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BACKGROUND: Somatic mutations are involved in hepatocellular carcinoma (HCC) progression, but the genetic mechanism associated to hepatocarcinogenesis remains poorly understood. We report that Eyes absent homolog 2 (EYA2) suppresses the HCC progression, while EYA2(A510E) mutation identified by exome sequencing attenuates the tumor-inhibiting effect of EYA2. METHODS: Whole-exome sequencing was performed on six pairs of human HCC primary tumors and matched adjacent tissues. Focusing on EYA2, expression level of EYA2 in human HCC samples was evaluated by quantitative real-time PCR, western blot and immunohistochemistry. Loss- and gain-of-function studies, hepatocyte-specific deletion of EYA2 (Eya2-/-) in mice and RNA sequencing analysis were used to explore the functional effect and mechanism of EYA2 on HCC cell growth and metastasis. EYA2 methylation status was evaluated using Sequenom MassARRAY and publicly available data analysis. RESULTS: A new somatic mutation p.Ala510Glu of EYA2 was identified in HCC tissues. The expression of EYA2 was down-regulated in HCC and associated with tumor size (P = 0.001), Barcelona Clinic Liver Cancer stage (P = 0.016) and tumor differentiation (P = 0.048). High level of EYA2 was correlated with a favorable prognosis in HCC patients (P = 0.003). Results from loss-of-function and gain-of-function experiments suggested that knockdown of EYA2 enhanced, while overexpression of EYA2 attenuated, the proliferation, clone formation, invasion, and migration of HCC cells in vitro. Delivery of EYA2 gene had a therapeutic effect on inhibition of orthotopic liver tumor in nude mice. However, EYA2(A510E) mutation led to protein degradation by unfolded protein response, thus weakening the inhibitory function of EYA2. Hepatocyte-specific deletion of EYA2 in mice dramatically promoted diethylnitrosamine-induced HCC development. EYA2 was also down-regulated in HCC by aberrant CpG methylation. Mechanically, EYA2 combined with DACH1 to transcriptionally regulate SOCS3 expression, thus suppressing the progression of HCC via SOCS3-mediated blockade of the JAK/STAT signaling pathway. CONCLUSIONS: In our study, we identified and validated EYA2 as a tumor suppressor gene in HCC, providing a new insight into HCC pathogenesis.
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Carcinoma Hepatocelular/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Janus Quinases/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Nucleares/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Fatores de Transcrição STAT/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Adulto , Idoso , Animais , Carcinoma Hepatocelular/metabolismo , Progressão da Doença , Feminino , Xenoenxertos , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais/fisiologiaRESUMO
The γ-secretase complex is a presenilin-dependent aspartyl protease involved in the intramembranous cleavage of various type I transmembrane proteins. As a type I transmembrane protein, CD147 is highly expressed in hepatoma cells and promotes cell proliferation, migration, and invasion. However, the direct underlying mechanism of how CD147 promotes cancer cell proliferation is unknown. Here, we demonstrated that CD147 undergoes an intramembranous cleavage by the γ-secretase at lysine 231 to release its intracellular domains (ICDs). The nuclear translocation of the CD147ICD regulated Notch1 expression by directly binding to the NOTCH1 promoter and promoted the activation of the Notch signaling pathway. Simultaneously, overexpression of CD147ICD promoted cancer cell proliferation via Notch1 signaling. In 102 cases of human hepatocellular carcinoma (HCC) tissues, patients with a high positive rate of nuclear CD147ICD expression had a significantly poor overall survival compared with patients with a low positive rate of nuclear CD147ICD expression. We confirmed that nuclear CD147ICD predicted a poor prognosis in human HCC. The combined therapy of the γ-secretase complex inhibitor and CD147-directed antibody showed better efficacy than monotherapy in orthotopic transplantation HCC mouse models. In conclusion, CD147 is cleaved by the γ-secretase and releases CD147ICD to the cell nucleus, promoting Notch1 expression via direct binding to the NOTCH1 promoter. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Secretases da Proteína Precursora do Amiloide/metabolismo , Basigina/metabolismo , Carcinoma Hepatocelular/enzimologia , Proliferação de Células , Neoplasias Hepáticas/enzimologia , Receptor Notch1/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Antineoplásicos Imunológicos/farmacologia , Basigina/antagonistas & inibidores , Basigina/genética , Sítios de Ligação , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Regiões Promotoras Genéticas , Proteólise , Receptor Notch1/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Ginsenoside Rd (GSRd), one of the main active monomer compounds from the medical plant Panax ginseng, has been shown to promote neuronal survival in models of ischemic cerebral damage. As an extending study, here we examined whether GSRd could exert a beneficial effect in an experimental Parkinson disease (PD) model in vitro, in which SH-SY5Y cells were injured by 1-methyl-4-phenylpyridinium (MPP+), an active metabolic product of the classical Parkinsonian toxin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results, from the addition of different concentrations of GSRd (1, 10 and 50 µM), showed that GSRd at 1 and 10 µM could significantly attenuate MPP+-induced cell death. This protective effect may be ascribed to its ability to reduce intracellular reactive oxygen species levels, enhance antioxidant enzymatic activities, preserve the activity of respiratory complex I, stabilize the mitochondrial membrane potential and increase intracellular ATP levels. Additionally, the PI3K/Akt survival-signaling pathway was also involved in the protective effect of GSRd. Finally, using a mouse PD model in vivo, we also found that GSRd obviously reversed the loss of tyrosine hydroxylase-positive cells in substanitia nigra induced by MPTP. Thus, our findings demonstrated that GSRd showed a significant neuro-protective effect against experimental PD models, which may involve its antioxidant effects and mitochondrial function preservation.
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Antioxidantes/farmacologia , Ginsenosídeos/farmacologia , Intoxicação por MPTP/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , 1-Metil-4-fenilpiridínio/toxicidade , Trifosfato de Adenosina/metabolismo , Animais , Antioxidantes/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Neurônios Dopaminérgicos/efeitos dos fármacos , Complexo I de Transporte de Elétrons/metabolismo , Ginsenosídeos/uso terapêutico , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: The mechanism of hepatitis B virus (HBV)-induced carcinogenesis remains an area of interest. The accumulation of hepatitis B surface antigen in the endoplasmic reticulum (ER) of hepatocytes stimulates persistent ER stress. Activity of the unfolded protein response (UPR) pathway of ER stress may play an important role in inflammatory cancer transformation. How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV-related hepatocellular carcinoma (HCC) is still unclear. Here, we aimed to define the key molecule hyaluronan-mediated motility receptor (HMMR) in this process and explore its role under ER stress in HCC development. METHODS: An HBV-transgenic mouse model was used to characterize the pathological changes during the tumor progression. Proteomics and transcriptomics analyses were performed to identify the potential key molecule, screen the E3 ligase, and define the activation pathway. Quantitative real-time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines. Luciferase reporter assay, chromatin immunoprecipitation, coimmunoprecipitation, immunoprecipitation, and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress. Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues. RESULTS: We found sustained activation of ER stress in the HBV-transgenic mouse model of hepatitis-fibrosis-HCC. HMMR was transcribed by c/EBP homologous protein (CHOP) and degraded by tripartite motif containing 29 (TRIM29) after ubiquitination under ER stress, which caused the inconsistent expression of mRNA and protein. Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR. HMMR could alleviate ER stress by increasing autophagic lysosome activity. The negative correlation between HMMR and ER stress, positive correlation between HMMR and autophagy, and negative correlation between ER stress and autophagy were verified in human tissues. CONCLUSIONS: This study identified the complicated role of HMMR in autophagy and ER stress, that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression, which could be a novel explanation for HBV-related carcinogenesis.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Estresse do Retículo Endoplasmático/genética , Vírus da Hepatite B/genética , Camundongos Transgênicos , Carcinogênese , Proteínas de Ligação a DNA , Fatores de TranscriçãoRESUMO
Pyroptosis is an inflammatory form of programmed cell death that is involved in various cancers, including hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) were recently verified as crucial mediators in the regulation of pyroptosis. However, the role of pyroptosis-related lncRNAs in HCC and their associations with prognosis have not been reported. In this study, we constructed a prognostic signature based on pyroptosis-related differentially expressed lncRNAs in HCC. A co-expression network of pyroptosis-related mRNAs-lncRNAs was constructed based on HCC data from The Cancer Genome Atlas. Cox regression analyses were performed to construct a pyroptosis-related lncRNA signature (PRlncSig) in a training cohort, which was subsequently validated in a testing cohort and a combination of the two cohorts. Kaplan-Meier analyses revealed that patients in the high-risk group had poorer survival times. Receiver operating characteristic curve and principal component analyses further verified the accuracy of the PRlncSig model. Besides, the external cohort validation confirmed the robustness of PRlncSig. Furthermore, a nomogram based on the PRlncSig score and clinical characteristics was established and shown to have robust prediction ability. In addition, gene set enrichment analysis revealed that the RNA degradation, the cell cycle, the WNT signaling pathway, and numerous immune processes were significantly enriched in the high-risk group compared to the low-risk group. Moreover, the immune cell subpopulations, the expression of immune checkpoint genes, and response to chemotherapy and immunotherapy differed significantly between the high- and low-risk groups. Finally, the expression levels of the five lncRNAs in the signature were validated by quantitative real-time PCR. In summary, our PRlncSig model shows significant predictive value with respect to prognosis of HCC patients and could provide clinical guidance for individualized immunotherapy.
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T cell acute lymphoblastic leukemia (T-ALL) is invasive and heterogeneous, and existing therapies are sometimes unsuccessful. Chimeric antigen receptor (CAR) T cell therapy is a breakthrough tumor treatment method, particularly for B cell acute lymphoblastic leukemia. We found that CD147 was highly expressed in tumor T cells of T-ALL patients and T cell lymphoma. Therefore, CD147-CAR T cells that contain a humanized single-chain variable fragment targeting human CD147 and a second-generation CAR frame were constructed for treating T-ALL. CD147-CAR T cells were able to maintain a healthy proliferation rate, preserving a subset of CD62L+/CCR7+ memory T cells. CD147-CAR T cells showed a potent anti-tumor activity against human T-ALL cell line and T-ALL blasts, releasing high level of cytokines in the process. However, CD147-CAR T cells exhibited potential safety toward human normal cells and CD147-deficent cells. NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt mice were used to establish a T-ALL xenograft model and CD147-CAR T cells conferred robust protection against T-ALL progression and significantly improved survival in mice. Overall, we found that CD147 is a potential antigen target of CAR T cell therapy for T-ALL.
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Basigina , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos , Animais , Basigina/imunologia , Linhagem Celular Tumoral , Humanos , Imunoterapia Adotiva/métodos , Camundongos , Camundongos Endogâmicos NOD , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos TRESUMO
Genomic sequencing analysis of tumors provides potential molecular therapeutic targets for precision medicine. However, identifying a key driver gene or mutation that can be used for hepatocellular carcinoma (HCC) treatment remains difficult. Here, we performed whole-exome sequencing on genomic DNA obtained from six pairs of HCC and adjacent tissues and identified two novel somatic mutations of UBE2S (p. Gly57Ala and p. Lys63Asn). Predictions of the functional effects of the mutations showed that two amino-acid substitutions were potentially deleterious. Further, we observed that wild-type UBE2S, especially in the nucleus, was significantly higher in HCC tissues than that in adjacent tissues and closely related to the clinicopathological features of patients with HCC. Functional assays revealed that overexpression of UBE2S promoted the proliferation, invasion, metastasis, and G1/S phase transition of HCC cells in vitro, and promoted the tumor growth significantly in vivo. Mechanistically, UBE2S interacted with TRIM28 in the nucleus, both together enhanced the ubiquitination of p27 to facilitate its degradation and cell cycle progression. Most importantly, the small-molecule cephalomannine was found by a luciferase-based sensitive high-throughput screen (HTS) to inhibit UBE2S expression and significantly attenuate HCC progression in vitro and in vivo, which may represent a promising strategy for HCC therapy.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Antígeno Nuclear de Célula em Proliferação/genética , Proteína 28 com Motivo Tripartido/genética , Enzimas de Conjugação de Ubiquitina/genética , Carcinoma Hepatocelular/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Núcleo Celular/genética , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Ubiquitinação/genéticaRESUMO
As a member of the Rab GTPase family, Rab11a plays an important role in vesicle transport and tumor progression. However, it is not clear whether it can also be used as an oncoprotein in hepatocellular carcinoma (HCC). In this study, database and immunohistochemical analyses showed that Rab11a was highly expressed in HCC tissues, and associated with poor clinical prognosis. Rab11a overexpression promoted the proliferation, migration, invasion, and anti-apoptosis of human HCC cell lines, MHCC-97H and HCC-LM3, whereas the downregulation of Rab11a inhibited these biological tumor activities. Nude mice xenograft demonstrated that Rab11a had a positive effect on the growth of hepatocellular carcinoma cells in vivo. Further studies found that the PI3K/AKT pathway and matrix metalloproteinase 2 (MMP2) upregulation can be activated by over-expression of Rab11a. However, MMP2 upregulation induced by Rab11a can be inhibited by the PI3K/AKT pathway inhibitor, LY294002. Altogether, our study established for the first time that Rab11a can play a pro-cancer role in HCC, as a novel oncoprotein, by activating the PI3K/AKT pathway to regulate MMP2 expression.
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Carcinoma Hepatocelular/patologia , Metaloproteinase 2 da Matriz/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
The persistence of macrophage-derived foam cells in the artery wall fuels atherosclerosis development. However, the mechanism of foam cell formation regulation remains elusive. We are committed to determining the role that CD147 might play in macrophage foam cell formation during atherosclerosis. In this study, we found that CD147 expression was primarily increased in mouse and human atherosclerotic lesions that were rich in macrophages and could be upregulated by ox-LDL. High-throughput compound screening indicated that ox-LDL-induced CD147 upregulation in macrophages was achieved through PI3K/Akt/mTOR signaling. Genetic deletion of macrophage CD147 protected against foam cell formation by impeding cholesterol uptake, probably through the scavenger receptor CD36. The opposite effect was observed in primary macrophages isolated from macrophage-specific CD147-overexpressing mice. Moreover, bioinformatics results indicated that CD147 suppression might exert an atheroprotective effect via various processes, such as cholesterol biosynthetic and metabolic processes, LDL and plasma lipoprotein clearance, and decreased platelet aggregation and collagen degradation. Our findings identify CD147 as a potential target for prevention and treatment of atherosclerosis in the future.
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Hepatocellular carcinoma (HCC) is one of the most heterogeneous malignant cancers with no effective targets and treatments. However, the molecular pathogenesis of HCC remains largely uncertain. The aims of our study were to find crucial genes involved in HCC through multidimensional methods and revealed potential molecular mechanisms. Here, we reported the gene expression profile GSE121248 findings from 70 HCC and 37 adjacent normal tissues, all of which had chronic hepatitis B virus (HBV) infection, we were seeking to identify the dysregulated pathways, crucial genes and therapeutic targets implicated in HBV-associated HCC. We found 164 differentially expressed genes (DEGs) (92 downregulated genes and 72 upregulated genes). Gene ontology (GO) analysis of DEGs revealed significant functional enrichment of mitotic nuclear division, cell division, and the epoxygenase P450 pathway. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were mainly enriched in metabolism, cell cycle regulation and the p53 signaling pathway. The Mcode plugin was calculated to construct a module complex of DEGs, and the module was mainly enriched in cell cycle checkpoints, RHO GTPase effectors and cytochrome P450. Considering a weak contribution of each gene, gene set enrichment analysis (GSEA) was performed, revealing results consistent with those described above. Six crucial proteins were selected based on the degree of centrality, including NDC80, ESR1, ZWINT, NCAPG, ENO3 and CENPF. Real-time quantitative PCR analysis validated the six crucial genes had the same expression trend as predicted. Furthermore, the methylation data of The Cancer Genome Atlas (TCGA) with HCC showed that mRNA expression of crucial genes was negatively correlated with methylation levels of their promoter region. The overall survival reflected that high expression of NDC80, CENPF, ZWINT, and NCAPG significantly predicted poor prognosis, whereas ESR1 high expression exhibited a favorable prognosis. The identification of the crucial genes and pathways would contribute to the development of novel molecular targets and biomarker-driven treatments for HCC.
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Chimeric antigen receptor T cell (CAR-T) therapy to hematological malignancies has demonstrated tremendous clinical outcomes. However, the therapeutic efficacy of CAR-T cells in solid tumors remains limited due to the scarcity of tumor-specific antigen targets and the poor infiltration of CAR-T cells into tumor tissue. In this study, we developed a novel inducible CAR-T cell system which targets CD147, a tumor-associated antigen for hepatocellular carcinoma (HCC). To minimize potential toxicities of CAR-T cell therapy, the Tet-On 3G system was introduced to induce CD147CAR expression in the right place at the right time. Specifically, Tet-CD147CAR lentiviral vector (LV-Tet-CD147CAR) was constructed, which comprised CD147CAR controlled by the Tet-On system. Tet-CD147CART cells were successfully generated from activated T cells by infection with LV-Tet-CD147CAR. Proliferation, cytotoxicity, and cytokine secretion of Tet-CD147CART cells were significantly increased against CD147-positive cancer cells in the presence of doxycycline (Dox) compared to Tet-CD147CART cells in the absence of Dox and PBMCs. Consistently, in vivo studies indicated that the tumor growth in nude mice was significantly inhibited by (Dox+) Tet-CD147CART cells through multiple intratumoral administration. Taken together, our results indicated that the expression and activity of CD147CAR were controlled by Dox both in vitro and in vivo, which facilitated decreased toxicity and adverse effects to CAR-T cell therapy. Moreover, this study provides viable evidence in support of the potential benefits and translation of this strategy of CAR-T cells targeting CD147 for the treatment of patients with HCC.
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The formation of pressure ulcers and other skin wounds is considered to be a multifactorial process. Cycles of ischemia-reperfusion have been considered to be significant contributing factors in the pathogenesis of pressure ulcers. This study reports the development of a reproducible murine model of ischemia-reperfusion injury by the external application of magnets. Mice were sedated with 50% CO2:50% O2 for 50-60 s. Dorsal hair was shaved and the area cleaned. The skin was gently pulled and placed between two round ceramic magnetic plates (5 x 12 mm diameter, 2.4 g weight, 1000 G magnetic force). The resultant "pinch" procedure was designed to leave a 5-mm skin bridge between the magnets, creating 50 mm Hg pressure between the plates. Three 12-h ischemia-reperfusion cycles were employed to cause pressure ulcer formation. Animals tolerated the procedure well. They returned to normal activity a few minutes after magnet placement. The lesions reached their maximum at 10 days postinjury. Full-thickness skin loss with damage and necrosis of subcutaneous tissue (ulcer stage 3) was observed in all cases, reaching a mean stage score of 3.6 +/- 0.6 of based on a 0-5 scale for extent of injury by visual assessment. Thus, an inexpensive, reproducible murine pressure ulcer model was developed, which results in graded injury without long-term immobilization of the animals. This method will facilitate the development of new prevention and management strategies.
Assuntos
Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Úlcera por Pressão/fisiopatologia , Traumatismo por Reperfusão/fisiopatologia , Animais , Magnetismo , Camundongos , Úlcera por Pressão/patologia , Traumatismo por Reperfusão/patologia , Reprodutibilidade dos Testes , Temperatura CutâneaRESUMO
OBJECTIVE: This study was performed to evaluate the effectiveness of near-infrared low-level laser therapy (LLLT) treatment of pressure ulcers under temperature-controlled conditions. BACKGROUND DATA: Little information is available regarding the potential thermal effects of near-infrared photo-radiation during LLLT. METHODS: Pressure ulcers were created in C57BL mice by placing the dorsal skin between two round ceramic magnetic plates (12.0 x 5.0 mm, 2.4 g, 1 K Gauss) for three 12-h cycles. Animals were divided into three groups (n = 9) for daily light therapy (830 nm, CW, 5.0 J/cm(2)) on days 3-13 post ulceration in both groups A and B. A special heat-exchange device was applied in Group B to maintain a constant temperature at the skin surface (30 degrees C). Group C served as controls, with irradiation at 5.0 J/cm(2) using an incandescent light source. Temperature of the skin surface, and temperature alterations during treatment were monitored. The wound area was measured and the rate and time to complete healing were noted. RESULTS: The maximum temperature change during therapy was 2.0 +/- 0.64 degrees C in Group A, 0.2 +/- 0.2 degrees C in Group B and 3.54 degrees C +/- 0.72 in Group C. Complete wound closure occurred at 18 +/- 4 days in Groups A and B and 25 +/- 6 days in Group C (p = 0.05). The percentage of the wound closure at 14 days was 75. 4 +/- 7.2% and 77.7 +/- 5.6% for Groups A and B, respectively (NS differences). However, animals in Group C demonstrated a wound closure of 36.3 +/- 4.8% (p < 0.05). CONCLUSIONS: These results demonstrate that the salutary effects of LLLT on wound healing are temperature independent in this model.
Assuntos
Terapia com Luz de Baixa Intensidade , Úlcera por Pressão/radioterapia , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , TemperaturaRESUMO
OBJECTIVE: This study investigated the change in local skin temperature in black and white mice during irradiation at 830 nm. BACKGROUND DATA: The photostimulation effect low-level laser therapy (LLLT) (700-900 nm) is widely accepted and used. However, the exact biological mechanisms of biostimulation are not yet established. MATERIALS AND METHODS: Groups of C57BL/6J and BALB/cJ mice (n = 12 in each group) were lightly anesthetized with 50% carbon dioxide and 50% oxygen. The dorsum was shaved and a 1.0 x 0.5 cm spot was marked in the same location on each subject. Animals were photo-irradiated with a diode laser (CW, 830 nm, 36 mW output at 5 cm distance). Fluences of 0.0-5.0 J/cm(2) were delivered. Skin surface temperature was monitored by a thermal camera. Two thermocouples were placed 1 mm below the skin surface at the site of light exposure. RESULTS: Temperature increased with increasing fluences of exposure. The surface temperature change at 5.0 J/cm(2) was 6.25 x 10(-2) +/- 2.0 x 10(-3) vs. 1.2 x 10(-2) +/- 3.0 x 10(-3) degrees C/mW for black and white mice, respectively. The temperature change at 1.0 mm depth was 4.51 x 10(-2) +/- 3.0 x 10(-3) vs. 0.83 x 10(-2) +/- 1.0 x 10(-3), respectively. CONCLUSION: CW irradiation at 830 nm and 5.0 J/cm(2) fluence induces a small temperature increase at the surface and at 1 mm in depth. The smaller effects seen in white mice might be due in part to reflection. This suggests that the thermal effects of irradiation at 830 nm are unlikely to explain the LLLT effect. However skin color should be considered, particularly at higher fluences. Further investigations are warranted to correlate the melanin content of the skin with observed LLLT effects.