CENPH overexpression promotes the progression, cisplatin resistance, and poor prognosis of lung adenocarcinoma via the AKT and ERK/P38 pathways.

Overexpression of centromere protein H (CENPH) promotes cancer growth and progression. However, the roles and underlying mechanisms have not been elucidated. Therefore, we aim to explore the roles and mechanisms of CENPH in lung adenocarcinoma (LUAD) progression by using comprehensive data analysis and cell experiments. In this study, the relationship between CENPH expression, which was obtained from the TCGA, and GTEx databases, and the prognosis and clinical characteristics of LUAD patients was analyzed, and the diagnostic values of CENPH was evaluated. CENPH-related risk models and nomograms were constructed to evaluate the prognosis of LUAD via Cox and LASSO regression analysis. The roles and mechanisms of CENPH in LUAD cells were studied using CCK-8 assay, wound healing and migration tests, and western blotting. The relationship between CENPH expression and immune microenvironment and RNA modifications was explored through correlation analysis. We found that CENPH was overexpressed in LUAD tissues, and tumors with diameter >3 cm, lymph node metastasis, distant metastasis, late stage, men, and dead cancer patients. Increased expression of CENPH was related to the diagnosis, poor survival rate, disease specific survival rate, and progression of LUAD. CENPH-related nomograms and risk models could predict the survival rate of LUAD patients. Inhibiting the expression of CENPH in LUAD cells decreased their migration, proliferation, and invasion, and promoted their sensitivity to cisplatin, which was related to the downregulation of p-AKT, p-ERK, and p-P38. However, there was no effect on AKT, ERK, and P38. Enhanced expression of CENPH was significantly correlated with immune score, immune cells, cell markers, and RNA modifications. In conclusion, CENPH was strongly expressed in LUAD tissues and was associated with poor prognosis, immune microenvironment, and RNA modifications. CENPH overexpression could enhance cell growth and metastasis and promote resistance to cisplatin via the AKT and ERK/P38 pathways, indicating its potential as a biomarker for the prognosis of LUAD.

Exosome-mediated lnc-ABCA12-3 promotes proliferation and glycolysis but inhibits apoptosis by regulating the toll-like receptor 4/nuclear factor kappa-B signaling pathway in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a kind of malignant tumor with high incidence and mortality in the digestive system. The aim of this study is to explore the function of lnc-ABCA12-3 in the development of ESCC and its unique mechanisms. RT-PCR was applied to detect gene transcription levels in tissues or cell lines like TE-1, EC9706, and HEEC cells. Western blot was conducted to identify protein expression levels of mitochondrial apoptosis and toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway. CCK-8 and EdU assays were carried out to measure cell proliferation, and cell apoptosis was examined by flow cytometry. ELISA was used for checking the changes in glycolysis-related indicators. Lnc-ABCA12-3 was highly expressed in ESCC tissues and cells, which preferred it to be a candidate target. The TE-1 and EC9706 cells proliferation and glycolysis were obviously inhibited with the downregulation of lnc-ABCA12-3, while apoptosis was promoted. TLR4 activator could largely reverse the apoptosis acceleration and relieved the proliferation and glycolysis suppression caused by lnc-ABCA12-3 downregulation. Moreover, the effect of lnc-ABCA12-3 on ESCC cells was actualized by activating the TLR4/NF-κB signaling pathway under the mediation of exosome. Taken together, the lnc-ABCA12-3 could promote the proliferation and glycolysis of ESCC, while repressing its apoptosis probably by regulating the TLR4/NF-κB signaling pathway under the mediation of exosome.

Characterization of fatty acid metabolism-related lncRNAs in lung adenocarcinoma identifying potential novel prognostic targets.

Lung adenocarcinoma (LUAD), a malignant respiratory tumor with an extremely poor prognosis, has troubled the medical community all over the world. According to recent studies, fatty acid metabolism (FAM) and long non-coding RNAs (lncRNAs) regulation have shown exciting results in tumor therapy. In this study, the original LUAD patient data was obtained from the TCGA database, and 12 FAM-related lncRNAs (AL390755.1, AC105020.6, TMPO-AS1, AC016737.2, AC127070.2, LINC01281, AL589986.2, GAS6-DT, AC078993.1, LINC02198, AC007032.1, and AL021026.1) that were highly related to the progression of LUAD were finally identified through bioinformatics analysis, and a risk score model for clinical reference was constructed. The window explores the immunology and molecular mechanism of LUAD, aiming to shed the hoping light on LUAD treatment.

Sintilimab plus chemotherapy achieved symptom relief in stage IV lung squamous cell carcinoma with superior vena cava syndrome: a case report.

Lung cancer is the second most common and mortality disease in the world. Most patients with lung cancer are already at the advanced stage when diagnosed. There are multiple treatments for advanced lung cancer. Among them, immunotherapy plus chemotherapy has gradually become the first-line treatment. Lung cancer has multiple complications, superior vena cava syndrome (SVCS) is a common complication of patients with advanced lung cancer. The current treatments include radiotherapy, chemotherapy, and stent implantation. Stent implantation has the disadvantages of invasiveness and poor efficacy. Immunotherapy, as an emerging treatment for tumors, has shown significant advantages in treating patients with advanced lung cancer. However, the treatment of advanced lung cancer with SVCS using immunotherapy has rarely been reported. Here, we reported a 48-year-old male patient with stage IV (T4N3M1) lung squamous cell carcinoma. After receiving 1 cycle (3 weeks) of comprehensive treatment with sintilimab plus chemotherapy, the tumor mass shrank by 30% to achieve partial response (PR), collateral circulation was formed, and most of the symptoms caused by SVCS disappeared. After 3 cycles of treatment, the tumor shrank by nearly 90%, and the superior and inferior vena cava opened larger than before. Our case provides a novel treatment strategy for such patients.

Diagnosis and treatment of pericardial mesothelioma by mediastinal mass resection: a case report.

Background: Pericardial mesothelioma (PeM) is a rare disease with non-specific symptoms at the onset, because of its rarity, the relevant literature is limited to case reports and small case series, with no cases exceeding 100 in more than 20 years. As the most common initial symptoms are chest tightness and shortness of breath, early diagnosis is difficult, and the beginning of treatment is easily delayed. We present a rare case of difficult-to-diagnose PeM in which the diagnosis was clarified by surgery and the patient achieved a long survival, providing clinicians with our experience in treating this disease at an early stage of diagnosis and early treatment. Case Description: A 65-year-old female patient attended Affiliated Hospital of Zunyi Medical University, complaining about chest tightness and shortness of breath after activity for the last 2 months, accompanied by edema of the lower limbs in last month. A well circumscribed anterior-mediastinal, partially cystic mass was observed on the chest computed tomography. The patient's heart was compressed by the mass, and the patient had cardiac tamponade symptoms. Cardiac ultrasound showed the enlargement of the right heart, a widened pulmonary artery, pulmonary hypertension, and severe tricuspid regurgitation. The nature of the mass could not be determined prior to the surgery. Anterior superior mediastinal tumour resection and partial pericardial resection and closed thoracic drainage in a median open chest were performed, and pathohistological analysis revealed localized pericardial, epithelioid mesothelioma. In a follow-up after 19 months patient was generally well and without specific discomfort. Conclusions: Differential diagnosis of the anterior mediastinal mass is broad. In patients with a mediastinal tumour who have significant symptoms, are difficult to diagnose and can tolerate surgery, the thoracic surgeon can use surgery as early as possible to make a definitive diagnosis, save the patient's life, and/or improve the patient's quality of life, experienced pathologist is essential to make fast and correct diagnosis.

Acidic microenvironment enhances MT1-MMP-mediated cancer cell motility through integrin ß1/cofilin/F-actin axis.

Tumor acidic microenvironment is the main feature of many solid tumors. As a part of the tumor microenvironment, it has a profound impact on the occurrence and development of tumors. However, the research on how tumor cells sense the changes of the external microenvironment and how the intracellular subcellular structures transmit the signals from extracellular to intracellular is unclear. In this study, we identify that the acidic microenvironment enhances cancer cell motility, and the expression of membrane-anchored membrane type 1-matrix metalloproteinase is also associated with cell motility, which indicates more degradation of the ECM under the acidic microenvironment. Moreover, the expression of cofilin is low in the acidic microenvironment, and the F-actin filaments are distributed more along the cells. The cytoskeletal F-actin changes are consistent with the potential of a high-invasive phenotype. Further study reveals the upstream control of the signal transductions from extracellular to intracellular, that is, the integrin ß1 functions to trigger the biological responses under the acidic microenvironment. Our results demonstrate that the acidic microenvironment enhances cancer cell motility through the integrin ß1/cofilin/F-actin signal axis. This study clearly shows the scheme of the signal transmissions from extracellular to intracellular and further reveals the cytoskeletal roles for the contributions of cancer cell motility under acidic microenvironment, which provides new targets for cancer intervention from the biochemical and biophysical perspectives.

MICAL2 is a novel nucleocytoplasmic shuttling protein promoting cancer invasion and growth of lung adenocarcinoma.

MICAL2 is a tumor-promoting factor involved in cell migration, invasion, deformation, and proliferation not yet fully explored in lung adenocarcinoma (LUAD). This study demonstrated that MICAL2 was overexpressed and cytoplasm-enriched in LUAD tissues. Moreover, high cytoplasmic MICAL2 and/or total MICAL2 expression levels were positively correlated with lymphatic metastasis and shorter overall survival in LUAD patients. MICAL2 promoted LUAD cell proliferation, migration, invasion, and epithelial to mesenchymal transition-all of which involved the AKT and myosin-9 pathways. Furthermore, MICAL2 was identified as a nucleoplasm shuttling protein dependent on myosin-9 and its C-terminal fragment. MICAL2-ΔC-enriched in the nucleus-had less impact on tumor malignancy in LUAD cells in vitro and in vivo. Tumor promotion by MICAL2 was reduced by nuclear-export inhibitor, myosin-9 inhibitor, or si-myosin-9-all of which effectively inhibited MICAL2's nuclear export. Finally, the expression and subcellular location as well as clinical significance of MICAL2 and myosin-9 were analyzed across TCGA data and LUAD tissue arrays. Our data revealed that MICAL2 overexpression and nuclear export were associated with cancer progression; inhibiting its expression and/or nuclear export may provide a new target for LUAD therapy.

[Effect of perioperative treatment with ambroxol on lung cancer patients after video-assisted thoracic surgery lobectomy].

OBJECTIVE: To evaluate the influence of perioperative intravenous administration of ambroxol on pulmonary function, postoperative complications, postoperative hospital stay, and cost after video-assisted thoracic surgery lobectomy for lung cancer. METHODS: Sixty patients who underwent video-assisted thoracic surgery lobectomy for lung cancer in Xiangya Hospital, Central South University between May 2011 and May 2012 were randomly assigned into 2 groups: An ambroxol group (n=30) and a control group (n=30). In the ambroxol group, patients were given ambroxol (1 000 mg/d) on the day of operation and on the first 3 postoperative days. In control group, placebo was given. The pulmonary function tests, arterial blood gases, incidence of perioperative morbidity, postoperative mechanical ventilation time, duration of ICU stay, length and costs of postoperative hospital stay were compared between the 2 groups. RESULTS: The 2 groups were well matched for demographics and operative variables. The ambroxol group showed better the percent predicted forced expiratory volume in 1 second (FEV1%), the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC%), the percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) and arterial oxygen pressure than the control group. The postoperative pulmonary complications was significantly reduced, the duration of mechanical ventilation and the length of ICU stay were shortened, and the length and costs of postoperative hospital stay were significantly decreased in the ambroxol group compared with the control group (all P<0.05). CONCLUSION: Perioperative intravenous administration of ambroxol can improve the postoperative lung function, reduce the incidence of pulmonary complications, shorten the length of postoperative hospital stay, and lower the total cost of hospitalization after video-assisted thoracic surgery lobectomy for lung cancer.