EGFRvIII-specific CAR-T cells produced by piggyBac transposon exhibit efficient growth suppression against hepatocellular carcinoma.

Adoptive cellular immunotherapy employing chimeric antigen receptors-modified T (CAR-T) cells has demonstrated promising antitumor effects in hematologic cancers. However, CAR-T therapy confront many challenges in solid tumors like immunosuppressive microenvironment, molecular heterogeneity, etc. The cancer genome atlas (TCGA) of hepatocellular carcinoma (HCC) revealed many genetic characteristic and molecular tumorigenesis. EGFRvIII is a tumor specific antigen widely expressed in a variety of cancers including HCC and an ideal therapeutic target for cancer therapy. The liver cancer cell line SMMC7721 express high level EGFRvIII and widely applied in HCC investigations. Herein, we developed EGFRvIII CAR-T cells by piggyBac transposon system, and detected its specific killing effect against SMMC7721 cells in vitro and in vivo. Results indicated that transduction efficiency of CAR reached 53.1%. Expression of CAR protein was verified by immunoblotting as a band of approximate 57KD. The killing effect of CAR-T cells against SMMC7721 was positively correlated with E/T ratio (E:T=5:1, 10:1, 20:1, 40:1), and exceeded 50% at 20:1 ratio. Significant increase in IFN-γ and TNF-α secretion were detected in the co-culture supernatant of CAR-T cells and SMMC7721, comparable to the level of exogenous EGFRvIII-expressing U87 cells. The killing activity and cytokine secretion were both dependent on the expression level of EGFRvIII in target cells. In HCC xenograft models, CAR-T cells could effectively suppress the growth of SMMC7721. In conclusion, EGFRvIII CAR-T cells demonstrated specific antitumor effect against SMMC7721 in vitro and in vivo, providing basis for immunotherapy of HCC in future clinical use.

Malignant transformation of craniopharyngioma with detailed follow-up.

A 29-year-old male patient was admitted into hospital with the main complaint of progressive visual disturbance. Both CT SCAN and MRI demonstrated a cystic-solid contrast-enhancing sellar-suprasellar mass with obvious calcification. Histopathological examination of the first resected specimen showed a typical appearance of adamantinomatous craniopharyngioma. The patient received gamma knife therapy after his first operation because of partial tumor removal. He experienced two relapses in the subsequent 2 years, for which only surgical resection was performed. The later histopathology presented malignant appearance with tumor cells moderate to severe pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio, high mitotic activity (30/10 high power fields) and focal coagulative necrosis. The patient died 9 months after identification of histologic malignancy. Clinical and histopathological features, biological behavior of one case of malignant craniopharyngioma were discussed, with a brief review of the relevant literature.

Correlation between red blood cell distribution width and cardiovascular events in the patients receiving peritoneal dialysis: A Strobe-compliant article.

There are few studies on the correlation between red blood cell distribution width (RDW) and cardiovascular events in the patients receiving peritoneal dialysis (PD). We explored the correlation between RDW and cardiovascular events in PD patients and possible mechanism.A total of 138 PD patients were divided into RDW < 15% group (n = 104) and RDW ≥ 15% group (n = 34).The levels of serum C-reactive protein (CRP) [3.05 (0.79, 15.30) mg/L vs 2.15 (1.00, 6.50) mg/L] and parathyroid hormone (PTH) [260.0 (192.7, 352.6) ng/L vs 200.7 (118.0, 319.7) ng/L] were significantly higher, but the levels of serum albumin [30.65 (27.4,32.8) g/L vs 32.3 (29.25,34.95) g/L], prealbumin [(299 ±â€Š96) g/L vs (346 ±â€Š86) g/L], triglyceride [1.24 (0.72, 1.50) mmol/L vs 1.42 (1.12,1.84) mmol/L], and transferrin saturation [27.9 (16.4, 43.6)% vs 37.8 (23.3, 57.2)%] were significantly lower in the RDW ≥ 15% group than in the RDW < 15% group (all P < 0.05). The RDW was negatively correlated with albumin (r = - 0.258, P = 0.002), prealbumin (r = -0.236, P = 0.005), and triglyceride (r = -0.194, P = 0.023), but was positively correlated with CRP level (r = 0.174, P = 0.041). The incidence of cardiovascular events was significantly higher in the RDW ≥ 15% group (6 patients, 17.6%) than in the RDW < 15% group (6.7%) (7 patients, P < 0.01). Cox proportional hazard model showed that elevated RDW level was an independent risk factor for cardiovascular events in PD patients (HR = 1.622, 95% CI: 1.063-2.475, P = 0.025).The elevated RDW may be served as a risk factor to predict the cardiovascular events in PD patients.

Human leukocyte antigen DRB1 alleles predict risk and disease progression of immunoglobulin A nephropathy in Han Chinese.

The role of human leukocyte antigen (HLA) class II polymorphisms in the pathogenesis and progression of primary immunoglobulin A nephropathy (pIgAN) is unclear. This study aimed to explore the relationship of HLA-DRB1 alleles with the susceptibility and disease progression of pIgAN in Han Chinese. A PCR-based genotyping technique was used to detect HLA-DRB1 alleles in 139 patients with pIgAN and 143 healthy subjects. A total of 37 HLA-DRB1 alleles were detected, of which 30 were found in pIgAN patients and 29 in healthy subjects. In pIgAN patients, the frequencies of HLA-DRB1*140501 (belonging to DR*14) were significantly increased, while the frequencies of HLA-DRB1*070101 (belonging to DR*7) were significantly reduced compared with the healthy individuals. Further stratification analysis revealed that the frequencies of HLA-DRB1*030101 in pIgAN patients with normal renal function were significantly higher than those in patients with renal dysfunction. These findings suggest that HLA-DRB1 polymorphisms are related to the occurrence and disease progression of pIgAN patients in Han Chinese, with HLA-DRB1*140501 being a susceptible allele and HLA-DRB1*070101 a resistant allele. HLA-DRB1*030101 may serve as a predictor of disease progression and renal damage of pIgAN in Han Chinese. Further studies are warranted to explore the immunological mechanisms for the genotype-disease phenotype relationship.

Polymorphisms in the gene encoding estrogen receptor alpha are associated with osteoarthritis in Han Chinese women.

Polymorphisms in the Xba I and Pvu II restriction enzyme recognition sites in the estrogen receptor-alpha gene (ESR1) have been associated with multiple diseases, including osteoarthritis. To determine whether such polymorphisms are associated with osteoarthritis in a Han Chinese population, 98 women with osteoarthritis and 196 healthy women were genotyped by PCR-RFLP of ESR1 with Xba I and Pvu II. Absence of a restriction polymorphism is indicated as an X or P allele; presence of the restriction polymorphism is indicated as an x or p allele. Clinical information was collected on each participant, including body weight, body mass index (BMI), knee radiograms, and bone mineral density (BMD). Body weight and BMI were higher for each Xba I genotype (all P < 0.05) in individuals with osteoarthritis compared to controls (p < 0.05). Femoral BMD was also significantly higher in the osteoarthritis group (p < 0.05). Additionally, the xx genotype for ESR1 was a significant risk factor for osteoarthritis (OR=1.98, 95% CI: 1.13~4.20, p=0.036). Thus, consistent with findings in other populations, the estrogen receptor genotype xx appears to be associated with susceptibility to osteoarthritis among Han Chinese women.