No abstract

Abstract. NPe6 is a novel second-generation photosensitizer used for photodynamic therapy (PDT). PDT using NPe6 and diode laser (664 nm) induces cell death, inflammatory reactions, immunological responses and damage to the microvasculature. In this study, we evaluated the influence of the immunological responses and of enhanced angiogenesis on the anti-tumor effect of NPe6-PDT using cytokine-overexpressing Lewis lung carcinoma (LLC), LLC-IL-2 cells both in vitro and in vivo. We showed by DNA microarray analysis in vitro that IL-2 and GADD-45α (growth arrest and DNA damage 45 alpha) mRNA expressions were induced by 3 h after NPe6-PDT applied at a dose killing 90% of the cells (LD 90 ). IL-2-overexpressing cells (LLC/IL-2 cells) were resistant to the loss of clonogenicity as compared to the parental LLC cells in vitro. Furthermore, in female C57BL/6 mice, NPe6-PDT produced a cure rate of 66.7% in LLC tumors, whereas the cure rate was only 16.6% in LLC/IL-2 tumors, and overexpression of IL-2 caused failure of NPe6-PDT, with tumor recurrence, in vivo. These results suggest that IL-2 expression may play an unfavorable role in attenuation of the antitumor effect of NPe6-PDT. It has been reported that the expression of vascular endothelial growth factor (VEGF), in particular, may cause tumor recurrence after PDT and exert unfavorable effect in relation to attenuate the anti-tumor activity of PDT. Results of immunohistochemical analysis of LLC/IL-2 tumors have revealed that the expressions of GADD-45α and VEGF are induced in these tumors after PDT, and in particular, 12 h after PDT, the expression levels were much higher as compared with those in the LLC tumors. The results of our studies using in vitro and in vivo models suggest that the cell death caused by PDT was inhibited by induction of GADD-45α expression and that tumor recurrence was promoted by the enhancement of VEGF expression mediated by IL-2 upregulation. Therefore, it is speculated that the use of an IL-2 inhibitor may improve the efficacy of NPe6-PDT.

A 64-year-old neurologically asymptomatic woman with rheumatoid arthritis who was treated with the tumor necrosis factor (TNF)-α antagonist adalimumab developed disseminated tuberculosis (TB). After receiving anti-TB therapy and discontinuing adalimumab, she exhibited paradoxical worsening due to immune reconstitution inflammatory syndrome (IRIS) with the appearance of meningitis and brain tuberculomas. This case indicates that continuing anti-TNF therapy may be necessary to prevent IRIS in patients who develop TB, particularly disseminated TB, during the course of anti-TNF therapy. In addition, careful screening for central nervous system (CNS) TB should be performed prior to the initiation of therapy, as even neurologically asymptomatic patients can develop CNS manifestations of IRIS.

Abstract. Partial or complete spontaneous cancer regression is a rare phenomenon, particularly in patients with lung cancer. This is the case report of a patient with lung cancer who exhibited spontaneous regression of the primary as well as metastatic lesions, without receiving any treatment. Spontaneous regression commenced within a week of obtaining pathological specimens by transbronchial and percutaneous biopsies from the primary lesion and metastatic lymph nodes of the left side of the neck. The reason for this phenomenon is unknown; however, we hypothesized that there may be an immunological association between the stimulus of the biopsies and the spontaneous regression. This patient should be closely followed up to monitor the clinical course of this unusual case.

No abstract

The prevalence of underlying lung diseases, such as emphysema and interstitial lung disease in smokers with epidermal growth factor receptor (EGFR)-mutant lung cancer remains unclear. This study aimed to clarify the correlation between the EGFR mutation status and the prevalence of underlying lung disease in smokers with lung cancer. A total of 88 consecutive smokers with non-small cell or non-squamous cell lung cancer who underwent surgical resection at our hospital from January 2007 through December 2010 were included in this study. The patients were divided into two groups on the basis of the EGFR mutation status: the mutation-positive group (n=19) and the wild-type group (n=69). The results of radiographic assessment via computed tomography (CT) and pulmonary function analysis were compared between the two groups. In the radiological evaluation, CT images at three levels were evaluated by two reviewers. Radiographic assessment revealed that the mutation-positive group tended to have milder emphysematous changes and a lower prevalence of interstitial changes compared with the wild-type group (P=0.13, 0.06). When the analysis was limited to the ipsilateral lung at the nearest CT level to the tumor, emphysematous changes were found to be less common in the mutation-positive group (P=0.02). The prevalence of the emphysematous and/or interstitial changes in the ipsilateral lung at the nearest CT level to the tumor was lower in the mutation-positive group compared to the wild-type group (P=0.005). In the pulmonary function test, the results were comparable between the two groups. In conclusion, according to our results, EGFR-mutant lung cancer was commonly observed in the areas where emphysematous and interstitial changes were absent. EGFR-mutant lung cancer may develop in radiographically normal areas of the lungs, even in smokers. It would be of importance to evaluate the EGFR mutation status in patients with no emphysematous or interstitial changes in the ipsilateral lung near the tumor, regardless of their smoking history. These results should be confirmed in a future prospective study.

Among the dysfunctions and pathologies associated with sepsis, the underlying molecular mechanisms of sepsis-induced acute lung injury (ALI) are poorly understood. Endothelin (ET)-1, a potent vasoconstrictor and pro-inflammatory peptide, is known to be involved in the pathogenesis of ALI in a rat model of sepsis. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting β-blocker, plays a crucial role in ameliorating and attenuating LPS-induced ALI through modulation of the ET-1 system. Male Wistar rats at 8weeks of age were administered with either saline or lipopolysaccharide (LPS) for three hours (3h) and some of the LPS-administered rats were continuously treated with landiolol for 3h. ALI was induced by LPS, including levels of both circulatory and pulmonary TNF-α and IL-6 but [PaO] was significantly decreased. LPS also induced a significant increase in levels of pulmonary ET-1 and ET-A receptor, but levels of ET-B receptor, which has vasodilating effects, were remarkably diminished. Further, LPS administration upregulated the pulmonary expression of HIF-1α. Finally, the treatment of LPS-administered rats with landiolol for 3h ameliorated and prevented ALI, normalized the altered levels of pulmonary ET-1 and ET-A receptors. Landiolol also induced significant down-regulation of ET-B receptor in lung tissues in the early hours (phase) of sepsis. However, Landiolol treatment had no effect on the up-regulated inflammatory mediators (TNF-α, IL-6) in both plasma and lung tissues during sepsis, and expression of pulmonary HIF-1α also remained unchanged after landiolol treatment. Collectively, these data led us to conclude that landiolol may ameliorate sepsis-induced ALI via the pulmonary ET system.

TBLB for pathological and bacterial investigations would provide only a limited value for MAC diagnosis. Moreover, the presence of intrabronchial secretion may be an important manifestation of ongoing airway damage, which would require early treatment.