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Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
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Objective:To compare the clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer.Methods:The clinical data of 68 patients with advanced colorectal cancer from January 2018 to December 2020 in Baotou Tumor Hospital were retrospectively analyzed. Among them, 40 patients with treated with bevacizumab combined with chemotherapy (bevacizumab group), 28 patients were treated with cetuximab combined with chemotherapy (cetuximab group), and the chemotherapy of two group was FOLFOX/FOLFIRI program. The short-term clinical efficacy, adverse reactions and pharmacoeconomic evaluation result were compared between two groups.Results:There were no statistical differences in effective rate and disease control rate between bevacizumab group and cetuximab group: 30.00% (12/40) vs. 28.57% (8/28) and 67.5% (27/40) vs. 60.71% (17/28), P>0.05. The incidence of Ⅲ to Ⅳ grade erythra in bevacizumab group was significantly lower than that in cetuximab group: 2.50% (1/40) vs. 71.43% (20/28), and there was statistical difference ( P<0.01); there were no statistical differences in the incidences of Ⅲ to Ⅳ grade bone marrow suppression, nausea vomiting, hepatic functional lesion and diarrhea between two groups ( P>0.05). The pharmacoeconomic evaluation result showed that the cost of monoclonal antibody and total cost in bevacizumab group were significantly lower than those in cetuximab group: (9 009 ± 1 500) yuan vs. (27 840 ± 2 202) yuan and (11 242 ± 1 731) yuan vs. (29 867 ± 3 002) yuan, and there were statistical differences ( P<0.01); the cost-effectiveness ratio in bevacizumab group was 37 473.3, and it in cetuximab group was 104 430.1, the incremental cost-effectiveness ratio of two programs was 11 640.6. Conclusions:In the treatment of advanced colorectal cancer, the efficacy of bevacizumab combined with chemotherapy is similar to that of cetuximab combined with chemotherapy, but bevacizumab combined with chemotherapy has lower costs and fewer adverse reactions, so bevacizumab is more economical and applicable.
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Aim To investigate the effect of silencing circRNA ciRS-7 on cisplatin resistance of gastric cancer cells and its related mechanism. Methods Cisplatin-resistant gastric cancer cells HGC-27/DDP were constructed, ciRS-7 was silenced and HGC-27/DDP cells were treated with cisplatin. Real-time quantitative PCR (qRT-PCR) was used to detect the expression levels of ciRS-7 and microrNA-944 (miR-944). Cell counting kit-8 (CCK-8) was used to detect cell survival rate. Clone formation assay was used to detect the number of clones. Western blot was used to detect the protein expression levels of CyclinD1, proliferating cell nuclear antigen (PCNA), B-lymphocytoma-2-associated X protein (Bax), B-lymphocytoma-2 (Bcl-2) and cleaved aspartate-specific cysteine proteinase 3 (cleaved-caspase-3). Flow cytometry was used to detect cell apoptosis rate. In situ end labeling (TUNEL) was used to detect apoptosis index. Dual luciferase assay was used to verify the targeting relationship between ciRS-7 and miR-944. Results CiRS-7 was highly expressed in cisplatin-resistant gastric cancer tissues and cells, while miR-944 was low expressed in cisplatin-resistant gastric cancer tissues and cells. The survival rate, clonal formation number, protein expression levels of CyclinD1, PCNA and Bcl-2 in cisplatin-treated HGC-27/DDP cells were significantly reduced by silencing ciRS-7, while ciRS-7 expression level, apoptosis rate, apoptosis index, Bax, cleaved-caspase-3 protein expression levels of cisplatin-treated HGC-27/DDP cells were significantly raised. CiRS-7 targetedly inhibited the expression of miR-944. Conclusions Silencing ciRS-7 can reverse cisplatin resistance of gastric cancer cells, and the mechanism may be related to the promotion of miR-944 expression by silencing ciRS-7.
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Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.
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Objective@#To evaluate the clinical efficacy and side effects of cyberknife therapy in the treatment of retroperitoneal lymph node metastatic tumor.@*Methods@#Among the 81 patients presenting with postoperative retroperitoneal lymph node metastases, 33 cases suffered from abdominal pain or low back pain, 7 had unilateral hydronephrosis and ureteral dilatation, and 8 developed unilateral or bilateral lower limb swelling. Using stereotactic radiotherapy with a cyberknife, DT was delivered at 33-45 Gy/3-6 F. The improvement of symptoms, objective tumor response rate, and irradiation-induced side effects were observed.@*Results@#At 4 weeks after treatment, pain and swelling of the lower extremities were completely mitigated, and hydronephrosis was fully healed in all patients. Enhanced CT or MRI was performed every 2 to 3 months. After 6-month follow-up, the complete response (CR) rate was calculated as 77%(62/81), 21%(17/81) for the partial response (PR) rate, 3%(2/81) for the stable disease (SD) rate and the effective rate (CR+ PR) was 98%.No case progressed. The main side effect was intestinal injury, including grade 1 in 16%(13/81), grade 2 in 9%(7/81). Multivariate analysis demonstrated the CR rate was not correlated with the type of the primary tumor or the size of the tumor (P>0.05), but was significantly associated with the distance of>0.5 cm between the tumor and intestine and the BED (α/β=10)>70 Gy of the tumor irradiation (P<0.01). The incidence of irradiation-related side effects was correlated with the maximum diameter of tumor>5 cm and the distance of<0.5 cm between the tumor and intestine (P<0.01).@*Conclusion@#Cyberknife is an efficacious and safe approach in the treatment of retroperitoneal lymph node metastatic tumors.
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Objective To analyze the incidence and predictors of chronic subdural hematoma (CSDH) after surgical clipping between unruptured intracranial aneurysms (UIAs) and ruptured intracranial aneurysms (RIAs).Methods A retrospective cohort study was adopted to collect 486 cases of aneurysm patients (102 cases of UIAs patients and 384 RIAs patients) closed by aneurysm surgery who were admitted to the department of neurosurgery of The Fifth People's Hospital of Chengdu from October 2009 to December 2017.The clinical data,preoperative and postoperative imaging data and postoperative follow-up results were collected.The incidence of CSDH after operation in UIAs patients and RIAs patients was compared.The risk factors of CSDH after UIAs and RIAs patients were analyzed by multivariate Logistic regression model.Results The incidence of CSDH in UIAs and RIAs patients (10.78％ vs 3.13％,x2 =10.487,P =0.001) and the reoperation rate after CSDH (3.92％ vs 0.78％;x2 =5.599,P =0.018) were all statistically different,all of which showed that the patients with UIAs were higher than those of the patients with RIAs.Brain atrophy of grade 3-4 (OR =1.978,95％ CI:1.939-2.030,P ＜ 0.001),subdural effusion CT value ≥40 (OR =3.394,95％ CI:2.908-3.867,P ＜ 0.001) and subdural effusion (OR =2.872,95％ CI:2.648-3.019,P ＜0.001 grade) of Ⅰ B are independent risk factors of CSDH in patients with UIAs after aneurysm clipping (P ＜0.05).Subdural effusion CT value ≥ 40 (OR =3.442,95％ CI:2.918-3.8769,P ＜ 0.001) and grade Ⅰ B subdural effusion (OR =2.329,95％ CI:2.011-2.564,P ＜ 0.001) are independent risk factors for CSDH in patients with RIAs after aneurysm clipping (P ＜0.05).Conclusions The incidence of CSDH after aneurysm clipping in UIAs patients was significantly higher than that of RIAs patients.The risk factors for CSDH in the two groups were not the same.
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Objective To investigate the efficacy of high-intensity focused ultrasound(HIFU) ablation combined with gestrinone for treating adenomyosis.Methods Sixty patients with adenomyosis were divided into the HIFU group(n=30) and HIFU combined medication group(n =30).The change of dysmenorrheal,menstrual volume,volumes of uterus and lesion in the two group were compared between before and after treatment.Results The menstrual volume and dysmenorrhea scores at 6,12 months after treatment showed a statistical difference between the two groups(P＜0.05);the volumes of and adenomyotic lesion and uterus after treatment in the combined medication group were lower than those in the HIFU group,but the difference was not statistically significant(P＞0.05).The hemoglobin level after 6-month treatment had statistical difference between the combined medication group and HIFU group(P＜0.05).During the follow-up period,there were 5 cases of pregnancy without recurrence cases in the combine medication group,8 cases had slight abnormality in the liver function transaminase and recovered to normal in re-examination at 1 month after drug withdrawal;1 case had pregnancy and 4 cases had recurrence in the HIFU group.Conclusion HIFU ablation combined with gestrinone can effectively alleviate the clinical symptoms in the patients with adenomyosis.
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Objective To investigate the reproductive outcome after high intensity focused ultrasound (HIFU ) ablation for pa-tients with adenomyosis who have fertility requirements .Methods From October 2010 to June 2013 ,38 patients with adenomyosis who have fertility requirements treated by HIFU in our hospital were analyzed .Results In 38 cases ,the menorrhagia severity score ,the dysmenorrhea pain score and adenomyosis lesions after HIFU ablation were significantly different from the levels before HIFU treatment(P<0 .05) .Successful pregnancy occurred in 15 patients ,full-term birth was seen in 7 patients(three of Cesarean section ,four of vaginal delivery);the remaining patients accept routine prenatal examination .All pregnant patients showed no ab-normality .Conclusion Although large sample size study with long-term follow up is need ,based on our results ,HIFU ablation for patients with adenomyosis might improve the pregnancy rate safely .
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Objective To evaluate the feasibility of high intensity focused ultrasound (HIFU) associated microbubble-enhancing contrast (“SonoVue”) therapeutic ablation of uterine fibroids in patients with pelvic operation history. Methods A total of 100 patients with uterine fibroid from October 2010 to December 2012 in Suining Central Hospital of Sichuan were treated with HIFU associated SonoVue. Among them, 50 patients had pelvic operation history. The no-perfused volume, median fractional ablation, ablation power rate, ablation dose, treatment time and adverse reaction were recorded. Results There was no statistical significance between patients with operation history and without in no-perfused volume and ablation does. The ablation power was lower in patients with operation than without. The treatment time and room time were longer in patients with operation than without. The adverse reactions were higher in patients with operation than without, especially skin pain and lower abdominal pain ( <0.05) . According to short- and long-term follow-up results, no major complications were observed in any patients. Conclusion Pelvic operation history increases the difficulty in treatment of HIFU ablation uterine fibroids. HIFU associated contrast agent SonoVue ablation can be considered a safe and feasible approach to the management of uterine fibroids in patients with pelvic operation history after grasping the indications and contraindications.