untreated group, the effect is explained by the excessive tumor growth, while in the PDT group, the effect is caused by the blood flow arrest preventing delivery of oxygenated blood to the tumor. The blue light PDT procedure, on the contrary, demonstrates the preservation of the blood oxygen saturation in the tumor during the entire observation period due to superficial action of the blue-light PDT and weaker tumor growth inhibition. Irradiation-only regimes show a primarily insignificant decrease in tumor oxygen saturation owing to partial inhibition of tumor growth. The DOS observations are interpreted based on histology analysis.

2012 ◽  
Vol 59 (3) ◽  
Author(s):  
Tomasz Cichoń ◽  
Magdalena Jarosz ◽  
Ryszard Smolarczyk ◽  
Barbara Ogórek ◽  
Sybilla Matuszczak ◽  
...  

One of the preconditions of effective anticancer therapy is efficient transfer of the therapeutic agent (chemotherapeutic) to tumor cells. Fundamental barriers making drug delivery and action difficult include underoxygenation, elevated interstitial pressure, poor and abnormal tumor blood vascular network and acidic tumor milieu. In this study we aimed at developing an optimized scheme of administering a combination of an angiogenesis-inhibiting drug (vasostatin) and a chemotherapeutic (cyclophosphamide) in the therapeutic treatment of mice bearing experimental B16-F10 melanoma tumors. We report that the strongest tumor growth inhibition was observed in mice that received two, three or four vasostatin doses in combination with one injection of cyclophosphamide (i.e., V2 + CTX, V3 + CTX or V4 + CTX schemes). Double administration of vasostatin increases oxygenation of B16-F10 tumors. On the other hand, its five-fold administration lowers tumor oxygenation, breaks down tumor vascular network (increasing hypoxia) and leads in consequence to death of cancer cells and appearance of necrotic areas in the tumor. A decreased cyclophosphamide dose in combination with two doses of vasostatin (V2 + CTX scheme) inhibits tumor growth similarly to a larger dose of cyclophosphamide alone.


2017 ◽  
Author(s):  
Mikhail Kleshnin ◽  
Anna Orlova ◽  
Mikhail Kirillin ◽  
German Golubiatnikov ◽  
Ilya Turchin

1960 ◽  
Vol XXXIII (IV) ◽  
pp. 584-592 ◽  
Author(s):  
B.-A. Lamberg ◽  
C. A. Hernberg ◽  
Riitta Hakkila

ABSTRACT Treatment with a thyroid preparation was used in 75 cases of non-toxic goitre. In 63 cases there was nodular goitre in 12 diffuse goitre. The observation period varied from 3 to 42 months. The size of the goitre decreased in 50 cases (68 per cent) of which 40 had a nodular goitre and 10 a diffuse goitre. In the 63 cases with a nodular goitre the size of the nodules decreased in 39 cases and the nodules disappeared completely in 2 cases (65 per cent). In 5 cases (7 per cent) there was no change in the size of the thyroid or the nodules. Temporary factitious hyperthyroidism appeared in 7 cases but subsided rapidly after adjustment of the dose. In one case an endogenous hyperthyroidism evidently developed, probably owing to initial latent hyperthyroidism. Treatment of non-toxic goitre with thyroid preparations or hormones is recommended 1) in diffuse goitre, 2) in nodular goitre as a trial and 3) after thyroidectomy for compressive goitre. The value of radioactive iodine uptake or excretion tests for the assessment of the response to treatment and the adjustment of the dose is emphasized.


Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Keegan Guidolin ◽  
Lili Ding ◽  
Juan Chen ◽  
Brian C. Wilson ◽  
Gang Zheng

Abstract Porphysomes (PS) are liposome-like nanoparticles comprising pyropheophorbide-conjugated phospholipids that have demonstrated potential as multimodal theranostic agents for applications that include phototherapies, targeted drug delivery and in vivo fluorescence, photoacoustic, magnetic resonance or positron emission imaging. Previous therapeutic applications focused primarily on photothermal therapy (PTT) and suggested that PSs require target-triggered activation for use as photodynamic therapy (PDT) sensitizers. Here, athymic nude mice bearing subcutaneous A549 human lung tumors were randomized into treatment and control groups: PS-PDT at various doses, PS-only and no treatment negative controls, as well as positive controls using the clinical photosensitizer Photofrin. Animals were followed for 30 days post-treatment. PS-PDT at all doses demonstrated a significant tumor ablative effect, with the greatest effect seen with 10 mg/kg PS at a drug-light interval of 24 h. By comparison, negative controls (PS-only, Photofrin-only, and no treatment) showed uncontrolled tumor growth. PDT with Photofrin at 5 mg/kg and PS at 10 mg/kg demonstrated similar tumor growth suppression and complete tumor response rates (15 vs. 25%, p = 0.52). Hence, porphysome nanoparticles are an effective PDT agent and have the additional advantages of multimodal diagnostic and therapeutic applications arising from their intrinsic structure. Porphysomes may also be the first single all-organic agent capable of concurrent PDT and PTT.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A264-A264
Author(s):  
Shanshan Qi ◽  
Hongjuan Zhang ◽  
Ruilin Sun ◽  
Annie An ◽  
Henry Li ◽  
...  

BackgroundToll-like receptors (TLRs) serve critical roles in mediating innate immune responses against many pathogens. However, they may also bind to endogenous ligands and lead to the pathogenesis of autoimmunity. Although TLR8 belongs to the same TLR family as TLR7, its role in inflammation and tumor progression is not yet fully understood due to the lack of suitable animal models. In humans, both TLR7 and TLR8 recognize single-stranded self-RNA, viral RNA, and synthetic small molecule agonists.1, 2 However, mouse Tlr8 is non-functional due to the absence of 5 amino acids necessary for RNA recognition. In order to create a mouse model with functional TLR8, we replaced exon 3 of mouse Tlr8 with human TLR8, therefore developing a hTLR8 knock-in (KI) model. Both heterozygous and homozygous hTLR8 KI mice are viable with inflammatory phenotypes, i.e. enlarged spleens and livers, and significantly higher IL-12 p40 levels under TLR8 agonist treatment. In this study, we evaluated the potential use of hTLR8 mice for cancer immunotherapy studies.MethodshTLR8 mice, together with naïve C57BL/6 mice, were inoculated with MC38 syngeneic tumor cells. Tumor bearing mice were grouped at a mean tumor volume of approximately 100 mm3 for treatment with PBS or 10 mg/kg anti-PD-1 (RMP1-14) antibody. At the efficacy endpoint, spleens and tumors were collected for flow cytometry profiling.ResultsAnti-PD-1 treatment of MC38 tumors in naïve C57BL/6 led to moderate tumor growth inhibition (TGI = 54%). Interestingly, anti-PD-1 treatment showed improved efficacy in hTLR8 mice (TGI = 79%), including 2/10 tumors with complete tumor regression. In comparison, non-treated MC38 tumor growth rate was slower in hTLR8 mice than in naïve mice. Anti-PD-1 treated hTLR8 mice also had significantly increased IFN-γ and TNF-a positive CD4+ T cells in the spleen, along with higher numbers of differentiated effector T cells. In addition, hTLR8 mice have activated dendritic cells and macrophages, acting as critical steps in initiation of the inflammatory process, with higher levels of pro-inflammatory cytokines, such as IL-6, IFN-γ, TNF-a, and IL-1β, which may promote Th1 priming and differentiation of T cells into IFN-γ or TNF-a producing cells.ConclusionshTLR8 mice offer a great tool to model cancer immunotherapy in an inflammatory/autoimmunity prone background. Moreover, hTLR8 mice can be effectively used to shift a ‘cold’ tumor phenotype to ‘hot’ tumors in a syngeneic setting.Ethics ApprovalAnimal experiments were conducted in accordance with animal welfare law, approved by local authorities, and in accordance with the ethical guidelines of CrownBio (Taicang).ReferencesKugelberg E. Making mice more human the TLR8 way. Nat Rev Immunol 2014;14:6.Guiducci C, Gong M, Cepika A-M, et al. RNA recognition by human TLR8 can lead to autoimmune inflammation. J Exp Med 2013;210:2903–2919.


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