Case Report: Two cases of advanced primary cardiac angiosarcoma treated with anlotinib and a retrospective analysis of the literature.

Primary cardiac angiosarcoma is a rare malignant soft-tissue sarcoma derived from vascular endothelial cells or lymphatic endothelial cells, with a high malignancy, poor prognosis, and a lack of effective medical therapy. This article reports on two patients with primary cardiac angiosarcoma who received first-line treatment with multi-targeted anti-angiogenic agent, anlotinib monotherapy. The treatment rapidly controlled pleural and pericardial effusion, significantly reduced the tumor, improved symptoms, and showed satisfactory recent efficacy. This indicates that anlotinib offers a new first-line treatment option for advanced primary cardiac angiosarcoma.

Novel model for cancer-specific survival of patients with pulmonary sarcomatoid carcinoma: A population-based analysis and external validation.

BACKGROUND/OBJECTIVE: We aimed to develop a comprehensive and effective nomogram for predicting cancer-specific survival (CSS) in patients with pulmonary sarcomatoid carcinoma (PSC). METHODS: Data for patients diagnosed with PSC between 2004 and 2018 from the Surveillance, Epidemiology, and End Results database were retrospectively collected and randomly divided into training and internal validation sets. We then retrospectively recruited patients diagnosed with PSC to construct an external validation cohort from the Southwest Hospital. A prognostic nomogram for CSS was established using independent prognostic factors that were screened from the multivariate Cox regression analysis. The performance of the nomogram was evaluated using area under the receiver operating characteristic (ROC) curves, Harrell's concordance index (C-index), calibration diagrams, and decision curve analysis (DCA). The clinical value of the nomogram and tumor, nodes, and metastases (TNM) staging system was compared using the C-index and net reclassification index (NRI). RESULTS: Overall, 1356 patients with PSC were enrolled, including 876, 377, and 103 in the training, internal validation, and external validation sets, respectively. The C-index and ROC curves, calibration, and DCA demonstrated satisfactory nomogram performance for CSS in patients with PSC. In addition, the C-index and NRI of the nomogram suggested a significantly higher nomogram value than that of the TNM staging system. Subsequently, a web-based predictor was developed to help clinicians obtain this model easily. CONCLUSIONS: The prognostic nomogram developed in this study can conveniently and precisely estimate the prognosis of patients with PSC and individualize treatment, thereby assisting clinicians in their shared decision-making with patients.

Study on the application of percutaneous closed pleural brushing combined with cell block technique in the diagnosis of malignant pleural effusion.

INTRODUCTION: This study was to investigate the diagnostic value of percutaneous closed pleural brushing (CPBR) followed by cell block technique for malignant pleural effusion (MPE) and the predictive efficacy of pleural fluid carcinoembryonic antigen (CEA) for epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma patients with MPE. METHODS: All patients underwent closed pleural biopsy (CPB) and CPBR followed by cell block examination. MPE-positive diagnostic rates between the two methods were compared. Univariate and multivariate analyses were performed to determine factors influencing the EGFR mutations. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of pleural fluid CEA for EGFR mutations. RESULTS: The cumulative positive diagnostic rates for MPE after single and twice CPBR followed by cell block examination were 80.5% and 89.0%, higher than CPB (45.7%, 54.3%) (P < 0.001). Univariate analysis showed that EGFR mutation was associated with pleural fluid and serum CEA (P < 0.05). Multivariate analysis showed that pleural fluid CEA was an independent risk factor for predicting EGFR mutation (P < 0.001). The area under the curve (AUC) of pleural fluid CEA for EGFR mutation prediction was 0.774, higher than serum CEA (P = 0.043), but no difference with the combined test (P > 0.05). CONCLUSION: Compared with CPB, CPBR followed by the cell block technique can significantly increase the positive diagnostic rate of suspected MPE. CEA testing of pleural fluid after CPBR has a high predictive efficacy for EGFR mutation in lung adenocarcinoma patients with MPE, implying pleural fluid extracted for cell block after CPBR may be an ideal specimen for genetic testing.

Therapeutic outcomes of autologous CIK cells as a maintenance therapy in the treatment of lung cancer patients: A retrospective study.

OBJECTIVE: Few clinical studies have confirmed the role of cytokine-induced killer cells (CIKs) in the maintenance therapy of advanced lung cancer patients. We investigate effectiveness and tolerability of CIKs as a maintenance therapy in the treatment of advanced lung cancer patients. METHODS: 70 patients with advanced lung cancer (stage IIIB to IV) admitted to the First Affiliated Hospital of Third Military Medical University in Chongqing from Nov. 2011 to Jan. 2015 and treated with CIKs were enrolled as a CIKs group (T group), and another 70 advanced lung cancer patients treated with optimal supportive care during the same period were enrolled as a control group(C group). The changes of immune system, response rate, disease control rate, overall survival, and side effects were compared between the two groups. Furthermore, the factors that might influence the efficacy of CIKs therapy were evaluated. RESULTS: Compared with the healthy people, the ratios of CD3+, CD4+ and CD8+ T cells significantly decreased (P<0.05) in lung cancer patients. After CIKs treatment, the ratios of CD3+ and CD4+ T cells and CD4+/CD8+ significantly increased (P<0.05). The response rate (RR) and disease control rate (DCR) were 34.3% and 80.0% in the CIKs group, which were significantly higher than those in the control group (11.4% and 54.3%, both P<0.05). Besides, the median PFS was significantly improved in the CIKs group than that in control group (6 months vs. 4 months, P<0.05). Although median OS was 28 months in CIKs group while 22 months in control group, no significant difference was observed (P>0.05). However, The 2-year, 3-year survival rates were 56.8% and 21.6% in the CIK group, respectively, which were significantly improved compared to that in the control group (both P<0.05). KPS score significantly increased in the CIKs group (P=0.001). 6 patients suffered from transient fever or chills in the process of CIKs transfusion, and no other side effect was observed. Furthermore, we also found that TNM stage, tumor size, metastasis in vital organs and KPS score were all factors associated with efficacy of CIKs treatment. CONCLUSION: CIKs treatment, as a maintenance therapy, is safe and effective for advanced lung cancer patients, and can also improve the immune imbalance, RR, DCR, PFS, OS and quality of life of the lung cancer patients.

The value of serum prealbumin in the diagnosis and therapeutic response of tuberculosis: a retrospective study.

OBJECTIVE: The aim of this study was to examine serum prealbumin (PA) levels in patients with tuberculosis and lung cancer, and to evaluate the correlations of serum PA levels with clinicopathological characteristics. METHOD: Total 760 patients were included in the study: 320 patients with tuberculosis, 320 patients with lung cancer, and 120 healthy subjects. Serum PA was detected using a biochemical analyzer to determine the value of serum PA in the diagnosis and therapeutic response of tuberculosis. RESULTS: Compared to lung cancer and healthy individuals, TB patients were more frequent in suffering from low serum PA (75.0% vs.30.9% vs.6.7%,P<0.01), and the serum PA levels of TB patients were significantly reduced (137.5 ± 42.4 mg/L vs. 183.5 ± 49.1 mg/L vs. 240.0 ± 43.9 mg/L, P<0.01). Among various clinical characteristics, type (with pleuritis), age (≥ 60), ESR (>20 mm/h) and smoking status (≥ 20 pack × years) were associated with low serum PA levels of TB patients, while ECOG performance status (≥ 2) was associated with low serum PA levels of lung cancer patients. The change of serum PA levels was in accordance with the therapeutic effects of anti-TB drugs, which might present a valuable and objective indicator for monitoring the therapeutic effects of TB drugs on TB patients. CONCLUSION: Low serum prealbumin levels are very common in TB patients and can be served as a potential indicator for differential diagnosis of lung cancer and monitoring the therapeutic effects of TB drugs.

Identification of CD90 as a marker for lung cancer stem cells in A549 and H446 cell lines.

Accumulating evidence supports that cancer stem cells (CSCs) are responsible for tumor initiation, progression, distal metastasis and even drug resistance. Although CD90 has been identified as a marker for several types of stem cells, such as liver CSCs, the potential role of CD90 as a marker for lung CSCs has yet to be fully characterized. Our previous study demonstrated that the lung cancer stem-like cells isolated from A549 tumor spheres, which were cultured in serum-free conditioned medium, had stronger proliferation and self-renewal abilities, and expressed higher levels of the stem cell markers Sox2 and Oct4 as compared to A549 adherent cells. In the present study, we identified CD90 as a novel surface marker of CSCs in lung cancer cells. Furthermore, we isolated CD90+ CSCs from lung cancer cell lines A549 and H446. Our results revealed that the CD90+ cells, but not the CD90- cells, from lung cancer cells displayed higher tumorigenic capacity. These findings suggest that CD90 could be a potential marker of lung CSCs and thus provide new insight into further therapeutic strategies of lung cancer.

Akt1 enhances CA916798 expression through mTOR pathway.

Multi-drug resistance leads to the failure of chemotherapy for cancers. Our previous study showed that overexpression of CA916798 led to multi-drug resistance. However, the underlying mechanisms remain unknown. In the current study, we observed that the levels of phosphorylated AKT, phosphorylated mTOR and CA916798 all increased in the drug resistant human adenocarcinoma samples and paralleled with the change of drug resistance. The results of immunofluorescence and Co-IP indicated that the positive correlation of CA916798 expression with AKT1 activation might be associated with drug resistance of lung adenocarcinoma. Furthermore, AKT1 stimulated CA916798 expression through mTOR pathway in both A549 and A549/CDDP cell lines, which was also observed in the xenografted tumor in nude mice. The results showed that CA916798 located in the downstream of PI3K/AKT/mTOR pathway. Inhibition of PI3K by LY294002 could efficiently reduce CA916798 expression and tumor size in vivo as well. Additionally, LY294002 combined with rapamycin inhibited CA916798 expression and tumor size stronger than LY294002 alone. Our findings may also provide a new explanation for synergistic anti-tumor effects of PI3K and mTORC1 inhibitors.

[The study of PI3K/AKT pathway in lung cancer metastasis and drug resistance].

PI3K/AKT signal pathway is an important intracellular signal transduction pathway. It plays important roles in cell apoptosis and survival by affecting the activity of downstream effector molecules, and it is closely associated with the development and progression of human tumors. Recent researches of PI3K/AKT indicate that this pathway plays important roles in tumor cells proliferation, blood vessel neogenesis, tumor metastasis and resistance to chemotherapy and radiotherapy. The profound research of PI3K/AKT is beneficial to the prevention of tumor and to the finding of potential targets for new drugs. This article reviewed the composition, function and regulation of PI3K/AKT signal pathway, and its effect in metastasis and drug resistance of lung cancer.