Objective To evaluate the effects of rigorous surveillance and retroperitoneal lymph node dissection (RPLND) in the treatment of low-risk patients with clinical stage Ⅰ nonseminomatous germ cell testicular tumors (NSGCT) after radical orchiectomy.Methods The data of 71 patients with clinical stage Ⅰ NSGCT were analyzed retrospectively in Hunan Provincial Tumor Hospital,Xiangya Third Hospital of Central South University and Hunan Provincial People's Hospital between Feb,2001 and Apr,2012.Excluding lymphatic and vascular invasion,percentage of embryonal carcinoma＞50％ and increasing tumour markers (AFP/β-HCG) following orchiectomy,46 low-risk patients out of 71 patients with clinical stage Ⅰ NSGCT were selected and divided into rigorous surveillance group (30 cases) and RPLND group (16 cases) according to different therapeutic methods after radical orchiectomy.Univariate analysis was used to confirm variables associated with disease progression,and the disease free survival rates (DFSR) were compared by using Kaplan-Meier analysis.Results Five cases were lost,and 41 cases were followed up for an average of 61 months (range,15-147 months),with 58 months in rigorous surveillance group (range,19-147months) and 65 months in RPLND group (range,15-144 months).The survival rate was 100％ in 2 groups.The DFSR was 89％ (24/27) and 86％ (12/14),respectively,and there was no significant difference between the 2 groups (x2 =0.08,P=0.78).The DFSR was 83％ in patients with small amout of embryonal (percentage of embryonal carcinoma ＜ 50％),and 92％ in patients without embryonal carcinoma,and there was no significant difference between the 2 groups (x2=1.07,P=0.30).Also there was no significant difference between the patients less than 15 years and patients more than 15 years (x2=1.59,P =0.21).Conclusions There is no significant difference in recurrence rate and DFSR between rigorous surveillance group and RPLND group.Low-risk patients with clinical stage Ⅰ NSGCT may achieve satisfactory prognosis with surveillance after radical orchiectomy.
Key words:
Nonseminomatous germ cell testicular tumors; Testicular neoplasms; Surveillance; Risk factors; Age factors
Abstract Background: To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of primary hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size. Methods: A total of 433 participants were enrolled in this study including 266 cases with HCC, 87 cases with liver cirrhosis and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HCC patients with and without vascular invasion. Results: The level of AFP and PIVKA-II in HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P<0.01). When AFP and PIVKA-II were used as the individual tumor marker, the areas under the ROC curve (AUC) of HCC diagnosis were 0.765 (95% CI, 0.713～0.8170) for AFP, 0.901 (95% CI, 0.868～0.935) for PIVKA-II, and 0.917 (95% CI, 0.886～0.948) for AFP and PIVKA-II simultaneously. The serum levels of AFP and PIVKA-II were positively correlated with tumor differentiation and size. High AFP and PIVKA-II expression was significantly associated with the presence of vascular invasion (P was 0.007 and 0.014 respectively). The AFP level >64.4ng/ml or PIVKA-II level >957.61mAU/ml was the best critical value to predict the presence of vascular invasion. Conclusion: The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. And the proper concentration has important clinical value for judging tumor size, tumor cell differentiation and vascular invasion. Above results validate that AFP and PIVKA-II play a significant role in the diagnosis of HCC.
Numerous studies have shown that long non-coding RNA (lncRNA) is involved in various human diseases including non-small cell lung cancer (NSCLC). The aim of this study was to explore the potential role of lncRNA HCG11 in the pathogenesis of NSCLC.The mRNA expression of HCG11, miR-522-3p and SOCS5 was detected by RT-qPCR. The regulatory mechanism of lncRNA HCG11 was investigated by CCK-8, transwell and dual luciferase reporter assays.Downregulation of lncRNA HCG11 and upregulation of miR-522-3p were found in NSCLC tissues and cells, and abnormal expressions of lncRNA HCG11 and miR-522-3p were related to adverse clinical outcomes of NSCLC patients. LncRNA HCG11 acted as a molecular sponge for miR-522-3p. Functionally, lncRNA HCG11 inhibited cell viability, migration and invasion in NSCLC by downregulating miR-522-3p. Further, miR-522-3p directly targeted SOCS5. lncRNA HCG11 could positively regulate SOCS5 expression in NSCLC. In addition, HCG11 downregulation or miR-522-3p overexpression abolished the inhibitory effect of SOCS5 on cell viability, migration and invasion in NSCLC.LncRNA HCG11 inhibits cell viability, migration and invasion in NSCLC by functioning as a ceRNA of miR-522-3p to upregulate SOCS5.
Abstract Aging is a major risk factor for cardiovascular diseases. Our previous studies demonstrate that aging impairs the caveolar T‐type Ca V 3.2‐RyR axis for extracellular Ca 2+ influx to trigger Ca 2+ sparks in vascular smooth muscle cells (VSMCs). We hypothesize that the administration of senolytics, which can selectively clear senescent cells, could preserve the caveolar Ca V 3.2‐RyR axis in aging VSMCs. In this study, 10‐month‐old mice were administered the senolytics cocktail consisting of dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi‐weekly for 4 months. Using VSMCs from mouse mesenteric arteries, we found that Ca 2+ sparks were diminished after caveolae disruption by methyl‐β‐cyclodextrin (10 mM) in cells from D + Q treated but not vehicle‐treated 14‐month‐old mice. D + Q treatment promoted the expression of Ca V 3.2 in 14‐month‐old mesenteric arteries. Structural analysis using electron tomography and immunofluorescence staining revealed the remodeling of caveolae and co‐localization of Ca V 3.2‐Cav‐1 in D + Q treatment aged mesenteric arteries. In keeping with theoretical observations, Ca v 3.2 channel inhibition by Ni 2+ (50 μM) suppressed Ca 2+ in VSMCs from the D + Q group, with no effect observed in vehicle‐treated arteries. Our study provides evidence that age‐related caveolar Ca V 3.2‐RyR axis malfunction can be alleviated by pharmaceutical intervention targeting cellular senescence. Our findings support the potential of senolytics for ameliorating age‐associated cardiovascular disease.
Background Nowadays, the important roles of long non‐coding RNAs (LncRNAs) in lung adenocarcinoma (LAD) is being increasingly recognized. The purpose of this study was to explore the regulatory mechanism of lncRNA ZFAS1 in LAD. Methods The expression and function of lncRNA ZFAS1 were assessed by RT‐qPCR, CCK‐8, transwell and dual luciferase reporter assays. Results Upregulation of lncRNA ZFAS1 was found in LAD tissues and cells. Knockdown of lncRNA ZFAS1 restrained cell proliferation, migration and invasion in LAD cells. In addition, we determined that lncRNA ZFAS1 could directly bind to miR‐1271‐5p. MiR‐1271‐5p functioned as a tumor suppressor in LAD, and lncRNA ZFAS1 promoted LAD development by downregulating miR‐1271‐5p. Furthermore, FRS2 was a direct target of miR‐1271‐5p. FRS2 promoted progression of LAD by mediating lncRNA ZFAS1/miR‐1271‐5p axis. Conclusions LncRNA ZFAS1 promotes cell proliferation, migration and invasion in LAD by downregulating miR‐1271‐5p or upregulating FRS2.
Killer cell immunoglobulin-like receptors (KIRs) are involved in the pathogenesis of a variety of diseases. However, whether KIR polymorphism is associated with susceptibility to pulmonary tuberculosis was unknown. We examined a possible association of KIR polymorphism with susceptibility to pulmonary tuberculosis in Chinese Han. We analyzed 15 KIR genes in 109 pulmonary tuberculosis patients and 110 healthy controls using sequence-specific primer PCR analysis of genomic DNA. We found that the frequencies of KIR2DS1, 2DS3 and 3DS1 were significantly higher in patients than in the control group. In addition, the number of subjects carrying more than two activating KIR genes in the patient group was significantly higher than in the control group. The gene cluster containing KIR3DS1-2DL5-2DS1-2DS5 was also significantly more frequent in the patient group. In conclusion, KIR genes 2DS1, 2DS3 and 3DS1 appear to be associated with resistance to pulmonary tuberculosis in the Chinese Han population. KIR genes apparently have a role in resistance to pulmonary tuberculosis.
N6-methyladenosine (m6A) is one of the most prevalent RNA modifications in mRNA and non-coding RNA. In this study, we identified 10 upregulated m6A regulators at both mRNA and protein levels, and 2,479 m6A-related lncRNAs. Moreover, the m6A-related long noncoding RNAs (lncRNAs) could clearly stratify the colon adenocarcinoma (COAD) samples into three subtypes. The subtype 2 had nearly 40% of samples with microsatellite instability (MSI), significantly higher than the two other subtypes. In accordance with this finding, the inflammatory response-related pathways were highly activated in this subtype. The subtype-3 had a shorter overall survival and a higher proportion of patients with advanced stage than subtypes 1 and 2 ( p -value < 0.05). Pathway analysis suggested that the energy metabolism-related pathways might be aberrantly activated in subtype 3. In addition, we observed that most of the m6A readers and m6A-related lncRNAs were upregulated in subtype 3, suggesting that the m6A readers and the m6A-related lncRNAs might be associated with metabolic reprogramming and unfavorable outcome in COAD. Among the m6A-related lncRNAs in subtype 3, four were predicted as prognostically relevant. Functional inference suggested that CTD-3184A7.4, RP11-458F8.4, and RP11-108L7.15 were positively correlated with the energy metabolism-related pathways, further suggesting that these lncRNAs might be involved in energy metabolism-related pathways. In summary, we conducted a systematic data analysis to identify the key m6A regulators and m6A-related lncRNAs, and evaluated their clinical and functional importance in COAD, which may provide important evidences for further m6A-related researches.
Luteolin, a flavone, has been demonstrated to have anti‑cancer properties. In the current study, the effects of luteolin on certain carcinogenesis‑associated changes induced by pancreatitis, which are significant risk factors for pancreatic cancer, were investigated. Male six‑week‑old C57BL6 mice used in the current study were divided into three groups; the control group, acute pancreatitis group and luteolin group. Intra‑peritoneal injection of cearulein was performed in the acute pancreatitis group and luteolin group to induce acute pancreatitis whereas the luteolin group received intra‑peritoneal injection of luteolin. The control group received intra‑peritoneal injection of normal saline. Then, the expression of SOX9, phosphorylated (p‑) STAT3, p‑EGFR, cytokeratin‑19, Ki67 and N‑cadherin were determined by immunohistochemistry. Morphological changes of acinar cells were determined by hematoxylin and eosin staining. The mRNA expression of the epithelial‑mesenchymal transition markers CDH1, CDH2, Slug, Zeb1, EpCAM, ZO1, Vimentin, Snail and Twist was determined by reverse transcription‑quantitative polymerase chain reaction. It was identified that luteolin inhibits the formation of tubular complexes and ectopic expression of cytokeratin‑19 and luteolin also decreased proteins of SOX9, p‑STAT3 and p‑EGFR. In addition, luteolin inhibits proliferation and epithelial‑mesenchymal transition of acinar cells induced by acute pancreatitis. As tubular complex formation and ectopic expression of cytokeratin‑19 were two prominent characters of acinar‑ductal metaplasia, it was concluded that luteolin inhibits acinar‑ductal metaplasia induced by pancreatitis and also inhibits pancreatitis‑induced proliferation and epithelial‑mesenchymal transition of acinar cells. Acinar‑ductal metaplasia and proliferation have close associations with pancreatic carcinogenesis. It is suggested that luteolin has potential anti‑pancreatic carcinogenesis effects and merits further investigation.
Abstract Resection of completely endophytic renal tumors is a huge challenge for surgeons due to a lack of definite visual clues, especially in the laparoscopic approach. Three-dimensional (3D) kidney models, which can illustrate the clear relationship between renal masses and surrounding health tissues, were considered as reliable tools for understanding renal tumor characteristics in previous studies. We hypothesized that 3D kidney models can be used not only for planning but also for navigating laparoscopic partial nephrectomy (LPN) in patients with completely endophytic renal tumors. In this study, we successfully constructed five cases of 3D kidney models for assisted planning and navigation for LPN in endophytic renal tumors. The renal masses and surrounding normal parenchyma of the patient-specific 3D models were dyed by different colorants for clear illustration. All patients experienced acceptable perioperative outcomes, and no patient suffered serious relative complications. The 3D kidney models were considered as a reliable tool based on clinical outcome and postoperative questionnaire results. This study is the first report of 3D kidney models for patients with completely endophytic tumors. 3D kidney models can aid surgeons in understanding the characteristics of renal tumors and potentially support assisted planning and performance of LPN in endophytic tumor cases.
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