Background: The aim of the present study was to identify the potential long non-coding (lnc.)-RNA and its associated molecular mechanisms involved in the regulation of the radiosensitivity of esophageal squamous cell cancer (ESCC) in order to assess whether it could be a biomarker for the prediction of the response to radiotherapy and prognosis in patients with ESCC.Methods: Microarrays and bioinformatics analysis were utilized to screen the potential lncRNAs associated with radiosensitivity in radiosensitive (n = 3) and radioresistant (n = 3) ESCC tumor tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed in 35 ESCC tumor tissues (20 radiosensitive and 15 radioresistant tissues, respectively) to validate the lncRNA that contributed the most to the radiosensitivity of ESCC (named the candidate lncRNA). MTT, flow cytometry, and western blot assays were conducted to assess the effect of the candidate lncRNA on radiosensitivity in vitro in ECA109/ECA109R ESCC cells. A mouse xenograft model was established to confirm the function of the candidate lncRNA in the radiosensitivity of ESCC in vivo. The putative downstream target genes regulated by the candidate lncRNA were predicted using Starbase 2.0 software and the TargetScan database. The interactions between the candidate lncRNA and the putative downstream target genes were examined by Luciferase reporter assay, and were confirmed by PCR.Results: A total of 113 aberrantly expressed lncRNAs were identified by microarray analysis, of which family with sequence similarity 201-member A (FAM201A) was identified as the lncRNA that contributed the most to the radiosensitivity of ESCC. FAM201A was upregulated in radioresistant ESCC tumor tissues and had a poorer short-term response to radiotherapy resulting in inferior overall survival. FAM201A knockdown enhanced the radiosensitivity of ECA109/ECA109R cells by upregulating ataxia telangiectasia mutated (ATM) and mammalian target of rapamycin (mTOR) expression via the negative regulation of miR-101 expression. The mouse xenograft model demonstrated that FAM201A knockdown improved the radiosensitivity of ESCC.Conclusion: The lncRNA FAM201A, which mediated the radiosensitivity of ESCC by regulating ATM and mTOR expression via miR-101 in the present study, may be a potential biomarker for predicting radiosensitivity and patient prognosis, and may be a therapeutic target for enhancing cancer radiosensitivity in ESCC.
Purpose To validate and propose revision of the 8th edition American Joint Committee on Cancer (AJCC) clinical staging system for esophageal squamous cell cancer (ESCC) patients treated with definitive intensity-modulated radiation therapy combined with concurrent chemotherapy (Chemo-IMRT) based on computed tomography (CT) imaging. Methods The clinical data of patients with ESCC treated with Chemo-IMRT were collected and retrospectively reviewed. All CT images were independently reevaluated and restaged according to the 8th edition AJCC staging system. The overall survival (OS) rates were analyzed statistically. ROC curves of the various parameters of the primary tumor and metastatic lymph nodes were generated in order to identify the cutoff values correlated to patient survival using the area under curve. Results The gross tumor volume of the primary tumor (GTV-prT) and the clinical N stage (cN) were independent factors that influenced OS. The 5-year OS rate of patients with GTV-prT ≤28 cm 3 , GTV-prT > 28 and ≤ 56 cm 3 , and GTV-prT > 56 cm 3 were 54.6, 31.1 and 18.6%, respectively. The 5-year OS rate of patients with cN0, cN1 SLNM (−), cN2 SLNM (−), cN3 SLNM (−) and SLNM (+) were 62.8 ( P < 0.001), 34.0 ( P = 0.16), 20.0 ( P = 0.785), 0 (P < 0.001) and 26.9%, respectively. After restaging the SLNM as regional MLNs, the 5-year OS rates of the patients with cN0, 1, 2 and 3 were 62.8, 36.3, 23.7 and 7.8%, respectively. Various GTV-prT were combined with the cN to establish a new clinical TNM staging system: I, GTV-prT1 and cN0; II, GTV-prT2 or 3 and cN0, GTV-prT1 and cN1; III, GTV-prT1 and cN2, GTV-prT2 and cN1,2; Iva, GTV-prT3 and cN1,2; IVb, GTV-prT any and cN3; IVc, T any N any M1. Subsequently, the OS differed significantly between the adjacent GTV-prT cN categories, except those of stage I vs. II. Conclusion The SLNM should be dealt with as a regional rather than a distant disease in patients with ESCC when treated with CRT. The proposed nonsurgical staging system based on the GTV-prT and N appears to be a simple and accurate prognosis predictor for patients with ESCC who have undergone definitive Chemo-IMRT.
BackgroundThe aim of the present study was to assess the efficacy of adjuvant chemotherapy (AC) in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).MethodsThe clinical data of patients with ESCC treated with chemoradiotherapy with or without AC were collected and retrospectively reviewed. The overall survival (OS), locoregional failure-free survival (LFFS) and distant failure-free survival (DFFS) rates were analyzed statistically.ResultsA total of 187 patients fulfilled the inclusion criteria, 98 of whom were treated with CRT-alone, while 89 were treated with CRT-AC. Patient characteristics did not significantly differ between the CRT-alone and CRT-AC groups, with the exception of sex and the number of cycles of concurrent chemotherapy. Following CRT, 50 patients achieved complete response (CR), 67 had partial response (PR), 63 patients maintained stable disease (SD) and 7 developed progression of disease (PD). The OS, LFFS and DFFS at 1, 2 and 5 years for the entire cohort were 67.5, 41.4 and 27.2%; 68.7, 57.9 and 52.4%; and 78.5, 68.9 and 63.9%, respectively. The clinical N-stage, M-stage, and short-term response to CRT were identified as significant factors that influenced patient prognosis. No significant differences in OS, LFFS or DFFS were observed between the CRT-alone and CRT-AC groups for the entire cohort and for clinical N-stage, clinical M-stage and short-term response subgroups.ConclusionsThe short-term response to CRT and the tumor clinical stage were significant prognosis factors for patients with ESCC treated with CRT. With current chemotherapy regimens, AC did not improve survival for patients with ESCC treated with CRT. The retrospective nature of the current study serves as a limitation; thus, further clinical trials are required to evaluate the efficacy of AC in patients with ESCC treated with CRT.
Piperine, a kind of natural alkaloid found in the fruit of black ( Linn) and long ( Linn), has shown antitumor activities toward various cancer cell lines. However, the antitumor effects of Piperine on ovarian cancer and the underlying mechanism are not fully elucidated. Our result showed that Piperine reduced the cell viability of A2780 cells in a concentration and time-dependent manner, but has not any effect on normal ovarian cells. Flow cytometric analysis revealed that Piperine suppressed cells proliferation via induction of apoptosis, which was followed by release of mitochondrial cytochrome to cytosol, activation of caspase-3 and -9, as well as cleaved PARP. Moreover, Western blot results confirmed that Piperine (8, 16, and 20 μM) decreased phosphorylation of JNK and p38 MAPK in A2780 cells. In addition, caspase-3 inhibitor (Z-DEVD-FMK), caspase-9 inhibitor (Z-LEDH-FMK), JNK-inhibitor (SP600125), or p38 MAPK inhibitor (SB203580) could abate the apoptosis induced by Piperine (20 μM) treatment, while caspase-8 inhibitor (Z-IETD- FMK) exhibited no inhibitory effect on the induction of apoptosis in A2780 cells. These results provide the first evidence for the anticancer potential of Piperine in ovarian cancer cells, partially via JNK/p38 MAPK-mediated intrinsic apoptotic pathway.
Leiomyomatosis peritonealis disseminata (LPD) is a specific type of leiomyomatosis with an unclear pathogenesis that is rarely diagnosed by clinical evaluation. To date, <200 cases have been reported. The majority of the patients have a medical history of laparoscopic myomectomy for uterine fibroids. The use of laparoscopic power morcellation may be a contributor to the development of LPD, therefore, the specific surgical approach used in laparoscopic myomectomy should be carefully considered, and protective measures should be taken to prevent myoma fragments spreading if laparoscopic power morcellation is used. The present study reviewed and analyzed the medical history, diagnostic process and treatment strategy of a case of LPD to improve our understanding of the disease. In this report, the case of a 34 year-old female who underwent laparoscopic myomectomy to remove a uterine fibroid is presented. During the surgery, a myoma was resected using morcellators. Three years after surgery, exploratory laparotomy was performed due to uterine fibroid recurrence. During surgery, myoma was identified at the uterine bladder peritoneal reflection, where several unequally sized leiomyoma tubercles were identified on the uterine surface. Subsequently, myomectomy was performed. Postoperative pathology diagnosed leiomyoma. Two years later, gynecological ultrasound revealed a mass in the abdomen. Exploratory laparotomy was subsequently performed. During surgery, compact myoma tubercle-like cysts were identified on the surface of the intestine and mesentery, and an endometriotic cyst was identified on the left ovary. As the myomas were too compact to remove completely, the majority of leiomyoma on the intestine and mesentery was resected. The endometriotic cyst on the left ovary was also resected. Considering the patient’s medical history, observations during surgery and pathological results, the final diagnosis was LPD. Following surgery, the patient was treated with the gonadotropin-releasing hormone agonist, triptorelin acetate (3.5 mg, once every four weeks), for three months and followed-up every six months. In October 2014, a gynecological sonography examination revealed no abnormalities and at the time of writing, the patient remains alive and well.
Background The LKB1 tumor suppressor gene is commonly inactivated in non-small cell lung carcinomas (NSCLC), a major form of lung cancer. Targeted therapies for LKB1-inactivated lung cancer are currently unavailable. Identification of critical signaling components downstream of LKB1 inactivation has the potential to uncover rational therapeutic targets. Here we investigated the role of INSL4, a member of the insulin/IGF/relaxin superfamily, in LKB1-inactivated NSCLCs. Methods INSL4 expression was analyzed using global transcriptome profiling, quantitative reverse transcription PCR, western blotting, enzyme-linked immunosorbent assay, and RNA in situ hybridization in human NSCLC cell lines and tumor specimens. INSL4 gene expression and clinical data from The Cancer Genome Atlas lung adenocarcinomas (n = 515) were analyzed using log-rank and Fisher exact tests. INSL4 functions were studied using short hairpin RNA (shRNA) knockdown, overexpression, transcriptome profiling, cell growth, and survival assays in vitro and in vivo. All statistical tests were two-sided. Results INSL4 was identified as a novel downstream target of LKB1 deficiency and its expression was induced through aberrant CRTC-CREB activation. INSL4 was highly induced in LKB1-deficient NSCLC cells (up to 543-fold) and 9 of 41 primary tumors, although undetectable in all normal tissues except the placenta. Lung adenocarcinomas from The Cancer Genome Atlas with high and low INSL4 expression (with the top 10th percentile as cutoff) showed statistically significant differences for advanced tumor stage (P < .001), lymph node metastasis (P = .001), and tumor size (P = .01). The INSL4-high group showed worse survival than the INSL4-low group (P < .001). Sustained INSL4 expression was required for the growth and viability of LKB1-inactivated NSCLC cells in vitro and in a mouse xenograft model (n = 5 mice per group). Expression profiling revealed INSL4 as a critical regulator of cell cycle, growth, and survival. Conclusions LKB1 deficiency induces an autocrine INSL4 signaling that critically supports the growth and survival of lung cancer cells. Therefore, aberrant INSL4 signaling is a promising therapeutic target for LKB1-deficient lung cancers.
Background: Differential diagnosis of ovarian masses can influence both treatment selection and prognosis of ovarian tumor patients. A comprehensive review was performed with respect to the diagnostic value of conventional ultrasonography, Doppler ultrasonography and contrast-enhanced ultrasonography (CEUS) in differentiating benign from malignant ovarian masses. Methods: Databases were searched for relevant articles. Retrieved studies were screened according to the inclusion criteria. Pooled statistics including specificity, sensitivity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), diagnostic odds ratio (DOR) and area under curve (AUC) were utilized to calculate the overall diagnostic value for each diagnostic approach. Results: Sixty-seven high quality articles were finally enrolled in the present meta-analysis. The sensitivity and specificity of conventional US were 0.92 and 0.86, respectively. The corresponding sensitivity and specificity of Doppler US were 0.93 and 0.85, respectively. Additionally, these figures for CEUS were 0.97 and 0.92, respectively. Finally, the AUC values for conventional US, Doppler US and CEUS were 0.95, 0.96 and 0.99, respectively. Conclusion: All of the three US-related imaging modalities have relatively high diagnostic value in distinguishing malignant tumors from benign ones in ovarian tumors.
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