Malignant pleural effusion is one of the most common complications of advanced lung cancer and there is no effective clinical treatment at present. Here, we constructed an aptamer-siRNA chimeras/PEI/PEG/gold nanoparticle (AuNP)/collagen membrane that can progressively activate T cells by layer by layer assembly. Electron microscope showed this collagen membrane could be divided into 10 layers with a total thickness of 50–80μm, and AuNPs could be observed. Aptamer-siRNA chimeras could bind specifically to OX40+ cells and silencing programmed death receptor-1 (PD-1) gene. In vitro experiments demonstrated that chimeras/PEI/PEG/AuNPs gradually activated T cells to continuously kill lung adenocarcinoma cells in malignant pleural effusion. Animal experiments showed that chimeras/PEI/PEG/AuNP/collagen membrane effectively treated malignant pleural effusion. Compared with PD-1 inhibitor group, the number of cancer cells, ki-67 proliferation index and CD44 expression in the pleural effusion was significantly decreased and the lymphocyte/cancer cell ratio was significantly increased in the chimeras/AuNP-CM group. Flow cytometry showed that compared with PD-1 inhibitor group, T cell number in the chimeras/AuNP-CM group was significantly increased, while the proportion of PD-1+ T cells was markedly decreased. In conclusion, we constructed an chimeras/PEI/PEG/AuNP/collagen membrane, which was more effective in the treatment of malignant pleural effusion, and had less side effects than PD-1 inhibitors.
Background In traditional opinion, solid pulmonary nodule suspected lung cancer should be confirmed by pathology before the operation to exclude small cell lung cancer (SCLC), considering SCLC tends to be aggressive and surgical effect in the management of SCLC remains controversial. The aim of this study was to evaluate the survival result and risk factors of postoperative unsuspected SCLC. Methods A total of 120 patients with postoperative unsuspected SCLC who were confirmed by pathology and referred to Chinese PLA General Hospital between 2000 and 2021 were retrospectively analyzed (surgery group). Additionally, 120 patients with limited-stage SCLC who underwent chemotherapy and radiotherapy in the same period were enrolled in the chemoradiotherapy group.. Kaplan–Meier method was used to estimate survival; the Log-Rank test was used to compare survival rates between different groups; a COX stepwise regression model was used for multivariate analysis. Results Among 120 patients in the surgery group, 28 were with central type and other 92 with peripheral type. The median survival (OS) was 44.85 months, and the 5-year survival rate was 46%. The 5-year survival rates for stage I, II, and III were 52.1%, 45.4%, and 27.8%, respectively. The mean disease-free survival time (DFS) was 30.63 ± 4.38 months, and the 5-year DFS rate was 31.5%. In the chemoradiotherapy group, the mean OS was 21.4 ± 4.26 months, and the 5-year survival rate was 28.3%. The 5-year survival rates for clinical stage I, II, and III were 42.5%, 39.8%, and 20.5%, respectively. The mean progression-free survival (PFS) was 10.63 ± 3.6 months. In the surgery group, one-way ANOVA revealed that the gender, symptoms, smoking history, tumor location, and postoperative radiotherapy were not associated with OS (P ≥ 0.05), while age, surgical approach, surgical method, N stage, TNM stage, and vascular tumor thrombus were related to OS (P < 0.05). Multivariate analysis indicated that the N stage was associated with OS (HR = 1.86 P = 0.042). Conclusion Surgery and adjuvant therapy were found to have encouraging outcomes in postoperative unsuspected SCLC. Patients with stage I, stage II and part of stage IIIA SCLC could benefit from surgery and the standard lobectomy, and systematic lymph node dissection, is also recommended for these patients.
Background: Clear cell tumor of the lung (CCTL) is a rare and mostly benign pulmonary neoplasm arising from perivascular epithelioid cells. Only about 100 cases have been reported and half of them were in China. Limited details about CCTL often cause diagnostic or therapeutic problems. Case presentation: We describe a case of 28-year-old woman with gradually increased and enlarged multiple nodules in the left lower lobe. The patient underwent a fine-needle aspiration biopsy and was considered as CCTL. A left lower lobectomy and mediastinal lymph node dissection was performed. The gradual changes in size (1.4 cm to 2.8 cm) and quantity (10 to 49) of CCTL in this case was the biggest difference from previously reported cases. Conclusions: CCTL is a very uncommon and mostly benign PEComatous tumor with no specific morphologic features. We present a case of CCTL with multiplicity and rapid growth, which may indicate its aggressive nature. The accumulation of similar cases will help clarify its exact disease nature and to improve our understanding of such tumor.
Severe inflammatory response and functional impairment of endothelial progenitor cells (EPCs) often lead to the implantation failure of EPC-captured tissue-engineered blood vessels (TEBVs) in diabetes. Regulatory T cells (Treg cells) are the most important inhibitory immune cells, but their effects in angiogenesis remain undefined, and the differences in the microenvironment may be an important reason. Here, we constructed a TEBV coated with an anti-CD34 antibody-functionalized heparin-collagen multilayer (anti-CD34 antibody-modified TEBV) using layer-by-layer self-assembly. Then, TEBVs were implanted into diabetic pigs. All TEBVs remained unobstructed 60 days after implantation, although varying degrees of intimal hyperplasia were detectable. Severe intimal hyperplasia was observed in the control group and peripheral injection of Treg cells group. Intravenous injection of Treg cells significantly inhibited intimal hyperplasia, inflammation, and cell apoptosis. Moreover, intravenous injection increased the proportion of circulating EPCs, while peripheral injection did not have these effects and reduced microvessel density around the TEBV. Interestingly, many Nestin+ cells could be detected in TEBVs, most of which were fusiform, showing the characteristics of smooth-muscle cells. Treg cell intravenous transplantation markedly reduced the number of Nestin+ cells in the TEBV. In conclusion, Treg cells inhibited the intimal hyperplasia of TEBVs in diabetic pigs by promoting EPC mobilization, anti-inflammatory action, and cellular protection.
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