Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation.

Arsenic trioxide (As2O3) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of As2O3 on lung cancer and explored its possible mechanism. It was observed that As2O3 significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis in vivo. The inhibitory effect of As2O3 on cell proliferation in vitro was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that As2O3 inhibited the migration of vascular endothelial cells and disrupted vascular tube formation on Matrigel assays. In addition, a series of key signaling factors involved in multiple stages of angiogenesis, including matrix metalloproteinase (MMP)-2, MMP-9, platelet-derived growth factor (PDGF)-BB/PDGF receptor-ß, vascular endothelial growth factor (VEGF)-A/VEGF receptor-2, basic fibroblast growth factor (FGF)/FGF receptor-1 and delta like canonical Notch ligand 4/Notch-1, were regulated by As2O3. These findings suggested that anti-angiogenesis may be an underlying mechanism of As2O3 anticancer activity in lung cancer.

Clinical aspects and cytokine response in adults with seasonal influenza infection.

Cytokine responses play an important role in the pathogenesis of influenza infection. Previous studies found that cytokine expressions in patients infected with the novel A (H1N1) influenza virus (nvA (H1N1)) could reflect the severity of the disease. But the patterns of cytokine response in patients infected with seasonal influenza virus and the correlations between cytokine responses and clinical data are still unknown. Seventy-two outpatients for laboratory-confirmed seasonal influenza infection were studied: twenty-four seasonal influenza A patients and forty-eight seasonal influenza B patients. Thirty healthy volunteers were enrolled as a control group. Serum samples from influenza patients obtained on the admission day and 6 days later were measured for eight cytokines using enzyme-linked immunosorbent assay (ELISA). The clinical variables were recorded prospectively. The levels of interleukin (IL)-6, IL-33 and tumor necrosis factor (TNF)-α were significantly higher in influenza A patients than those in the control group while IL-6, IL-17A, IL-29, interferon (IFN)-γ and interferon gamma-induced protein (IP)-10 were significantly higher in influenza B patients than those in the control group. Furthermore, IL-17A, IL-29 and IP-10 were increased in seasonal influenza B patients when comparing with those in the seasonal influenza A patients. A positive correlation of IL-29 levels with fever (Spearman's rho, P-values < 0.05) and a negative correlation of IFN-γ and IP-10 levels with lymphocyte count (Spearman's rho, P-values < 0.05) were found in seasonal influenza infection. While a hyperactivated proinflammatory cytokine responses were found in seasonal influenza infection, a higher elevation of cytokines (IL-17A, IL-29 and IP-10) were found in seasonal influenza B infection versus influenza A. IL-29, IFN-γ and IP-10 were important hallmarks in seasonal influenza infection, which can help clinicians make timely treatment decision for severe patients.

[A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].

OBJECTIVE: To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death. RESULTS: The objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05). CONCLUSIONS: Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

Arsenic trioxide inhibits the growth of human lung cancer cell lines via cell cycle arrest and induction of apoptosis at both normoxia and hypoxia.

Arsenic trioxide (As(2)O(3)) has been established to be an effective agent for treating acute promyleocytic leukemia. Laboratory data suggest that As(2)O(3) induces apoptosis of several solid tumor cells including lung cancer cells. Regions of tissue hypoxia often arise in aggressive solid tumors, and hypoxic tumors exhibit augmented invasiveness and metastatic ability in several malignancies. Furthermore, hypoxia may impair the treatment efficiency; therefore, we studied the cytotoxic effect of As(2)O(3) on human lung adenocarcinoma cell lines A549 and A549/R (resistant to vincristine, adriamycin and mitomycin etc.) grown under normoxic and hypoxic (1% oxygen) conditions. At both normoxia and hypoxia, 5, 10 and 15 microM As(2)O(3) induced evident growth inhibition and apoptosis in A549 cells as well as A549/R cells after 48 hours of exposure. In contrast, the conventional chemotherapeutic drug vincristine showed lowered efficiency in hypoxic A549 cells. As(2)O(3) induced G(2)/M cell cycle arrest in both normoxic and hypoxic A549 cells. As(2)O(3) significantly decreased the messenger RNA (mRNA) levels of Cyclin B(1) and survivin and the protein levels of Cyclin B(1), phospho-CDC(2) (Thr 161) and survivin in both normoxic and hypoxic A549 cells. Together, our findings indicated that As(2)O(3) significantly inhibited the proliferation of lung cancer cells via G(2)/M cell cycle arrest and induction of apoptosis at both normoxia and hypoxia, and the induction of apoptosis was associated with down regulation of survivin.

[Effects of arsenic trioxide on apoptosis and proliferation of human lung cancer cells under hypoxia].

OBJECTIVE: To observe the effects of different concentrations of arsenic trioxide (As(2)O(3)) on apoptosis and proliferation of human lung cancer cell line A549 in vitro under hypoxia and normoxia. METHODS: A549 cells were treated with 0, 1, 2, 4 micromol/L As2O3 for 12, 24 and 48 h under hypoxia (5% O(2)) and normoxia (21% O(2)). The proliferative inhibition rate of A549 cells was measured with methyl thiazolyl tetrazolium assay, and the apoptotic rate of A549 cells was detected by Annexin V/propidium iodide (PI) double staining. RESULTS: Under normoxia and hypoxia, 1, 2, 4 micromol/L As(2)O(3) could significantly inhibit the proliferation of A549 cells and induce the apoptosis of A549 cells. The results depended on the drug concentration and action time. And the hypoxia couldn't influence the effects of As(2)O(3). CONCLUSION: As(2)O(3) can inhibit the proliferation and induce the apoptosis of A549 cells under hypoxia and normoxia.

Case report: dramatic recovery of lung adenocarcinoma-associated dermatomyositis with targeted lung cancer therapy alone.

This case report details the sudden onset of severe dermatomyositis (DM) symptoms followed by rapid progression of adenocarcinoma of the lung and an obvious diminution of the primary tumor with the administration of lung cancer targeted drug therapy alone, followed by nearly complete disappearance of the DM symptoms, with no conspicuous improvement in the DM symptoms when using corticosteroids.

[Irinotecan plus cisplatin for the treatment of advanced non-small cell lung cancer].

OBJECTIVE: To evaluate the efficacy and adverse events of irinotecan (CPT-11) combined with cisplatin (DDP) in the treatment of patients with advanced non-small cell lung cancer (NSCLC). METHODS: Of 36 NSCLC patients consisting of 23 males and 13 females with a medium age of 52 years included, there were 26 adenocarcinomas, 7 squamous cell carcinomas, 1 adeno-squamous cell carcinoma and 2 unclassified types; 13 stage III B and 23 stage IV; 24 chemonaive and 12 previously treated by chemotherapy with a medium Karnofsky status of 90. All patients had measurable or evaluable parameters. The regimen was administered as following: CPT-11 60 mg/m2, IV, D1, 8 and 15; DDP 80 mg/m2, IV, D1; every 28 days as a cycle. RESULTS: Totally, 97 cycles were carried out in these 36 patients with a medium cycles of 3. Of 35 evaluable patients, 22.9% (8/35) achieved partial response, 60.0% (21/35) had stable disease and 17.1% (6/35) progressive disease. The response rate was 29.2% (7/24) for chemonaive patients and 9.1% (1/11) for these previously treated. The 1-year survival rate was 45.4% with a medium time to tumor progression (TTP) of 199 days for the responders. The incidence rate of grade III/IV adverse events were: 16.7% for neutropenia, 13.9% alopecia, 5.6% diarrhea, 2.8% nausea and vomiting, respectively. CONCLUSION: Irinotecan plus cisplatin is effective with tolerable adverse events in treating patients with advanced non-small cell lung cancer, but further investigation trials are needed.

[Treatment of spontaneous metastatic lung cancer with interleukin-12 gene-modified dendritic cells vaccine].

BACKGROUND & OBJECTIVE: Although many works have been done in treatment of metastatic lung cancer, effective method is lacked. This study was designed to investigate the treatment of spontaneous metastatic lung cancer by interleukin-12 (IL-12) gene-modified dendritic cells (DC) vaccine. METHODS: The spontaneous metastatic lung cancer model, prepared by injection of the 3LL Lewis lung cancer cells into the footpads of C57BL/6 mice, were treated by subcutaneous vaccination with tumor antigen peptide Mut1-pulsed, IL-12 gene-modified dendritic cells (DC-IL-12/Mut1) derived from the normal bone marrow. After treatment, the lung weight, the number of lung metastatic nodes, the survival time of the tumor-bearing mice were observed, and the NK and CTL activities were respectively determined. RESULTS: Compared with mice treated with Mut1-pulsed, control LacZ gene modified DC and untreated DC, tumor-bearing mice treated with DC-IL-12/Mut1 had the lightest lung weights (P < 0.01), the least lung metastatic node numbers (P < 0.01), the longest survival time (P < 0.01), also with the induction of potent CTL activity (P < 0.01) and NK activity (P < 0.01). CONCLUSION: Tumor antigen-pulsed, IL-12 gene-modified dendritic cells have significant therapeutic effects on the spontaneous metastatic lung cancer, the possible mechanism involved with induction of CTL activity and enhancement of NK activity.