LINC00472 suppresses non-small cell lung cancer progression via regulating miR-23a-3p/CCL22 axis.

Long non-coding RNA (lncRNA) LINC00472 has a close connection with the development of tumors. The aim was to explore the role of LINC00472 on NSCLC cell biological function in vivo and its potential mechanisms. The mRNA levels of LncRNA 00472 and microRNA-23a-3p, were determined by RT-qPCR. Cell Counting Kit-8, cell scratches and western blot assays were used to analyze the proliferation, migration and level of apoptosis-associated proteins. Luciferase reporter assay validates the binding between LINC00472/CCL22 and miR-23a-3p. LINC00472 and CCL22 were lowly expressed in NSCLC tissues and cells, while miR-23a-3p expression was upregulated. LINC00472 overexpression significantly depressed NSCLC cell cellular behavior, whereas promoting cell death. MiR-23a-3p could reverse these above-mentioned biological behavior changes caused by LINC00472 overexpression. Additionally, LINC00472 increased CCL22 expression through sponging miR-23a-3p. Knocking down CCL22 antagonized the inhibitory effect of LINC00472 on NSCLC cell survival. LINC00472 may reduce the cellular growth, and accelerate death of NSCLC through increasing CCL22 expression by targeting miR-23a-3p.

LINC01133 contributes to the malignant phenotypes of non-small cell lung cancer by targeting miR-30b-5p/FOXA1 pathway.

This study aimed to explore the mechanism of action of LINC01133 in non-small cell lung cancer. LINC01133 expression in NSCLC patient tissues and cells was detected by qRT-PCR. After transfecting siRNA-LINC01133 in NSCLC cells, the proliferation and invasive migration ability of the cells were assessed via CCK-8 and Transwell assay, respectively. The sublocalization of LINC01133 in NSCLC cells was analyzed by bioinformatics prediction and nucleoplasm separation assay and RNA-FISH assay. Analysis of the binding relationship between LINC01133, FOXA1 and miR-30b-5p was all through bioinformatics website analysis, dual-luciferase reporter and RNA Pulldown assay. Functional rescue experiments confirmed the character of miR-30b-5p and FOXA1 in LINC01133 regulating the NSCLC cells biological behavior. LINC01133 high expressions were found in NSCLC tissues and cells. siRNA-LINC01133 treatment inhibited NSCLC cells malignant behavior. Mechanistically: LINC01133 promoted FOXA1 expression through adsorption binding of miR-30b-5p. Knocking down miR-30b-5p expression or up-regulating FOXA1 expression was able to reverse siRNA-LINC01133 inhibitory effect of tumor cell malignant behavior. LINC01133 promoted FOX1 expression by competitively binding miR-30b-5p, which attenuated the targeting inhibitory effect of miR-30b-5p on FOXA1 and ultimately promoted proliferation and invasive migration of NSCLC cells.

Outcomes following the excision of sarcoma and chest wall reconstruction using 3D printed implant.

The survival outcomes of patients with chest wall sarcomas (CWS) were evaluated after receiving wide excision and chest wall reconstruction by using three-dimensional printed (3DP) implants. The survival outcomes evaluating the effect of 3DP implants for chest wall reconstruction is lacking. Here, forty-nine patients with CWS underwent radical wide excision and chest wall reconstruction using 3DP implants. The surgical data and long-term survival outcomes were collected and analyzed. With a median follow-up of 36 months, the disease-free survival (DFS) and overall survival (OS) were 31.7% and 58.5%, respectively. In addition, the 3-year DFS and OS can be significantly differentiated using the classification criteria of tumor grade, tumor size tumor area. Hence, wide excision and chest wall reconstruction using three-dimensional printed implants are a safe and effective treatment for chest wall sarcoma. The novel classification criteria of tumor size and area have the potential to predict the prognosis of CWS.

Clinical Application of Anlotinib Combined with Docetaxel: Safe and Effective Treatment for Lung Carcinoma.

Objective: To compare the clinical efficacy and long-term survival between anlotinib monotherapy and anlotinib plus docetaxel in patients with lung carcinoma. Methods: Between October 2019 and December 2021, 84 patients with lung cancer diagnosed and treated at our hospital were enrolled and randomly allocated to the control (n = 42) and experimental (n = 42) groups. Patients in the control group only received anlotinib, whereas those in the experimental group were administered both anlotinib and docetaxel. The clinical effectiveness, long-term survival, and other associated variables of the two groups were compared. Results: There were no CR cases, 7 PR cases, 22 SD cases, and 13 PD cases in the control group. In the experimental group, there were 4 cases of CR, 20 cases of CR, 11 cases of SD, and 7 cases of PD. The overall clinical effectiveness of the experimental group was much higher than that of the control group. There were 3 cases of anemia, 5 cases of pyrexia, 6 cases of proteinuria, 9 cases of nausea and vomiting, and 4 cases of abnormal liver and renal function in the control group. (P < 0.05). In the experimental group, there were 2 cases of anemia, 3 cases of pyrexia, 1 case of proteinuria, 5 cases of nausea and vomiting, and 1 case of abnormal liver and kidney function. The incidence of adverse reactions in the experimental group was significantly lower than in the control group (64.29%) (P < 0.05). According to the two-year follow-up results, the survival rate was 19.05% in the control group and 54.76% in the experimental group, and the mortality rate was 80.95% in the control group and 45.24% in the experimental group. The experimental group had a significantly higher survival rate than the control group (P < 0.05). Conclusion: Anlotinib combined with docetaxel is a safe and effective treatment for lung carcinoma to reduce the incidence of adverse reactions and improve the long-term survival rate. These benefits make it worthy of a broader clinical application. Although pharmacological treatment was applied in this study based on the mechanism, specific bioeffective markers are yet to be identified, presenting a direction for future research.

The inhibition of centromere protein K causes anticancer effects in breast carcinoma via effects on the FAK/PI3K/AKT/mTOR pathway.

The overexpression of centromere protein K (CENPK) is a major contributor to the malignant progression of numerous cancers. To date, the detailed functions and mechanisms of CENPK in breast carcinoma are not fully elucidated. The goals of this project were to comprehensively address the relevance of CENPK in breast carcinoma. The initial investigation by TCGA analysis revealed a high expression level of CENPK in breast carcinoma. Subsequently, an immunoblotting assay confirmed that CENPK is highly expressed in the clinical samples of breast carcinoma. In vitro experiments elucidated that the inhibition of CENPK produced substantial anticancer effects, including a reduction of proliferation, the inhibition of epithelial-mesenchymal transition, the induction of cell cycle arrest and chemosensitivity. Mechanism research unveiled a role for CENPK in mediating the focal adhesion kinase (FAK1)/PI3K/AKT/mTOR pathway. Inhibiting the FAK/PI3K/AKT/mTOR pathway was able to reverse CENPK-elicited cancer-promoting effects. Additionally, CENPK-silenced breast carcinoma cells exhibited low tumorigenicity in vivo. In summary, our data demonstrated that CENPK inhibition provided an excellent anticancer effect for breast carcinoma by regulating FAK/PI3K/AKT/mTOR pathway. This work illustrates a novel molecular mechanism for CENPK in breast carcinoma and suggests CENPK inhibition as a promising targeted therapy for breast carcinoma.

Identification of OTUD6B as a new biomarker for prognosis and immunotherapy by pan-cancer analysis.

Background: Ovarian-tumor (OTU) domain-containing protein 6B (OTUD6B), one of newly identified OTU deubiquitylating enzyme families, is proved to be associated with tumor progression. However, whether it plays a key role in pan-cancer still remains unknown. Methods: The profiles of OTUD6B expression in multiple cancers were analyzed using The Cancer Genome Atlas (TCGA) database. Information of protein expression was performed based on the HPA, GeneCards, and String databases. K-M plotter and survival data analysis were used to analyze the prognostic value of OTUD6B expression, including overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). R package "clusterProfiler" was used for enrichment analysis of OTUD6B. Furthermore, we analyzed the correlation between the expression of OTUD6B, immune infiltration, and immune-related genes. Additionally, we preliminarily validated its tumorigenic effect in lung cancer cell lines. Findings: OTUD6B expression was upregulated in most cancers, such as COAD, CHOL, and LUAD, and predicted poor prognosis in most cancers in TCGA. Results showed that OTUD6B expression was positively correlated with memory CD4+ T cells, Th1 CD4+ T cells, and CD8+ T cells. In terms of the immune-related genes, OTUD6B was found to be associated with most types of genes, such as immunostimulatory genes KDR, TGFBR1, and IL-10. Moreover, for most types of tumors, the immune score was found to be negatively correlated with OTUD6B expression. In addition, lung cancer cell lines with OTUD6B knockdown significantly inhibited proliferation and invasion ability of lung cancer cells. Conclusions: The study indicated that OTUD6B is an oncogene and may serve as a new potential biomarker in various tumors. OTUD6B may play a part in TIME, which could be applied as a new target for cancer therapy.

Optimal Adjuvant Therapy in Resected Stage IIIA-N2 Non-Small-Cell Lung Cancer Harboring EGFR Mutations.

BACKGROUND: Some non-small-cell lung cancer (NSCLC) patients are unexpectedly diagnosed with stage IIIA-N2 disease at the time of thoracoscopy or thoracotomy. Because of the limited statistical evidence of induction chemotherapy for these patients, it is necessary to develop more profound treatment strategies. METHODS: The demographic and clinical characteristics of patients with stage IIIA-N2 NSCLC harboring epidermal growth factor receptor (EGFR) mutations after radical resection were retrospectively reviewed. The patients were divided into 3 groups based on treatment: EGFR tyrosine kinase inhibitors (EGFR-TKIs, erlotinib or gefitinib), adjuvant chemotherapy (docetaxel plus cisplatin), and combination treatment (chemotherapy plus EGFR-TKIs). The effect of adjuvant therapy on survival rate was assessed using univariate and Cox regression analyses. RESULTS: Patients receiving EGFR-TKIs alone showed significantly improved disease-free survival (DFS; p = 0.025) when compared to those receiving chemotherapy alone. Compared to chemotherapy alone, the combination of chemotherapy and EGFR-TKIs resulted did not significantly improve DFS (p < 0.001) and overall survival (OS p < 0.001). The combination of EGFR-TKIs with chemotherapy as adjuvant therapy led to improvements in both DFS (p = 0.116) and OS (p = 0.039) compared to patients receiving a EGFR-TKI monotherapy. Toxicities were mild in the 3 treatment groups. CONCLUSIONS: Our study demonstrated that adjuvant EGFR-TKI treatment significantly increased the DFS of patients with stage IIIA-N2 NSCLC when compared with cisplatin-based chemotherapy. The use of EGFR-TKIs and chemotherapy is recommended in the setting of combined-modality therapy.

Three-dimensional printing flexible models: a novel technique for Nuss procedure planning of pectus excavatum repair.

BACKGROUND: Pectus excavatum (PE), one of the most common congenital chest wall deformities, is characterized by posterior depression of the sternum and lower costal cartilages. In this study, we demonstrated the application of flexible three-dimensional printing thoracic models for surgical approach planning of extrapleural Nuss procedure for patients with pectus excavatum. METHODS: Six patients with pectus excavatum were referred to our hospital for extrapleural Nuss procedure. Each patient's chest was reconstructed based on their computed tomography imaging data, and the three-dimensional (3D) thoracic model was manufactured with flexible material using 3D printing technique. The individual surgical approach and custom-made steel bars were designed and produced using these models. RESULTS: The surgical approach was evaluated by using the three-dimensional thoracic model. In all patients received extrapleural Nuss surgery, it has been proven the uniformity of repair efficacy in both models and patients. Moreover, an individualized and well-fitting steel bar can be fabricated once the surgical approach was confirmed. All the steel bars were loaded against the ribs rigorously and seamlessly. CONCLUSIONS: The flexible three-dimensional thoracic models were very helpful for the preoperative planning of extrapleural Nuss procedure.

Clinical application of 3D printed titanium chest and rib implants in chest wall reconstruction / 中国胸心血管外科临床杂志

@#Objective    In this study, three-dimensional printed (3DP) titanium implants were used for skeletal reconstructions after wide excision of chest wall. 3DP titanium implants were expected to provide a valid option with perfect anatomic fitting and personalized design in chest wall reconstruction. Methods    There were 13 patients [mean age of 46 (24-78) years with 9 males and 4 females] who underwent adequate radical wide excision for tumors and chest wall reconstruction using 3DP titanium implants. Surgical data including patient demographic characteristics, perioperative clinical data and data from 1-year follow-up were collected and analyzed. Results    Six patients of rib tumors, six patients of sternal tumors and one patient of sternal pyogenic osteomyelitis were finally selected for the study. The chest wall defect area was 221.0±206.0 cm2. All patients were able to maintain the integrity of the chest wall after surgery, and no abnormal breathing was found, achieving personalized and anatomical repair. Thirteen patients were successfully discharged from the hospital. Two patients developed pneumonia in the perioperative period. During the follow-up period in the first year after surgery, no implant related adverse reaction was observed, including implant rupture, implant shift, rejection reaction and allergies. One patient had wound ulcer after chemotherapy. Three patients had tumor recurrence, with the recurrence rate of 25.0%. Two patients died of tumor recurrence, with a mortality rate of 16.7%. Conclusion    3DP titanium implant is a safe and effective material for chest wall reconstruction. 

Competing risk analysis of primary tracheal carcinoma based on SEER database.

PURPOSE: To analyze the prognostic factors of primary tracheal carcinoma. PATIENTS AND METHODS: All patients of primary tracheal carcinoma were extracted from the Surveillance, Epidemiology, and End Results database during 1973-2015. The potential prognostic factors were analyzed by using the competing risk analysis of R statistical software. RESULTS: A total of 485 eligible patients were enrolled. The univariate analysis indicated that age, sex, diagnostic confirmation, extension, lymph node, metastasis, multiple primary tumors, primary site surgery, and lymph node dissection were statistically significant for the patients' death due to tracheal tumor. The multivariate analysis indicated that age (P=0.0000, CI: 1.0255-1.0630), lymph node (P=0.0000, CI: 1.6031-3.4890), metastasis (P=0.0100, CI: 1.1342-2.5790), multiple primary tumors (P=0.0000, CI: 0.0276-0.1090), and primary site surgery (P=0.0001, CI: 0.3565-0.7110) were independent prognostic factors affecting survival, and there were significant differences in the stratification of each prognostic factors. CONCLUSION: Age, lymph node, metastasis, multiple primary tumors, and primary site surgery were independent prognostic factors of primary tracheal carcinoma.

Three-Dimensional Printing PEEK Implant: A Novel Choice for the Reconstruction of Chest Wall Defect.

BACKGROUND: The purpose of this study is to use 3-dimensional printing (3DP) polyetheretherketone (PEEK) implants for skeletal reconstructions after wide excision of chest wall. 3DP PEEK implants were expected to provide a better physiological simulation than traditional ones because of a closer elastic modulus to cortical bone and similar biomechanical properties. METHODS: Eighteen patients (mean age 44.5 years), comprising 6 males and 12 females, underwent adequate radical wide excision for tumors and chest wall reconstruction using 3DP PEEK implants. Surgical data, which include patient demographic characteristics, implant preparation parameters, and preoperative and postoperative pulmonary function test results, were collected and analyzed. RESULTS: Ten patients with rib tumors and 8 patients with sternum tumors were selected for the study. The mean chest wall defect size was 173.6 ± 151.5 cm2 (range, 55 to 625 cm2). The mean weight of a single 3DP PEEK rib and sternum was 28 g and 104 g, respectively. The flexural and tensile strength of PEEK implants were 141 ± 7 MPa and 89 ± 3 MPa, respectively. Preoperative and postoperative pulmonary function tests revealed that mean forced vital capacity was from 2.79 ± 0.68 L to 2.40 ± 0.70 L with a reduction of 14.0% (p < 0.001). No side effects were observed 6 to 12 months after the operation. CONCLUSIONS: These findings suggest that 3DP PEEK implant is a safe and effective alternative in the reconstruction of chest wall defects. The pulmonary function of the patient may be preserved effectively after surgery.

Mesenchymal stem cells inhibited development of lung cancer induced by chemical carcinogens in a rat model.

Mesenchymal stem cells (MSCs) may play a significant role in carcinogenesis; however, data have shown that MSCs can both promote and inhibit tumor growth. We investigated the effect of MSCs on the development of lung cancer in a rat model. Bone marrow-derived MSCs were isolated from male Wistar rats and fluorescently labeled. Genotoxic carcinogens 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) were instilled into the left lung lobes of female rats to induce tumors. Labeled male MSCs were infused into the female rats via tail vein, and the rats were sacrificed on days 3 and 7. MSC survival and distribution were detected by PCR and fluorescence, respectively. Labeled MSCs aggregated at the injection site in the left lobe (MCA/DEN-treated) on day 3 but not the untreated right lobe. Survival of the MSCs in vivo was confirmed by detection of the male SRY gene in lung tissues by PCR at day 3; however, by day 7, lung tissues were SRY-negative. Next, carcinogen-treated rats were divided into two groups and infused with normal MSCs (experimental group) or PBS (control group) every week for 10 weeks, then sacrificed. Cell proliferation in lung tissues was calculated by Ki67 and PCNA expression. Eighty-percent (8/10) of rats in the control group had tumors, while none of the rats in the experimental group had tumors. There was no difference in cell proliferation in lung tissues between the groups. Therefore, bone marrow-derived MSCs prevented development of carcinogen-induced lung cancer in a rat model. Additional studies are needed to determine mechanism.