Hypertension as a predictive biomarker in patients with advanced non-small-cell lung cancer treated with apatinib.

BACKGROUND: Hypertension (HTN) is a common adverse event of the vascular endothelial growth factor pathway inhibitor apatinib. This study was conducted to evaluate the association of apatinib-induced HTN with clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: We retrospectively analyzed 110 consecutive patients with advanced NSCLC who were treated with apatinib from August 2014 to January 2018. All patients were classified as normotensive or hypertensive based on blood pressure measurements after initiating therapy. Therapeutic response, progression-free survival (PFS), and overall survival (OS) were evaluated. Univariate and multivariate analyses were performed using the Cox proportional hazards method. RESULTS: A total of 46 patients (42%) were diagnosed with HTN. The median PFS for the hypertensive and normotensive groups were 5.6 months and 4.2 months, respectively (P=0.0027). The median OS times for the hypertensive and normotensive groups were 9.9 months and 7.8 months, respectively (P=0.005). Thirty percent of patients who experienced HTN showed partial response to apatinib as compared with 6.3% of non-hypertensive patients (P=0.002). HTN was independently associated with improved PFS and OS on both univariate and multivariate analyses. CONCLUSION: Apatinib-induced HTN may be an inexpensive, valid, and easily measurable biomarker for apatinib antitumor efficacy in patients with advanced NSCLC.

Apatinib as post second-line therapy in EGFR wild-type and ALK-negative advanced lung adenocarcinoma.

In the absence of a driver mutation, chemotherapy is the standard treatment option as first- and second-line therapy for advanced non-small-cell lung cancer (NSCLC). Though a large number of patients are suitable for post second-line therapies, the quality and quantity of the available drugs in this setting is poor. Apatinib, a small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, is a first-generation oral antiangiogenesis drug approved in the People's Republic of China for use as a subsequent line of treatment for advanced gastric cancer. Herein, we report three cases of advanced NSCLC with epidermal growth factor receptor wild-type and anaplastic lymphoma kinase-negative status, wherein the patients showed partial response to apatinib. Moreover, the three patients have achieved a progression-free survival of 2.8, 5.8, and 6 months, respectively. The main toxicities were hypertension, proteinuria, and hand-foot syndrome. Apatinib may provide an additional option for the treatment of advanced NSCLC, especially for advanced lung adenocarcinoma without a driver mutation.

Efficacy of Whole-Lung Lavage in Treatment of Pulmonary Alveolar Proteinosis.

The aim of the study was to investigate the therapeutic effect of whole-lung lavage (WLL) for pulmonary alveolar proteinosis (PAP). The cohort studies that investigated the therapeutic effect of WLL for PAP were selected strictly on the basis of the inclusion and exclusion criteria. The statistical analysis was performed using STATA statistical software (version 12.0; Stata Corporation, College Station, TX). Twelve studies were included in this meta-analysis. Totally, 206 PAP patients who received WLL were recruited in the 12 studies. We compared the differences in blood gas analysis and lung function before and after the treatment in this meta-analysis. The results indicated that there were statistical differences in the levels of diffusing capacity for carbon monoxide, forced expiratory volume in 1 second, forced vital capacity, and arterial partial pressure of oxygen after the treatment of WLL for patients with PAP, whereas there were no evident differences in the levels of arterial partial pressure of carbon dioxide and arterial oxygen saturation. In conclusion, WLL can evidently improve the diffusing capacity for carbon monoxide, forced expiratory volume in 1 second, forced vital capacity, and arterial partial pressure of oxygen of patients with PAP, thus WLL may be an important treatment of PAP.

MMP-9 1562C>T Gene Polymorphism and Efficacy of Glucocorticoid Therapy in Idiopathic Pulmonary Fibrosis Patients.

OBJECTIVE: To investigate the relationship between matrix metalloproteinase 9 (MMP-9) gene polymorphism and the efficacy of glucocorticoid therapy in idiopathic pulmonary fibrosis (IPF) patients. METHODS: We conducted a case-control study. Between January 2013 and September 2014, 115 patients at the Nine Department of Respiratory Medicine, Nanjing Chest Hospital, diagnosed with IPF were enrolled to be the IPF group and 100 healthy subjects were enrolled to be the control group. Prednisone was used to treat IPF patients. Polymerase chain reaction-restriction fragment length polymorphism was used to identify MMP-9 1562C> T polymorphism. The Sandwich enzyme-linked immunosorbent assay was used to measure the serum level of MMP-9 and tissue inhibitor of metalloproteinases 1 (TIMP-1) in the IPF patients before and after the glucocorticoid treatment. RESULTS: The frequencies of the TT genotype and the T allele of MMP-9 1562C> T gene were found significantly higher in the IPF group compared with the control group (both p < 0.05). Serum levels of MMP-9 and TIMP-1 in IPF patients in each of the three genotype groups before glucocorticoid treatment were significantly higher than those in the control group (all p < 0.05). After the glucocorticoid treatment, MMP-9 and TIMP-1 levels decreased significantly compared with the levels before the glucocorticoid treatment in the IPF patients in each genotype group (all p < 0.05), but were still higher than those in the control group (all p < 0.05). The proportion of "remarkable effect" in the IPF patients of the CC genotype group was significantly higher than that in the other two genotype groups, while the rate of adverse reactions of the CC group was significantly lower than the other two groups (all p < 0.05). CONCLUSION: MMP-9 gene 1562C> T polymorphism may affect the efficacy of the glucocorticoid therapy for IPF and may be a predictor of IPF treatment outcome.

Effect of Endostar combined with angiopoietin-2 inhibitor on malignant pleural effusion in mice.

The present study was designed to investigate the synergetic effect of Endostar combined with an angiopoietin-2 specific inhibitor L1-10 on malignant pleural effusion (MPE) mouse model. A MPE mouse model was established by injecting Lewis lung carcinoma (LLC) cells into pleural cavity of C57BL/6 mice. The mice were randomly divided into four treatment groups: saline, Endostar, L1-10, and Endostar + L1-10. In the present study, we reported for the first time that Endostar combined with L1-10 had significant synergistic effects on the formation of MPE and tumor growth. Moreover, Endostar combined with L1-10 had additive effect on the attenuation of pleural inflammation, inhibition of tumor angiogenesis and pleural vascular hyperpermeability, which are central to the inhibition of MPE. Finally, these studies also found that Endostar combined with L1-10 could have complementary actions by reducing VEGF and IL-6 local release and downregulating VEGF expression in pleural tumors, which involved in the pathogenesis of MPE. Therefore, combined therapy with Endostar and L1-10 may be an encouraging strategy for the treatment of MPE.

Serum CA125 and NSE: biomarkers of disease severity in patients with silicosis.

BACKGROUND: We investigated the clinical significance of tumor markers in patients with silicosis. METHODS: Eighty silicosis patients without malignancy and 50 healthy volunteers were compared for serum tumor marker concentrations. Pulmonary function and several routine laboratory tests were performed. Correlation between serum tumor marker concentrations and severity markers for silicosis was analyzed. Tumor marker concentrations were detected in both blood and BALF samples in silicosis patients. The pre- and post-lavage differences in the serum tumor marker concentrations were also investigated. Immunohistochemical staining for tumor markers was performed in a lung biopsy specimen from a silicosis patient. RESULTS: Both serum NSE and CA125 concentrations were significantly higher in cases compared with controls. Significant positive correlations were found between values of NSE and CA125 and LDH concentration. Significant negative correlations were also observed between values of NSE and CA125 and spirometric parameters. Patients with silicosis had higher concentrations of NSE in BALF than that in serum. 11 of 14 patients experienced a decrease in NSE concentrations following whole lung lavage. Immunohistochemical studies showed positive NSE staining in lung biopsy specimen. CONCLUSIONS: Serum NSE and CA125 concentrations would provide valuable clinical information to assess disease severity in silicosis.

[The long-term therapeutic effects of silicosis by repeat the whole lung lavage].

OBJECTIVE: To preliminary study the long term therapeutic effects of repeat the whole lung lavage (RWLL) in the treatment of silicosis. METHODS: A total of 60 patients with silicosis in the same stone mine were randomly and equally divided into repeat the whole lung Lavage (RWLL) group and whole lung Lavage (WLL) group based on silicosis staging, age and working age of dust exposure. Comparative analysis was performed to evaluate the long-term therapeutic efficacy and safety of RWLL. The cell count and SiO2 content were measured in twice right lung bronchoalveolar lavage fluid(BALF) of the RWLL group. RESULTS: Four years after treatment, the cough and asthma improvement rates of the RWLL group were 68.4% and 75.0% higher than those (52.4%and 57.9%) of the WLL group (P > 0.05). Six years after treatment, the asthma improvement rate (70.0%) of the RWLL group was significantly higher than that (36.8%) of the WLL group (P < 0.05). The RWLL group showed slight decrease in forced vital capacity (FVC) and forced expiratory volume in one second (FEV1.0) after treatment (P > 0.05), while the WLL group showed significant decrease in FVC and FEV1.0 in the six years after treatment (P<0.05). Four and Six years after treatment, the RWLL group had higher no change rate and lower progression rate and significant progression rate than the WLL group in terms of chest X-ray (P>0.05). In the RWLL group,the first time the right lung BALF test showed a number of cells 6.71×10(7)∼2.14×10(9)/L, average 4.50×10(8)/L, pulmonary alveoli macrophages (PAM) ratio of 0.873∼0.980, average 0.954 and SiO2 content of 18∼104.7 mg, average 93.7 mg; the second test showed a number of cells 5.71×10(6)∼1.30×10(9)/L, average 9.12×10(7)/L; PAM ratio 0.710∼0.926, average 0.870 and SiO2 content of 6∼90.2 mg, average 46.2 mg. The RWLL group happened hemoptysis, chest pain one case in perioperative period, the incidence of 6.7%. The RWLL group complicated by left pneumothorax, pulmonary infection one case and the WLL group complicated by one case of lung cancer in a year of follow-up. CONCLUSION: RWLL is reasonable and safe treatment which could help to further improve the long-term effects of WLL for silicosis.

Elevated tumor markers in patients with pulmonary alveolar proteinosis.

BACKGROUND: The role of tumor markers in pulmonary alveolar proteinosis (PAP) remains unclear. This study investigated the tumor markers in serum and bronchoalveolar lavage fluid (BALF) in PAP patients and explored the relationship between tumor markers and the severity of PAP. METHODS: We retrospectively reviewed 38 patients with PAP. RESULTS: Mean serum carcinoembryonic antigen (CEA) and CYFRA21-1 levels were higher than the cut-off values (12.7 ± 17.5 ng/mL and 10 ± 10.66 ng/mL, respectively). Significant correlations were found between levels of CEA and neuron-specific enolase (NSE) in serum and serum lactate dehydrogenase (LDH) values (r=0.60, p<0.001 and r=0.56, p<0.001, respectively). A significant correlation was also observed between levels of squamous cell carcinoma (SCC) in serum and PaO2 and PA-aO2 (r=-0.49 p=0.01 and r=-0.51, p=0.01, respectively). The changes of CEA, SCC and NSE levels were consistent with the changes of LDH and PaO2. The serum levels of CEA, NSE and SCC were significantly lower after whole lung lavage compared with those before (8.7 ± 10.6 vs. 15.7 ± 22, 7.9 ± 5.2 vs. 16.6 ± 11.8, 0.4 ± 0.24 vs. 0.59 ± 0.42; p<0.05, respectively). CONCLUSIONS: Elevated serum tumor marker levels were found in PAP patients. The serum levels of CEA, NSE and SCC may reflect the severity of the disease and predict the therapeutic effect of whole lung lavage.