Pretreatment Clinical Mediastinal Nodal Bulk and Extent do not Influence Survival in N2-Positive Stage IIIA Non-small Cell Lung Cancer Patients Treated with Trimodality Therapy

Background

Treatment for patients with N2-positive stage IIIA non-small cell lung cancer has been a controversial issue. The current study evaluated the outcomes in patients treated with trimodality therapy, which consisted of neoadjuvant radiation therapy concurrent with chemotherapy followed by surgical resection, with emphasis on clinical and pathologic nodal status.

Methods

We reviewed the records of 355 patients who were treated with trimodality therapy between 1997 and 2011.

Results

After completion of neoadjuvant chemoradiation, overall down-staging and complete response rates were 50.4 % (179 patients), and 13.2 % (47 patients), respectively. With median follow-up of 35.3 months, median times of progression-free survival (PFS) and overall survival (OS) were 16.3 months and 45.5 months, respectively. Seventeen patients (4.8 %) died of postoperative complications, and the remaining 338 patients were analyzed on prognostic factors. Old age (p = 0.032), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were found to be the significant prognosticators for worse PFS, and old age (p = 0.013), pneumonectomy (p < 0.001), and ypN+ (p < 0.001) were related to worse OS. Clinical N2 status did not influence either OS or PFS: the number of involved stations (single station vs. multi-station; p = 0.187 for PFS; p = 0.492 for OS), and bulk (clinically evident vs. microscopic; p = 0.902 for PFS; p = 0.915 for OS).

Conclusion

ypN stage was the most important prognosticator for both PFS and OS; however, neither initial bulk nor extent of cN2 disease influenced prognosis. Surgery following neoadjuvant chemoradiation should have contributed to improved clinical outcomes regardless of clinical nodal bulk and extent.     

Anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)- 2-butenal are mediated by inhibition of the STAT3 pathway

Background and Purpose

Products of Maillard reactions between aminoacids and reducing sugars are known to have anti-inflammatory properties. Here we have assessed the anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal and its possible mechanisms of action.

Experimental Approach

We used cultures of LPS-activated macrophages (RAW264.7 cells) and human synoviocytes from patients with rheumatoid arthritis for in vitro assays and the collagen-induced arthritis model in mice. NO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities were measured in vitro and in joint tissues of arthritic mice, along with clinical scores and histopathological assessments. Binding of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal to STAT3 was evaluated by a pull-down assay and its binding site was predicted using molecular docking studies with Autodock VINA.

Key Results

(E)-2,4-bis(p-hydroxyphenyl)-2-butenal (2.5–10 μg·mL⁻¹) inhibited LPS-inducedNO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities in macrophage and human synoviocytes. This compound also suppressedcollagen-induced arthritic responses in mice by inhibiting expression of iNOS and COX2, and NF-κB/IKK and STAT3 activities; it also reduced bone destruction and fibrosis in joint tissues. A pull-down assay showed that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal interfered with binding of ATP to STAT3. Docking studies suggested that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal bound to the DNA-binding interface of STAT3 possibly inhibiting ATP binding to STAT3 in an allosteric manner.

Conclusions and Implications

(E)-2,4-bis(p-hydroxyphenyl)-2-butenal exerted anti-inflammatory and anti-arthritic effects through inhibition of the NF-κB/STAT3 pathway by direct binding to STAT3. This compound could be a useful agent for the treatment of arthritic disease.     

Comparison of toxicity of different nanorod‐type TiO2 polymorphs in vivo and in vitro

It is predicted that the toxicity of nanoparticles may be different depending on the properties of the nanoparticles and biological system being tested. However, the factors that influence the toxicity of nanoparticles have not been adequately investigated. In this study, we characterized two types of TiO₂ nanorods, anatase (ATO) and brookite (BTO), and compared their toxicity in vivo and in vitro. ATO and BTO differed from each other most notably in their surface areas. Treatment with the two TiO₂ nanorods (10 µg ml^–1) produced similar effects on the cell cycle in eight cell lines which are derived from potential target organs of nanoparticles, with the BTO eliciting stronger responses than ATO in all cell lines, among the cell lines, H9C2 showed the maximal change. Similarly, when mice were exposed to two TiO₂ nanorods (1 mg kg^–1), BTO induced clearer histopathological lesions and triggered a more robust secretion of inflammatory cytokines than ATO. Furthermore, we compared the cellular response of both TiO₂ nanorods using BEAS‐2B cells, the human bronchial epithelial cell line. Both nanorods induced cell death by increasing the formation of autophagosome‐like vacuoles. The mitochondrial calcium concentration decreased by exposure of both types, but the distribution of lysosome and endoplasmic reticulum (ER) showed a clear difference between the two nanorods. Thus, we conclude that the surface area acts as an important factor which depends on toxicity of nanorod type‐TiO₂ nanoparticles. Furthermore, the toxicity of nanoparticles varies according to the type of cells tested, and that the assembly of autophagosome‐like vacuoles is a critical part of the cellular response to nanoparticle exposure. Copyright © 2013 John Wiley & Sons, Ltd.     

Comparison of ICC patients with hepatitis B infection to those with no major risk factors for HCC

BackgroundThere has been renewed interest in HBV-associated ICC, because it could share a common carcinogenesis disease process with HCC. We investigated whether there is a difference in clinical outcome between ICC patients with HBV infection and those without any major risk factors for HCC.MethodsA total of 253 curatively resected, surgically diagnosed ICC patients were analyzed and divided into two groups according to the presence or absence of major risk factors for HCC: an HBV group (n = 45) and a non–HCC–risk (NHR) group (n = 208).ResultsLymph node metastasis was more frequently observed in the NHR group (HBV vs. NHR: 8.89% vs. 24.52%, P = 0.027). Patients in the HBV group demonstrated more favorable survival than those in the NHR group. However, this difference was not statistically significant (5-year survival rate, 54.7% vs. 42.3%, P = 0.128). Cumulative recurrence rate in the HBV group was 62.2%, which was not significantly different from 63.0% in the NHR group (P = 1.000).ConclusionThis study found that while ICC patients with HBV infection showed some favorable tumor characteristics, patients' stage-specific survival and recurrence rates were not significantly different compared to those without any major risk factors for HCC.     

Intramedullary tuberculosis manifested as Brown-Sequard syndrome in a patient with systemic lupus erythematosus

A 25-year-old girl presented with progressive deterioration of right side weakness with decreased sensation on the left trunk. She had been treated with high dose steroid due to autoimmune thrombocytopenia for 2 months. Clinical, laboratory and immunologic studies revealed that she had systemic lupus erythematosus (SLE), MRI of spinal cord showed marginal contrast enhancing and fluid containing mass in the cord of the C5-6 level, suggesting intramedullary abscess. She underwent surgery of mass removal with biopsy. The pathologic findings from cord tissues revealed numerous acid fast bacilli (AFB) in necrotic tissues. After surgery and anti-tuberculous treatment, her neurologic symptoms were markedly improved with restoration of right side motor weakness. To our knowledge, this is the first case report of intramedullary tuberculosis in a patient with SLE. Since intramedullary tuberculosis may sometimes mimic neurologic complication of SLE itself, it may pose diagnostic and therapeutic confusion for clinicians. We report a case of spinal cord tuberculosis affecting C5, 6 level which was manifested as Brown-Sequard syndrome in a patient with SLE.