Photodynamic Therapy of Cancer Cells with Methanesulfonate Salts of 5-Aminolevulinic Acid and Its Derivatives

A series of 5-aminolevulinic acid and its alkylester methanesulfonates was exploited to photodynamic therapy（PDT） of human lymphocytic cells, U-937 in vitro. The PDT efficiency is influenced by the concentration and incubation time. Generally, for ALA and its alkylester methanesulfonates, the cell survival rate decreases and the accumulation ability of PplX increases with the concentration and incubation time. We found that the longer carbon chain methanesulfonates（C5-S, C6-S, C8-S） exhibit better PDT effect than ALA methanesulfonate. This possibly provides a promising route to the clinical application ofPplX-mediated PDT to cancer cell.

OPTIMIZATIONS FOR 5-AMINOLEVULINIC ACID BASED PHOTODYNAMIC THERAPY IN PURGING LEUKEMIA CELL HL60

Objective To optimize experimental parameters for the photosensitization of 5-aminolevulinic acid (ALA) in promyelocytic leukemia cell HL60 and compare them with normal human peripheral blood mononuclear cell (PBMC). Methods ALA incubation time, wavelength applied to irradiate, concentration of ALA incubated, irradiation fluence may modulate the effect of 5-aminolevulinic acid based Photodynamic Therapy (ALA-PDT).The high-pressure mercury lamps of 400W served as light source, the interference filter of 410nm, 432nm, 545nm, 577nm were used to select the specific wavelength. Fluorescence microscope was used to detect the fluorescence intensity and location of protoporphyrin IX (PpIX) endogenously produced by ALA. MTT assay was used to measure the survival of cell. Flow cytometry with ANNEXIN V FITC kit (contains annexin V FITC, binding buffer and PI) was used to detect the mode of cell death. Results ① 1mmol/L ALA incubated 1×105/mL HL60 cell line for 4 hours, the maximum fluorescence of ALA induced PpIX was detected in cytomembrane. ② Irradiated with 410nm for 14.4J/cm2 can result in the minimum survivability of HL60 cell. ③ The main mode of HL60 cell death caused by ALA-PDT is necrosis. Conclusion ALA for 1mmol/L, 4 hours for dark incubation time, 410nm for irradiation wavelength, 14.4J/cm2 for irradiation fluence were the optimal parameters to selectively eliminate promyelocytic leukemia cell HL60 by ALA based PDT. The photosensitization of ALA based PDT caused the necrosis of HL60 cell, so it could be used for inactivation of certain leukemia cells.

Topical 5-aminolevulinic acid photodynamic therapy improved refractory acne conglobata and perifolliculitis capitis abscedens et suffodiens rather than hidradenitis suppurativa

Acne conglobata(AC),perifolliculitis capitis abscedens et suffodiens(PCAS)and hidradenitis suppurativa(HS)are uncommon refractory chronic,inflammatory,scarring diseases but cause serious damage to the quality of life.These three diseases are associated with follicular occlusion.Several studies indicated topical 5-aminolevulinic acid photodynamic therapy(ALA-PDT)improved follicular occlusion besides acne treatment.So we attempted to apply ALA-PDT to medicine resistant AC,PCAS and HS.Topical ALA-PDT was applied to 10 patients with AC,seven patients with PCAS and three patients with HS for more than three sessions.All the patients completed the dermatology life quality index(DLQI)questionnaire and were assessed for the efficacy at the baseline and on two weeks after each treatment.Adverse effects were recorded at each visit.The results showed 25.5%(5/20,two cases of AC and three cases of PCAS)of patients achieved excellent improvement after three sessions of PDT and another 60.0%(12/20,eight cases of AC and four cases of PCAS)of patients achieved good improvement.15.0%(3/20,three cases of HS)got poor response(<20%lesions clearance).Anotherfive cases(three cases of AC and two cases of PCAS)also achieved excellent response after 5–7 sessions of PDT.We also found that papular/nodular,cyst/abscess showed higher clearance rate than sinus/¯stula(88.5%,86.1%versus 11.1%).DLQI was reduced after three sessions of PDT in AC and PCAS patients rather than HS patients.5-ALA-PDT could improve refractory AC and PCAS but could not lead to improvement in late stage of HS.The e±cacy increased with more treatment sessions.

Recent advances in photodynamic diagnosis of gastriccancer using 5-aminolevulinic acid

Photodynamic diagnosis based on 5-aminolevulinic acidinduced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative realtime fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma.

Development of a Photodynamic Diagnosis Method for Oral Squamous Cell Carcinoma Using 5-Aminolevulinic Acid and a Luminescence Plate Reader

Purpose: To establish a simple and accurate photodynamic diagnosis (PDD) method for oral squamous cell carcinoma (OSCC). Methods: OSCC cell lines HSC-2, HSC-3, HSC-4, and Sa3, and normal human oral keratinocytes (HOK) were used. First, we examined the amount of cells needed to detect differences in fluorescence intensities for PDD. OSCC cell lines were adjusted to concentrations of 1 × 104 (104), 1 × 105 (105), and 1 × 106 (106) cells/ml. The experimental groups comprised a group with 5-aminolevulinic acid (5-ALA (+)), and a group without 5-ALA (5-ALA (-)). For each OSCC cell line, 100 μl of each concentration of cells of the 5-ALA groups was seeded onto fluorescence plates, and fluorescence intensity was measured at 60-min intervals for 240 min. Results are expressed as the ratio of fluorescence intensity in 5-ALA (+) to 5-ALA (-). As cells at the concentration of 106 cells/ml provided the clearest results, fluorescence intensities of all cell lines were measured using this concentration at 20-min intervals for 700 min using the same methods. Results: The 5-ALA (+) to (-) ratio increased in a cell concentration-dependent manner at 240 min;the ratio was highest with 106 cells/ml and lowest with 104 cells/ml. With 106 cells/ml in the 5-ALA (+) group, fluorescence intensity increased in a metabolic time-dependent manner;the increase was highest in HSC-2 cells, followed by HSC-4 cells, HSC-3 cells, Sa3 cells, and HOK. Fluorescence intensity was significantly enhanced after 40 min in HSC-2, HSC-3, and HSC-4 cells, after 60 min in Sa3 cells, and after 100 min in HOK compared to the 5-ALA (-) group (P < 0.05). Moreover, fluorescence intensity was significantly increased in OSCC cell lines compared to HOK after 40 min. Conclusion: Early detection of OSCC is possible by screening only microplate reader measurements of fluorescence intensity for PDD.

5-aminolaevulinic Acid-photodynamic Therapy for the Treatment of Cervical Condylomata Acuminata

Objective To investigate the efficacy and safety of photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) on cervical condylomata acuminata. Methods Patients with cervical condylomata (n=30) were allocated into primary and recurrent group, and were given topical ALA under occlusive dressing for 3 hours followed by irradiation with semiconductor laser at a dose of 100 Jcm-2 and a power of 100 mW. The treatment was repeated 7 days later if the lesion was not completely removed after the first treatment. Complete response rate and recurrence rate of wart lesions as well as rate of adverse reaction were analyzed. Results The total complete response rate of PDT was 100% and the total recurrence rate was 5% after 3 months of follow-up. Recurrence rate of recurrent group was significantly lower than that of prior managements (100%, P<0.01). The side effects of PDT in patients mainly included mild burning and/or stinging restricted to the illuminated areas, and was significant lower than their own control (25% vs. 100%, P<0.05). Conclusion Compared with conventional therapies, topical application of ALA-PDT is a simple, effective, safe, well-tolerated, and low recurrence rate treatment for cervical condylomata acuminata.

Photodynamic therapy with topical aminolevulinic acid

Photodynamic therapy(PDT) is a relatively new therapy in dermatology that uses the topical application of a porphyrin derivative to selectively destroy a cutaneous target. The action is implemented by the application of a specific light frequency. The ability of porphyrin to selectively target tumor tissue has been known since the 1960 s. In the late 1970 s, the underlying mechanism was defined, and Dougherty's discovery of the first chromophore led to the production and commercialization of Photofrin. Many other chromophores that can act as photosensitizers have been studied since then, with aminolevulinic acid currently the most commonly used chromophore in clinical practice. PDT is simple, minimally invasive and can be administered on an outpatient basis. The efficacy of PDT has been proven for actinic keratosis, Bowen's disease and basal cell carcinoma; another of its well-known applications is the treatment of photoaging. Indications for its use are continuously increasing, and promising results are reported for various skin diseases. In this paper we report the mechanism of action of PDT with aminolevulinic acid, the literature concerning the most common diseases treated with PDT and the subsequent level of evidence.

Clinical applications of 5-aminolevulinic acid-mediated fluorescence for gastric cancer

5-aminolevulinic acid(ALA) is a naturally occurring amino acid that is a protoporphyrin IX(Pp IX) precursor and a next-generation photosensitive substance. After exogenous administration of ALA, Pp IX specifically accumulates in cancer cells owing to the impaired metabolism of ALA to Pp IX in mitochondria, which results in a red fluorescence following irradiation with blue light and the formation of singlet oxygen. Fluorescence navigation by photodynamic diagnosis(PDD) using ALA provides good visualization and detection of gastric cancer lesions and is a potentially valuable diagnostic tool for gastric cancer for evaluating both the surgical resection margins and extension of the lesion. Furthermore, PDD using ALA might be used to detect peritoneal metastases during preoperative staging laparoscopy, where it could provide useful information for the selection of a therapeutic approach. Another promising application for this modality is in the evaluation of lymph node metastases. Photodynamic therapy(PDT) using ALA to cause selective damage based on the accumulation of a photosensitizer in malignant tissue is expected to be a non-invasive endoscopic treatment for superficial early gastric cancer. ALA has the potential to be used not only as a diagnostic agent but also as a therapeutic drug, resulting in a new strategy for cancer diagnosis and therapy. Here, we review the current use of PDD and PDT in gastric cancer and evaluate its future potential beyond conventional modalities combined with a light energy upconverter, a light-emitting diode and nearinfrared rays as light sources.

5-Aminolevulinic Acid (5-ALA): Analysis of Preclinical and Safety Literature

Problem: 5-ALA has been used for many years at relatively high dose amounts in single doses for photodynamic therapy and immunofluorescence of tumors. An analysis of compiled data relating to safety and any side-effects about the use of 5-ALA at low doses has not yet been published. Purpose: This report analyzes data about the safety of the use of 5-Aminolevulinic Acid (5-ALA) in low doses as a supplement over an extended period of time. Methods: This investigation is a systematic analysis of the current literature ((Medline, and SBI) and snowballing techniques) related to the safety and efficacy of 5-ALA in animals and humans. Clinical trials in progress using 5-ALA were also analyzed. Constant comparative analyses were used to synthesize the findings. Results: The safety of low-dose 5-ALA as a supplement has been demonstrated by animal and human studies. The results suggest that none of the investigations document the presence of symptoms or abnormal laboratory results of clinical significance. The minor laboratory changes documented were judged not clinically significant.

CO_(2)LASER PLUS PHOTODYNAMIC THERAPY VERSUS CO_(2)LASER IN THE TREATMENT OF CONDYLOMA ACUMINATUM:A RANDOMIZED COMPARATIVE STUDY

To compare the efficacy and safety of CO_(2)laser plus 5-aminolevulinic acid(ALA)photodynamic therapy(PDT)with CO_(2)laser for the treatment of multiple condyloma acuminatum(CA),120 patients with multiple CA were allocated into two groups—combined group(CO_(2)laser plus ALA-PDT,n=60)and CO_(2)laser group(CO_(2)laser plus placebo-PDT,n=60).After CO_(2)laser,a 20%ALA or a placebo solution was applied to the CA area 3 h before illumination with red light(635 nm,100mW/cm^(2),80 J/cm^(2)).The treatment was repeated seven days after the first treatment if the lesions were not completely resolved.The complete response rate,recurrence rate and adverse effects in the two groups were analyzed.After two treatments,the complete response rates in the CO_(2)laser group and combined group were 100%(509/509)and 100%(507/507)in the CA(p>0:05),respectively.The recurrence rates in the CO_(2)laser group and combined group were 44.9%(229/509)and 10.6%(54/507)in the CA(p<0:05),respectively.The adverse effects in CO_(2)laser group was more than that in combined group.The combined group is a more effective treatment for multiple CA compared with CO_(2)laser group.T/S.Style the highlighted text as abstract.

Low Frequency Ultrasonication Induced Antitumor Effect in 5-Aminolevulinic Acid Treated Malignant Glioma

We investigated the feasibility of sonodynamic therapy for glioma by low frequency ultrasoundwith5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX) in heme synthetic process. In vivo tumor model was made by inoculating human glioma cell line U87-MG subcutaneously in nude mice. The tumor was sonicated by 25-kHz ultrasound 4 hours following administration of 5-ALA. The tumor size decreased in 5-ALA administered (ALA(+)US(+)) mice, while increased in non-5-ALA administrated (ALA(-)US(+)) mice and non-sonicated mice (ALA(+)US(-)). The immunohistochemical analysis revealed an apoptotic change in tumor tissue of ALA(+)US(+) mice. The results showed the therapeutic effect of 25 kHz ultrasound for the glioma in 5-ALA administered tumor-bearing mice by inducing apoptotic change of tumor cells. This is a first report to elucidate the feasibility of therapeutic use of 25 kHz, relatively low frequency, ultrasound in sonodynamic therapy using 5-ALA as a sonosensitizer precursor. The utilization of this frequency will contribute to the development of sonodynamic therapy for gliomas and the spread of this technique in many hospitals that possess ultrasonic aspirators.

Clinical Effect of Photodynamic Therapy Combined Cryotherapy on Nonmelanoma Skin Cancer

The purpose of this study was to investigate the clinical efficacy of photodynamic combined freezing in patients with non-melanoma skin cancer(NMSC).First,according to the treatment regimen,96 patients with NMSC were divided into study group(n=50)and control group(n=46).The control group was treated with 5-amino-ketovalic acid photodynamic therapy(ALAPDT),while the study group was treated with ala-PDT combined with cryotherapy.Visual analogue scale(VAS)scores,visual satisfaction,clinical efficacy,adverse reactions,and progression-free survival were compared between the two groups.The results showed that VAS score in the study group was slightly higher than that in the control group,but the difference was not statistically significant(P>0.05).The appearance satisfaction and total effective rate of patients in the study group were higher than those in the control group,and the difference was statistically significant(P<0.05).The total incidence of adverse reactions in the study group was slightly higher than that in the control group,but the difference was not statistically significant(P>0.05).3 years progressionfree survival time and 3 years progression-free survival rate were compared between the two groups,and the difference was not statistically significant(P>0.05).Therefore,the combination of PDT and cryotherapy for non-melanoma skin cancer has a good clinical effect,which is conducive to the recovery of skin lesions,high patient satisfaction,fewer adverse reactions,and longer progression-free survival.In addition,the combined therapy can provide a new treatment idea for non-melanoma skin cancer patients who are not suitable for surgical treatment.

5-氨基酮戊酸光动力治疗对鲍温病皮损中p53 Caveolin-1表达的影响

目的:探讨5-氨基酮戊酸光动力疗法对鲍温病皮损中p53、Caveolin-1表达的影响及意义。方法:运用5-氨基酮戊酸光动力疗法治疗鲍温病及周围正常皮肤组织各40例,采用免疫组织化学技术(SP法)检测光动力治疗前后鲍温病及周围正常皮肤组织中p53、Caveolin-1的阳性细胞表达率。结果:治疗前p53蛋白在正常皮肤组织及BD中表达的阳性率分别为10%、40%(χ^(2)=11.202,P<0.001),差异有统计学意义。治疗后p53在正常皮肤组织及BD的阳性率为10%、5%(χ^(2)=0.712,P=0.399),两者间差异无统计学意义。治疗前后p53在BD中的阳性表达率差异有统计学意义(χ^(2)=14.811,P<0.001)。治疗前Caveolin-1在正常皮肤组织及BD中阳性表达率为15%、55%(χ^(2)=14.449,P<0.001),两者间差异有统计学意义。治疗后正常皮肤组织及BD中Caveolin-1的阳性率为5%、12.5%(χ^(2)=0.816,P=0.366),差异无统计学意义。治疗前后Caveolin-1在BD中的阳性表达率差异有统计学意义(χ^(2)=19.013,P<0.001)。BD中p53与Caveolin-1阳性表达呈正相关性(r=0.533,P=0.015)。结论:p53及Caveolin-1的高表达可能与BD的发生密切关联,且ALA-PDT能够抑制p53及Caveolin-1的表达,从而抑制疾病的发展。通过更大样本量的研究,p53及Caveolin-1可能会成为皮肤相关疾病的诊断工具,并为其治疗提供新的靶点。

中医外治法联合光动力治疗中重度痤疮的疗效及安全性

目的探讨中医外治法联合5-氨基酮戊酸光动力治疗中重度痤疮的有效性及安全性。方法根据纳排标准将入选的52例中重度痤疮患者按治疗方式不同分为治疗组及对照组,治疗组给予患者中医外治法联合光动力治疗,对照组仅给予光动力治疗,每组治疗3次,疗程共计6周。比较两组治疗的有效率、不良反应、患者生活质量改善等情况。结果第12周,两组患者痤疮综合分级系统评分较治疗前均明显降低,且治疗组低于对照组(P<0.05);治疗组有效率(92.30%)显著高于对照组(84.70%,P<0.05),治疗组主要不良反应为预处理时可耐受的疼痛。两组共有的主要不良反应为照光时的疼痛、照光后一过性红斑、水肿等,经对症处理可好转,安全性较好。结论中医外治法联合光动力治疗中重度痤疮疗效确切,起效快,优于单独光动力治疗,且具有良好的安全性,值得临床推广应用。

光动力疗法联合CO_(2)激光治疗尖锐湿疣患者的疗效及对Ang-2、HBD-2、Bcl-2和IL-8水平的影响

目的探讨光动力疗法联合CO_(2)激光治疗尖锐湿疣(CA)的疗效及对促血管生成素-2(Ang-2)、人β-防御素2(HBD-2)、B淋巴细胞瘤-2基因(Bcl-2)、白介素-8(IL-8)水平的影响。方法选取2021年1月至2022年10月苏州大学附属常熟医院收治的68例CA患者作为研究对象。采用随机数字表法将其分为激光组和光动力组,每组34例。激光组采用CO_(2)激光治疗,光动力组在激光组基础上联合使用5-氨基酮戊酸光动力疗法(ALA-PDT)治疗,比较两组临床疗效、皮损组织中人乳头瘤病毒(HPV)转阴率、治疗前后外周血水平变化,统计两组治疗期间不良反应发生情况。结果治疗后6个月,光动力组总复发率显著低于激光组,光动力组治疗总有效率显著高于激光组,差异具有统计学意义(P<0.05)。治疗后1、2、3、6个月,两组皮损组织HPV转阴率逐渐升高,且光动力组HPV转阴率显著高于激光组,差异具有统计学意义(P<0.05)。治疗后,两组Ang-2、IL-8、Bcl-2水平均显著降低(P<0.05),HBD-2显著升高(P<0.05),且光动力组治疗后上述指标与激光组比较,差异具有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论ALA-PDT联合CO_(2)激光治疗CA患者的疗效显著,可促进HPV转阴,改善患者免疫相关指标,安全性好。

行为改变轮理论在5-氨基酮戊酸光动力疗法治疗尖锐湿疣患者中的应用

目的探讨行为改变轮(BCW)理论在5-氨基酮戊酸光动力疗法(ALA-PDT)治疗尖锐湿疣(CA)患者中的应用。方法回顾性分析2021年10月至2023年5月89例在安徽省宣城市中心医院确诊CA的患者的临床资料,根据治疗方案的不同将患者分为观察组(n=47)和对照组(n=42)。两组均接受ALA-PDT治疗,对照组采用常规CA护理方式,观察组在对照组基础上采用BCW理论干预,均干预1个月。在干预前后,比较两组焦虑自评量表(SAS)评分、皮肤病生活指数(DLQI)、健康行为量表(HPL)和自我健康管理能力量表(ESCA)评分。随访3个月,比较两组人乳头瘤病毒(HPV)感染根除率。结果干预后,两组SAS评分均低于干预前,且观察组低于对照组(P<0.05);干预后,两组DLQI各维度评分均低于干预前,且观察组低于对照组(P<0.05);干预后,两组HPL、ESCA评分均高于干预前,且观察组高于对照组(P<0.05)。随访3个月后,观察组HPV感染根除率为89.36%(42/47),对照组HPV感染根除率为83.33%(35/42),两组无显著差异(P>0.05)。结论采用BCW理论干预ALA-PDT治疗的CA患者,可改善患者生活质量,提高其自我管理能力和促进健康行为。

5-氨基酮戊酸光动力学疗法联合干扰素栓对持续高危型人乳头瘤病毒感染患者病毒清除率及阴道微环境的影响

目的探究5-氨基酮戊酸光动力学疗法(ALA-PDT)联合干扰素栓对持续高危型人乳头瘤病毒(HPV)感染患者HPV清除率及阴道微环境的影响。方法选取2020年1月至2023年1月景德镇市第一人民医院收治的80例持续高危型HPV感染患者作为研究对象,采用随机数字表法将其分为对照组和观察组各40例,对照组采用干扰素栓治疗,观察组采用干扰素栓联合ALA-PDT治疗,观察两组病毒载量变化和HPV清除率、菌群密集度、菌群多样性、优势菌情况、阴道pH变化、Nugnet评分变化以及6个月内复发率。结果观察组治疗后的病毒载量低于对照组,HPV清除率高于对照组,差异有统计学意义(P<0.05);观察组治疗后的菌群密集度正常率、菌群多样性正常率、优势菌群健康率均高于对照组,差异有统计学意义(P<0.05);观察组治疗后的阴道pH、Nugnet评分均低于对照组,差异有统计学意义(P<0.05);观察组6个月内复发率低于对照组,差异有统计学意义(P<0.05)。结论ALA-PDT联合干扰素栓治疗持续高危型HPV感染患者可以提高HPV清除率,改善阴道微环境,降低复发率。

ALA-PDT、卡介菌多糖核酸注射液联合胸腺肽肠溶片治疗尖锐湿疣的效果

目的研究艾拉光动力治疗(ALA-PDT)、卡介菌多糖核酸注射液联合胸腺肽肠溶片治疗尖锐湿疣的效果。方法选取2020年2月至2022年6月郑州大学附属郑州中心医院收治的82例尖锐湿疣患者为研究对象,以随机双盲法分为联合组、对照组,各41例。对照组接受胸腺肽肠溶片联合ALA-PDT治疗,联合组在对照组基础上接受卡介菌多糖核酸注射液治疗。比较两组临床疗效、治疗前和治疗3个月后疣体数、皮损面积、免疫功能指标(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、血清细胞因子[脂质过氧化物(Lpo)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)]水平、6个月复发率。结果联合组临床总有效率高于对照组(P<0.05);治疗3个月后,联合组疣体数、皮损面积小于对照组(P<0.05);治疗3个月后与对照组相比,联合组CD3^(+)、CD4^(+)/CD8^(+)、CD4^(+)水平较高,CD8^(+)水平较低(P<0.05);治疗3个月后,联合组血清GM-CSF、TNF-α、Lpo、hs-CRP水平低于对照组(P<0.05);治疗后随访6个月,联合组复发率(2.56%)低于对照组(21.05%)(P<0.05)。结论采用ALA-PDT、卡介菌多糖核酸注射液与胸腺肽肠溶片联合治疗可促进尖锐湿疣患者免疫功能改善,抑制炎症反应,减轻临床症状,提高临床疗效,且复发风险较低。

尖锐湿疣差异基因筛选及CXC趋化因子配体10与人乳头瘤病毒分型及复发的相关性研究

目的探讨CXC趋化因子配体10(CXCL10)在尖锐湿疣(CA)组织中的表达及其与人乳头瘤病毒(HPV)分型及复发的关系。方法采用GEO数据库筛选CA组织和正常组织的差异表达基因。另选取2022年1月至12月无锡市惠山区人民医院收治的120例CA患者(CA组)和40例健康体检者(对照组)作为研究对象,检测其血清CXCL10表达水平。对CA组皮损进行HPV分型检测,采用5-氨基酮戊酸光动力疗法且随访CA组6个月,根据是否复发分为未复发组和复发组。探讨CA患者治疗后复发的独立危险因素及CXCL10表达水平预测CA治疗后复发的临床效能。结果CA组织和正常组织中差异表达基因共184个,其中显著上调58个(包括CXCL10、IGFL1等),显著下调126个(包括MFAP5、PRG4等)。120例CA患者皮损中HPV高危型占64.17%(以HPV16和HPV18感染为主),低危型占37.50%(以HPV6和HPV11感染为主),两种感染占5.83%,两种以上感染占6.67%。与对照组比较,CA组血清CXCL10表达水平显著升高,差异具有统计学意义(P<0.05)。复发组和未复发组疣体数量、疣体直径、合并人类免疫缺陷病毒(HIV)/梅毒、HPV分型、CXCL10表达水平比较,差异具有统计学意义(P<0.05);HPV分型(OR=1.563,P=0.001)、合并HIV/梅毒(OR=1.842,P<0.001)、CXCL10表达(OR=2.061,P<0.001)是CA患者治疗后复发的独立危险因素。血清CXCL10表达水平预测CA治疗后复发的曲线下面积(AUC)为0.911,当CXCL10截断值为26.66 ng/mL时,诊断灵敏度和特异度分别为89.34%和91.56%。结论CA患者血清CXCL10表达水平显著升高,其可作为CA治疗后复发的一项预测指标。

氨基酮戊酸-光动力疗法对宫颈低级别鳞状上皮内病变的疗效及特定免疫因子的影响

目的探究氨基酮戊酸-光动力疗法(ALA-PDT)对高危型人乳头瘤病毒(HR-HPV)持续感染的宫颈低级别鳞状上皮内病变(LSIL)的临床疗效及可能的免疫炎症作用机制。方法选取200例经组织病理学检查证实为宫颈LSIL合并HR-HPV感染的女性患者,根据患者意愿分为2组,研究组接受ALA-PDT治疗,对照组接受CO_(2)激光治疗。在治疗后3个月和6个月随访,随访项目包括有效性(细胞学检查、HPV检测、阴道镜检查及阴道镜定向活检)、安全性(不良反应);进一步用免疫组化法比较治疗前及治疗后6个月宫颈LSIL组织Toll样受体(TLR4)、核转录因子-κB(NF-κB)的表达变化。结果治疗后3个月和6个月,研究组HR-HPV转阴率、病变逆转率均高于对照组,治疗后6个月2组差异更显著(P<0.05);治疗后6个月,研究组和对照组间的宫颈病变持续率、进展率和复发率差异均无统计学意义(P>0.05);研究组患者治疗期间不良反应少,阴道分泌物增加、下腹部不适和外阴瘙痒是最常见的症状。ALA-PDT治疗前后宫颈病变组织中TLR4、NF-κB的阳性表达率差异有统计学意义(P<0.05)。结论ALA-PDT对宫颈LSIL患者的HR-HPV感染疗效显著,HR-HPV转阴率、病变逆转率优于CO_(2)激光治疗。ALA-PDT促进宫颈病变消退及清除HPV感染的免疫机制之一可能是通过减少TLR4和NF-κB的表达来发挥作用。