Search

Objective and design: Cisplatin-based chemotherapy has been widely used in the perioperative period of cancer surgery, which exacerbates the risk of renal injury. In this study, we examined whether dexmedetomidine (DEX), a commonly used anesthetic adjuvant, shows a protective effect against cisplatin-induced acute kidney injury. Materials: Acute kidney injury in mice was induced by cisplatin. Treatments: Mice were administered with DEX 25 μg/kg or atipamezole 250 μg/kg (once a day, for 3 days) after cisplatin treatment. Methods: The renal function and tubular damage score were evaluated at 72 h following cisplatin administration. Apoptotic tubular cells were detected by TUNEL assay. Caspase-3, p53, Bax, F4/80 macrophages, CD3 T cells, and NF-κB were examined by immunohistochemistry staining or Western blot. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1 in kidney were measured using real-time polymerase chain reaction. Results: DEX treatment preserved renal function and reduced tubular damage score of mice after cisplatin administration. Mice treated with DEX exhibited less apoptotic tubular cells in response to cisplatin insult, which was associated with decreased Bax and reduced activation of p53 and caspase-3. DEX suppressed the infiltration of macrophages and T cells into the kidneys following cisplatin treatment, which was involved in the inhibition of NF-κB activation and decreased expression of TNF-α, IL-1β, IL-6, and MCP-1. Furthermore, we showed that the renoprotective effect conferred by DEX may be related to α adrenoceptor-dependent pathway. Conclusion: We demonstrate that DEX protects the kidney against cisplatin-induced AKI by the regulation of apoptosis and inflammatory response. [ABSTRACT FROM AUTHOR]

Objective To evaluate the feasibility of malignant pleural effusions ( MPE) as surrogate samples for the detection of echinoderm microtubule-associated protein-like4 ( EML4)-anaplastic lymphoma kinase ( ALK) and to investigate the prognostic and predictive value of EML4- ALK in MPE of non-small-cell lung cancer ( NSCLC). Methods One hundred and nine NSCLC patients were retrospectively analysed. EML4- ALK was identified using paraffin-embedded tumour cells in MPE samples by immunohistochemistry ( IHC, Ventana) and confirmed by fluorescence using in situ hybridisation ( FISH) and qRT- PCR. The EGFR mutation was determined by MPE, using denaturing high-performance liquid chromatography ( DHPLC). Results A total of 5 out of 109 (4.58%) patients were identified as EML4- ALK rearrangement in MPE by IHC.; In addition to two metachronous samples, the consistency of MPE and tissue for EML4- ALK detection was 100% (21/21), and the sensitivity and specificity were 100% (2/2) and 100% (19/19), respectively. EML4- ALK rearrangement cases were confirmed by FISH and qRT- PCR; the sensitivity were both 100% (2/2) when compared with tissue, and it was 60% (3/5) and 100% (5/5), respectively, when compared with MPE by IHC. The overall response rate ( ORR) was 100% (2/2) for patients with EML4- ALK in MPE. Moreover, the PFS of these patients appeared to be prolonged in chemotherapy (9.27 versus 6.53 and versus 4.67 months, P = 0.122), compared with the EGFR mutation and the EGFR/ ALK double negative group, respectively. Conclusion EML4- ALK rearrangement detection in malignant pleural effusions is a complementary method for EML4- ALK detection. VETANA and qRT- PCR are more appropriate for MPE detection. EML4- ALK rearrangement in pleural effusions has a predictive value for treatment. [ABSTRACT FROM AUTHOR]

Optimal treatment of esophageal small-cell cancer, a rare disease, lacks consensus. Based on its lung small-cell cancer analog, we hypothesized that chemotherapy with adjuvant radiotherapy would be optimal. This hypothesis was tested by studying the collective published literature. A meta-analysis of individual patients from 148 articles (1952-2010) explored treatment and outcome of 577 patients with esophageal small-cell cancer. Hazard function frailty modeling identified optimum therapy after accounting for article-level and patient-level heterogeneity. Fifty-nine percent of publications reported one patient and 25% five or more. Sixty-six percent of patients were men, mean age was 63 ± 11 years, and 64% had localized disease. One, 3-, and 5-year survival was 37%, 14%, and 11%, respectively. Survival variation among articles was substantial ( P = 0.004), with survival improving across time ( P < 0.0004). Chemotherapy was associated with better survival (hazard ratio [ HR] = 0.53, 68% confidence interval [ CI] = 0.44-0.65; P = 0.002) than surgery alone, radiotherapy alone, nonstandard therapy, or no therapy. Adding local therapy, either surgery ( HR = 0.41, 68% CI = 0.34-0.51; P < 0.0001) or radiotherapy ( HR = 0.33, 68% CI = 0.27-0.41; P < 0.0001), to chemotherapy further improved survival. Adding both did not provide further benefit. The strategy of borrowing from consensus treatment of lung small-cell cancer and analyzing the scarce available esophageal small-cell cancer literature may be beneficial in the study of rare diseases. It confirmed that chemotherapy should be the mainstay of therapy, with additional benefit from adjuvant therapy with either surgery or radiotherapy; both are not needed. [ABSTRACT FROM AUTHOR]