Downregulation of kynureninase restrains cutaneous squamous cell carcinoma proliferation and represses the PI3K/AKT pathway.
- 作者列表："Ci C","Wu C","Lyu D","Chang X","He C","Liu W","Chen L","Ding W
BACKGROUND:The protein kynureninase (KYNU) has recently been reported to participate in the pathological processes of various diseases. AIM:To explore the expression and the biological function of KYNU in cutaneous squamous cell carcinoma (cSCC). METHODS:Expression of KYNU in cSCC cell lines and tissues was firstly evaluated based on the Gene Expression Omnibus and the Oncomine databases. Quantitative reverse transcription-PCR was performed to determine the mRNA expression of KYNU in cSCC cell lines. Small interfering RNA (siRNA) was used for silencing KYNU. The effect of KYNU on the growth and motility of cSCC cells was determined by cell counting kit-8, wound-healing and Transwell assays, and western blotting was used to determine the protein expression of KYNU, AKT, phosphoinositide 3-kinase (PI3K), phosphorylated (p)-AKT and p-PI3K. RESULTS:KYNU was significantly upregulated in cSCC tissues and cell lines. Knockdown of KYNU using siRNA noticeably suppressed the proliferation, migration and invasion ability of SCL-1 cells (P < 0.01). Western blotting revealed that phosphorylation of AKT and PI3K was markedly inhibited after silencing KYNU. The ratios of p-AKT/AKT and p-PI3K/PI3K were significantly decreased in the si-KYNU group compared with the control group. CONCLUSION:Depletion of KYNU could inhibit the growth of cSCC cells, possibly through modulating PI3K/AKT pathway. These data indicate that KYNU takes a key part in the malignant progression of cSCC, and could be considered as a promising therapeutic target for cSCC treatment.
背景: 蛋白kynureninase (KYNU) 最近被报道参与多种疾病的病理过程。 目的: 探讨KYNU在皮肤鳞状细胞癌 (cSCC) 中的表达及其生物学功能。 方法: 首先根据Gene Expression Omnibus和Oncomine数据库评价KYNU在cSCC细胞系和组织中的表达。进行定量逆转录-PCR测定cynu在cSCC细胞系中的mRNA表达。小干扰RNA (siRNA) 用于沉默KYNU。通过细胞计数试剂盒-8 、伤口愈合和Transwell试验测定KYNU对cSCC细胞生长和运动的影响，western blotting测定KYNU、AKT、磷酸肌醇 3-激酶 (PI 3K) 、磷酸化 (p)-AKT和p-PI 3K的蛋白表达。 结果: KYNU在cSCC组织和细胞系中显著上调。SiRNA敲除KYNU可显著抑制SCL-1 细胞的增殖、迁移和侵袭能力 (P <0.01)。Western blotting发现沉默KYNU后AKT和PI3K的磷酸化明显被抑制。与对照组相比，si-KYNU组p-AKT/AKT和p-PI3K/PI3K比值显著降低。 结论: 缺失KYNU可能通过调节PI3K/AKT通路抑制cSCC细胞的生长。这些数据表明KYNU在cSCC的恶性进展中起着关键作用，可以被认为是cSCC治疗的一个有前途的治疗靶点。
METHODS::Blue rubber bleb naevus syndrome (BRBNS) is an extremely rare venous malformation that often manifests as multiple haemangioma-like lesions in the skin and gastrointestinal tract. The drug sirolimus plays a key role in the signalling pathway of angiogenesis and subsequent development of BRBNS and its use has been described in several case reports. We present a case series of four patients with BRBNS who exhibited good treatment response to sirolimus. All four patients were administered oral sirolimus at doses of 1.0-1.5 mg/m2 /day with a target drug level of 5-10 ng/mL and median treatment duration of 20 months. All patients had a reduction in the size of the lesions and a normalization of coagulopathy with tolerable drug adverse reactions at follow-up. Sirolimus may be effective and safe in paediatric patients with BRBNS. Further prospective studies are suggested to evaluate the long-term effectiveness of this drug.
METHODS:BACKGROUND:Human papillomavirus (HPV) infections are associated with common dermatologic and nondermatologic diseases. Although HPV vaccines are well established as preventive measures for genital warts and cervical neoplasia, their use as therapeutic agents deserves greater attention. OBJECTIVE:To evaluate the use of HPV vaccine(s) as a treatment modality for cutaneous and/or mucosal disease. METHODS:A primary literature search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in January 2019 by using the PubMed and Cochrane databases. RESULTS:A total of 63 articles with 4439 patients were included. The majority of patients with cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas were successfully treated with HPV vaccination. Preliminary data on patients with pre-existing anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia is promising. LIMITATIONS:This review was limited by the lack of controls, patients' previous HPV vaccination status, and publication bias. CONCLUSION:The commercially available three-dose, quadrivalent HPV vaccine is a potential therapeutic option for the treatment of cutaneous warts, recurrent respiratory papillomatosis, and squamous and basal cell carcinomas. Noncommercially available HPV vaccines demonstrate therapeutic response for treating anogenital warts, cervical intraepithelial neoplasia, anal intraepithelial neoplasia, and vulvar intraepithelial neoplasia. The vaccine's efficacy as an adjunct therapy for HPV-associated cutaneous and/or mucosal disease warrants further exploration.
METHODS::Our understanding of melanoma precursors and progression to melanoma has developed as a result of advances in the field of molecular diagnostics. We now better understand the potential for genetic heterogeneity within a single lesion. Combined tumors can pose a diagnostic challenge when deciding the line between benign and malignant, which in turn has direct implications for patient management. Primary cilia (PC) are ubiquitous sensory organelles that have essential functions in cellular proliferation, differentiation, and development. The ciliation index (percentage of ciliated melanocytes) has been shown to reliably differentiate melanoma, which fail to ciliate, from melanocytic nevi, which retain PC. We therefore analyzed the potential for using the ciliation index to differentiate benign and malignant components in combined melanocytic lesions. We collected patient samples (n = 10) of unequivocal combined lesions with both melanoma and associated nevus components. Melanocytes were highlighted with SOX10 and costained with gamma-Tubulin and acetylated alpha-Tubulin to highlight the basal body and cilium, respectively. The number of melanocytes retaining cilia under high-power microscopy was examined. The melanoma component had average of 4% ciliation (SD: 7%), whereas the associated nevus component was significantly higher with 59% ciliation (SD: 17%). These data show that PC may be a reliable means of distinguishing benign from malignant components within a single tumor. The ciliation index may be a helpful tool in distinguishing challenging cases of combined lesions of melanoma in situ with a dermal nevus component from invasive melanoma, thus promoting improved staging and clinical management.