Immunogenicity and safety of COVID-19 vaccine in lung cancer patients receiving anticancer treatment: A prospective multicenter cohort study.

This study assessed the immunogenicity and safety of the BNT162b2 mRNA vaccine in lung cancer patients receiving anticancer treatment. We enrolled lung cancer patients receiving anticancer treatment and non-cancer patients; all participants were fully vaccinated with the BNT162b2 vaccine. Blood samples were collected before the first and second vaccinations and 4 ± 1 weeks after the second vaccination. Anti-severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein S1 subunit receptor-binding domain antibody titers were measured using the Architect SARS-CoV-2 IgG II Quant and Elecsys Anti-SARS-CoV-2 S assays. Fifty-five lung cancer patients and 38 non-cancer patients were included in the immunogenicity analysis. Lung cancer patients showed significant increase in the geometric mean antibody concentration, which was significantly lower than that in the non-cancer patients after the first (30 vs. 121 AU/mL, p < .001 on Architect; 4.0 vs 1.2 U/mL, p < .001 on Elecsys) and second vaccinations (1632 vs. 3472 AU/mL, p = .005 on Architect; 213 vs 573 A/mL, p = .002 on Elecsys). The adjusted odds ratio (aOR) for seroprotection was significantly lower (p < .05) in lung cancer patients than that in non-cancer patients. Analysis of the anticancer treatment types showed that the aOR for seroprotection was significantly lower (p < .05) in lung cancer patients receiving cytotoxic agents. They showed no increase in adverse reactions. BNT162b2 vaccination in lung cancer patients undergoing anticancer treatment significantly increased (p < .05) antibody titers and showed acceptable safety. Immunogenicity in these patients could be inadequate compared with that in non-cancer patients.

Inhaled steroid therapy and hospitalization for bronchial asthma: trend in Tokushima University Hospital.

With the recognition that airway inflammation is present even in patients with mild bronchial asthma, therapy with inhaled corticosteroids is now indicated in various stages of patients. In the present article, we retrospectively examined the prescriptions for inhaled corticosteroids and other drugs for the treatment of outpatients with bronchial asthma at Tokushima University Hospital. We also analyzed asthma control in these patients, in terms of the incidence of emergency consultations and hospitalizations due to asthma exacerbations. To analyze the recent trend, the patients observed from 1998 to 2000 (recent years) were included, and for control purpose, those in 1990 and 1991 (earlier years) were also included. The percentage of patients treated with inhaled corticosteroids remarkably increased in recent years (mean; 81.3%) compared to earlier years (mean; 23.5%). In contrast, the usage of oral corticosteroids, oral xanthine derivatives, beta-adrenergic receptor agonists and anti-allergic agents tended to decrease in the 10 years period. After the introduction in 1995, considerable patients up to 25% have been treated with anti-leukotrienes. Emergency consultations decreased in recent years (mean; 0.18/patient/year) compared to earlier years (mean; 0.79/patient/year). Emergency hospitalizations also decreased in recent years (mean; 0.043/patient/year) compared to earlier years (mean; 0.23/patient/ year). In the present study, spread of inhaled corticosteroid therapy and decline in incidence of emergency consultation and hospitalization were simultaneously observed at Tokushima University Hospital, and the former has, at least in part, a contribution to the latter.

A third-generation matrix metalloproteinase (MMP) inhibitor (ONO-4817) combined with docetaxel suppresses progression of lung micrometastasis of MMP-expressing tumor cells in nude mice.

The lung is the common target organ of hematogenous metastasis that restricts the prognosis of cancer patients. MMPs play a pivotal role in metastasis by promoting tumor invasion and angiogenesis; therefore, a large number of MMPIs have been developed. Our purpose was to determine the therapeutic efficacy of a selective-spectrum MMPI, ONO-4817 (inhibits MMP-2 and MMP-9 but not MMP-1), against established lung micrometastasis in combination with a cytotoxic anticancer drug, DOC, in a nude mouse model. Human non-small cell lung cancer PC14PE6 (adenocarcinoma) or H226 (squamous cell carcinoma) cells, expressing MMP-2, MMP-9 and/or MMP-1, were injected i.v. into nude mice on day 0. Mice received a single injection of DOC on day 7 (after establishment of micrometastasis) and/or ONO-4817 mixed with food from day 7 to the end of experiments. Monotherapy with ONO-4817 or DOC inhibited formation of lung metastasis by PC14PE6 and H226 cells. In addition, combined use of ONO-4817 with DOC significantly suppressed the tumor burden of H226 and PC14PE6 cells in the lung and prolonged the survival of PC14PE6-bearing mice compared to ONO-4817 or DOC alone. These therapies did not affect the body weight or food intake of tumor-bearing mice. FIZ revealed that lung lesions, but not nontumor parenchyma of the lung, expressed gelatinolytic activity and that treatment with ONO-4817 abrogated the gelatinolytic activity in lung lesions. These results suggest that the combined use of MMPIs with cytotoxic anticancer drugs may be helpful in the control of established lung micrometastasis by tumor cells expressing MMPs.

Organ heterogeneity of host-derived matrix metalloproteinase expression and its involvement in multiple-organ metastasis by lung cancer cell lines.

Cancer metastasis is tightly regulated by the interaction of tumor cells and host organ microenvironments. Matrix metalloproteinases (MMPs), produced by both tumor cells and host stromal cells, play a central role in tumor invasion and angiogenesis. We determined whether metastatic potential of lung cancer to multiple organs is dependent solely on the expression of MMPs by tumor cells, using two metastasis models of human lung cancer cell lines expressing various levels of MMPs and a MMP inhibitor (ONO-4817). In the lung metastasis model, tumor cells (PC14, PC14PE6, H226, A549) inoculated i.v. into nude or SCID mice metastasized only in the lung. In the multiple-organ metastasis model, tumor cells (RERF-LC-AI, SBC-3/DOX, H69/VP, which express low levels of MMPs) inoculated i.v. into natural killer cell-depleted SCID mice metastasized into the liver, kidneys, and systemic lymph nodes. Film in situ zymography analysis revealed that the nontumor parenchyma of the lung had no gelatinolytic activity, whereas gelatinolytic activity of the liver and kidney was high and low, respectively. In the lung metastasis model, gelatinolytic activity of lung nodules directly correlated with the in vitro expression of MMP-2 and MMP-9 by tumor cells. Inhibition of MMP activity by ONO-4817 suppressed lung metastasis by the cell lines that expressed MMPs, but not those that did not express MMP, via the inhibition of MMP activity of lung tumors. In the multiple-organ metastasis model, liver parenchyma, but not liver nodules, showed gelatinolytic activity. The MMP inhibition reduced metastasis to the liver, but not to the kidney or lymph nodes, via inhibition of MMP activity of liver parenchyma. These findings suggest that MMP expression varies among the host organ microenvironments and that stromal MMPs may promote metastasis of lung cancer. Therefore, antimetastatic effects based on MMP inhibition may be dependent on MMPs derived not only from tumor cells but also from organ-specific microenvironments.