Klotho predicts good clinical outcome in patients with limited-disease small cell lung cancer who received surgery

Background

The important role of surgery in early-stage small cell lung cancer (SCLC) has been recognized, and curative surgical resection is recommended. However, the role of adjuvant chemotherapy for stage I SCLC has not yet been evaluated, and novel approaches focusing on the specific genomic characteristics of SCLC may be invaluable for customized therapy. In this study, we focused on the Klotho gene, which is an anti-aging gene known to be a potential tumor suppressor. We investigated whether the expression of Klotho, assessed by immunohistochemistry, can predict survival in patients with resected SCLC.

Methods

The medical records of patients diagnosed as having limited-disease (LD) SCLC and treated by surgical resection (n = 30) at Tokyo Medical University Hospital were retrospectively reviewed. The expression status of Klotho, and of the ATP-binding cassette (ABC) transporters MRP1, MDR and breast cancer resistant protein (BCRP), which can cause resistance to anticancer drugs, including irinotecan, was assessed by immunohistochemical analysis in resected surgical specimens of patients with early-stage SCLC.

Results

Of the 30 patients, Klotho expression was seen in the specimens from 18 patients (60.0%), but not in those of the remaining 12 patients (40.0%). The immunostaining for Klotho was mostly localized in the cytoplasm. The expression of Klotho was significantly associated with the overall survival (OS) (ratio 0.088; 95% confidence interval 0.019-0.409; P = 0.002). The administration of perioperative chemotherapy had no significant effect in improving the survival, as assessed by the Kaplan-Meier method. However, the patients showing Klotho expression in the resected specimens in p-stage I and II, may have benefited from perioperative chemotherapy. A multivariate analysis revealed no significant association between the expression status of MRP1, MDR or BCRP and the OS.

Conclusion

Expression of Klotho was predictive of a favorable outcome following resection in limited-disease SCLC patients, and the Klotho expression status may serve as a new biomarker for the need of additional therapies to be developed in the future.     

Validation of inflationary non-invasive blood pressure monitoring in adult surgical patients

Oscillometric determination of blood pressure may be advantageous, as cuff inflation requires lower cuff pressure and shorter duration than deflation. In this observational study, we compared the blood pressure value, cuff pressure, and duration of cuff inflation between a prototype of inflationary non-invasive blood pressure (NIBP) and conventional deflationary NIBP in adult patients during anesthesia. Three hundred and twenty-three pairs of measurements were obtained from 64 subjects. The bias and precision of systolic pressure and diastolic pressure were 2.9 ± 8.3 and 5.6 ± 6.1 mmHg, respectively. Inflationary NIBP could better determine NIBP with lower cuff pressure than deflationary NIBP (124 ± 22 vs. 160 ± 33 mmHg, p < 0.05). Inflationary NIBP could also determine NIBP more quickly (13.0 ± 2.3 vs. 32.7 ± 13.6 s, p < 0.05). These data suggest that inflationary NIBP may reduce cuff-related discomfort and complications, and has reasonable accuracy compared to deflationary NIBP in adult surgical patients.     

Characterization of skin inflammation induced by repeated exposure of toluene,xylene, and formaldehyde in mice

Volatile organic compounds (VOCs) are considered the main cause of sick building syndrome and they are likely to irritate the skin, eyes, and mucous membrane; however, the toxic threshold and the mechanisms of cutaneous reaction induced by long‐time VOC exposure have not been clarified. In the present study, we investigated the effect of repeated painting of VOCs onto mouse skin. Various concentrations of toluene, xylene, and formaldehyde (FA) were applied once a week for 5 weeks. While FA solution (2–10%) induced remarkable ear swelling and caused evident infiltration of inflammatory cells, high concentrations of toluene and xylene (50 or 100%) evoked mild ear swelling and marginal inflammatory cell invasion. In addition, FA exposure markedly increased the expression of interleukin‐4 (IL‐4), brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3), and transient receptor potential vanilloid‐1 (TRPV‐1) mRNAs in the ears and IL‐4 and NT‐3 mRNAs in the cervical lymph nodes. Furthermore, capsazepine, a TRPV‐1 antagonist, significantly suppressed ear swelling caused by repeated painting of 5% FA. These findings demonstrate that FA has more potent irritancy against skin than toluene or xylene and suggest that the Th2 response, neurotrophins and TRPV‐1 play important roles in FA‐induced skin inflammation. © 2009 Wiley Periodicals, Inc. Environ Toxicol, 2011.     

Successful surgical treatment of ventricular tachycardia that induced left ventricular aneurysm in 12-year-old boy

A surgical treatment of ventricular tachycardia (VT) that induced a congenital left ventricular aneurysm (LVA) in a 12-year-old boy was performed. The VT disappeared after epicardial cryoablation and a reinforcement of LVA with a composite patch. Epicardial cryoablation, based on an intraoperative electrophysiologic study (EPS), is effective in treating VT resistant to antiarrhythmia drugs.     

Carcinosarcoma of the urinary bladder: Expression of epithelial markers and different expression of heat shock proteins between epithelial and sarcomatous elements

A case of carcinosarcoma composed of both adenocarcinoma and saarcomataus elements in the non-trigone region of the urinary bladder is presented. The epithelial element was a well to pooriy differentiated adenocarcinome with focal squamous metaplasia. The sarcomatous elements disclosed spindle cell sarcoma with focal epltheliold pattern and myxold change In the stroma, together with chondrosarcomatous and rhabdomyosarcomatous elements. By Immunohistochemical examination, not onty the carcinoma element but also the sarcomatous elements showed a positive lmmunoreaction for cytokeratin (CK), epithelial membrane antigen (EMA) and carcinoembryonic antigen. Some population of sarcomatous elements expressed smooth muscle actin and muscle specific actin (MSA) and a limited portion of epitheliold area showed a positive Immunoreaction for desmin, MSA and myoglobin, Indicating leiomyosarcomatous and rhabdomyosarcomatous differentiation, respectively. Unexpectedly, tumor cells In the chondrosarcomatws element revealed a simultaneous positvity of CK and EMA as well as S-100 protein. Both epithelial and sarcomatous elements showed an Intensive positive Immunoreaction for p53 and heat shock protein (HSP) 70. However, HSP27 and HSPGO were detected in most epitheilal elements and only in a small number of tumor cells in the sarcomatous area. These findings indicate that sarcomatous elements, Including heterologous elements, may derive from epithelial elements with partial or complete loss of epithelial features, and different factors other than p53 and HSP7O may associate wtth the morphological alteration of carcinoma.     

Sasa veitchii extracts suppress 2,4-dinitrofluorobenzene-induced contact hypersensitivity in mice

We examined the therapeutic effect of the extract from Sasa veitchii leaves (Sasa extract: SE) on the allergic skin inflammation model. SE derived from 0.141 g (low dose) or 0.562 g (high dose) of the leaves was administered orally for 15 days. High dose of SE suppressed ear swelling response induced by repeated 2,4-dinitrofluorobenzene (DNFB) paintings, and both low and high doses of SE reduced infiltration of immune cells into the ear dermis. Although the number of T cells, Treg, CD4⁺T cells and CD8⁺T cells in draining lymph nodes (dLNs) was not changed by SE, IFN-γ secretion from dLN induced by concanavalin A or 2,4-dinitrobenzenesulfonic acid was suppressed by a high dose of SE while IL-10 levels remained unchanged. These results suggest that SE suppresses allergic skin inflammation via reducing IFN-γ secreted from immune cells, especially T cells.