An iPSC-derived exosome-pulsed dendritic cell vaccine boosts antitumor immunity in melanoma.

Induced pluripotent stem cells (iPSCs) express a broad spectrum of tumor-associated antigens and exert prophylactic effects on various tumors. However, some problems remain, such as potential tumorigenicity, challenges in transport to the lymph nodes and spleen, and limited antitumor effects. Thus, designing a safe and effective iPSC-based tumor vaccine is necessary. We prepared iPSC-derived exosomes and incubated them with DCs (dendritic cells) for pulsing to explore their antitumor effects in murine melanoma models. The antitumor immune response induced by the DC vaccine pulsed with iPSC exosomes (DC + EXO) was assessed in vitro and in vivo. After DC + EXO vaccination, extracted spleen T cells effectively killed a variety of tumor cells (melanoma, lung cancer, breast cancer, and colorectal cancer) in vitro. In addition, DC + EXO vaccination significantly inhibited melanoma growth and lung metastasis in mouse models. Furthermore, DC + EXO vaccination induced long-term T cell responses and prevented melanoma rechallenge. Finally, biocompatibility studies showed that the DC vaccine did not significantly alter the viability of normal cells and mouse viscera. Hence, our research may provide a prospective strategy of a safe and effective iPSC-based tumor vaccine for clinical use.

Reconstruction of chronic anterior cruciate ligament rupture using the ligament advanced reinforcement system artificial ligament-comparisons between patients over 50 years and under 50 years.

Background: With the increasing physical activity level in elderly population, anterior cruciate ligament (ACL) injuries are becoming more frequent. Due to the possible surgery complications, treatment for ACL rupture in patients with advanced age is still controversial. The purpose of this study was to compare the therapeutic effects of reconstruction using the ligament advanced reinforcement system (LARS) artificial ligament in patients older than 50 and patients younger than 50 with chronic ACL rupture. Methods: Indications included: (I) concurrent history of subjective symptomatic anterior knee instability despite nonoperative rehabilitation for least 3 months, (II) positive preoperative Lachman and pivot shift tests, (III) ACL stump still connecting the femur with the tibia as demonstrated by Magnetic Resonance Imaging (MRI), and (IV) some residual ligament fibers still connecting the femur with the tibia as demonstrated by arthroscopy. Participants were divided into groups based on their age. Participants were divided into groups based on their age. A total of 37 patients who underwent reconstruction of chronic ACL rupture using the LARS artificial ligament were divided into group A (≥50 years, n=16) and group B (<50 years, n=21). Results: The outcome measures were compared between the 2 groups. These included the baseline clinical data, the International Knee Documentation Committee (IKDC) scoring system, Pivot shift test, Lachman test, Kneelax arthrometer measurements, Tegner activity scale, Lysholm knee scoring scale, and Kellgren-Lawrence radiographic classification of arthritis and complications. Postoperative knee laxity and the functional examination were significantly improved compared to preoperative measurements for both groups (all P<0.01). No significant differences were found in postoperative knee laxity and functional examination between the 2 groups (all P>0.05). The level of osteoarthritis did not statistically increase in either group during follow-up (all P>0.05). No complications associated with the arthroscopic surgery were found in either group. Conclusions: The reconstruction of chronic ACL rupture using the LARS artificial ligament showed similar therapeutic effects in patients over the age of 50 and those under the age of 50.

Erratum: Meprin α combined with CEA and CA19-9 improves prognostic prediction for surgically treated colorectal cancer patients.

[This corrects the article on p. 10441 in vol. 10, PMID: 31966381.].

The prognostic significance of FBXO2 expression in colorectal cancer.

Colorectal cancer is the third most frequently diagnosed malignancy, and the prognosis at advanced tumor stages remains poor. FBXO2, a member of the F-box protein family, is a cytoplasmic protein and an ubiquitin ligase. The aim of this study was to investigate the role of FBXO2 in colorectal cancer. The expression levels of Ki67, N-cadherin and FBXO2 were detected in 195 pairs of primary CRC tissues using immunohistochemistry (IHC). The associations among Ki67, N-cadherin, and FBXO2 expression, as well as the clinicopathological parameters, were analyzed. Survival curves were calculated with the Kaplan-Meier method. Univariate and multivariate analyses were performed to explore the prognostic significance of Ki67, N-cadherin, and FBXO2 expression. We found that the positive rates of Ki67, N-cadherin and FBXO2 expression in CRC tissue samples were 55.9%, 65.1%, 62.6%, respectively. The high expression levels of Ki67 and N-cadherin were significantly correlated with CRC size (P = 0.01) and metastasis (P = 0.01), respectively. The high expression level of FBXO2 was significantly correlated with CRC metastasis (P = 0.04) and AJCC stage (P = 0.029). A Cox regression analysis revealed that FBXO2 is an independent prognostic factor for CRC patients (HR 1.817, 95% CI 1.106-2.983, P = 0.018). FBXO2 may serve as a biomarker for metastasis and a reliable predictor for poor prognosis in CRC patients.

miR-133b suppresses metastasis by targeting HOXA9 in human colorectal cancer.

Functions and mechanisms of microRNA (miRNA) involved in colorectal cancer (CRC) metastasis are largely unknown. Here, a miRNA microarray analysis was performed in CRC primary tissues and metastatic hepatic tissues to disclose crucial miRNA involved in CRC metastasis. MiR-133b was decreased and negatively correlated with metastasis in CRC. Overexpression of miR-133b significantly suppressed metastasis of CRC in vitro and in vivo. HOXA9 was identified as a direct and functional target of miR-133b. In addition, HOXA9 was negatively correlated with miR-133b and promoted CRC malignant progress. Moreover, miR-133b decreased HOXA9 expression, and subsequently downregulated ZEB1 and upregulated E-cadherin expression. Intriguingly, lower miR-133b and higher HOXA9 expression significantly contributed to poorer outcomes in CRC patients. Multivariate analysis indicated that miR-133b was an independent and significant predictor of CRC patient overall survival. In conclusion, we newly determined that miR-133b targeted the HOXA9/ZEB1 pathway to promote tumor metastasis in CRC cells. This axis provided insights into the mechanism underlying miRNA regulation of CRC metastasis and a novel therapeutic target for CRC treatment.

Survival changes in Patients with Synovial Sarcoma, 1983-2012.

Background: Synovial sarcoma (SyS) is a rare malignancy that typically invades the extremities and occurs predominantly in adolescents. Studies on incidence and survival in SyS that were based on a large population had not been reported yet. Methods: To evaluate changes in incidence and survival in SyS over three decades, we accessed data on SyS cases in each decade between 1983 and 2012 (1983-1992, 1993-2002, and 2003-2012) from the Surveillance, Epidemiology, and End Results (SEER) database. The survival difference between decades, age groups, sexes, race, pathologic types, sites, stages and socioeconomic status (SES) over three decades were accessed by comparing Kaplan-Meier curves. Results: We located 2,070 SyS cases in 18 SEER registry regions between 1983 and 2012. Our study demonstrated that the incidence of SyS per 1,000,000 continued to increase from 0.906 to 1.348 to 1.548 in the total population and in most age groups and that the age of incidence peak was 15-29 years in three decades. But, the survival of patients with SyS did not significantly improve throughout the three decades, with 5-year survival rates of 69.4%, 61.1% and 60.5% respectively (p > 0.05). Interestingly, the widening survival gaps among races, sexes, pathological types and various SES over time were observed, with narrowing p values. Conclusions: This study demonstrated the increasing incidence and unimproved survival rates across three decades in a large sample, indicating the urgency for further development of diagnosis, improving health care providers' awareness of SyS and lead to the development of novel treatments.

Meprin α combined with CEA and CA19-9 improves prognostic prediction for surgically treated colorectal cancer patients.

BACKGROUND: Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are generally used as tumour markers in patients with colorectal cancer (CRC), and meprin α might be an additional marker. METHODS: The preoperative expression of serum CEA and CA19-9 was evaluated using a C12 protein biochip system, and tissue meprin α expression in CRC cells was detected by immunohistochemistry. The relationships of these indexes with clinicopathological parameters and the survival of CRC patients were analysed. RESULTS: Of the 147 CRC patients, the preoperative seropositive rates for CEA and CA19-9 were 51.70% and 44.22%, respectively, and the tissue meprin α positive rate was 39.46%. Preoperative seropositivity for CEA was correlated with tumour size (P = 0.019), T stage (P = 0.005) and staging of CRC based on the American Joint Committee on Cancer (AJCC) guidelines (P = 0.032). The preoperative seropositive rate for CA19-9 was correlated with AJCC tumour stage (P = 0.031). High expression of meprin α was significantly correlated with distant CRC metastasis (P = 0.003), serum CEA (P = 0.002) and serum CA19-9 (P = 0.001). The combination of the three markers was an independent prognostic factor in patients with CRC (HR 3.985, 95% CI 1.106-14.361, P = 0.035 for overall survival). CONCLUSIONS: Tissue meprin α expression may be a useful predictor of metastasis and prognosis in CRC. The combined detection of the three markers may also be helpful to improve the accuracy of CRC prognosis monitoring.

The autophagy inhibitor 3-methyladenine restores sevoflurane anesthesiainduced cognitive dysfunction and neurons apoptosis.

This study was designed to explore the effect of 3-methyladenine (3-MA) on sevoflurane anesthesia-induced cognitive dysfunction. A total of 60 C57BL/6 (5-8 months old) mice were randomly arranged into 3 groups: Control, sevoflurane (Sev) and Sev+3-MA group with 3-MA administration was performed during Sev administration. Morris water maze and Y-maze test were performed to examine the behavioral disorders. Moreover, hippocampal neuronal cell apoptosis and expression of autophagy related genes were detected. Sevoflurane induced cognitive dysfunction in mice showing significant longer escape latency, lower number of correct response, higher apoptotic neurons, and higher expression of autophagy related genes. However, additional 3-MA administration inhibited the effect of sevoflurane on cognitive dysfunction by shorting escape latency, reducing correct response number, inhibiting neurons apoptosis and autophagy genes expression. 3-MA additional administration inhibited sevoflurane anesthesia-induced cognitive dysfunction on mice. 3-MA might be usefull as an inhibitor for sevoflurane anesthesia-induced cognitive dysfunction in clinical trials.

Protective effect of rosuvastatin treatment by regulating oxidized low-density lipoprotein expression in a rat model of liver fibrosis.

The present study aimed to evaluate the protective effect of rosuvastatin treatment on the mechanism of oxidized low-density lipoprotein (Ox-LDL) in rats with liver fibrosis. In total, 72 male Sprague-Dawley rats were divided into 3 groups: 24 in the control group (A), 24 in the obstructive jaundice models group (B) and 24 in the rosuvastatin group (C). Each group was further divided into four subgroups for assessment at different time-points. The obstructive jaundice models were established and rosuvastatin was administered by gavage. Liver fibrosis indicators, Ox-LDL, malonaldehyde (MDA) and superoxide dismutase (SOD), were measured and liver pathological changes were observed at weeks 1, 2, 3 and 4 after model induction. In groups B and C, the rat models were successfully established, and there were significant changes in the expression of Ox-LDL and the three liver fibrosis indicators when compared to group A (P<0.01). However, the expression of Ox-LDL and the three liver fibrosis indicators in group C were decreased compared with group B (P<0.05), while SOD increased (P<0.05) and MDA decreased (P<0.05). The three liver fibrosis indicators were different in comparison to group B (P<0.05). Thus, there appeared to be an association between the expression of Ox-LDL and liver fibrosis. Treatment with rosuvastatin could regulate the expression of Ox-LDL and improve liver fibrosis in rat models with obstructive jaundice.

Comparison of recovery parameters for xenon versus other inhalation anesthetics: systematic review and meta-analysis.

STUDY OBJECTIVE: To summarize and evaluate the available data describing the recovery parameters of xenon anesthesia. DESIGN: Systematic review and meta-analysis. SETTING: Anesthesia for elective surgeries. PATIENTS: Systematic review of randomized controlled trials (RCTs) from databases including Medline (1964-2013), the Cochrane Central Register of Controlled Trials (CENTRAL, 1990-2012), and Google Scholar (1966-2013). INTERVENTIONS: Inhalation of xenon or other anesthetics was administered in elective surgery. MEASUREMENTS: Recovery parameters (time to recovery, alertness/sedation scale scores at "eye opening," bispectral index at "reaction on demand," time to extubation, and time to orientation). MAIN RESULTS: Eleven RCTs (N = 661 patients) met the inclusion criteria. Recovery from xenon anesthesia was significantly faster in terms of the time to eye opening (mean difference [MD], -4.18 minutes; 95% confidence interval [CI], -5.03 to -3.32 minutes; P < .00001), the time to reaction on demand (MD, -5.35 minutes; 95% CI, -6.59 to -4.11 minutes; P < .00001), the time to extubation (MD, -4.49 minutes; 95% CI, -5.40 to -3.58 minutes; P < .00001), and the time to orientation (MD, -4.99 minutes; 95% CI, -6.45 to -3.52 minutes; P < .00001). CONCLUSIONS: This meta-analysis confirmed that recovery from xenon anesthesia is faster than other inhalation anesthesia.