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Madelung's disease is a rare clinical disease with a low incidence. The main feature of the disease is lipodystrophy, which is more common in men between the ages of 30 and 60. At present, there is no standard and effective treatment for this disease in the world. Here, we reported a case of Madelung's disease with surgical treatment of the neck and reviewed relevant literature to improve the understanding of this disease. [ABSTRACT FROM AUTHOR]

A previous study has elucidated that circular RNA circCLK3 acts as an oncogenic gene in cervical cancer. However, the role and regulatory mechanism of circCLK3 in tongue squamous cell carcinoma (TSCC) remain unknown. Quantitative real‐time PCR was used to examine targeted gene expression in different groups. Cell viability and proliferation were investigated by MTT and 5‐ethynyl‐2′‐deoxyuridine assays. Cell migration and invasion were detected by Transwell assays, and cell apoptosis was measured by flow cytometry analysis. The interaction among genes was investigated using luciferase reporter assay, RNA pull‐down assay, and RNA immunoprecipitation assay. In the present study, our findings revealed the upregulated expression of circCLK3 in TSCC tissues and cell lines. CircCLK3 knockdown suppressed cell proliferation, migration invasion, and induced cell cycle arrest at G0/G1 phase in TSCC. Moreover, circCLK3 acted as a molecular sponge for miR‐455‐5p. PARVA was the target gene of miR‐455‐5p. Furthermore, the negative correlation between expression of miR‐455‐5p and circCLK3 or PARVA in TSCC tissues was discovered. Rescue assays indicated that PARVA overexpression reversed the circCLK3 knockdown‐mediated inhibitory effects on the progression of TSCC. In summary, circCLK3 exerts its carcinogenic effects on TSCC progression via absorbing miR‐455‐5p to upregulate PARVA, which expands our knowledge on the underlying mechanism of TSCC. [ABSTRACT FROM AUTHOR]

Abstract Thyroid cancer keeps rapidly increasing worldwide and the most frequent type is papillary thyroid carcinoma (PTC). MicroRNAs (miRNAs) are proved dysregulated in many types of malignancies, including thyroid cancer. Although miR-let-7e has been implicated in several types of cancer regulation, relatively little is known about the function of miR-let-7e in PTC. In this study, we showed that the overexpression of miR-let-7e or knockdown of high mobility group box 1 (HMGB1) inhibited cell migration and invasion. MiR-let-7e downregulates HMGB1 expression by directly targeting the HMGB1 3′-UTR. Furthermore, HMGB1 reintroduction reversed the anti-proliferation, anti-migration, and anti-invasion roles of miR-let-7e. miR-let-7e might function as a tumor suppressor in papillary thyroid carcinoma through HMGB1. Therefore, our study demonstrates that miR-let-7e plays an important role in papillary thyroid carcinoma progression and might represent a new potential therapeutic target for treatment. [ABSTRACT FROM AUTHOR]

The study aimed to explore the specific function and mechanism of miR-144-3p in glioblastoma ( GBM) cells with different phosphatase and tensin homolog (PTEN) phenotypes. We demonstrated that the miR-144-3p level was significantly down-regulated in glioma compared with the non-neoplastic brain tissues, and decreased with ascending grades. The loss of miR-144-3p effectively predicted the decreased overall survival in glioma patients. Interestingly, the expression of MET was up-regulated and inversely associated with miR-144-3p level in glioma tissues. Next, we certified that miR-144-3p specifically bound to MET 3′-untranslated region (3′ UTR) and inhibited its expression. miR-144-3p potently repressed GBM cell proliferation and invasion via suppressing MET in vitro and in vivo. In addition, our results showed no difference in malignancy inhibition induced by miR-144-3p in GBM cells with different PTEN phenotypes. miR-144-3p inhibited several survival signaling pathways by targeting MET independent of PTEN status in GBM cells. Over-expression of miR-144-3p inhibited survival capability and increased apoptosis, resulting in enhancement of radiation and temozolomide sensitivity. Our data provide new insights into the potential application of miR-144-3p in GBM therapy by targeting MET and then inhibiting the downstream signaling. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To investigate the protective effects of berberine on radiation-induced lung injury (RILI) in non-small cell lung cancer (NSCLC) patients treated with radiotherapy. Patients and methods: In this randomised, double-blind study, 90 patients with NSCLC were divided into two groups. The trial group received radiation therapy plus berberine, and the control group received radiation therapy plus a placebo for 6 weeks. Soluble intercellular adhesion molecular-1 (sICAM-1) and transforming growth factor-beta-1 (TGF-β1) were measured. RILI and pulmonary function were evaluated at 6 weeks and 6 months after treatment, respectively. Results: Of the 90 patients enroled, 43 in the control group and 42 in the trial group completed the study. The incidence of RILI was significantly lower in the trial group at 6 weeks and 6 months than that in the control group (45.2% versus 72.1% and 35.7% versus 65.1%, respectively, both P <0.05). sICAM-1 levels in the trial group were significantly lower at weeks 6 and 12 (373.64±89.33 versus 459.53±123.59 and 447.83±111.21 versus 513.91±150.46, both P <0.01), and plasma TGF-β1 levels were lower at week 3 and 6 (5.43±1.47 versus 6.22±1.78 and 5.93±2.39 versus 7.67±2.74, P <0.05 and 0.01, respectively) in comparison with the control group. Significant differences were observed in FEV1 (P =0.033) and DLCO (P =0.003) between patients receiving berberine and those receiving placebo. Independent-samples T-test showed reductions from baseline FVC at week 6 (P <0.05), and FEV1 and DLCO at month 6 (P <0.05 and 0.01, respectively) in the trial group were significantly smaller than that in the control group. Conclusion: Berberine significantly reduced the incidence of RILI, improved PF and decreased the levels of sICAM-1 and TGF-β1. The exact mechanisms remain to be further explored. [Copyright &y& Elsevier]

Investigates the development of education for the publishing industry in China from 1980 to 2000. List of universities in China that offer publishing majors; Employment and professional demands for publishing major graduates; Formal professional training for employees in the publishing industry.

Objective: We aimed to explore the role of long intergenic non‐protein coding RNA 460 (LINC00460) in tongue squamous cell carcinoma (TSCC). Methods: We enrolled 27 TSCC patients to explore LINC00460 expression in clinical TSCC samples. RT‐qPCR measured expression of molecules in this research. Loss‐of‐function assays explored biological function of LINC00460 in TSCC cells. RNA pull‐down assay, luciferase reporter assay, and RIP assay investigated mechanism of LINC00460 underlying TSCC cells. Results: TSCC tissues and cell lines both showed high expression of LINC00460. Functionally, LINC00460 downregulation inhibited TSCC cell growth and promoted TSCC cell apoptosis. Additionally, LINC00460 silencing suppressed tumor growth in vivo. Mechanistically, LINC00460 bound with microRNA 320b (miR‐320b) in TSCC cells. MiR‐320b overexpression suppressed TSCC cell growth and promoted TSCC cell apoptosis. Moreover miR‐320b targeted insulin‐like growth factor 2 mRNA‐binding protein 3 (IGF2BP3) 3′untranslated region in TSCC cells. Furthermore, IGF2BP3 silencing suppressed TSCC cell growth and promoted TSCC cell apoptosis. IGF2BP3 upregulation countervailed effects of silenced LINC00460 on TSCC cells. The LINC00460/miR‐320b/IGF2BP3 axis was associated with lymph node metastasis of TSCC patients. Conclusion: Our research illustrated that LINC00460 facilitated TSCC progression via the miR‐320b/IGF2BP3 axis, highlighting a potential insight for the treatment of TSCC. [ABSTRACT FROM AUTHOR]

Accumulating evidence has suggested that long noncoding RNAs (lncRNAs) are involved in the progression of types of human cancers. It has been known that exosomes can mediate cell-cell crosstalk by transferring lncRNAs in tumor progression. This study aimed to investigate the role of exosomal lncRNA HEIH on cisplatin (DDP) resistance in tongue squamous cell carcinoma (TSCC). The expression of HEIH in human oral keratinocytes cell line (HOK), DDP-sensitive TSCC cell line (SCC4/S) and DDP-resistant TSCC cell line (SCC4/DDP) was measured. SCC4/S and SCC4/DDP cells were transfected with sh-HEIH to examine TSCC cell proliferation and apoptosis. The DDP-resistant exosomes were extracted and identified. The expression of miR‑3619-5p and TDGF in DDP-sensitive recipient cells was determined. The binding capacity between HEIH and miR‑3619-5p, along with miR‑3619-5p and TDGF was verified. HEIH expression was significantly upregulated in SCC4/DDP cells. Downregulation of HEIH inhibited DDP resistance and cell proliferation and promoted cell apoptosis. HEIH acted as a competing endogenous RNA (ceRNA) for miR‑3619-5p to upregulate HDGF expression. Exosomal HEIH promoted cell proliferation and drug resistance and inhibited cell apoptosis by sponging miR‑3169-5p and upregulating HDGF. Exosomal HEIH acted as a ceRNA for miR‑3619-5p to upregulate HDGF, thereby promoting DDP resistance in TSCC cells. [ABSTRACT FROM AUTHOR]

Objective: Stenting is the preferred treatment for iliac vein lesions. For the treatment of occlusions in the junction of the iliac vein and the inferior vena cava (IVC), the stent needs to be positioned in the IVC to cover the lesion. However, the pathological changes in the contralateral iliac vein due to stent coverage on its ostium remain unclear. We observed the patency of the contralateral iliac vein via animal experiments. Methods: The stents were placed in the left iliac vein and extended into the IVC in 8 beagle dogs. Doppler ultrasonography, angiography, and histopathological examination were used to assess the patency and histopathological changes in the contralateral iliac vein. Results: Angiography showed patency of the contralateral iliac vein and no sign of thrombosis or stenosis. Twelve months after stenting, Doppler ultrasonography showed a stenotic change in the ostium of the contralateral iliac vein. The histopathological examination showed that the stent strut at the ostium of the contralateral iliac vein was mostly covered by the intima, and the cross-sectional stenosis rate was greater than 60%. Conclusions: The coverage of the iliac vein stent on the ostium of the contralateral iliac vein does not cause complete occlusion of the contralateral vein but can cause significant stenosis at the ostium of the contralateral iliac vein, which is considered to be a potential risk factor for thrombosis. [ABSTRACT FROM AUTHOR]

Introduction: Whether supraclavicular lymph node (SCLN) metastasis in patients with oesophageal cancer belongs to regional disease is controversial, leading to heterogeneity in clinical treatment decisions. This study aimed to determine the optimal treatment for lower thoracic oesophageal cancer (LTOC) with SCLN metastasis. Methods: Patients with LTOC registered in the Surveillance, Epidemiology, and End Results database during 2010–2015 were identified. Selected patients were grouped according to disease spread as those with locoregional disease, with SCLN metastasis or with distant metastasis, as well as according to treatment modality (neoadjuvant chemoradiotherapy followed by surgery (nCRT+S group), upfront surgery ± adjuvant therapy (upfront S group) and definitive chemoradiotherapy (dCRT group)). The Cox regression analysis and inverse probability of treatment weighting (IPTW) were used to identify the optimal treatment modality for different groups. Results: Of 11,767 LTOC patients identified from the database, the 5‐year overall survival (OS) rates for patients with the locoregional disease (n = 7,541), SCLN metastasis (n = 120) and distant metastasis (n = 4,106) were 28.3%, 10.0% and 3.0%, respectively (P < 0.001). Among patients with SCLN metastasis, median OS in the nCRT+S, upfront S and dCRT groups were 25, 14 and 8 months, respectively (P < 0.001). After IPTW, the nCRT+S group was still associated with better median OS compared with other groups. The multivariate analysis identified treatment modality as an independent prognostic factor for OS. Conclusions: Neoadjuvant chemoradiotherapy followed by oesophagectomy may be the optimal treatment modality for LTOC with SCLN metastasis. The findings of this study need to be validated in large prospective studies. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has made significant advances in the treatment of extensive-stage small-cell lung cancer (ES-SCLC), but data in combination with radiotherapy are scarce. This study aims to assess the safety and efficacy of chemoimmunotherapy combined with thoracic radiotherapy in patients with ES-SCLC. Methods: This single-center retrospective study analyzed patients with ES-SCLC who received standard platinum–etoposide chemotherapy combined with atezolizumab or durvalumab immunotherapy as induction treatment, followed by consolidative thoracic radiotherapy (CTRT) before disease progression in the first-line setting. Adverse events during radiotherapy with or without maintenance immunotherapy and survival outcomes were assessed. Results: Between December 2019 and November 2021, 36 patients with ES-SCLC were identified to have received such treatment modality at one hospital. The number of metastatic sites at diagnosis was 1–4. The biological effective dose of CTRT ranged from 52 to 113 Gy. Only two patients (6%) developed grade 3 toxic effect of thrombocytopenia, but none experienced grade 4 or 5 toxicity. Four patients developed immune-related pneumonitis during the induction treatment period but successfully completed later CTRT. The rate of radiation-related pneumonitis was 8% with grades 1–2 and well tolerated. The median progression-free survival (PFS) was 12.8 months, but the median overall survival (OS) was not determined. The estimated 1-year OS was 80.2% and 1-year PFS was 53.4%. Conclusions: Immunotherapy combined with CTRT for ES-SCLC is safe and has ample survival benefit. [ABSTRACT FROM AUTHOR]

Purpose: As for local advanced non-small cell lung cancer (NSCLC), synchronous radiotherapy and chemotherapy is the standard treatment mode. But for patients with progress in half a year, which means the second-line chemotherapy effect is not ideal for them. We observed the efficacy and safety of anlotinib hydrochloride combined with PD-1 blockade as the second-line treatment for those patients in this trial. Patients and Methods: From January 2018 to December 2019, 57 patients with the progress of local advanced NSCLC treated with anlotinib plus PD-1 blockade until disease progression or intolerance as a result of adverse events. Patients have been assessed using computed tomography prior to treatment and during follow-up every 2 months until disease progression or death. The primary endpoint was objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS) and safety. Survival curves were created using the Kaplan–Meier method. Results: 57 patients were enrolled. The median age was 64 years, and 61.4% of the patients were men. The ORR was 50.9% with a median OS time of 14 months and the 1-year OS rates and PFS rates were 81.8% and 33.3%, respectively. The patients with squamous cell carcinoma, no brain or liver metastases had longer PFS than patients with liver metastasis. When the PFS was calculated from the time of second treatment, the median PFS was 9 months. Most adverse events (AEs) were grade 1– 3, one drug-related death was noted. Conclusion: The expected outcome of this study is that anlotinib combined with PD-1 blockade has tolerable toxicity and better ORR, OS than second-line chemotherapy. The results may indicate additional treatment options for patients with progress of local advance NSCLC in half a year after standard treatment. [ABSTRACT FROM AUTHOR]

Temozolomide ( TMZ) has been widely used in the treatment of glioblastoma ( GBM), although inherent or acquired resistance restricts the application. This study was aimed to evaluate the efficacy of sulforaphane ( SFN) to TMZ-induced apoptosis in GBM cells and the potential mechanism. Biochemical assays and subcutaneous tumor establishment were used to characterize the function of SFN in TMZ-induced apoptosis. Our results revealed that β-catenin and miR-21 were concordantly expressed in GBM cell lines, and SFN significantly reduced miR-21 expression through inhibiting the Wnt/β-catenin/ TCF4 pathway. Furthermore, down-regulation of miR-21 enhanced the pro-apoptotic efficacy of TMZ in GBM cells. Finally, we observed that SFN strengthened TMZ-mediated apoptosis in a miR-21-dependent manner. In conclusion, SFN effectively enhances TMZ-induced apoptosis by inhibiting miR-21 via Wnt/β-catenin signaling in GBM cells. These findings support the use of SFN for potential therapeutic approach to overcome TMZ resistance in GBM treatment. [ABSTRACT FROM AUTHOR]

Background: To study lymphatic recurrence distribution after radical surgery in the real world and guide clinical tumor volume delineation for regional lymph nodes during postoperative radiotherapy for lower thoracic squamous cell esophageal carcinomas.Methods: We enrolled patients who underwent radical esophagectomy, without radiation before or after surgery, at 3 cancer hospitals. Patients were classified into groups according to tumor locations. We included patients with tumors in the lower thoracic segment and analyzed the postoperative lymph node recurrence mode. A cutoff value of 10% was used to differentiate high-risk lymph node drainage areas from others.Results: We enrolled 1905 patients in the whole study series, including 652 thoracic esophageal carcinomas that met our inclusion criteria; there were 241 cases of lower thoracic esophageal carcinomas. 1st, 2nd, 4th, 7th, 8th groups of lymph nodes, according to the 8th edition of the AJCC classification, displayed as high-risk recurrence areas, representing 17.8%, 23.9%, 11.7%, 10.9% and 12.2% of lymph node recurrence. Stage III-IV tumors located in the lower segment of the thoracic esophagus showed a tendency to recur in the left gastric nodes (7.9%) and celiac nodes (10.6%).Conclusions: According to our results, we recommended including the 4th, 7th and 8th groups of lymph nodes in the radiation field, and for patients with stage III-IV disease, the 17th and 20th groups of nodes should be irradiated during postoperative treatment. Whether including 1st/2nd groups in preventive irradiation needed more proofs. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: T helper 1 cell (Th1) polarization persists in the autoimmune response found in immune thrombocytopenia (ITP). Toll-like receptor 7 (TLR7) expression, which also plays an important role in autoimmune diseases, was verified to increase in ITP. However, the exact role of TLR7 in ITP is not well elucidated. Here, we explored the hypothesis that TLR7 participates in the pathophysiology of ITP by affecting Th1 polarization. Materials and methods: Twenty-two ITP patients and twenty-one controls were enrolled in this study. We examined the cytokine secretion of macrophages in ITP patients and controls using both TLR7 agonist (imiquimod) and antagonist (IRS 661). The influence of macrophage secretion from these groups and its effects on Th1/Th2 differentiation were subsequently studied. Effects of TLR7 on Th1/Th2 balance and platelet counts were also studied in vivo using a thrombocytopenic mouse model. Results: In in vitro assays, imiquimod enhanced interleukin (IL)-12 secretion in macrophages from ITP patients inducing Th1 differentiation. However, IRS 661 had the exact opposite effect and skewed Th differentiation towards the Th2 subset in ITP. Results from our in vivo studies indicated that injection of imiquimod in ITP mice resulted in elevated plasma levels of IFN-γ and decreased platelet counts. Nevertheless, injection of IRS 661 resulted in elevated plasma levels of IL-4 and platelet counts. Conclusion: These findings indicate that TLR7 promotes Th1 polarization and may contribute thus in the pathogenesis of ITP. [Copyright &y& Elsevier]

To explore the value of modified intraoperative real-time 125I seed implantation planning for lumbar lymph nodes metastases. We collected 26 lymph nodes metastases patients, who received 125I seed implantation from January 2015 to December 2021. 13 patients procedure were guided by modified intraoperative real-time treatment plan, and the rest were guided by conventional treatment plan. To compare the differences of the dosimetric parameters between pre-plan and post-plan of the 2 groups, and the percentage difference of the dosimetric parameters between the 2 groups. Then evaluate the curative effect and side effects after 6-month. There were no significant differences in dosimetric parameters between pre-plan and post-plan in modified intraoperative real-time treatment plan group, and showed significant differences in V 150 between pre-plan and post-plan in conventional treatment plan group(z =-3.045, P <0.001), and the rest dosimetric parameters of conventional treatment plan group showed no significant differences beforeand after operation(P >0.05). The percentage difference of V 150 between the 2 groups showed statistically significant(z =2.103 , P =0.004), and the rest dosimetric parameters showed no significant differences(P >0.05).6 months after the brachytherapy, the effective rate of Modified intraoperative real-time treatment plan group was 77%(10/13), and 46%(6/13) in Conventional treatment plan group, and no peritonitis and hemorrhage were observed. The application of modified real-time planning improved accuracy of dosimetric, reduced the high dose rate area, and provide guarantee for 125I seed implantation planning for lumbar lymph nodes metastases. [ABSTRACT FROM AUTHOR]

To investigate the relationship between dose parameters and tumor volume reduction ratio after 125I seed implantation for recurrent cervical squamous cell carcinoma, and to obtain the better parameters to predict the curative effect. 26 cervical squamous cell carcinoma patients with 30 lesions were studied retrospectively in our clinic. All patients underwent dose verification immediately after operation, and obtained postoperative D 90 (the minimum peripheral dose accepted by 90% target volume). The patients were followed up regularly. According to the CT images during the actual follow-up, the tumor volume reduction ratio at the end of t months (R t),the tumor volume reduction ratio 1 month after operation (R 1), the first month actual absorbed dose (D 1m), the first month efficacy corrected absorbed dose (D 1e), the first month sensitivity corrected absorbed dose (D 1s) and the t months actual absorbed dose (D t) were calculated. Curve fitting was performed for postoperative D90 and R1, and curve fitting was performed for postoperative D 90 , D 1m , D 1e , D 1s and R t to find the correlation between each parameter and tumor volume reduction ratio. The mean values of D 90 ,D 1m ,D 1e ,D 1s ,R t ,R 1 were (105.4±22.8) Gy,(30.9±7.4)Gy,(37.1±8.9)Gy,(37.8±11.6)Gy,(39.4±17)%,(20.4±12)%. Postoperative D 90 and R 1 , postoperative D 90 , D 1m , D 1e , D 1s andR t all have positive relationship. The equations are as follows y=6.856×10-7x3-2.66×10-4x2+0.031x-0.879(R2=0.139),y=1.573×10-6x3-4.47×10-4x2+0.045x-0.967(R2=0.027),y=7.11×10-5x3-0.07x2+0.193x-1.402(R2=0.043),y=3.546×10-5x3-0.003x2+0.108x-0.744(R2=0.126),y=1.022×10-5x3-0.001x2+0.048x-0.275(R2=0.243). PostoperativeD 90 , D 1m , D 1e and D 1s were positively correlated with postoperative tumor volume reduction ratio, which can be used to predict the efficacy of primary recurrent cervical squamous cell carcinoma patients with particle implantation. Compared with D 90 and D 1m , and D 1e , D 1s can be better predictors. [ABSTRACT FROM AUTHOR]

• Induction ICIs followed by RT might improve survival and locoregional control. • RT after ICIs brought survival benefits compared with historical evidence. • Consolidation ICIs after RT might be associated with improved survival. • 1These authors contributed equally to the work. The study aimed to investigate the efficacy of induction immunochemotherapy before radiotherapy (RT) for patients with locally advanced or metastatic esophageal cancer. Patients with unresectable locally advanced or metastatic esophageal cancer who received induction immunochemotherapy followed by RT (ICIs + RT group) and RT alone (RT group) were retrospectively identified in two cancer centers, respectively. Propensity score matching (PSM) was used to balance the potential confounders between the two groups. Overall survival (OS), progression-free survival (PFS), and recurrence patterns were evaluated. A total of 467 patients were reviewed, and 66 were matched in each group. After PSM, the 1- and 2-year OS rates were 84.6% and 57.9% in ICIs + RT group, and 71.1% and 43.0% in RT group (HR 0.60, 95% CI 0.36–1.00, p = 0.050). The absolute increase of restricted mean survival time (RMST) for OS in ICIs + RT group compared with RT group were 0.89 years (p = 0.023) at one year and 2.59 years at two years (p = 0.030). The median PFS time, 1- and 2-year PFS rates were 20.3 months, 69.3%, and 45.7% in ICIs + RT group, and 12.2 months, 51.4%, and 35.8% in RT group (HR 0.64, 95% CI 0.41–0.99, p = 0.045). The cumulative locoregional recurrence (LRR) rate was significantly lower in ICIs + RT group (1-year rate, 17.4% vs. 38.8%, p = 0.011), and distant metastasis (DM) rates were comparable (p = 0.755). Consolidation ICIs was associated with a trend of improved 1-year OS and PFS. Induction immunochemotherapy followed by RT might improve locoregional control and survival outcomes for patients with unresectable locally advanced or metastatic esophageal cancer. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on the definition or recommended radiotherapy treatment of ultracentral non‐small cell lung cancer (NSCLC). Here, we report our institution's experience in treating ultracentral lung cancer patients with stereotactic ablative radiotherapy (SABR) of 60 Gy in eight fractions. Methods: We retrospectively reviewed the outcomes of 21 ultracentral NSCLC patients treated with 60 Gy SABR in eight fractions. We defined ultracentral lung cancer as the planning target volume (PTV) directly abutting or overlapping central structures, including the proximal bronchial tree, heart, and great vessels but not the esophagus. The Kaplan‐Meier method was used to estimate overall survival (OS), progression‐free survival (PFS) and local control (LC). Toxicity was scored per the CTCAE v4.03. Results: The median follow‐up time was 15 months, and the median OS was 15 months. The one‐ and two‐year OS rates were 87.5% and 76.6%, respectively. The one‐ and two‐year PFS rates were 71.1% and 64.0%, respectively. The one‐ and two‐year LC rates were 92.9% and 92.9%, respectively. The rate of grade 2 treatment‐related toxicities was 19.1%. There was no grade ≥ 3 treatment‐related toxicity. Conclusion: SABR of 60 Gy in eight fractions is feasible for ultracentral NSCLC. [ABSTRACT FROM AUTHOR]

Purpose: Exosomal miRNAs that play an important role in cell-cell communication have attracted major attention as potential diagnostic and prognostic biomarkers for various cancers. The aim of this study was to determine the diagnostic/prognostic significance of serum exosomal miR-301a in glioma patients. Methods: Quantitative real-time PCR was used to determine the serum exosomal expression levels of miR-301a. Kaplan-Meier survival analyses, Cox regression analyses and ROC working curve analyses were applied to assess the diagnostic and prognostic values of miR-301a in glioma patients. Also, several in vitro assays were used, including proliferation, invasion and cell signaling assays. Results: First, we established that serum exosomal miR-301a extracted from grade IV glioblastoma (GBM) patients was biologically active, i.e., promoted the proliferation and invasion of glioma-derived H4 cells. Subsequently, we found that serum exosomal miR-301a levels were significantly up-regulated in glioma patients compared to healthy controls. Additionally, we found that increased serum exosomal miR-301a levels were correlated with ascending pathological grades and lower Karnofsky performance status (KPS) scores. Importantly, we also found that the serum exosomal miR-301a levels were significantly reduced after surgical resection of primary tumors and increased again during GBM recurrence. Kaplan-Meier analysis of patients with an advanced pathological grade (III or IV) and an increased serum exosomal miR-301a level revealed a longer overall survival (OS) compared to those with a lower level ( p < 0.01). Both univariate and multivariate Cox regression analyses confirmed that serum exosomal miR-301a levels are independently associated with OS. Finally, we found that miR-301a may activate the AKT and FAK signaling pathways by down regulating PTEN. Conclusions: Our data indicate that serum exosomal miR-301a levels may reflect the cancer-bearing status and pathological changes in glioma patients. Serum exosomal miR-301a expression may serve as a novel biomarker for glioma diagnosis and as a prognostic factor for advanced grade disease. [ABSTRACT FROM AUTHOR]

Background: The vascular endothelial cells are important targets of radiotherapy, which may be involved in the pathogenesis of radiation pneumonitis (RP). This study investigated the variations of circulating endothelial progenitor cells (EPCs) and transforming growth factor-beta-1 (TGF-β1) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer (NSCLC) and analyzed the correlation between these variations with the occurrence of RP.Patients and Methods: From November 2008 to November 2009, eighty-four consecutive patients receiving 3D-CRT for stage III disease were evaluated prospectively. Circulating EPCs and TGF-β1 levels were measured at baseline, every 2 weeks during, and at the end of treatment. RP was evaluated prospectively at 6 weeks after 3D-CRT.Results: Thirty-eight patients (47.5%) experienced score 1 or more of RP. The baseline levels of EPCs and TGF-β1 were analyzed, no difference was found between patients with and without RP during and after 3D-CRT. By serial measurement of TGF-β1 and EPCs levels, we found that the mean levels of EPCs in the whole population remained stable during radiotherapy, but the mean levels of TGF-β1 increased slowly during radiotherapy. TGF-β1 and EPCs levels were all significantly higher at week 2, week 4 and week 6 in patients with RP than that in patients without RP, respectively. During the period of radiation treatment, TGF-β1 levels began to increase in the first 2 weeks and became significantly higher at week 6 (P < 0.01). EPCs levels also began to increase in the first 2 weeks and reached a peak at week 4. Using an ANOVA model for repeated-measures, we found significant associations between the levels of TGF-β1 and EPCs during the course of 3D-CRT and the risk of developing RP (P < 0.01). Most of the dosimetric factors showed a significant association with RP.Conclusion: Early variations of TGF-β1 and EPCs levels during 3D-CRT are significantly associated with the risk of RP. Variations of circulating TGF-β1 and EPCs levels during 3D-CRT may serve as independent predictive factors for RP.Trial Registration: Trials registration number: 20070618. [ABSTRACT FROM AUTHOR]

Background and Aim: MicroRNAs are short noncoding RNA molecules that are responsible for the posttranscriptional regulation of target genes. The aim of this study was to determine whether microRNA-199b-5p (miR-199b) plays a role in the progression and prognosis of hepatocellular carcinoma (HCC), and to elucidate whether hypoxia-inducible factor-1α (Hif1α) is regulated by miR-199b. Methods: In this study, 35 matched HCCs and cirrhosis tissues were assayed for miR-199b and Hif1α expression. To evaluate the role of miR-199b, we assessed cell proliferation rate and clonogenic survival of miR-199b- or negative control-transfected cells by MTT and clone formation assay, respectively. In addition, the regulation of Hif1α by miR-199b was evaluated by Western blotting and luciferase assay. MiR-199b was downregulated in 77% of HCCs, whereas Hif1α protein was upregulated in 69% of cases. A significant inverse correlation between miR-199b and Hif1α was observed in HCCs. Results: Patients with lower levels of miR-199b expression had poorer overall survival and progression-free survival rates, whereas patients with higher levels of miR-199b expression had better survival. Moreover, miR-199b could restrain cell growth and obviously enhance the radiosensitizing effect of HepG2 cells. MiR-199b and pGL3-Hif1α vector-transfected cells showed suppressed Hif1α protein expression and significant reduced luciferase activity. Conclusions: Underexpressed miR-199b, which may be via the upregulation of Hif1α in HCCs, is inversely correlated with survival and directly correlated with the malignant status of HCC patients. [ABSTRACT FROM AUTHOR]