梅花针叩刺增强咪喹莫特治疗SKH-1小鼠皮肤鳞状细胞癌的疗效

目的 评估咪喹莫特联合梅花针治疗SKH-1小鼠皮肤鳞状细胞癌(鳞癌)的疗效,探讨其免疫学机制.方法 将紫外线诱导成瘤的40只SKH-l皮肤鳞癌小鼠随机分4组,每组10只:对照组无处理;梅花针组:每天梅花针叩刺所有瘤体1次;咪喹莫特组:每天外涂5％咪喹莫特乳膏1次,剂量为1.2 g/kg;联合组:先梅花针叩刺所有瘤体,止血后再外涂5％咪喹莫特乳膏1次,剂量同前.各组小鼠连续治疗30 d.每日观察并拍照记录各组小鼠肿瘤形态学变化,每3d测量1次瘤体大小,比较4组瘤体体积变化及小鼠生存率变化.治疗结束后取各组小鼠瘤体,比较4组瘤体组织病理学变化.实时荧光定量PCR检测各组小鼠瘤体内干扰素(IFN)-α、IFN-β、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)及IL-12 mRNA表达.结果 联合组小鼠背部瘤体生长缓慢,部分小的瘤体有消退现象;对照组、梅花针组和咪喹莫特组瘤体一直在增长,但梅花针组、咪喹莫特组生长速度较对照组慢.治疗前,4组小鼠瘤体体积差异无统计学意义(F=0.90,P＞0.05).治疗24d后,4组小鼠瘤体体积差异有统计学意义(F=5.16,P＜0.05),LSD-t检验示,联合组瘤体体积显著低于对照组(P＜ 0.01),余各组间差异均无统计学意义(P＞ 0.05).经Log-rank检验,4组小鼠生存率曲线分布不同(x2=8.32,P＜0.05),联合组生存情况优于对照组(x2=4.62,P=0.03),而梅花针组、咪喹莫特组与对照组、联合组比较,小鼠生存率差异均无统计学意义(P＞0.05).组织病理学检查显示,对照组、梅花针组细胞异形性明显,排列密集,可见大量的肿瘤细胞,部分可见角化珠,咪喹莫特组肿瘤细胞少许死亡;联合组肿瘤细胞大量死亡,核异形不明显,角化增多.实时荧光定量PCR显示,联合组IFN-α、IFN-β、IL-12、IL-1β及TNF-α mRNA相对表达量均显著高于对照组、梅花针组和咪喹莫特组(均P＜0.05),咪喹莫特组IL-1β mRNA相对表达量显著高于对照组(P＜ 0.01),余各组间比较差异均无统计学意义(P＞0.05).结论 梅花针叩刺能有效增强咪喹莫特抗SKH-1小鼠皮肤鳞癌活性及免疫学效应.     

Imiquimod-induced regression of actinic keratosis is associated with infiltration by T lymphocytes and dendritic cells: a randomized controlled trial

BACKGROUND: Imiquimod 5% cream is a topically applied immune response modifier that has been shown to give effective treatment of actinic keratosis (AK). The therapeutic effects of imiquimod are likely to involve the provocation of a cutaneous immune response against abnormal cells, an assumption based on a strong correlation between complete clearance rates and the severity of the local skin reactions (erythema, oedema, erosion/ulceration, weeping/exudation and scabbing/crusting); however, no clinical studies have conclusively proved this mechanism. OBJECTIVES: To determine the nature of cellular infiltrates induced by the application of imiquimod to AK lesions and to study cells involved in the cutaneous immune response. METHODS: Eighteen patients participated in this phase I, randomized, double-blind, parallel group, vehicle-controlled study. Enrolled patients were randomized in a 2 : 1 ratio to receive imiquimod cream or vehicle cream and applied study cream to five lesions on the scalp, forearm or upper trunk once daily, three days per week for up to 16 weeks. Each patient had punch biopsies of two distinct AK lesions: a lesion was biopsied before treatment to obtain baseline biomarker levels, and a different lesion was biopsied after 2 weeks of treatment. Biopsy specimens were examined using routine and immunohistochemical staining. RESULTS: The imiquimod group showed statistically significant increases from baseline to week 2 in tissue biomarker levels for CD3, CD4, CD8, CD11c, CD86/CD11c, CD68, HLA-DR and TUNEL. No significant differences were seen for the vehicle group. Complete clearance of all treated AK lesions was achieved in five of 11 (45%) imiquimod patients and in none of six vehicle patients. CONCLUSIONS: Imiquimod stimulates a cutaneous immune response characterized by increases in activated dendritic cells and CD4+ and CD8+ T cells.     

Imiquimod,a topical immune response modifier,in the treatment of cutaneous metastases of malignant melanoma

BACKGROUND: Imiquimod 5% cream (Aldara, a novel topical immune response modifier, has been approved for the topical treatment of anogenital HPV-induced warts. In addition, several studies have demonstrated antitumoral activity in solar keratoses, superficial basal cell carcinomas and Bowen's disease. AIM: Given the convincing therapeutic results of imiquimod when used for treating selected types of epithelial skin cancer, we became interested to study imiquimod as an adjuvant for treating cutaneous metastases of malignant melanoma. METHODS: Three patients with multiple, i.e. more than 15, cutaneous in-transit metastases of malignant melanoma in unilateral localization on the leg were treated topically with imiquimod 5% cream. RESULTS: Twice daily application under occlusive conditions for a period of 21-28 weeks resulted in >90% regression of cutaneous metastases in 2 patients. The third patient showed marked response only when topical imiquimod was intermittently supplemented by intralesional interleukin (IL)-2 for 2 weeks. Unwanted side effects were mild in all patients. CONCLUSION: Overall, imiquimod as a single agent or in combination with intralesional IL-2 may be a promising immunomodulatory compound for the adjuvant topical treatment of patients with multiple cutaneous metastases of malignant melanoma.     

Efficacy of imiquimod 5% cream in the treatment of recalcitrant warts in children

Long-lasting cutaneous warts are a therapeutic challenge, especially widespread or symptomatic recalcitrant warts in children. It can be speculated that natural immunity to these human papillomavirus (HPV)- induced lesions is extremely poor. Therefore ideally treatment should focus on increasing local immune response. Recently imiquimod, a topical immune modifier, has been successfully used in the treatment of external genital warts. Our purpose is to report on our experiences with imiquimod 5% cream applied to therapy-resistant, long-lasting (duration 2-7 years) common warts in children. In 18 children, imiquimod cream was self-applied by the patients or by their parents to the warts twice a day. Assessment for response and occurrence of adverse effects was performed every 4 weeks until clinical cure. Follow-ups could be arranged in 14 of the 18 patients 1-2 years after total clearance. Sixteen of 18 patients experienced total clearance of their warts; 2 showed partial improvement but were lost to follow-up. The mean duration of treatment was 5.8 months. Two of the 14 patients in whom a follow-up was performed showed a small number of new warts after a period of at least 1 year without recurrence. Our data demonstrate that the topical application of imiquimod 5% cream is an effective treatment for long-lasting cutaneous warts in children.     

激光免疫疗法对多发性皮肤鳞状细胞癌小鼠的抗肿瘤效应研究

目的 探讨激光免疫疗法对多发性皮肤鳞状细胞癌（鳞癌）小鼠的抗肿瘤效应。方法 用紫外线持续照射SKH?1无毛小鼠建立免疫功能正常的小鼠多发性皮肤鳞癌模型后,分成激光免疫组、激光组、咪喹莫特组和对照组（每组5只）。激光免疫组：联合外用咪喹莫特乳膏及808 nm激光照射;激光组：仅予808 nm激光照射;咪喹莫特组：仅予咪喹莫特乳膏外用;对照组不予任何处理。治疗后记录小鼠瘤体体积、生存情况和肿瘤形态学变化。第27、60天用t检验和Mantel?Cox logrank检验两两比较4组小鼠背部瘤体体积和生存率。另取12只鳞癌小鼠分成4组,每组3只,治疗后第5天,取瘤体组织进行病理学观察。结果 第27天时,对照组和咪喹莫特组瘤体体积均较治疗前明显增大（均P < 0.05）,激光组和激光免疫组瘤体无明显增大（均P > 0.05）,其中咪喹莫特组瘤体体积略小于对照组（P > 0.05）,而激光组和激光免疫组瘤体体积明显小于对照组（均P < 0.05）。第60天时激光组瘤体体积增大,体积明显大于激光免疫组（P < 0.05）。对照组小鼠在40 d内全部死亡;咪喹莫特组小鼠在50 d内全部死亡;激光组小鼠在第52、53天分别死亡1只,余存活60 d以上;激光免疫组小鼠在60 d内无死亡。第60天与对照组比较,咪喹莫特小鼠生存时间稍有延长,差异无统计学意义（P > 0.05）;激光组和激光免疫组小鼠生存时间明显延长（均P < 0.05）,但激光免疫组与激光组间比较,差异无统计学意义（P > 0.05）。组织病理学显示咪喹莫特外用5 d无细胞死亡,而激光组及激光免疫组细胞大量死亡,瘤周可见多种炎症细胞,较对照组明显增多,尤以激光免疫组更明显。结论 激光免疫疗法是一种安全且有效的治疗皮肤鳞癌方法,尤其对多发性或转移性皮肤鳞癌具有潜在价值。     

Topical 5% imiquimod long-term treatment of cutaneous warts resistant to standard therapy modalities

BACKGROUND: Long-lasting cutaneous warts may represent an unbearable stigma to patients and therefore pose a singular challenge for the physician. Generally, these warts are induced by human papillomavirus (HPV) 2, HPV-27 or HPV-57. OBJECTIVES: The present study was conducted to evaluate the efficacy and safety of long-term treatment with imiquimod 5% cream applied to long-lasting (mean duration 6.3 years) common warts, which had been resistant to previous therapeutic interventions. PATIENTS AND METHODS: Imiquimod cream was self-applied by the patients twice daily. Assessment of response and occurrence of side-effects was performed every 4 weeks until clinical cure or up to a maximum of 24 weeks. A total of 37 patients were recruited. RESULTS: 31 out of 37 patients completed the treatment. 10 out of 37 patients experienced a total clearance of their warts (27%). The mean duration to clearance was 19.2 weeks. 18 patients (49%) showed a reduction of more than 50% and 5 patients (14%) a reduction of less than 50%. CONCLUSION: Our data demonstrate that the long-term topical application of imiquimod 5% cream is an effective treatment for otherwise therapy-resistant cutaneous warts without causing any meaningful side-effects.     

Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals

BACKGROUND: Viral warts may cause significant morbidity in individuals unable to mount an adequate T-helper 1 cell-mediated immune response to human papillomavirus. Imiquimod is a potent inducer of antiviral cytokine activity which has shown significant efficacy in the treatment of genital warts. Similar efficacy in cutaneous warts is not yet established. OBJECTIVES: To assess the response of persistent cutaneous warts to 5% imiquimod cream in immunosuppressed individuals. METHODS: Fifteen immunosuppressed patients with warts on the hands and/or feet present for more than 18 months, which had failed to respond to a minimum of 12 weeks of topical salicylic acid and four cycles of cryotherapy, were recruited. Imiquimod 5% cream was applied in an open label, right vs. left comparison study for 24 weeks (three times weekly for 8 weeks, daily for 8 weeks, then daily with occlusion for 8 weeks). RESULTS: Twelve (80%) patients completed the study protocol. Benefit was seen in five patients [36% in the intent-to-treat analysis (14 patients)], including more than 30% clearance of warts in three patients and reduction in overall size of warts in two further cases. Local skin reactions occurred in four (29%) patients and were usually mild. A transient rise in creatinine (11-29% above baseline) was measured in three renal transplant recipients, but we did not consider that this was related to imiquimod exposure. CONCLUSIONS: This is the first controlled study to assess therapeutic efficacy of topical 5% imiquimod cream in persistent warts associated with immunosuppression. It provides preliminary evidence that topical imiquimod may benefit a subgroup of immunosuppressed patients with recalcitrant cutaneous warts.     

咪喹莫特对BALB/c小鼠细胞因子生成的影响

目的 探讨咪喹莫特的免疫调节机制。方法 ELISA检测经咪喹莫特灌胃(30mg/kg)后不同时间点的BALB/c小鼠血清干扰素α(IFN-α)、白介素12(IL-12)、干扰素γ(IFN-γ)、白介素4(IL-4)浓度的变化。ELISA检测喂食咪喹莫特的BALB/c小鼠脾细胞在与0.25μg/mL刀豆素A共孵育时分泌IFN-γ、IL-4的能力。结果 咪喹莫特体内诱导BALB/c小鼠生成IFN-α、IL-12,在诱导后2h达高峰;咪喹莫特体内无诱导BALB/c小鼠生成IFN-γ、IL-4的作用;接受咪喹莫特灌胃的BALB/c小鼠脾细胞体外受ConA诱导时,分泌IFN-γ和IL-12的能力增强。结论 咪喹莫特诱导BALB/c小鼠分泌IFN-α、IL-12等前炎症因子,并由此促进机体获得性免疫。     

Topically applied imiquimod inhibits vascular tumor growth in vivo

Vascular tumors occur in approximately 10% of all infants and may be associated with significant morbidity. Available therapies for vascular tumors, such as systemic corticosteroids, vincristine, and interferon-alpha, may cause toxicity, limiting their use to complicated cases. Using a mouse hemangioendothelioma model, we investigated the efficacy and mechanism of action of imiquimod, a topically applied inducer of cytokines. Application of imiquimod cream, whether initiated at the time of cell inoculation or when tumors became visible, significantly decreased tumor growth and increased animal survival in comparison with control mice. Imiquimod-treated tumors showed decreased tumor cell proliferation, increased tumor apoptosis, and increased expression of tissue inhibitor of matrix metalloproteinase-1 with decreased activity of matrix metalloproteinase-9. The demonstration that local application of imiquimod inhibits vascular tumor enlargement in the mouse vascular tumor model suggests a novel, less toxic means of treating infantile hemangioendotheliomas and perhaps other cutaneous vascular tumors.     

抑制树突细胞MMP-13基因对咪喹莫特诱导的小鼠银屑病样炎症模型的影响

目的：明确抑制树突细胞MMP-13基因对咪喹莫特诱导的小鼠银屑病样炎症模型的影响。方法：构建树突细胞MMP-13基因特异性敲除的小鼠模型（MMP-13^LOX/LOX）,应用咪喹莫特诱导小鼠银屑病样皮损的发生。将小鼠分为野生型对照组、MMP-13^LOX/LOX对照组、咪喹莫特诱导的野生型实验组和咪喹莫特诱导的MMP-13^LOX/LOX实验组,分析不同组别小鼠皮损临床表现并记录PASI评分,检测各组小鼠皮损中IL-1β、IL-6、IL-23和IL-17A表达。结果：与咪喹莫特诱导的野生型实验组小鼠比较,咪喹莫特诱导的MMP-13^LOX/LOX实验组银屑病皮损表现相比更加温和,仅有轻度的棘层肥厚和真皮细胞浸润,皮损中IL-1β、IL-6表达下调,而IL-23和IL-17A表达无明显改变。结论：抑制树突细胞MMP-13基因可降低炎症因子IL-6、IL-1β的表达及减弱小鼠皮肤银屑病炎症反应。     

Mechanisms underlying imiquimod-induced regression of basal cell carcinoma in vivo

BACKGROUND: Imiquimod is a local immune response modifier that has demonstrated potent antiviral and antitumor activity. It enhances innate and acquired immune responses via endogenous cytokine production and has proven efficacious in clearing superficial basal cell carcinoma (sBCC). OBJECTIVE: To evaluate the mechanisms by which topical imiquimod treatment leads to sBCC clearance in vivo. DESIGN: A pilot, open-label, nonrandomized study. SETTING: Zurich, Switzerland. PATIENTS: Six persons 18 years or older who had nonrecurrent primary tumors that had not undergone previous biopsy or treatment but were suitable for treatment by surgical excision. The tumors were located on the scalp, extremities, or trunk; had a minimum diameter of 1 cm and a maximum diameter of 2 cm; and were clinically and histologically consistent with sBCC. INTERVENTIONS: Daily application of 5% imiquimod cream 5 times per week for a maximum of 6 weeks. When the tumor began to show signs of erosion, it was surgically excised. OUTCOME MEASURES: Parameters reflecting tumor apoptotic status (Bcl-2), expression of death receptors (Fas and Fas ligand [FasL]), intercellular adhesion molecule (ICAM) 1, immunosuppressive microenvironment (interleukin 10), and antigen presentation machinery (transporter associated with antigen presentation [TAP] 1) before and after imiquimod treatment were evaluated. The changes in the interferon gamma messenger RNA (mRNA) levels relative to CD4 and CD8 mRNA were assessed using quantitative polymerase chain reaction. RESULTS: Tumor cells became more susceptible to apoptosis through decreased Bcl-2 expression after treatment with 5% imiquimod cream. Inflammatory infiltrate developed rapidly (within 3 to 5 days after treatment initiation) and was associated with the enhanced expression of ICAM-1. This early response tended to be a mixed cellular response of macrophages and lymphocytes. Interferon gamma was produced by CD4 and CD8 T cells. Imiquimod treatment induced a massive increase in macrophage peritumoral and intratumoral infiltration. Interleukin 10 was produced by infiltrating cells but was not produced by tumor cells. Tumor expression of TAP-1 and Fas/FasL appeared to be unaffected in the first 5 days of treatment.     

Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with topical imiquimod 5% cream

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by solar sensitivity, photophobia, early onset of freckling, and solar‐induced cutaneous neoplastic changes. Management of patients with XP is a therapeutic challenge as they usually develop multiple cutaneous malignancies, making surgical therapy difficult, and continue to form skin malignancies at a high rate. We describe a 30‐year‐old Chinese man with XP who had been previously treated with excision and dermatoplasty. Upon recurrence of multiple superficial, ulcerative, and pigmented lesions, imiquimod 5% cream was recommended for 4 months. His multiple facial lesions demonstrated an excellent response to topical imiquimod 5% cream with minor side effects. This favorable response indicates that topical application of imiquimod 5% cream is an effective means of treating multiple basal cell carcinomas in XP.     

Imiquimod enhances the systemic immunity attained by local cryosurgery destruction of melanoma lesions

Melanoma lesions can be frozen in vivo, resulting in necrotic death of malignant cells and in tumor antigen release suitable for cross-presentation by professional antigen-presenting cells. Imiquimod is a small molecule with adjuvant pro-inflammatory effects that can be topically delivered as a cream. Local cryosurgery of B16/ovalbumin (OVA)-derived subcutaneous tumor nodules leads to curative destruction of the lesions. If imiquimod is repeatedly applied on the cryo-treated lesion, a conspicuous, leukocyte-rich inflammatory infiltrate appears during the days following treatment. Mice treated by cryosurgery plus imiquimod rejected rechallenges of B16/OVA in 90% of the cases, whereas cryosurgery alone failed to prevent tumor grafting in 70% of the cases. The combination treatment of B16/OVA tumors was also able to protect 60% of the mice against outgrowth of a lethal dose of non-transfected B16 tumor cells. Addition of imiquimod to cryosurgery results in increases of the cellular immune response against tumor antigens as measured by in vitro IFN-gamma production and T-cell proliferation in response to OVA. The potent memory response is not only directed against the OVA epitope, but also toward a broader range of B16 antigens. Our data indicate that these combined treatments turn the treated tumor lesion into an autologous tumor vaccine, which is even able to cause vitiligo in several cases. These preclinical data and the simplicity of the procedures warrant the design of a pilot clinical trial.     

Combined treatment with intratumoral injection of dendritic cells and topical application of imiquimod for murine melanoma

BACKGROUND: The maturation state of dendritic cells is one of the factors that affect their capacity to induce antigen-specific cytotoxic T lymphocytes. Topical cutaneous application of imiquimod can induce the maturation and migration of cutaneous dendritic cells. OBJECTIVES: To evaluate the synergistic effect of topical application of imiquimod plus intratumoral injection of syngeneic bone marrow-derived dendritic cells in the treatment of melanoma. METHODS: For the B16F10 melanoma model, naive C57BL/6 mice were inoculated intradermally with 2x10(3) B16F10 melanoma cells in the right upper flank. Four groups (untreated control, dendritic cells alone, imiquimod alone and imiquimod plus dendritic cells) were included in the animal study, with five mice in each group. Tumour size was measured every 2 weeks, and histochemical and immunohistochemical staining carried out. ELISpot and PKH assays were performed to assess immune activity. RESULTS: Combined treatment of topical application of imiquimod and intratumoral injection of dendritic cells led to significant tumour regression, in contrast to partial eradication of the tumours with imiquimod or dendritic cells alone. CONCLUSION: These findings suggest that combination therapy with topical application of imiquimod and intratumoral administration of dendritic cells is a potent strategy for the treatment of melanoma.     

Squamous cell carcinoma in situ of the penis successfully treated with imiquimod 5% cream

BACKGROUND: Multiple treatments for squamous cell carcinoma in situ (SCCIS) of the penis have been used with variable success and morbidity. Surgery and destructive treatment modalities have significant risk of scarring, deformity, and impaired function. OBJECTIVE: The purpose of this study was to determine whether topical imiquimod 5% cream is a potentially effective treatment for SCCIS of the penis and to qualify treatment associated morbidity. METHODS: The case of a patient with extensive penile SCCIS is reported. The patient was treated with topical imiquimod 5%, administered daily until blistering occurred (2 cycles). Biopsy specimens were obtained to confirm tumor clearance. RESULTS: One month after therapy was completed, no clinical or histologic evidence of residual tumor was found. Adverse effects of imiquimod included localized tenderness and erythema. No evidence of scarring, deformity, loss of function, or tumor recurrence was noted 18 months after treatment. CONCLUSION: Imiquimod 5% cream may represent an alternative treatment option for SCCIS of the penis.     

Transient effect of topical treatment of cutaneous leishmaniasis with imiquimod

BACKGROUND: Treatment of cutaneous leishmaniasis can be painful and protracted and cosmetic results are often unsatisfying. The immune modulator imiquimod has been reported to be suitable for the treatment of a variety of infectious skin diseases and neoplasias. OBJECTIVE: We investigated the efficacy of topical application of imiquimod in the treatment of old world leishmaniasis in a placebo-controlled prospective study. METHODS: Twelve patients were treated with imiquimod cream using a standard protocol, i.e. topical application three times a week, and a further three served as control group. RESULTS: Lesions of cutaneous leishmaniasis regressed within the first 2-4 weeks in 10 of the 12 patients, whereas in two patients no change was observed. However, after 8 weeks all lesions showed progression. CONCLUSION: Our results thus demonstrate that topical application of imiquimod alone is ineffective in treating old world cutaneous leishmaniasis. Further studies are required to demonstrate a possible benefit of imiquimod in combination with other, preferably orally administered medicines.     

Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials

BACKGROUND: The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers. OBJECTIVE: Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp. METHODS: A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit. RESULTS: The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (> or =75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated. CONCLUSION: Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.     

重组Ad-SOCS1介导的树突状细胞源外泌体对银屑病样小鼠模型的影响

目的:明确重组腺病毒(Ad-SOCS1)介导的树突状细胞(DCs)分泌的外泌体对银屑病样小鼠模型的影响。方法:Ad-SOCS1腺病毒感染小鼠骨髓来源的DCs,分离纯化培养物中的外泌体,Western blot分析鉴定外泌体中的CD63、SOCS1和ICAM-1蛋白。咪喹莫特(IMQ)诱导10只银屑病样小鼠模型,其中5只给予外分泌体治疗(外分泌体组)组,5只作为对照(IMQ组)。RT-PCR检测小鼠外周血IL-17A、IL-22和IL-23 mRNA的表达水平。结果:外泌体中能够鉴定到SOCS1、CD63和ICAM-1蛋白。外分泌体组小鼠的银屑病样表现较IMQ组轻。外分泌体组小鼠外周血IL-17A和IL-23 mRNA的表达低于IMQ组(P0.01),IL-22水平两组间无显著差异(P0.05)。结论:Ad-SOCS1感染DC后培养物分离的外泌体可改善银屑病的症状,其机制可能与外泌体SOCS1抑制IL-17A有关。     

CCL18趋化性细胞因子对A375黑素瘤细胞株增殖和侵袭的影响

目的 探讨CCL18对A375黑素瘤细胞株增殖、侵袭及血管增殖的影响.方法 提取成人外周血单核细胞,IL-4诱导48 h后,与A375黑素瘤细胞株共培养,通过MTT法检测CCL18对A375增殖的影响;通过趋化试验及重组基底膜侵袭实验,测定CCL18对肿瘤细胞的趋化能力及侵袭作用的影响.通过将A375黑素瘤细胞株接种于鸡胚尿囊膜,测定不同情况下CCL18对肿瘤血管生成的影响.结果 IL-4诱导单核细胞组、非诱导单核细胞组呈现促进A375细胞增殖的作用,而CCL18与对照组比较差异无统计学意义.IL-4诱导单核细胞组及CCL18重组细胞因子组与对照组比较均对肿瘤细胞存在趋化作用,并促进肿瘤细胞的侵袭(P＜0.05);IL-4诱导组及CCL18组在鸡胚尿囊膜试验中可促进肿瘤血管的生成(P＜0.05).结论 CCL18具有促进A375黑素瘤细胞株侵袭及血管增殖的作用.