SWI/SNF family mutations in advanced NSCLC: genetic characteristics and immune checkpoint inhibitors' therapeutic implication.

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

Correlation between angiotensin and acute kidney injury in patients with sepsis.

OBJECTIVE: The aim of the study was to analyze the changes in angiotensin (Ang) levels in patients with sepsis complicated with acute kidney injury (AKI) and evaluate the relationship between Ang and AKI. PATIENTS AND METHODS: Prospective research methods were used in this study. A total of 66 sepsis patients admitted to the Intensive care Unit (ICU) of the First Hospital of Hebei Medical University from October 2020 to January 2021 were enrolled. According to the occurrence of AKI, patients were divided into the sepsis-associated AKI (SA-AKI) group and the non-AKI group. The levels of Ang-1 and Ang-2 were compared between the two groups. The relationship between Ang and glomerular filtration rate (GFR) in sepsis patients was studied by correlation analysis. RESULTS: Plasma Ang-1 in the SA-AKI group was significantly higher than that in the non-AKI group (0.39±1.05 ng/ml vs. 0.10±0.24 ng/ml, p=0.039). The Ang-2/Ang-1 in the SA-AKI group was lower than that in the non-AKI group with a significant difference (52.55±191.38 vs. 349.50±327.49, p=0.001). Correlation analysis indicated that Ang-1 was negatively correlated with GFR (r=-0.12, p=0.031), while Ang-2/Ang-1 was positively correlated with GFR (r=0.21, p<0.001). The Ang-2 was positively correlated with GFR (r=0.204, p<0.001) CONCLUSIONS: Plasma Ang-1 and Ang-2 levels are suggestive for assessing the risk of AKI in patients with sepsis.

Volar plate fixation vs. non-operative management for distal radius fractures in older adults: a meta-analysis.

OBJECTIVE: The aim of the study was to perform a systematic literature search and conduct a meta-analysis of studies comparing clinical and functional outcomes of open reduction with internal fixation (ORIF) using a volar plate and closed reduction with casting for distal radius fracture in older adults (≥60 years of age). MATERIALS AND METHODS: A comprehensive electronic search was done for PubMed, Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), and Google scholar databases. Only randomized controlled trials (RCTs) comparing the two treatment modalities for functional and clinical outcomes were eligible to be included. RESULTS: A total of 5 RCTs were included. The pooled estimates suggested reduced DASH scores (WMD 5.62; 95% CI, -8.55, -2.69) and improved grip strength [Grip strength compared to the contralateral side (%): WMD 13.07; 95% CI, 6.11, 20.02] in subjects receiving ORIF with volar plating. There were no significant differences in the range of motion of the wrist joint, pain scores, and rates of complications between the two treatment modalities. The overall quality of the included studies was moderate. CONCLUSIONS: Our study indicates that older adults treated with volar plating for fracture of distal radius have better DASH scores and improved grip strengths. However, improved DASH scores may not be clinically relevant. Furthermore, there may be no difference in pain scores, ROM, and the rates of complications between the two treatment modalities. Further trials with large sample size are required to provide more robust evidence on this topic.

LncRNA MIR503HG regulated cell viability, metastasis and apoptosis of cervical cancer via miR-191/CEBPB axis.

OBJECTIVE: The long non-coding RNA MIR503 host gene (MIR503HG) plays a role in suppressing or promoting cancer in many types of human malignant tumors. The role of MIR503HG in cervical cancer is still unknown. PATIENTS AND METHODS: The expression level of MIR503HG in cervical cancer tissues and cell lines was accessed using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. The Cell Counting Kit-8 (CCK-8) assay and flow cytometric analysis were performed to assess cell proliferation and apoptosis in cervical cancer. The nude mouse xenograft experiment was used to examine the ability of MIR503HG in tumor formation. In our study, we found that the expression of MIR503HG was significantly reduced in cervical cancer tissues and cell lines. In vitro studies have shown that MIR503HG inhibited cell proliferation and invasion, and enhanced cell apoptosis in cervical cancer through the miR-191/CEBPB axis. MIR503HG regulated the expression of miR-191 via directly binding to miR-191. RESULTS: The expression of MIR503HG had a negative correlation with miR-191 expression in cervical cancer tissues. MiR-191 regulated the expression of CEBPB by directly targeting 3'-UTR of CEBPB mRNA. Overexpression of MIR503HG inhibited cell proliferation, invasion and apoptosis in vitro, and inhibited tumor growth in vivo. CONCLUSIONS: MIR503HG plays a role in suppressing tumors in cervical cancer and is a long-term non-coding RNA.

Identification of hub prognosis-associated oxidative stress genes in skin cutaneous melanoma using integrated bioinformatic analysis.

OBJECTIVE: Oxidative stress (OS) significantly correlates with cancer progression. However, targeting OS has not been considered as a therapeutic strategy in skin cutaneous melanoma (SKCM) due to a lack of systematical studies on validated biomarkers. The work presented here aimed to identify hub prognosis-associated OS genes in SKCM and generated an effective predictive model. PATIENTS AND METHODS: Gene expression profiles of SKCM samples and normal skin tissues were obtained from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases to identify differentially expressed OS genes. The validation cohort was obtained from the Gene Expression Omnibus (GEO) database. RESULTS: Thirteen hub prognosis-associated OS genes were recognized and incorporated into the prognostic risk model. Our constructed model was significantly associated with overall survival of SKCM patients as well as was shown to be associated with cancer progression. Our prognostic risk model was found to improve the accuracy of diagnostics, as shown using both TCGA and GEO cohorts. Both hub gene expression and risk score were used to generated nomograms that displayed favorable discriminatory abilities for SKCM. CONCLUSIONS: Overall, our study presents a model that may provide novel insights into the prognosis and survival of SKCM patients, as well as the development of individualized treatment therapy.

Whole-body magnetic resonance imaging is superior to skeletal scintigraphy for the detection of bone metastatic tumors: a meta-analysis.

OBJECTIVE: The meta-analysis aims to compare the diagnostic performance of whole-body magnetic resonance imaging (MRI) and skeletal scintigraphy (SS) for the detection of skeletal metastases. MATERIALS AND METHODS: We searched Medline, Scopus, Embase and Cochrane library databases for identifying fifteen eligible studies with a total of 1939 participants, and the quality of these studies was assessed according to Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Sensitivities, specificities, diagnostic odds ratios (DOR), positive likelihood ratios (PLR), and negative likelihood ratios (NLR) were calculated. Summary receiver operating characteristic curves (sROC) were generated using bivariate models for whole-body MRI and skeletal scintigraphy. RESULTS: Whole-body MRI had higher but comparable patient-based higher specificity compared to SS (99% vs. 95%). However, it had markedly higher sensitivity (94% vs. 80% respectively), DOR (966 vs. 82), and LPR (54.4 vs 17.1). LNR of whole-body MRI was <0.1 (0.06), while LNR of SS was >0.1 (0.22). The area under curves (AUC) for whole-body MRI and SS were 0.99 and 0.95 respectively. CONCLUSIONS: We demonstrate that both whole-body MRI and SS have good diagnostic performance. However, MRI is superior for diagnostics of bone metastases, as it has higher sensitivity, higher diagnostic accuracy, and can be used for both confirmation and exclusion of metastatic bone disease.

LINC00473 functions as an oncogene and predicts poor prognosis in pancreatic cancer via the cAMP/ß-catenin axis.

OBJECTIVE: To investigate the expression and function of LINC00463 in pancreatic cancer (PC), and to demonstrate the relationship between LINC00473 expression and clinical pathological characteristics and prognosis of PC. PATIENTS AND METHODS: Expressions of LINC00473 in PC tissues and cell lines were detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00473 siRNA was synthesized to knock down the LINC00473 expression in PANC-1 cells. Proliferation, invasion, and migration abilities of experimental cells were analyzed using cell counting kit-8 (CCK-8) assay and transwell assay, respectively. cAMP activity was detected and protein expression of ß-catenin was measured to explain the underlying mechanism of LINC00473 in PC. The prognosis and clinical pathological features of PC patients were illustrated. RESULTS: LINC00473 was highly expressed in PC tissues and cells. Higher level of LINC00473 was relative with larger tumor size, worse tumor node metastasis (TNM) stage, worse tumor differentiation, higher rates of perineural invasion, and lymphatic invasion. Knockdown of LINC00473 significantly inhibited cell growth, invasion, and migration of PANC-1 cells. LINC00473 activated cAMP and then promoted the phosphorylation of ß-catenin to promote the progression of PC. Furthermore, high expression of LINC00473 and ß-catenin remarkedly indicated poor prognosis of PC patients. CONCLUSIONS: LINC00473 was upregulated in PC tissues and cells, indicating a poor prognosis and clinical pathological features of PC. It promoted PC progression via activating the cAMP/ß-catenin axis, which provided a novel target for the prediction for PC diagnosis, biological therapy, and prognosis.

Regulation of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia.

OBJECTIVE: To explore the regulatory effect of magnesium sulfate combined with nifedipine and labetalol on disease-related molecules in serum and placenta in the treatment of preeclampsia. PATIENTS AND METHODS: Altogether 100 patients with preeclampsia admitted to the Children & Women's Healthcare of Laiwu City were selected. They were divided into control group and experimental group according to different treatment methods. Among them, 51 patients in the control group were treated with magnesium sulfate combined with nifedipine, and 49 patients in the experimental group were treated with labetalol on the basis of the treatment in the control group. The therapeutic effects of the two methods were compared. The levels of the following factors in the two groups were compared: kallikrein expression, pregnancy-associated plasma protein A (PAPP-A), pregnancy-specific ß1 glycoprotein (SPI), placental growth factor (PLGF), human placental prolactin (HPL), transforming growth factor ß1(TGF-ß1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin in serum and placenta tissues. RESULTS: After treatment, the blood pressure in the experimental group was lower than that in the control group (p<0.05). The expression of kallikrein in serum and placental tissue of the patients in the experimental group was higher than that of the patients in the control group (p<0.05); PAPP-A level was lower than that in the control group (p<0.05); TGF-ß1 level was higher than that in the control group (p<0.05); VCAM-1 and E-selectin were lower than those in the control group (p<0.05), and kallikrein and TGF-ß1 in serum and placenta in the non-occurrence group were higher than those in the occurrence group (p<0.05). The serum and placenta PAPP-A, VCAM-1, and E-selectin in the non-occurrence group were lower than those in the occurrence group (p<0.05). CONCLUSIONS: Magnesium sulfate combined with nifedipine and labetalol has good efficacy in the treatment of preeclampsia. They can promote the expression of endogenous kallikrein, reduce the level of pregnancy-related hypertension predictors, and weaken the infiltration ability of cytotrophoblasts.

Long non-coding RNA MNX1-AS1 promoted osteosarcoma proliferation and invasion via inhibiting KISS1.

OBJECTIVE: Recent studies revealed that long non-coding RNAs (lncRNAs) participate in the progression and development of many human diseases. In this work, we are committed to uncovering the association between lncRNA MNX1-AS1 and the development of osteosarcoma. PATIENTS AND METHODS: MNX1-AS1 expression of osteosarcoma cells and tissue samples was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Besides, we conducted functional assays including cell proliferation assay, colony formation, and transwell assays. Furthermore, the underlying mechanism including RT-qPCR and Western blot assay was performed. RESULTS: MNX1-AS1 was higher-expressed in osteosarcoma samples than that in adjacent tissues. The abilities of proliferation and invasion were suppressed after MNX1-AS1 was knocked down in vitro. Moreover, KISS1 expression was upregulated at mRNA and protein level via silence of MNX1-AS1. Furthermore, the underlying mechanism of the development of osteosarcoma were investigated by RT-qPCR and Western blot assay. CONCLUSIONS: Our study demonstrated that MNX1-AS1 could enhance osteosarcoma cell proliferation and invasion by inhibiting KISS1, which might contribute to the therapy for osteosarcoma.

Charge Order in the Holstein Model on a Honeycomb Lattice.

The effect of electron-electron interactions on Dirac fermions, and the possibility of an intervening spin-liquid phase between the semimetal and antiferromagnetic (AF) regimes, has been a focus of intense quantum simulation effort over the last five years. We use determinant quantum Monte Carlo simulations to study the Holstein model on a honeycomb lattice and explore the role of electron- phonon interactions on Dirac fermions. We show that they give rise to charge-density-wave (CDW) order and present evidence that this occurs only above a finite critical interaction strength. We evaluate the temperature for the transition into the CDW which, unlike the AF transition, can occur at finite values owing to the discrete nature of the broken symmetry.

Development of Individualized Induced Pluripotent Stem Cells From Fibroblasts of Keloid Lesions in Patients.

OBJECTIVE: Presently, interesting research related to induced pluripotent stem cells (iPSCs) is emerging. However, the development of new therapies and techniques for treatment of refractory diseases is still required in dermatology. We are exploring novel methods to provide stem cell therapy and elucidate research mechanisms underlying troublesome diseases by reprogramming iPSCs from the fibroblasts of keloid lesions from patients in vitro. METHOD: Here, we identified the expression of fibroblastic genes in the fibroblast derived from diseased individuals. Corresponding iPSCs were then produced by transfecting patient fibroblasts with non-modified RNA cocktails, expressing OCT4, SOX2, KLF4, cMYC, NANOG, and LIN28 reprogramming factors. The pluripotency of these patient-derived iPSCs was identified by immunocytochemistry, real-time quantitative polymerase chain reaction, and teratoma formation in vivo in non-obese diabetic/severe combined immunodeficiency mice. RESULTS: All iPSCs derived from patients significantly expressed the pluripotent transcription factors and could be expanded in vitro. Furthermore, induction of terminal differentiation in long-term culture and the capability of forming embryonic bodies to differentiate into all 3 germ layers in vivo were confirmed in immune-deficient mice. CONCLUSION: Fibroblasts from a keloid patient were successfully reprogrammed to iPSCs in vitro. This reprogramming may provide a basis for the production of individualized modified artificial skin to prevent rejections after xenogeneic skin transplantation and trauma through autologous skin transplantation. These cells can also offer a new platform for research on mechanisms underlying skin diseases and personal medical applications.

Polymorphisms in lncRNA PTENP1 and the risk of oral squamous cell carcinoma in a Chinese population.

OBJECTIVE: PTENP1, a long noncoding RNA, has previously been reported to be involved in tumorigenesis and cancer progression. The relationship between PTENP1 and susceptibility tumors is reported, while, an association of PTENP1 with the risk of oral squamous cell carcinoma (OSCC) in Chinese population is lacked. This research is designed to investigate the association of PTENP1 with susceptibility of OSCC. PATIENTS AND METHODS: In this research, TaqMan technology was used to test genotype in 342 OSCC patients and 711 healthy controls, so as to analyze the association between PTENP1 polymorphisms (rs7853346 rs865005 and rs10971638) and susceptibility of oral squamous cell carcinoma. RESULTS: The results of this research showed that rs7853346 [Additive model: Adjusted odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.66-0.99] was related to the OSCC risk. It was not found that the other two sites were associated with the susceptibility of OSCC. CONCLUSIONS: This research indicated that rs7853346 is statistically correlated with the OSCC risk.

Propofol compared with sevoflurane general anaesthesia is associated with decreased delayed neurocognitive recovery in older adults.

BACKGROUND: The choice of general anaesthetics may affect postoperative cognitive outcomes. This study was designed to compare the potential impact of propofol-based vs sevoflurane-based general anaesthesia on the development of delayed neurocognitive recovery in older adults early after major cancer surgery. METHODS: Older adults (aged ≥65 and <90 yr) who were scheduled to undergo major cancer surgery (≥2 h) were randomised to receive either propofol- or sevoflurane-based general anaesthesia. Cognitive function was assessed before and 1 week after surgery with a battery of neuropsychological tests. Age- and education-matched non-surgical controls were recruited, and their cognitive functions were tested at comparable time intervals in order to adjust for learning effects from repeated tests. Delayed neurocognitive recovery was diagnosed according to the International Study of Postoperative Cognitive Dysfunction 1 definition. RESULTS: From April 1, 2015 to October 15, 2016, 392 patients were enrolled and randomised. Of these patients, 387 completed the intervention and 30-day follow-up, and 379 completed 1-week neuropsychological tests. Fifty-nine control subjects were enrolled and completed repeated neuropsychological tests. The incidence of delayed neurocognitive recovery at 1 week was significantly lower in the propofol group [14.8% (28/189)] than in the sevoflurane group [23.2% (44/190); odds ratio=0.577; 95% confidence interval, 0.342-0.975; P=0.038]. Safety outcomes did not differ between the two groups. CONCLUSIONS: When compared with sevoflurane-based general anaesthesia, propofol-based general anaesthesia might decrease the incidence of delayed neurocognitive recovery in older adults after major cancer surgery. CLINICAL TRIALS REGISTRATION: NCT02662257; Chinese Clinical Trial Registry (identifier: ChiCTR-IPR-15006209).

Mutation profile and associated clinical features in Chinese patients with cytogenetically normal acute myeloid leukemia.

INTRODUCTION: Cytogenetically normal acute myeloid leukemia (CN-AML), which accounted for nearly half of total AML patients, is a highly heterogeneous subset of AML. The specific genetic profile and the ethnic features of CN-AML are worth to be studied. METHODS: Using deep sequencing technology, we detected the mutation pattern of 39 genes in 152 Chinese CN-AML patients and analyzed their clinical features. RESULTS: A total of 503 mutations of 39 genes were identified in 145 (95.4%) patients, with the median number of 3 mutations per case. Nine genes (NPM1, CEBPA, DNMT3A, GATA2, NRAS, TET2, FLT3, IDH2, and WT1) mutated in more than 10% patients. Function groups of myeloid transcription factors, activated signaling, and DNA methylation were most affected. The distribution of variant allele frequencies (VAF) of recurrent genes was different among functional groups. High mutation rates of CEBPA and GATA2 together with the low frequency of FLT3-ITD mutation seemed to be the distinct characteristics of Chinese patients. Furthermore, CEBPAbi and GATA2 were found to mutate most in M2 subtype, while NPM1 and DNMT3A mutated more in M4 and M5. The prognostic analysis identified CEBPAmo mutation as an inferior factor. FLT3-ITD, TP53, DNMT3A, CEBPAmo, and WT1 mutations were selected as high-risk markers to identify the CN-AML patients with poor prognosis. CONCLUSION: Our study provided the valuable information of ethnic genetic characteristics and the clinical relevance of Chinese CN-AML patients.

Preoperative vitamin D deficiency increases the risk of postoperative cognitive dysfunction: a predefined exploratory sub-analysis.

BACKGROUND: Vitamin D is important for maintaining physiological functions including cognition and its deficiency is associated with the occurrence of cognitive impairment. This study was to explore the association between preoperative vitamin D status and the occurrence of postoperative cognitive dysfunction (POCD) in elderly patients undergoing major surgery. METHODS: This was a predefined exploratory sub-analysis of one-centre data from a randomized controlled trial. In all, 123 elderly (≥ 65 years) patients who were scheduled to undergo major cancer surgery were recruited. Serum 25-hydroxyvitamin D concentration was measured before surgery. In total, 59 nonsurgical control subjects with comparable age and education level were also enrolled. A battery of neuropsychological tests was administered the day before and the 7th day after surgery in patients or at the same time interval in control subjects. POCD was diagnosed according to the ISPOCD1 definition. RESULTS: 71.5% (88/123) of elderly patients had vitamin D deficiency (serum 25-hydroxyvitamin D concentration < 12 ng/ml) before surgery; 24.4% (30/123) of them developed cognitive dysfunction at 1 week after surgery. After adjusting for confounding factors, high preoperative serum 25-hydroxyvitamine D concentration was related to a decreased risk of POCD (odds ratio [OR]: 0.829, 95% confidence interval [CI]: 0.708-0.971; P = 0.020), whereas preoperative vitamin D deficiency was associated with an increased risk of POCD (OR: 8.427, 95% CI: 1.595-44.511; P = 0.012). CONCLUSIONS: Vitamin D deficiency is prevalent in elderly patients undergoing major cancer surgery and increases the risk of early POCD development. Whether prophylactic vitamin D supplementation can reduce POCD in the elderly deserves further study.

LncRNA TUC338 promotes invasion of lung cancer by activating MAPK pathway.

OBJECTIVE: Lung cancer is highly heterogeneous and the 5-year survival rate is less than 15%. It is currently difficult to determine the heterogeneity of lung cancer and the underlying pathogenetic of metastasis. We aimed to investigate the effect of long non-coding RNA (lncRNA) TUC338 on the invasion of lung cancer by activating MAPK pathway and to understand the heterogeneity and metastasis mechanism of lung cancer. PATIENTS AND METHODS: The expression of lncRNA TUC338 in 42 samples of lung cancer and paracancerous tissues were accessed by RT-qPCR. The relationship between the expression of lncRNA and clinicopathological parameters was analyzed. After overexpressing and interfering with lncRNA TUC338, effects of lncRNA TUC338 on cell proliferation and invasion were determined by cell counting kit-8 (CCK8) and transwell assay. The protein expression was evaluated by Western blot. RESULTS: Higher expression of TUC338 in lung cancer was observed in comparison with that in paracancerous tissues. The survival time of TUC338 was correlated with the expression of TUC338. Clinical data analysis revealed that the expression of TUC338 was correlated with the overall survival, tumor size and lymph node metastasis in patients, but not with age and gender. After interfering and overexpressing TUC338, it was found that the activity of lung cancer cells was decreased, as well as the invasion ability after interference with TUC338. After overexpression of TUC338, we found that lung cancer cell activity increased, as well as the invasion ability. By Western blot, we found that TUC338 can promote the development of lung cancer through regulating MAPK pathway. CONCLUSIONS: TUC338 was overexpressed in lung cancer, and its expression may have a relationship to the prognosis of lung cancer. MAPK pathway was involved in the invasion of lung cancer regulated by TUC338.

Experimental study on the prevention of liver cancer angiogenesis via miR-126.

OBJECTIVE: The aim of the present work was to study the prevention of liver cancer angiogenesis via miR-126. For this purpose, experimentations were conducted. MATERIALS AND METHODS: The precursor sequence of miR-126 was amplified in the DNA of human liver cancer cell lines. We, therefore, constructed the overexpression and interference vectors of miR-126 in vitro; which were respectively transferred to liver cancer cells in the logarithmic phase and inoculated under both sides of the back skin of Balb/c-nu nude mice aged 4-6 weeks with 10 mu l (1 x 105) cell suspension. The experiment consisted of non-vector control group, miR-126 overexpression group, and miR-126 inhibition group. Eight weeks later, the mice were sacrified; the tumor volumes and serum ALT, AFP, VEGF levels were compared. VEGF expression, as well as the microvascular density of the liver tissues, was detected via immunohistochemistry. RESULTS: Tumors volumes, serum ALT, AFP and VEGF levels and positive rates of VEGF were low in the miR-126 overexpression group and high in the miR-126 inhibition group, the difference being statistically significant (p < 0.05). CONCLUSIONS: At the end of this study, we conclude that miR-126 inhibits liver cancer angiogenesis.

Correlation of preoperative ROMA scores with clinical stage in epithelial ovarian cancer patients

Purpose. The significance of the Risk of Ovarian Malignancy Algorithm (ROMA) in differentiating benign and malignant ovarian lesions has been evidenced. In our clinical work, we found that advanced ovarian cancer were accompanied commonly with high ROMA scores. Thus, this study aimed to clarify the performance of ROMA in different disease stage of epithelial ovarian cancer (EOC) prior to surgery. Methods. Carbohydrate antigen (CA125) and human epididymis protein 4 (HE4) levels and ROMA scores in 221 patients with FIGO stage I, II or III/IV stage EOC were analyzed. The positive rates of CA125, HE4 and ROMA at each disease stage were calculated. Their cutoff values, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for distinguishing patients with FIGO stage I/II from those with FIGO stage III/IV were estimated via ROC curves. Results. Serum CA125 and HE4 levels and ROMA scores rose significantly with advancing stage. ROMA and CA125 were significantly elevated more frequently in comparing with HE4 in EOC patients at with the same stage. Based on ROC curves, the cutoff values for FIGO stage III/IV EOC were 110 IU/mL, 126 pmol/L, 78 and 68% for CA125, HE4, premenopausal and postmenopausal ROMA, respectively. ROMA was the strongest predictor of FIGO stage, with the highest specificity, accuracy, and PPV, which were 84.4, 82.5, and 87.0% for postmenopausal patients, 89.3, 85.6, and 74.3% for premenopausal patients. Conclusions. Our data suggest high ROMA scores correlated with advanced ovarian cancer prior to surgery. These observations suggest potential utility of ROMA in the comprehensively preoperative evaluation of EOC patients (AU)

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Correlation of preoperative ROMA scores with clinical stage in epithelial ovarian cancer patients.

PURPOSE: The significance of the Risk of Ovarian Malignancy Algorithm (ROMA) in differentiating benign and malignant ovarian lesions has been evidenced. In our clinical work, we found that advanced ovarian cancer were accompanied commonly with high ROMA scores. Thus, this study aimed to clarify the performance of ROMA in different disease stage of epithelial ovarian cancer (EOC) prior to surgery. METHODS: Carbohydrate antigen (CA125) and human epididymis protein 4 (HE4) levels and ROMA scores in 221 patients with FIGO stage I, II or III/IV stage EOC were analyzed. The positive rates of CA125, HE4 and ROMA at each disease stage were calculated. Their cutoff values, sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for distinguishing patients with FIGO stage I/II from those with FIGO stage III/IV were estimated via ROC curves. RESULTS: Serum CA125 and HE4 levels and ROMA scores rose significantly with advancing stage. ROMA and CA125 were significantly elevated more frequently in comparing with HE4 in EOC patients at with the same stage. Based on ROC curves, the cutoff values for FIGO stage III/IV EOC were 110 IU/mL, 126 pmol/L, 78 and 68% for CA125, HE4, premenopausal and postmenopausal ROMA, respectively. ROMA was the strongest predictor of FIGO stage, with the highest specificity, accuracy, and PPV, which were 84.4, 82.5, and 87.0% for postmenopausal patients, 89.3, 85.6, and 74.3% for premenopausal patients. CONCLUSIONS: Our data suggest high ROMA scores correlated with advanced ovarian cancer prior to surgery. These observations suggest potential utility of ROMA in the comprehensively preoperative evaluation of EOC patients.

Caffeic acid n-butyl ester-triggered necrosis-like cell death in lung cancer cell line A549 is prompted by ROS mediated alterations in mitochondrial membrane potential.

OBJECTIVE: The aim of the present study was to evaluate the anticancer activity of caffeic acid n-butyl ester against lung cancer cell line A549 and to investigate the underlying mechanism. MATERIALS AND METHODS: IC50 was determined by MTT assay. Fluorescent probes DCFH-DA, Indo 1/AM, DiOC6 were used to determine ROS, Ca2+, and mitochondrial membrane potential (ΔΨm). ATP levels were determined by using ATP liteTM kit. DNA damage was investigated by DAPI and comet assays. Protein expression was investigated by Western blotting. RESULTS: Caffeic acid n-butyl ester exhibited lowest IC50 of 25 µM against lung A549 cell line. Caffeic acid n-butyl ester reduced the cell viability of A549 cells concentration and time-dependently. It also augmented the discharge of ROS and Ca2+ and lessened the mitochondrial membrane potential (ΔΨm) and ATP levels in A549 cells. Additionally, caffeic acid n-butyl ester also prompted DNA damage in A549 cell line. Notably, caffeic acid n-butyl ester-stimulated the cytochrome c release only and exhibited no effect on the expression of apoptosis-related protein levels such as caspase-3, caspase-8, and Apaf-1. DISCUSSION: Caffeic acid n-butyl ester exhibited significant anticancer activity against lung cancer cell line A549. However, the anticancer activity was not due to apoptosis as no significant change was observed in the expression of apoptosis-related proteins. The anticancer activity of caffeic acid n-butyl ester may be attributed to necrosis-like cell death prompted by ROS-mediated alterations in ΔΨm. CONCLUSIONS: Taken together, we conclude that caffeic acid n-butyl ester-induced A549 cells death displayed a cellular pattern characteristic of necrotic cell death and not of apoptosis.