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1.
Acta Pharmaceutica Sinica B ; (6): 451-466, 2022.
Article in English | WPRIM | ID: wpr-929306

ABSTRACT

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

2.
Article in Chinese | WPRIM | ID: wpr-920572

ABSTRACT

Objective@#To determine the clinical problems and outcome indicators that need to be included in the expert consensus of 5-aminolevulinic acid (ALA) photodynamic therapy in the treatment of oral potential malignant diseases. @*Methods@# Based on the relevant literature, the clinical problems and outcome indicators were drafted during the meeting. The Delphi method was used for expert consultation and expert opinion collection. The average and standard deviation of the voting results were calculated to determine the importance of the indicators, and the positive coefficient, variation coefficient and coordination coefficient were calculated for quality control. @* Results@#In the first round of the Delphi method, 12 outcome indicators (the main reference elements include photon integral flux, power density, illumination time, and spot diameter were identified; the specific parameters are photon integral flux of 100 J/cm2 and power density of 100-600 mW/cm2. A diode laser of (630 ± 5) nm wavelength should be chosen. The analgesic regimen is local anesthesia supplemented by hypothermia and intermittent laser irradiation before treatment. Lesions with hyperkeratotic require pretreatment. The concentration of ALA administered was set at 20%. Eight clinical problems (main reference elements of photodynamic irradiation dose, specific parameters, choice of light source, evaluation criteria of efficacy, prevention of adverse effects, dosing concentration, whether oral potentially malignant diseases with hyperkeratosis should be pretreated, administration of photosensitizers) were included according to the literature and expert discussion. In the second round, 89 experts completed the questionnaire and gave very important evaluations of 9 outcome indicators (the main reference elements included photon integral flux, power density and illumination time; the specific parameters were a photon integral flux of 100 J/cm 2 and a power density of 100-600 mW/cm2). A diode laser of (630 ± 5)nm wavelength should be chosen. The concentration of ALA administered was set at 20%. Six clinical problems (main reference elements of photodynamic irradiation dose, specific parameters, choice of light source, evaluation criteria of efficacy, dosing concentration, administration of photosensitizers), and the remaining 3 were given important evaluations, with good consistency.@*Conclusion@# In this study, the irradiation dose, mode of administration and concentration, evaluation criteria of efficacy, prevention of adverse effects and pretreatment regimen of ALA photodynamic therapy for oral potentially malignant diseases determined by the Delphi method had good agreement among experts.

3.
Acta Pharmaceutica Sinica B ; (6): 1329-1340, 2021.
Article in English | WPRIM | ID: wpr-881202

ABSTRACT

5-Aminolevulinic acid (5-ALA) has been approved for clinical photodynamic therapy (PDT) due to its negligible photosensitive toxicity. However, the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells. Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair, a liposomal nanomedicine (MFLs@5-ALA/DFO) with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA, which was prepared by co-encapsulating 5-ALA and DFO (deferoxamine, a special iron chelator) into the membrane fusion liposomes (MFLs). MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery. MFLs@5-ALA/DFO could efficiently reduce iron ion, thus blocking the biotransformation of photosensitive protoporphyrin IX (PpIX) to heme, realizing significant accumulation of photosensitivity. Meanwhile, the activity of DNA repair enzyme was also inhibited with the reduction of iron ion, resulting in the aggravated DNA damage in tumor cells. Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.

4.
Acta Pharmaceutica Sinica ; (12): 865-871, 2021.
Article in Chinese | WPRIM | ID: wpr-876530

ABSTRACT

The article was to study the effect of local photodynamics therapy combined with carbon dioxide lattice laser - "light needles" for the treatment of basal cell carcinoma (BCC). 5-Aminolevulinic acid (5-ALA) cubic liquid crystal using glyceryl monostearate (GMO) as the substrate was prepared. The cytotoxicity of 5-ALA cubic liquid crystal combined with light needles in vitro were evaluated. The pharmacodynamics study of 5-ALA cubic liquid crystal combined with light needles of high or low energy for BCC was carried out based on the pathological changes, tumor volume, vascular endothelial growth factor (VEGF) expression and the recurrence rate, which has been approved by the Ethics Committee of Beijing Institute of Radiation Medicine. The cubic liquid crystal was isotropic with the lattice of PN3M. The cytotoxicity of 5-ALA cubic liquid crystal combined with light needles was much higher than that of 5-ALA or light needles alone. Compared with light needles or photodynamic therapy alone, 5-ALA cubic liquid crystal combined with light needles of high energy could prevent the BCC metastasis and of low energy could inhibit BCC growth. It demonstrated the obvious therapeutical effects for BCC. 5-ALA cubic liquid crystal combined with light needles can effectively treat BCC, which provides a new choice for clinical BCC treatment.

5.
Acta Pharmaceutica Sinica ; (12): 306-313, 2021.
Article in Chinese | WPRIM | ID: wpr-872611

ABSTRACT

To improve the efficacy of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT), a fluorocarbon microemulsion-based gel (FMBG) loaded with both 5-ALA and carbon dioxide (CO2) was prepared in this study. Its physical and chemical properties such as particle size, zeta potential, morphology, pH value and viscosity were characterized. Acid-base titration experiment was used to determine the CO2 loading, a fluorescence derivatization method was established to determine the content of 5-ALA, and the confocal laser scanning microscope and Franz diffusion cell method were carried out to investigate its transdermal ability. Through the laser speckle contrast imaging, the CO2-affected blood flow perfusion of skin was measured. Finally, the skin irritation test was tested by hematoxylin-eosin staining (H&E) method. These results showed that the prepared FMBG was a milky white gel, with an average particle size of 202.4 nm, a zeta potential of -25.3 mV, a pH of 6.0, and a viscosity of 1 062.0 mPa·s. It can be stored stably for seven days at room temperature. The 5-ALA content of FMBG was measured to be approximately equal to 20% (w/w). At room temperature and normal pressure, the CO2 loading content of FMBG was 5.016 mg·L-1, which was 1.5 times as much as that of water. The transdermal absorption experiment and blood perfusion results showed that the FMBG can effectively enable the transdermal delivery of 5-ALA and CO2, and significantly increased the blood perfusion of skin. H&E staining results indicated that FMBG had negligible skin irritation (all animal tests were approved by the Ethics Committee of 900 Hospital of the Joint Logistics Team). In this study, a safe and stable FMBG loaded with both 5-ALA and CO2 was successfully prepared. It was suitable for transdermal application, having the potential of enhancing the efficacy of 5-ALA-mediated PDT.

6.
Chinese Journal of Biotechnology ; (12): 4314-4328, 2021.
Article in Chinese | WPRIM | ID: wpr-921508

ABSTRACT

5-aminolevulinic acid (5-ALA) plays an important role in the fields of medicine and agriculture. 5-ALA can be produced by engineered Escherichia coli and Corynebacterium glutamicum. We systematically engineered the C4 metabolic pathway of C. glutamicum to further improve its ability to produce 5-ALA. Firstly, the hemA gene encoding 5-ALA synthase (ALAS) from Rhodobacter capsulatus and Rhodopseudomonas palustris were heterologously expressed in C. glutamicum, respectively. The RphemA gene of R. palustris which showed relatively high enzyme activity was selected. Screening of the optimal ribosome binding site sequence RBS5 significantly increased the activity of RphemA. The ALAS activity of the recombinant strain reached (221.87±3.10) U/mg and 5-ALA production increased by 14.3%. Subsequently, knocking out genes encoding α-ketoglutarate dehydrogenase inhibitor protein (odhI) and succinate dehydrogenase (sdhA) increased the flux of succinyl CoA towards the production of 5-ALA. Moreover, inhibiting the expression of hemB by means of sRNA reduced the degradation of 5-ALA, while overexpressing the cysteine/O-acetylserine transporter eamA increased the output efficiency of intracellular 5-ALA. Shake flask fermentation using the engineered strain C. glutamicum 13032/∆odhI/∆sdhA-sRNAhemB- RBS5RphemA-eamA resulted in a yield of 11.90 g/L, which was 57% higher than that of the original strain. Fed-batch fermentation using the engineered strain in a 5 L fermenter produced 25.05 g/L of 5-ALA within 48 h, which is the highest reported-to-date yield of 5-ALA from glucose.


Subject(s)
Aminolevulinic Acid/metabolism , Corynebacterium glutamicum/metabolism , Fermentation , Metabolic Engineering , Rhodobacter capsulatus/enzymology , Rhodopseudomonas/enzymology
7.
Arq. bras. neurocir ; 39(3): 207-212, 15/09/2020.
Article in English | LILACS | ID: biblio-1362422

ABSTRACT

Metastasis to the calvarium with direct pericranium or dural infiltration may be treated with radical surgical removal in selected cases. We describe microsurgical resection of calvarial metastases with fluorescence-guided technique using 5-aminolevulinic acid (5-ALA) in two female patients with breast cancer. Fluorescence findings were positive in both cases. Margins in the scalp and dural layer were 5-ALA negative at the end of surgical removal. Intraoperative pathology was performed in all cases to confirm if oncological limits were free of disease. One case was 5-ALA positive in the outer layer of the dura-mater and another in the pericranium. At the end of the removal in both cases, the surgicalmargins were 5-ALA fluorescence-free. Intraoperative pathology confirmed oncological limits of the resection. 5-aminolevulinic acid fluorescence-guided surgery for calvarial metastases with pericranium and/or dural extension seems to be a safe and reliable method to aid the surgical margins for complete removal, possibly delaying or avoiding adjuvant irradiation for progression control.


Subject(s)
Skull Base Neoplasms/surgery , Fluorescence , Aminolevulinic Acid , Neoplasm Metastasis , Skull/abnormalities , Skull/surgery , Retrospective Studies , Skull Base Neoplasms/diagnosis , Margins of Excision
8.
Braz. J. Pharm. Sci. (Online) ; 56: e18544, 2020. graf
Article in English | LILACS | ID: biblio-1132048

ABSTRACT

The purpose of the study was to evaluate the antibacterial effect of protoporphyrin IX (PpIX) generated by the exogenous administration of 5-aminolevulinic acid or δ-ALA and activated with an argon laser over a planktonic and biofilm of Enterococcus faecalis (E. faecalis) as a pharmacological therapy alternative. A planktonic strain of E. faecalis was cultured with a solution of ∂-ALA (40 µg/mL)-thioglycolate solution for 13 min, and a biofilm of E. faecalis was cultured in a δ-ALA (80 µg/mL)-thioglycolate solution for 13 min. Then, both were irradiated with an argon laser. Finally, the antibacterial effect was evaluated by counting the CFU in planktonic form, and a LIVE/DEAD viability cell test. The production and accumulation of PpIX from exogenously administered δ-ALA on E. faecalis in planktonic and biofilm forms was confirmed by spectrofluorometry. The irradiation of PpIX with an argon laser produced an antibacterial effect on E. faecalis in planktonic and biofilm form, even without biofilm disruption, at a concentration of 40 µg/mL and 80 µg/mL of δ-ALA, respectively. The exogenous administration of δ-ALA in combination with laser irradiation on planktonic and biofilm forms of E. faecalis produces an effective antibacterial effect as complement or alternative to pharmacological therapies


Subject(s)
Protoporphyrins/adverse effects , Enterococcus faecalis/classification , Photochemotherapy/methods , Spectrometry, Fluorescence/methods , Cells , Biofilms , Drug Therapy , Aminolevulinic Acid/administration & dosage
9.
Article in Chinese | WPRIM | ID: wpr-826367

ABSTRACT

To investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on () biofilm. biofilms were constructed on a cell slide and treated with ALA-PDT.According to different light doses,the biofilms were divided into six groups:ALA-PDT group [ALA-PDT1 (50 J/cm),ALA-PDT2 group (100 J/cm),ALA-PDT3 group (200 J/cm)],ALA-only group (ALA group),light-only group (LED),and a negative control group (ALA-PDT-group).The biofilm structure and the ratio of the dead bacteria/live bacteria were observed using a laser confocal microscope (CLSM).Biofilm viability was measured using the XTT assay. CLSM showed that the biofilm structures of ALA group and LED group were not significantly different from that of ALA-PDT-group,whereas the biofilm structure was more seriously damaged in ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group than in the ALA-PDT-group.The ratios of the dead/live bacteria in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group were 0.350±0.033, 0.305±0.046, 0.330±0.032, 1.525±0.439, 2.293±0.148 and 3.092±0.189,respectively.ALA group(=0.003, =1.000)and LED group(=-0.025, =1.000)did not significantly differ from the ALA-PDT-group.However,the ratio of dead/live bacteria in ALA-PDT-group was significantly lower than those in ALA-PDT1 group (=-0.162, <0.001),ALA-PDT2 group (=-0.254, <0.001),and ALA-PDT3 group (=-0.352, <0.001).The values of the XTT assay were were 0.462±0.028,0.465±0.044,0.437±0.047,0.301±0.040,0.207±0.001,and 0.110±0.007,respectively,in ALA-PDT-group,ALA group,LED group,ALA-PDT1 group,ALA-PDT2 group,and ALA-PDT3 group.Although the values of XTT assay in ALA(=-0.044, =1.000)and LED groups (=-0.020, =1.000)did not significantly differ from that in ALA-PDT-group,it was significantly higher in ALA-PDT-group than in ALA-PDT1 group (=1.175, <0.001),ALA-PDT2 group (=1.942, <0.001),and ALA-PDT3 group (=-0.352, =2.742, <0.001). ALA-PDT has an inhibitory effect on biofilm.ALA-PDT destroys biofilm structure and inhibits biofilm viability.


Subject(s)
Aminolevulinic Acid , Biofilms , Photochemotherapy , Photosensitizing Agents , Propionibacterium acnes
10.
Article in Chinese | WPRIM | ID: wpr-751625

ABSTRACT

Metronomic photodynamic therapy (mPDT) is a new type of photodynamic therapy (PDT) that has received much attention in recent years. It has a similar therapeutic mechanism to traditional PDT, i.e. the photosensitizer is irradiated by visible light irradiation with a specific wavelength, and tissue oxygen photochemical reactions produce cytotoxic reactive oxygen species (ROS) that selectively kill rapidly proliferating tumor cells. Unlike traditional PDT, the photosensitizer and light in mPDT are continuously transmitted at a low time and at a low rate, and the specificity of tumor treatment is enhanced by apoptosis. In this paper, the current researches on the in vitro and in vivo effects and mechanisms of mPDT, as well as the research status of photosensitizers and light sources for in vivo research, were reviewed, with a view to understanding the existing mPDT technology and providing reference for the further studies. This review paper can provide a basic for promoting the clinical research and application of mPDT.

11.
Article in Chinese | WPRIM | ID: wpr-790202

ABSTRACT

Objective To study the application of urinary 5-aminolevulinic acid (5-ALA) detection in screening and identification of colorectal cancer and adenomatous polyps. Methods The clinical data of 500 high-risk patients(including 22 cases with colorectal cancer, 134 cases with adenomatous polyps, and 344 cases with other patients) at the First Affiliated Hospital of Hebei North University from January 2018 to October 2018 were collected. High performance liquid chromatography (HPLC) was used to detect urinary 5-ALA and fecal occult blood test was used to detect faeces. Sensitivity and specificity of two methods was compared. At the same time, urine samples of 431 cases (including 22 cases with colorectal cancer, 134 cases with adenomatous polyps and 275 cases with colorectal normal mucosa)were collected, and the difference of the content of urinary 5-ALA among three groups was compared. Results The sensitivity of urinary 5-ALA for the colorectal cancer screening was 74.9% , and the specificity was 72.5% . The sensitivity of urinary 5-ALA for the adenomatous polyps screening was 70.1% , and the specificity was75.0% . The sensitivity of fecal occult blood test for the colorectal cancer screening was 63.6% , and the specificity was 62.1% . The sensitivity of fecal occult blood test for the adenomatous polyps screening was 42.3%, and the specificity was 62.5%. The content of urinary 5-ALA of the colorectal cancer group [(9.35 ± 0.46) μmol/g] was significantly higher than that of the adenomatous polyps group [(7.24 ± 0.64) μmol/g] (P<0.05) and normal colorectal mucosa group [(3.12 ± 0.24) μmol/g] (P<0.05), and the content of urinary 5-ALA of the adenomatous polyps group was significantly higher than that of colorectal normal mucosa group (P<0.05). Conclusions For screening of colorectal cancer and adenomatous polyps, the content of urinary 5-ALA by HPLC is better than fecal occult blood test, and this approach can do great help to identify colorectal cancer, adenomatous polyps and normal colorectal mucosa.

12.
Acta Pharmaceutica Sinica B ; (6): 937-951, 2019.
Article in English | WPRIM | ID: wpr-774932

ABSTRACT

Artemisinin and its derivatives (ARTs) were reported to display heme-dependent antitumor activity. On the other hand, histone deacetylase inhibitors (HDACi) were known to be able to promote heme synthesis in erythroid cells. Nevertheless, the effect of HDACi on heme homeostasis in non-erythrocytes remains unknown. We envisioned that the combination of HDACi and artesunate (ARS) might have synergistic antitumor activity through modulating heme synthesis. studies revealed that combination of ARS and HDACi exerted synergistic tumor inhibition by inducing cell death. Moreover, this combination exhibited more effective antitumor activity than either ARS or HDACi monotherapy in xenograft models without apparent toxicity. Importantly, mechanistic studies revealed that HDACi coordinated with ARS to increase 5-aminolevulinate synthase (ALAS1) expression, and subsequent heme production, leading to enhanced cytotoxicity of ARS. Notably, knocking down significantly blunted the synergistic effect of ARS and HDACi on tumor inhibition, indicating a critical role of ALAS1 upregulation in mediating ARS cytotoxicity. Collectively, our study revealed the mechanism of synergistic antitumor action of ARS and HDACi. This finding indicates that modulation of heme synthesis pathway by the combination based on ARTs and other heme synthesis modulators represents a promising therapeutic approach to solid tumors.

13.
Chinese Journal of Stomatology ; (12): 176-182, 2019.
Article in Chinese | WPRIM | ID: wpr-804810

ABSTRACT

Objective@#To investigate the in vitro and in vivo effects of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy against oral squamous cell carcinoma (OSCC) and preliminarily explore the possible mechanisms.@*Methods@#SCC25 cells were divided into the control group (5-ALA of 0 mg/L) and the experimental group (5-ALA of 10, 25, 50, 100 and 150 mg/L). The production of protoporphyrin Ⅸ (PpⅨ) induced by 5-ALA in SCC25 cells was detected using the flow cytometry. SCC25 cells were divided into the control group (5-ALA of 0 mg/L), lazer alone group, 5-ALA alone group (5-ALA of 100 mg/L) and the 5-ALA combined with laser irradiation group (5-ALA of 5, 10, 25, 50 and 100 mg/L), the cytotoxicity of 5-ALA combined with laser irradiation (wave length 635 nm, power density 87 mW/cm2 and laser dose 10.4 J/cm2) was evaluated in SCC25 cells using the methyl thiazolyltetrazolium assay (incubation times of 4, 8 and 12 h in each group) and the induction effect of combination treatment on the cell apoptosis was assessed by the flow cytometry (incubation time of 12 h in each group). The intracellular production of reactive oxygen species (ROS) triggered by 5-ALA combined with laser irradiation was determined using a fluorescence probe method (incubation time of 12 h in each group). A mouse OSCC xenograft model bearing SCC25 tumor was built, and the mice were divided into control group (saline), 5-ALA group (5-ALA of 50 mg/kg) and 5-ALA combined with laser irradiation group (5-ALA of 10, 25 and 50 mg/kg). Antitumor effect of 5-ALA combined with laser irradiation (wave length 635 nm, power density 158 mW/cm2 and laser dose 94.8 J/cm2) was further measured.@*Results@#5-ALA induced the production of PpⅨ in SCC25 cells in a drug concentration (0-150 mg/L)-and incubation time (0-24 h)-dependent manner. When the 5-ALA concentration was 100 mg/L, the intracellular PpⅨ production was in a relatively stable state. Cell viability and apoptosis rate of 5, 10, 25, 50, 100 mg/L 5-ALA combined with laser irradiation are, respectively, (82.3±5.2)%, (3.13±0.38)%; (74.6±9.3)%, (5.38±0.55)%; (38.3±9.7)%, (17.97±2.72)%; (9.2±3.8)%, (24.47±3.37)%; (7.2±0.8)%, (43.01±5.96)%, which indicated that 5-ALA combined with laser irradiation notably inhibited the growth of SCC25 cells and also induced significant cell apoptosis compared with the control group [(96.3±6.0)%, (0.35±0.13)%, P<0.05]. After combination treatment (5-ALA of 5, 10, 25, 50 and 100 mg/L combined with laser irradiation, the mean fluorescence intensity of dichlorofluorescein is (1.46±0.12)×104, (2.16±0.30)×104, (3.57±0.34)×104, (81.70±13.05)×104, (113.00±7.35)×104, respectively, a large amount of ROS was produced in SCC25 cells compared with the control group [(0.96±0.15) ×104, P<0.05], which was in positive correlation with the intracellular PpⅨ content. 5-ALA (concentration of 10, 25 and 50 mg/kg) combined with laser irradiation greatly suppressed the tumor growth in SCC25 tumor-bearing mice compared to the control group (P<0.05).@*Conclusions@#5-ALA-mediated photodynamic therapy can trigger the generation of intracellular ROS that has significant cytotoxicity and apoptosis induction effect, and thus inhibit the tumor growth both in vitro and in vivo.

14.
Article in Chinese | WPRIM | ID: wpr-797100

ABSTRACT

Objective@#To study the application of urinary 5-aminolevulinic acid (5-ALA)detection in screening and identification of colorectal cancer and adenomatous polyps.@*Methods@#The clinical data of 500 high-risk patients(including 22 cases with colorectal cancer, 134 cases with adenomatous polyps, and 344 cases with other patients) at the First Affiliated Hospital of Hebei North University from January 2018 to October 2018 were collected. High performance liquid chromatography(HPLC) was used to detect urinary 5-ALA and fecal occult blood test was used to detect faeces. Sensitivity and specificity of two methods was compared. At the same time, urine samples of 431 cases(including 22 cases with colorectal cancer, 134 cases with adenomatous polyps and 275 cases with colorectal normal mucosa)were collected, and the difference of the content of urinary 5-ALA among three groups was compared.@*Results@#The sensitivity of urinary 5-ALA for the colorectal cancer screening was74.9%, and the specificity was 72.5%. The sensitivity of urinary 5-ALA for the adenomatous polyps screening was 70.1%, and the specificity was75.0%. The sensitivity of fecal occult blood test for the colorectal cancer screening was 63.6%, and the specificity was 62.1%. The sensitivity of fecal occult blood test for the adenomatous polyps screening was 42.3%, and the specificity was 62.5%. The content of urinary 5-ALA of the colorectal cancer group [(9.35 ± 0.46) μmol/g] was significantly higher than that of the adenomatous polyps group [(7.24 ± 0.64) μmol/g] (P < 0.05) and normal colorectal mucosa group [(3.12 ± 0.24) μmol/g] (P < 0.05), and the content of urinary 5-ALA of the adenomatous polyps group was significantly higher than that of colorectal normal mucosa group (P < 0.05).@*Conclusions@#For screening of colorectal cancer and adenomatous polyps, the content of urinary 5-ALA by HPLC is better than fecal occult blood test, and this approach can do great help to identify colorectal cancer, adenomatous polyps and normal colorectal mucosa.

15.
Arq. bras. neurocir ; 37(2): 88-94, 24/07/2018.
Article in English | LILACS | ID: biblio-912122

ABSTRACT

Introduction The improvement on the extent of resection (EOR) of gliomas with the combination of 5-aminolevulinic acid (5-ALA) and intraoperative magnetic resonance imaging (iMRI) has been demonstrated in previous studies. We present our results with the combined use of 5-ALA and (iMRI) in the surgery of glial lesions. Methods A total of 64 cases of patients with intracranial gliomas who underwent image-guided surgery using 5-ALA with and without (iMRI) were reviewed. All patients underwent an early postoperative MRI to evaluate the EOR. Other intra-operative techniques (awake surgery, electrophysiological stimulation and monitoring) were also performed according to the location of the tumor. Results A total of 18 tumors did not show intraoperative 5-ALA fluorescence (according to the World Health Organization [WHO] classification of tumors, 2 WHO-grade I, 14 WHOgrade II, 1 WHO-grade III and 1 WHO-grade IV), and 46 tumors showed intraoperative 5-ALA fluorescence (3 WHO-grade II, 3 WHO-grade III, 40 WHO-grade IV). In 28 of the 46 5-ALA positive cases, a safe 5-ALA free resection was achieved. In the 5-ALA negative cases, the (iMRI) findings guided the EOR, and complete resection was achieved in 11 cases. Complete resection was opted out in gliomas infiltrating eloquent areas. Conclusions The combined use of 5-ALA and IMRI showed improved results in glioma surgery, offering the safest maximal EOR. In the 5-ALA positive cases (mostly highgrade), fluorescence was a more useful tool. In the 5- ALA negative cases (mostly lowgrade), the (iMRI) was decisive to guide the EOR of the tumor.


Introdução Em estudos anteriores, foi demonstrado um aperfeiçoamento na extensão da resecção (EDR) de gliomas com a combinação de ácido 5-aminolevulínico (5-ALA) e a imagem de ressonância magnética intraoperatória (iRM). Nossos resultados são apresentados com o uso combinado de 5-ALA e (iRM) para a cirurgia de lesões gliais. Métodos Foram revisados 64 casos de gliomas intracranianos submetidos a cirurgia guiada por imagem por meio do uso de 5-ALA, com ou sem RMI. Todos os pacientes foram submetidos a ressonância magnética (RM) pré-operatória para a avaliação da EDR do tumor. Outras técnicas intraoperatórias (cirurgia acordado, estimulação eletrofisiológica e monitoração) também foram realizadas segundo a localização do tumor. Resultados Um total de 18 tumores não apresentaram fluorescência com o 5-ALA (segundo a classificação de tumores da Organização Mundial de Saúde [OMS], 2 com grau OMS I, 14 com grau II, 1 com grau III e 1 com grau IV) e 46 tumores foram fluorescentes (3 com grau II, 3 com grau III, 40 com grau IV). Dos 46 casos positivos para 5-ALA, em 28 foi obtida uma ressecção segura e livre. Nos casos negativos para 5-ALA, os achados da (iRM) orientaram a EDR, e alcançou-se ressecção total em 11 casos. A ressecção total foi descartada em gliomas com infiltração em áreas eloquentes. Conclusões O uso combinado de 5-ALA e (iRM) mostrou melhores resultados na cirurgia de gliomas, oferecendo uma EDR de segurança máxima. Nos casos positivos para 5-ALA (a maioria de grau alto), a fluorescência mostrou-se um instrumento mais útil. Nos casos negativos para 5-ALA (a maioria de grau baixo), a RMI foi decisiva para orientar a EDR tumoral.


Subject(s)
Humans , Brain Neoplasms , Glioma/surgery , Magnetic Resonance Spectroscopy , Aminolevulinic Acid
16.
Article in Chinese | WPRIM | ID: wpr-734830

ABSTRACT

Objective To explore a method to generate regulatory dendritic cells (DCregs) from murine bone marrow induced by 5-Aminolevulinic acid combined with ferrous iron (ALA/SFC).Methods Bone marrow cells were obtained from male C57BL/6 mice.To generate conventional DCs (BM-DCcons),the ceils were cultured in RPMI-1640 medium supplemented with 10% FCS,10 ng/mL GM-CSF,10 ng/mL IL-4 for 7 days.The cells were collected for the analysis.To generate DCregs by ALA/SFC,the cells were cultured in RPMI-1640 medium supplemented with 10% FCS,20 ng/mL GM-CSF,5-ALA 1 mmol/L + SFC 0.5 mmol/L for 7 days.The morphology of ALA-DCregs was observed by microscope and eytospin with May-Grunwal&Giemsa stain.The surface markers of ALA-DCregs were observed by FACS.The function of ALA-DCregs was detected by in vitro mixed lymphocyte reaction (MLR) and in vivo lymphocyte proliferation assay.Results The generated ALA-DCregs displayed an irregular shape with areas of protrusion and demonstrated higher CD11b/CD11c and higher MHC-II but lower CD40,CD80,CD86 expression levels than DCcons.They also had immune regulation effects in both in vitro and in vivo lymphocyte proliferation assay.Conclusion This study illustrated a feasible approach for generating functional DCregs from murine bone marrow induced by ALA/SFC.These cells can be useful for research and application of DC immunotherapy in the future.

17.
Article in Chinese | WPRIM | ID: wpr-693824

ABSTRACT

The prognosis of glioma remains poor because of the infiltrative nature and the high local relapse rate.The current goals for patients with gliomas is maximal safe resection and adjuvant therapy.Tumor-specific photosensitizer,such as hematoporphyrin derivative (HpD) 5-aminolevulinic acid (5-ALA),can be selective up-taken and accumulated in tumor tissue.Light with appropriate wavelength can penetrate tumor tissue and excite the photosensitizer.The excited photosensitizer within glioma cells permits fluorescence visualization of tumor tissue during surgery and has been introduced in treatment of glioma as fluorescence-guided surgery (FGS).On the other hand,the toxicity of singlet oxygen generated by the excited photosensitizer has been used as photodynamic therapy (PDT) in selective destruction of the tumor.Some reports demonstrated the usefulness of adding PDT as an intraoperative adjuvant therapy,but the complexity associated with its implementation and the introduction of TMZ prevented PDT from becoming a routine therapy.However,FGS using 5-ALA in patients with malignant brain tumors has surfaced globally and may become a useful tool in increasing the extent of resection in gliomas.

18.
Annals of Dermatology ; : 438-443, 2016.
Article in English | WPRIM | ID: wpr-171611

ABSTRACT

BACKGROUND: Pattern hair loss is a very common problem. Although effective therapeutics for the treatment of pattern hair loss have been used, novel therapeutic modalities are still required to enhance hair growth. OBJECTIVE: We investigated the efficacy and safety of a complex (ALAVAX) of 5-aminolevulinic acid (5-ALA) and glycyl-histidyl-lysine (GHK) peptide for the treatment of pattern hair loss. METHODS: Forty-five patients with male pattern hair loss were treated with ALAVAX 100 mg/ml (group A), ALAVAX 50 mg/ml (group B) or placebo (group C) once a day for 6 months. Total hair count, hair length, hair thickness, patient's assessment and adverse events were evaluated at month 1, 3, and 6. RESULTS: An increase in hair count for 6 months was 52.6 (p<0.05) in group A, 71.5 (p<0.05) in group B, and 9.6 in group C. The ratio of changes in hair count between group B (2.38) and group C (1.21) at 6 months showed a statistically significant difference (p<0.05). The proportion above good satisfaction was higher in group A (26.7%) than in the other groups (group B: 14.3%, group C: 7.1%). There was no statistically significant difference in hair length and hair thickness among 3 groups at 6 months. There was no adverse event in 3 groups. CONCLUSION: Our study showed that a complex of 5-ALA and GHK peptide may be considered as one of the complementary agents for the treatment of male pattern hair loss.


Subject(s)
Hair , Humans , Male
19.
Article in Chinese | WPRIM | ID: wpr-495377

ABSTRACT

Objective To explore effect of 5 -aminolevulinic acid -photodynamic therapy combined with thymopentin -5 on IL -17,IL -23 expression of recurrent condylomata acuminata patients.Methods 140 patients with recurrent condylomata acuminata were randomly divided into 3 groups.53 cases in observation group were treated by 5 -aminolevulinic acid -photodynamic therapy combined with thymopentin -5,42 cases in control group 1 were treated by 5 -aminolevulinic acid -photodynamic therapy,and 45 cases in control group 2 were treated by thymopen-tin -5.24 healthy subjects were served as normal controls.IL -17,IL -23 levels were determined by enzyme linked immunosorbent assay before and after the clinical therapy.Results IL -17,IL -23 levels in the patients with recur-rent condylomata acuminata were significantly lower than those in healthy subjects(t =28.10,P <0.01;t =11.10, P <0.01).There were significant differences in IL -17,IL -23 between recurrent condylomata acuminata patients and healthy persons before treatment.There was significant difference after treatment(t =61.17,P <0.01;t =28.02, P <0.01).Conclusion 5 -aminolevulinic acid -photodynamic therapy combined with thymopentin -5 in the treat-ment of recurrent condylomata acuminata inhibited IL -17,IL -23 expression,so as to achieve therapeutic effect.

20.
Practical Oncology Journal ; (6): 396-399, 2016.
Article in Chinese | WPRIM | ID: wpr-504348

ABSTRACT

Objective To evaluate the therapeutic effect of 5-aminolevulinic acid mediated photody-namic therapy(ALA-PDT)in combination with recombinant human interferon alpha 2b ointment on superficial basal cell carcinoma(BCC)in elderly.Methods A total of 143 elderly patients with superficial BCC was ran-domly divided into PDT group(n=72 cases)and the surgical group(n=71 cases).The patients in the two groups were given the ALA-PDT in combination with IFN-α2b and routine surgical treatment respectively .The effica-cy after treatment was observed according to surgical wound area , lesion area , recurrence and security during 1 year follow-up.Results The results displayed the complete remission rate of lesion in the PDT group was sig-nificantly higher than that in the surgical group (81.94%vs.57.75%,P0.05).During 1 year follow-up after treatment,the results showed the rate of recurrence in the PDT group was significantly lower than that in the surgical group (9.72% vs.22. 54%,P<0.05).Moreover,the mean wound area,the lesion area in the PDT group after treatment were also sig-nificantly smaller than that in the surgical group (P<0.05).Conclusion ALA-PDT in combination with IFN is an effective method with lower recurrence and minor trauma in the treatment of superficial basal cell carcino -ma.

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