The incidences of adverse events in small-cell lung cancer patients after radiotherapy and immunotherapy treatment: a systematic review and meta-analysis.

Immunotherapy is important in treating small-cell lung cancer (SCLC), and its anti-tumor effects are better when combined with radiotherapy. However, the toxicity of this combination is little known. This study assessed the incidences of adverse events when adding radiotherapy to ICIs in patients with SCLC. We searched the online databases to identify eligible studies and included nine references. For extensive-stage SCLC patients, the median PFS ranged from 4.5 to 12.5 months, and median OS ranged from 8.4 to NR months, respectively. The incidences of grade 3 or higher pneumonitis, lung infection, diarrhea, and fatal adverse events were 8.7% (95% CI: 5%-14.7%), 6.7% (95% CI: 2.5%-16.5%), 12.6% (95% CI: 7.6%-20%), and 5.1% (95% CI: 2.1%-11.6%), respectively. Our findings suggest that radiotherapy plus ICIs may provide acceptable safety and favorable efficacy for SCLC patients.

[Expression of hepatocyte nuclear factor 4γ in gastric carcinoma and its role in cell proliferation and stemness].

Objective: To explore the role and molecular mechanism of hepatocyte nuclear factor 4γ (HNF4γ) in proliferation and stemness of gastric cancer. Methods: A total of 102 cases of paraffin-embedded gastric cancer tissues and matched adjacent gastric tissues and 42 cases of fresh-frozen tissues derived from gastric patients who received radical gastrectomy were collected from the First Affiliated Hospital of Zhengzhou University between 2012 to 2015. The expression of HNF4γ was tested by immunohistochemical staining, quantitative real-time polymerase chain reaction (qRT-PCR). HNF4γ overexpressed (AGS-HNF4γ) and shRNA silenced (HGC27-shHNF4γ) gastric cell lines were established. The effects of HNF4γ on cell proliferation and stemness were verified by XTT, clone formation and sphere formation assay. The expression of CD44 was detected by western blot. Results: The mRNA expression level of HNF4γ in fresh-frozen gastric cancer tissue was (12.43±2.702), which was significantly higher than (3.639±1.109) in normal tissue (P<0.001). The high protein expression rate of HNF4γ in paraffin-embedded gastric cancer tissues was 41.2% (42/102), which was significantly higher than 8.8% (9/102) in normal gastric mucosa tissue (P< 0.001). The protein expression of HNF4γ was closely related to the tumor differentiation, infiltration depth, lymph node metastasis and tumor stage (P<0.05). The median survival interval of patients with HNF4γ high expression was 25 months, the 3-year survival rate was 4.8% (2/42), significantly lower than 38 months and 51.7% (31/60) of patients with normal HNF4γ expression (P<0.001). The proliferation and CD44 protein expression of AGS-HNF4γ cells were significantly higher than those of the AGS-Vector cells. The number of clone formation, sphere formation rate of AGS-HNF4γ cells were 243.5±24.5 and (83.5±3.9)%, significantly higher than 81.0±16.0 and (21.8±5.6)% of AGS-Vector cells (P=0.030 and P=0.010, respectively). The proliferation and CD44 protein expression of HGC27-shHNF4 cells were significantly lower than those of the HGC27-vector cells. The number of clone formation, sphere formation rate of HGC27-shHNF4 cells were 26.0±1.0 and (20.8±8.4)%, significantly higher than 83.5±4.5 and (72.5±4.8)% of HGC27-vector cells (P=0.006 and P=0.030, respectively). Conclusions: HNF4γ is upregulated in the gastric cancer tissues and related with the poor prognosis of patients with gastric cancer. Overexpression of HNF4γ promotes the proliferation and remains the stemness of gastric cancer cells by upregulating the expression of CD44.

[Long-term oncological outcomes of laparoscopic versus abdominal surgery in stage â a1 （LVSI+）-â b1 cervical cancer patients with different tumor size: a big database in China].

Objective: To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI+）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods: Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results: (1) A total of 4 891 patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.367, 95%CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS (HR=1.420, 95%CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS (P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups (P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.705, 95%CI: 1.088-2.674, P=0.020). Conclusions: For patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

[Clinical characteristics and prognosis of high-risk neuroblastoma with bone marrow metastasis in children].

Objective: To analyze the clinical characteristics of newly treated high-risk group neuroblastoma (NB) patients with bone marrow metastasis and to explore the prognostic factors. Methods: The clinical features (sex, age, stage, risk group, pathological type, metastatic site, etc.) of 203 newly treated high-risk NB patients with bone marrow metastasis admitted to Hematology Oncology Center, Beijing Children's Hospital from January 2007 to December 2016 were analyzed retrospectively. There were 118 males (58.1%) and 85 females (41.9%). Kaplan-Meier method was used for survival analysis and Cox regression was used to analyze the prognostic factors. Results: The age at onset of the 203 patients was 41 months (9-147 months). The metastatic sites at diagnosis were as follows: bone in 195 cases (96.1%), distant lymph nodes in 104 cases (51.2%), skull and endomeninx in 61 cases (30.0%), orbit in 30 cases (14.8%), pleura in 16 cases (7.9%), liver in 13 cases(6.4%), canalis spinalis in 13 cases (6.4%), other sites in 11 cases (5.4%) and skin and soft tissue in 10 cases (4.9%). In all, 194 cases were enrolled for prognostic analysis. The follow-up time was 36 months (1 day-138 months) , and the 5-years event free survival (EFS) and overall survival (OS) were 36.1% and 39.7%, respectively. A total of 118 patients (60.8%) had events (first relapse or death) with the time to event occurrence was 15 months (1 day-72 months), whereas 112 patients (57.7%) died with the event occurrence to death time was 3 months (1 day-21 months). There was no significant difference in 5-years OS between radiotherapy group and non-radiotherapy group (42.3% vs. 38.3%, χ(2)=3.671, P=0.055). The 5-years OS in transplantation group was significantly better than the non-transplantation group (44.3% vs. 35.5%, χ(2)=8.878, P=0.003), and the radiotherapy combined transplantation group also had a better 5-years OS rate than the non-radiotherapy combined transplantation group (45.8% vs. 37.3%, χ(2)=5.945, P=0.015). Univariate survival analysis showed lactate dehydrogenase ≥ 1 500 U/L, the amplification of MYCN, the metastatic sites of orbit, canalis spinalis and pleura were associated with poor prognosis of newly diagnosed high-risk NB patients (χ(2)=21.064, 13.601, 3.998, 6.183, 15.307, all P<0.05). The amplification of MYCN and the metastatic sites of pleura were risk factors for prognosis of newly diagnosed high-risk NB patients by Cox regression models (HR=1.896,1.100, 95%CI: 1.113-3.231, 1.020-1.187, both P<0.05). Conclusions: The prognosis is unfavorable in high-risk group NB patients with BM metastasis. Radiotherapy combined with transplantation can further improve the prognosis of these patients. The amplification of MYCN and the metastatic sites of pleura were the poor prognostic factors for high-risk NB patients with bone marrow metastasis.

[Influence of polymorphisms of VEGFR2 on clinical outcomes and safety of advanced non-small-cell lung cancer treated by first line Bevacizumab plus chemotherapy regimens].

Objective: To investigate the influence of polymorphisms of vascular endothelial growth factor receptor-2(VEGFR2) on clinical outcomes and safety of advanced non-small-cell lung cancer (NSCLC) treated by first line Bevacizumab plus chemotherapy regimens. Methods: A total of 148 patients with advanced NSCLC who were treated by bevacizumab based first line regimens from January 2013 to January 2017 in the Department of Oncology of the First Affiliated Hospital of Zhengzhou University were included in this study. Peripheral blood and the biopsy tissue specimens of the NSCLC patients were collected for the genotyping of genetic variation and VEGFR2 mRNA expression, respectively. The association between genotype and other characteristics and VEGFR2 mRNA expression were analyzed. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, and multivariate analysis were adjusted by Cox regression analysis. Results: Of the polymorphisms analyzed, only 889C>T was of clinical significance. Located in the coding region, the prevalence of 889C>T in VEGFR2 among the study population were as follows: CC genotype 108 cases (72.97%), CT genotype 36 cases (24.32%), TT genotype 4 cases (2.71%), minor allele frequency of 889C>T was 0.15. The distribution of three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.636). TT and CT genotype patients were merged in the comparison of clinical outcomes. The analysis of patients with different genotypes found that the objective response rates (ORR) of CT/TT genotypes and CC genotypes were 40.00% and 48.15% (P=0.377), respectively. And the median progression free survival (mPFS) of patients with CT/TT genotype and CC genotype were 6.1 and 8.7 months, respectively, which was statistically significant (P=0.002). In terms of overall survival (OS), the median overall survival (mOS) of the two genotypes were 18.7 and 21.4 months (P=0.012), respectively. Adjusted in multivariate analysis, 889C>T were an independent factor for progression free survival (OR=1.96, P=0.014). No association between the 889C>T and adverse reactions was found in the safety analysis. Of the 69 biopsy tissue specimens, gene expression analysis showed that the mRNA expression of VEGFR2 in cancer tissues of the patients with CT/TT genotypes were significantly higher than those of the CC genotype patients (P<0.001). Conclusion: The polymorphism 889C>T of VEGFR2 may have worse influence on clinical outcomes of advanced NSCLC treated by first line bevacizumab plus chemotherapy regimens, while no significant impact on safety.

A Preliminary Study of the Value of Plasma microRNA-193b and Soluble Urokinase-Type Plasminogen Activator Receptor in Identifying Patients with Early-Stage Colorectal Cancer and.

BACKGROUND: Early detection and management of colorectal cancer (CRC) and colorectal adenoma (CRA) reduces the mortality and morbidity of CRC, but there is a lack of ideal circulation biomarkers. METHODS: A total of 80 patients with early-stage CRC and CRA and 30 healthy controls were included in this preliminary study. Plasma samples were collected before colonoscopy and prepared for measurement of microRNA193b and soluble uPAR. RESULTS: Plasma level of miR-193b was decreased through the normal-adenoma-carcinoma sequence with no significant difference between patients with CRC and advanced CRA. The AUC of ROC curve evaluating the value of miR-193b in discriminating patients with early stage CRC or advanced CRA from patients with non-advanced CRA or normal control subjects was 0.849 (95% CI 0.773 - 0.923, p < 0.001). Significant alteration of plasma suPAR is only observed in CRC group (p < 0.001). CONCLUSIONS: Plasma miR-193b may be a novel candidate biomarker for screening patients with early-stage CRC and advanced CRA.

Comparison of four infectious bursal disease viruses isolated from different bird species.

Four isolates of infectious bursal disease virus (IBDV), isolated from chicken, duck, goose and sparrow in Jiangsu province of China in 2002, were compared. The viruses were stable to the treatments of 60 degrees C for 1 h, pH 2.0 and lipid solvents. Their antigenic relatedness values (R) were from 0.76 to 0.78. Chickens infected with the chicken isolate showed severe clinical symptoms of IBD and the mortality rate was 33.3% (2/6). Chickens infected with the other three viruses survived but their bursas were damaged and the bursa/body-weight ratios were lower than those of the uninfected control (p< 0.01). The titers of anti-IBDV antibody in infected chicken sera reached up to 1600 by virus neutralization and 6400 by ELISA at 10 days post infection. The sequences of the variable region of VP2 were aligned and compared, showing nucleotide variations ranging from 1.5 to 6.7% and deduced aminoacid variations from 0.8 to 2.2%. All had the same heptapeptide, S-W-S-A-S-G-S, Asp279, and Ala284. The four viruses clustered on a phylogenetic tree and were distant from the STC strain. These findings suggested that different bird species naturally infected with IBDV could serve as carriers or reservoirs in IBDV transmission and might play a role in the emergence of variant IBDV.

Regionally specific compensation for bone loss in the tibial trabeculae of estrogen-deficient rats.

BACKGROUND: Bone mineral density (BMD) and microstructural variations have been extensively investigated in recent years; however, the compensation for bone loss between different regions is still unclear. PURPOSE: To fully characterize regional variations in bone mineral density (BMD) as well as the microstructure and dynamic changes of rat tibial trabeculae that occur with bone loss associated with estrogen deficiency. MATERIAL AND METHODS: Female Sprague-Dawley rats were ovariectomized (OVX), sham-operated (sham), or left unoperated (baseline control). The left tibiae were harvested at baseline, and at postoperative weeks 3 and 15. High-resolution micro-computed tomography (microCT) was used to identify the densitometric and microstructural properties of trabeculae in the proximal ends of the rat tibia, specifically the epiphysis and metaphysis. RESULTS: Volumetric BMDs at the organ (organ BMD) and tissue (tissue BMD) levels were significantly higher for trabeculae at the epiphysis than metaphysis. Moreover, trabeculae at the epiphysis were thicker, and fewer in number and connectivity than those at the metaphysis, which were more rod like. Trabeculae at the metaphysis were more susceptible to bone loss induced by estrogen deprivation than at the epiphysis, and the regions varied greatly in their adaptation to this loss. At the metaphysis, trabecular tissue BMD and thickness were unexpectedly higher at postoperative week 15 than week 3 or baseline. In contrast, at the epiphysis, tissue BMD did not change with time, but trabecular thickness significantly increased at week 15 compared to baseline and was also greater in OVX compared to sham rats. CONCLUSION: Metaphyseal and epiphyseal trabeculae show regionally specific variations in BMD and microstructure. The former are more susceptible to bone loss induced by estrogen deficiency and would be strengthened by either hypertrophy or hypermineralization, while epiphyseal trabeculae are mainly strengthened by thickening.