Yun Zou

MicroRNA-346 functions as an oncogene in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is an epidermal keratinocyte-derived skin tumor, which is the second most common skin cancer in the general population. Recently, studies showed that microRNAs (miRNAs) played an important role in the development of cancer. In our study, we showed that the expression of SRCIN1 was lower in cSCC tissues than in the matched normal tissues. Moreover, there was significant inversed correlation between miR-346 and SRCIN1 in cSCC tissues. The luciferase reporter assay data showed that miR-346 can target the SRCIN1 message via the 3′-untranslated region (UTR) of SRCIN1. Overexpression of miR-346 inhibited the messenger RNA (mRNA) and protein expression of SRCIN1 in the A431 cells. In addition, ectopic expression of miR-346 promoted the A431 cell proliferation and migration. Meanwhile, SRCIN1 overexpression inhibited the A431 cell proliferation and migration. Rescue experiment has showed that SRCIN1 overexpression reduced the miR-346-induced A431 cell proliferation and migration. Herein, this study may provide miR-346 as a new therapeutic target for cSCC.

High Expression of Stearoyl-CoA Desaturase 1 Predicts Poor Prognosis in Patients with Clear-Cell Renal Cell Carcinoma

Stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzymes in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, have been gradually recognized as a potential therapeutic target for various malignancies, particularly in clear-cell renal cell carcinoma (ccRCC). However, the prognostic value of SCD1 in ccRCC is still unknown. The aim of this study is to evaluate the clinical significance of SCD1 expression in patients with ccRCC. SCD1 expression in tumor tissues obtained from 359 patients who underwent nephrectomy for ccRCC are retrospectively assessed. During a median follow-up of 63 months (range: 1–144month), 56 patients in total died before the last follow-up in this study. Survival curves were plotted with the Kaplan–Meier method and compared with the log-rank test. Meanwhile, univariate and multivariate Cox regression models were applied to evaluate the prognostic value of SCD1 expression in overall survival (OS) for ccRCC patients. Moreover, SCD1 was enrolled into a newly built nomogram with factors selected by multivariate analysis, and the calibration was built to evaluate the predictive accuracy of nomogram. High SCD1 expression occurred in 61.6% (221/359) of ccRCC patients, which was significantly associated with age (p = 0.030), TNM stage (p = 0.021), pN stage (p = 0.014), Fuhrman grade (p = 0.014) and tumor sizes (p = 0.040). In multivariate analysis, SCD1 expression was confirmed as an adverse independent prognostic factor for OS. The prognostic accuracy of TNM stage, Fuhrman grade and tumor sizes was significantly increased when SCD1 expression was added. The independent prognostic factors, pT stage, pN stage, Fuhrman grade and tumor sizes, as well as SCD1 expression were integrated to establish a predictive nomogram with high predictive accuracy. Calibration curves revealed optimal consistency between observations and prognosis. In conclusion, high SCD1 expression is an independent prognostic factor for OS in patients with ccRCC. Our data suggest that the expression of SCD1 might guide the clinical decisions for patients with ccRCC.

Prospective, open-label, rater-blinded and self-controlled pilot study of the treatment of proliferating superficial infantile hemangiomas with 0.5% topical timolol cream versus 595-nm pulsed dye laser

Topical timolol and 595‐nm pulsed dye laser (PDL) are both widely used in the treatment of superficial infantile hemangiomas (IH). However, to date, there is no reliable study comparing the therapeutic outcomes between the two treatment options. We designed the present study to evaluate and compare the efficacy and safety of timolol cream and PDL in the treatment of superficial proliferating IH. Twenty‐one patients with superficial IH were included in the study. Each lesion was divided into two regions; one part was treated with 0.5% topical timolol cream four times daily, and the other part was treated monthly with PDL. Both treatments were continued for 2–6 months. Five independent and blinded assessors were asked to judge the results in both the topical timolol‐treated and PDL‐treated parts by comparing photographs taken before and after treatment. Both treatments resulted in significant clinical improvements after 3.39 sessions in the 2‐month follow up. The average visual evaluation showed that PDL had significantly better results than topical timolol (6.55 ± 2.26 to 4.98 ± 2.92, P < 0.01). No patients experienced permanent side‐effects during the treatment. Our short‐term study revealed that PDL had better results compared with topical timolol cream application in the treatment of superficial proliferating IH. Further studies with longer follow‐up time and larger sample size are required to validate our findings.

Overexpression of cannabinoid receptor 1 promotes renal cell carcinoma progression

Renal cell carcinoma (RCC) is a common urologic tumor with a poor prognosis. Cannabinoid receptor 1 (CB1), which is a G protein-coupled receptor, has recently been reported to participate in the genesis and development of various cancers. However, the exact role of CB1 in RCC is unknown. The aim of this study was to determine the role of CB1 in RCC cell lines and RCC prognosis, thus underlying its potential as a therapeutic target. Immunohistochemistry and western blots were performed to investigate the expression of CB1 in RCC tissues and to determine its clinicopathological significance in RCC patients. Additionally, we explored CB1 expression in RCC cell lines and evaluated the effect of AM251, a CB1 inverse agonist, and in vitro siRNA knockdown of CB1 on the cellular proliferation, migration, and apoptosis of RCC cell lines. CB1 was overexpressed in cancerous tissues compared with adjacent normal tissues. Furthermore, CB1 expression levels were an independent risk factor for overall survival for RCC patients. AM251 significantly decreased tumor cell proliferation and induced cell apoptosis by upregulating the expression of the pro-apoptotic protein Bax and decreasing the expression of the anti-apoptotic proteins survivin and Bcl-2. Migration of the RCC cell lines was also significantly inhibited after treatment with AM251 compared with untreated control groups. In addition, knockdown of CB1 expression significantly decreased cell proliferation and invasion and significantly increased apoptosis of RCC cells. CB1 expression is functionally associated to cellular proliferation, apoptosis, and invasion ability of RCC. Our data suggest that CB1 might be a potential target for RCC clinical therapy.

Cannabinoid receptor 2 as a novel target for promotion of renal cell carcinoma prognosis and progression.

PurposeRenal cell carcinoma (RCC) is the most common malignancy of urogenital system, and patients with RCC may face a poor prognosis. However, limited curable therapeutic options are currently available. The aim of this study is to investigate the role of Cannabinoid receptor 2 (CB2) in RCC progression.MethodsImmunohistochemistry was to investigate the expression pattern of CB2 in 418 RCC tissues and explore its prognostic function in RCC patients. Furthermore, the role of used CB2 si-RNA knockdown and inhibited by AM630, a CB2 inverse agonist, on cell proliferation, migration, and cell cycle of RCC cell lines in vitro was also investigated.ResultsWe observed that CB2 was up-regulated in RCC tissues, and presented as an independent prognostic factor for overall survival of RCC patients and higher CB2 expression tends to have poor clinical outcomes in survival analyses. Moreover, we also observed that CB2, incorporated with pN stage, pathological grade, and recurrence or distant metastasis after surgery, could obviously enhance their prognostic accuracy in a predictive nomogram analysis. In addition, knockdown or inhibition by AM630 for the expression of CB2 in vitro could significantly decreased cell proliferation and migration, and obviously induced cell cycle arrest in G2/M of RCC cells.ConclusionsCB2 expression is functionally related to cellular proliferation, migration, and cell cycle of RCC cells. Our data suggest that CB2 might be a potential therapeutic target for RCC.

Treatment of Early-stage Extracranial Arteriovenous Malformations with Intralesional Interstitial Bleomycin Injection: A Pilot Study

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes.

The selective MEK1 inhibitor Selumetinib enhances the antitumor activity of everolimus against renal cell carcinoma in vitro and in vivo

Renal cell carcinoma (RCC) is a urologic malignant cancer and often diagnosed at an advanced stage, which results in high mortality. Targeted therapy may improve the quality of life and survival of patients who are not suitable for nephrectomy. Everolimus, an mTOR inhibitor, is currently used as sequential or second-line therapy for RCC refractory to Sunitinib or sorafenib. However, its efficiency is palliative. In this study, we evaluated whether the antitumor activity of everolimus against RCC is enhanced by selumetinib, a selective MEK1 inhibitor. We discovered that everolimus in combination with selumetinib synergistically inhibited the proliferation of Caki-1, 786-O and 769-P cells in vitro. Mechanistically, this combination decreased p-RPS6 and p-4E-BP1 dramatically, which causes G1 cell cycle arrest and prevents reactivation of AKT and ERK. In vivo, the antitumor efficacy and pharmacodynamic biomarkers of the combination therapy were recapitulated in Caki-1 xenograft model. In addition, this combination treatment potently inhibited angiogenesis in xenograft models by impairing VEGF secretion from tumor cells. Our findings provide a sound evidence that combination of everolimus and selumetinib is a potential dual-targeted strategy for renal cell carcinoma.

Stepwise, Multi-Incisional, and Single-Stage Approach to Reshape Facial Contour After Large Cutaneous Lesion Resection

Background: Removal of large facial benign cutaneous lesions remains challenging. Serial or complete excisions together with local flaps or expander-based reconstructions are required. However, those techniques are time-consuming and may contribute to poor cosmetic and functional outcomes. Objective: The authors describe the resection and reconstruction of large facial benign cutaneous lesions by using Stepwise, Multi-Incisional, and Single-Stage (SMISS) approach. Methods: The authors performed a retrospective review from all patients with large facial benign cutaneous lesions who underwent “SMISS” approach for reconstruction between September 2013 and December 2014. Results: The authors treated 47 patients (32 female and 15 male; mean age 23.5 years, range 9–50 years). Follow-up was for 12 months or longer. The mean length of major axis was 43.91 mm, minor axis 32.10 mm, and scar 66.91 mm. Good to excellent outcomes were achieved in all patients with a mean Vancouver scar scale score of 3.46 ± 0.39 (Cronbach &agr; = 0.890) and mean visual analog scale score of 8.02 ± 0.69 (Cronbach &agr; = 0.946). Limitations: This was a nonrandomized, unblinded clinical case series with a limited sample size. Conclusion: For the excision and reconstruction of large facial benign cutaneous lesions, “SMISS” technique can be considered as a suitable option, leading to excellent results and a high patient satisfaction.

Microsurgical Replantation of Total Avulsed Scalp: Extending the Limits.

Background: Avulsion of the scalp is a rare but severe trauma and challenging to the reconstructive surgeon. It poses not only physical concussion but also significant persisting psychological distress to the patients. Methods: Medical records from 5 patients who suffered scalp avulsion were reviewed retrospectively. The following data and methods were assessed: age, number of vessels repaired, method of replantation, vein grafts required, blood transfusion, ischemia time, total operating time, and percentage of scalp survival. Results: In 4 patients, the replantation was performed at the anatomic site. Two arteries and 2 veins were anastomosed in 2 patients; a single artery and a single vein were anastomosed in 2 patients. The middle temporal vein was chosen for anastomosis as a recipient vessel in 2 patients. In the fifth patient with simultaneous cervical fracture that makes primarily replantation technically not possible, the scalp was implanted ectopically in the forearm for the purpose of secondary replantation at the anatomic site. After a mean follow-up of 22.6 months (range 13–29 months), 4 of 5 patients exhibited successful survival of the replanted scalp. Conclusions: The success of scalp replantation is determined by a comprehensive management of the trauma and well-trained microsurgical technique. The middle temporal vein can be used as a reliable alternative recipient vessel for microvascular anastomosis when replanting the avulsed scalp. In patients in whom primary replantation is not possible, temporary ectopic implantation of the avulsed scalp and anatomic replantation at a second stage is considerable.BACKGROUND Avulsion of the scalp is a rare but severe trauma and challenging to the reconstructive surgeon. It poses not only physical concussion but also significant persisting psychological distress to the patients. METHODS Medical records from 5 patients who suffered scalp avulsion were reviewed retrospectively. The following data and methods were assessed: age, number of vessels repaired, method of replantation, vein grafts required, blood transfusion, ischemia time, total operating time, and percentage of scalp survival. RESULTS In 4 patients, the replantation was performed at the anatomic site. Two arteries and 2 veins were anastomosed in 2 patients; a single artery and a single vein were anastomosed in 2 patients. The middle temporal vein was chosen for anastomosis as a recipient vessel in 2 patients. In the fifth patient with simultaneous cervical fracture that makes primarily replantation technically not possible, the scalp was implanted ectopically in the forearm for the purpose of secondary replantation at the anatomic site. After a mean follow-up of 22.6 months (range 13-29 months), 4 of 5 patients exhibited successful survival of the replanted scalp. CONCLUSIONS The success of scalp replantation is determined by a comprehensive management of the trauma and well-trained microsurgical technique. The middle temporal vein can be used as a reliable alternative recipient vessel for microvascular anastomosis when replanting the avulsed scalp. In patients in whom primary replantation is not possible, temporary ectopic implantation of the avulsed scalp and anatomic replantation at a second stage is considerable.