Loss of LKB1 Expression Decreases the Survival and Promotes Laryngeal Cancer Metastasis.

Background: Given recent results indicating that diminished LKB1 expression in laryngeal cancer correlates with shorter survival. We aim to perform an analysis estimate the role of decreased liver kinase B1(LKB1) and in the prognostication of human laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study and evaluate the expression of LKB1 and p16INK4a (p16) in 208 clinical advanced-stage LSCC tissue samples by using immunohistochemistry. The specimens were received at Sun Yat-sen University Cancer Center (Guangzhou, China). To evaluate the independent prognostic relevance of LKB1, univariate and multivariate Cox regression models were used, overall survival (OS) and distant metastasis-free survival (DMFS) were compared using the Kaplan-Meier method. Results: Immunohistochemical analyses revealed that 80/208 (38.5%) of the LSCC tissue samples expressed high LKB1. Low LKB1 expression was associated with a significantly shorter OS and DMFS than high LKB1 expression (P = 0.041 and 0.028, respectively; log-rank test), and there was a poorer OS in the p16-positive than p16-negative group. In the subgroup stratified by p16 status, the shorter OS were also seen with low LKB1 expression. Multivariate survival analysis indicated that high LKB1 expression was an independent prognostic factor for OS (hazard ratio [HR]: 1.628, 95% confidence interval [CI]: 1.060-2.500, P = 0.026) and DMFS (HR: 2.182, 95% CI: 1.069-4.456, P = 0.032). Conclusions: Our data indicated that low expression of LKB1 was significantly associated with poor prognosis and it may represent a marker of tumor metastasis in patients with LSCC. When combined with p16, LKB1 was also of prognostic value.

DNA-dependent protein kinase catalytic subunit functions in metastasis and influences survival in advanced-stage laryngeal squamous cell carcinoma.

Background: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is known to function in several types of cancer. In this study, we investigated the expression and clinicopathologic significance of DNA-PKcs in laryngeal squamous cell carcinoma (LSCC). Methods: We conducted a retrospective study of 208 patients with advanced-stage LSCC treated at Sun Yat-sen University Cancer Center, Guangzhou, China. We assessed DNA-PKcs and p16INK4a (p16) status using immunohistochemistry. We examined the association between DNA-PKcs expression and clinicopathologic features and survival outcomes. To evaluate the independent prognostic relevance of DNA-PKcs, we used univariate and multivariate Cox regression models. We estimated overall survival (OS) and distant metastasis-free survival (DMFS) using the Kaplan-Meier method. Results: Immunohistochemical analyses revealed that 163/208 (78.4%) of the LSCC tissue samples exhibited high DNA-PKcs expression. High DNA-PKcs expression was significantly associated with survival outcomes (P = 0.016) and distant metastasis (P = 0.02; chi-squared test). High DNA-PKcs expression was associated with a significantly shorter OS and DMFS than low DNA-PKcs expression (P = 0.029 and 0.033, respectively; log-rank test), and was associated with poor OS in the p16-positive subgroup (P = 0.047). Multivariate analysis identified DNA-PKcs as an independent prognostic indicator of OS and DMFS in all patients (P = 0.039 and 0.037, respectively). Conclusions: Our results suggest that patients with LSCC in whom DNA-PKcs expression is elevated have a higher incidence of distant metastasis and a poorer prognosis. DNA-PKcs may represent a marker of tumor progression in patients with p16-positive LSCC.

[The effect of zinc on inflammatory reaction in rats with focal cerebral ischemia/reperfusion].

This study was conducted to investigate the effect of N,N-diethyldithiocarbamate (DEDTC) on the changes of inflammatory cytokines after focal cerebral ischemia-reperfusion injury in rats and to explore the potential mechanism. Two hundred Sprague Dawley male rats were randomly divided into sham group, middle cerebral artery occlusion (MCAO) group and DEDTC (Zn chelator) treated group. MCAO model was established by the suture method. Rats were sacrificed at 6, 12 and 24 h after reperfusion. 2,3,5-Triphenyltetrazolium chloride (TTC) was conducted to measure the brain infarct volume. Newport Green was adopted to detect the chelatable zinc in the cerebral penumbra. Enzyme linked immunosorbent assay(ELISA) was performed to determine the release of TNF-α and IL-6. Furthermore Western blot was used to analyze the expression of the PI3K/Akt/NF-κB signaling pathway. The results showed that DEDTC resulted in a significant reduction of brain infarct volume and an obvious improvement of neurological function compared to the model group. DEDTC also decreased the release of inflammatory cytokines such as TNF-α and IL-6. The activation of PI3K/Akt/NF-κB signaling pathway induced by I/R injury was drastically inhibited by the treatment with DEDTC. In conclusion, DEDTC could protect the brain against ischemic injury induced by MCAO, which might be relevant to the inhibition of PI3K/Akt/NF-κB signaling pathway, and the decreased release of inflammatory cytokines.

Benefits of iron supplementation for low birth weight infants: a systematic review.

BACKGROUND: A number of studies have reported on the effects of iron supplementation in low birth weight infants; however, no systematic review of the available evidence has been conducted to date. Hence, we performed a systematic review of the literature to examine the effects of iron supplementation on hematologic iron status, growth, neurodevelopment, and adverse effects in low birth weight/premature infants. METHODS: We searched the Cochrane Library, Medline, and PubMed for articles reporting on the effects of iron supplementation in low weight infants. The following search terms were used: "preterm born infant(s)/children"; "preterm infants"; "prematurely born children" "weight less than 1500 g at birth"; "born prematurely"; "low birth weight infant(s)"; "infants born preterm"; "prematurity"; "small-for-gestational age"; "very small gestational age infants"; "iron supplementation"; "iron intake"; "iron supplements"; "ferric and/or ferrous compounds"; and "ferrous sulphate/fumarate/sulfate". RESULTS: A total of 15 studies were identified and included in the systematic review. Supplemental iron was given orally or as an iron-fortified formula in 14/15 studies. The duration of treatment ranged from 1 week to 18 months. Iron supplementation significantly increased hematologic measures of iron status (including hemoglobin, hematocrit, serum ferritin) relative to placebo or over time in most studies. All controlled studies that examined iron-deficiency anemia (IDA)/ID reported a decreased prevalence of IDA/ID with iron supplementation. Dose dependent decreases in the prevalence of IDA/ID were reported in several studies. Of the 5 studies reporting on growth, none found any significant effect on growth-related parameters (length, height, weight, and head circumference). Only 2 studies reported on neurodevelopment; no marked effects were reported. There were no consistently reported adverse effects, including oxidative stress, inhibited nutrient absorption, morbidity, or the requirement for blood transfusion. CONCLUSION: The available data suggest that iron supplementation increases the levels of hematologic indicators of iron status and reduces the prevalence of IDA/ID in low birth weight/premature infants. There is insufficient evidence to make a definitive statement regarding the effects of iron supplementation on growth, neurodevelopment, or the occurrence of adverse effects in low birth weight/premature infants.

Overexpression of SGLT1 and EGFR in colorectal cancer showing a correlation with the prognosis.

Na+-dependent glucose cotransporter (SGLT1), reported overexpression in tumor tissues while its clinical significance was not established, and epidermal growth factor receptor (EGFR) with potential relation to SGLT1 were studied in order to investigate their clinical significance in colorectal cancer (CRC). Eighty-five patients of CRC who received chemotherapy in Sun Yat-sen Cancer Center from March 1st 2005 to December 31st 2008 were enrolled. SGLT1 and EGFR expression in these cancer tissues and 28 normal tissues were tested by immunohistochemistry. (1) Expression of SGLT1 (P = 0.00) and EGFR (P = 0.01) in cancer tissues was higher than that in normal tissues. (2) Their expression related with clinical stage (P = 0.03 and P = 0.02), but not with other clinical characteristics. (3) For first-line chemotherapy, expression of SGLT1 (P = 0.06 and P = 0.21) and EGFR (P = 0.37 and P = 0.31) had no influence on objective response rate (ORR) and disease control rate (DCR). EGFR overexpression was associated with lower disease-free survival (P = 0.00) and overall survival (P = 0.01), while SGLT1 did not (P = 0.79 and P = 0.34). Conclusions Both SGLT1 and EGFR overexpression in CRC was related to higher clinical stages. SGLT1 had a potential impact on the ORR of first-line chemotherapy in CRC. EGFR was associated with prognosis, while SGLT1 did not.

[Efficacy of cetuximab combined with chemotherapy on advanced colorectal cancer: a report of 53 cases].

BACKGROUND AND OBJECTIVE: Studies showed that cetuximab combined with chemotherapy was effective on advanced colorectal cancer (ACRC) in recent years, however, few reports based on large case cohort are available in China. This study was to analyze the efficacy of cetuximab combined with chemotherapy for 53 chinese patients with ACRC. METHODS: Clinical data of 53 patients with ACRC, treated with cetuximab combined with chemotherapy in Sun Yat-sen Cancer Center from March 2005 to April 2008, were analyzed for short-term efficacy and safety. The efficacy of the regimen used as first-line and non-first-line treatment was compared by Chi-square test; the effect of the regimen on prognosis was analyzed by multivariate Cox proportional hazards model. RESULTS: Of the 53 patients with colorectal adenocarcinoma, 40 were men and 13 were women, with a median age of 55 years. A total of 572 weeks (median, 8 weeks) of cetuximab treatment were completed. The overall response rate (RR) of the regimen was 39.6% and the disease control rate 66.0%. The disease control rates were similar when the regimen was used as first-line and non-first-line treatment (80.3% vs. 60.5%, P=0.177). For all 53 patients, clinical stage was an independent prognostic factor (P=0.002, OR>1). The most common Grade 3 to 4 adverse events included acne-like rash (7.5%), neutropenia (18.9%), and diarrhea (5.6%). No hypersensitive reaction or treatment-related death was observed. Only one patient discontinued treatment because of Grade 4 diarrhea and neutopenia. CONCLUSIONS: Cetuximab combined with chemotherapy can achieve relatively high disease control rate for ACRC patients, with less adverse events. Whether cetuximab has better effect in first-line treatment than in non-first-line treatment needs further study.

[Treatment of hepatic functional reserve injury after TACE in hepatocellular carcinoma with Chinese herbal medicines].

BACKGROUND & OBJECTIVE: Transcatheter arterial chemoembolization (TACE) has been proved to injure hepatic functional reserve. The current study was designed to evaluate the effect of Chinese herbal medicines in treatment of hepatic functional reserve injury after TACE. METHODS: Sixty-one advanced hepatocellular carcinoma patients were divided into two groups: groups A (Western medicine combined with Chinese herbal medicine group, n = 30) and group B (Western medicine group, n = 31). Western medicines were used to protect hepatic function and alleviate TACE syndrome in both group A and group B. Invigorating the spleen and activating blood circulation Chinese herbal medicines were added only in group A before and after TACE. Retention rate of Indocyanine green at 15 minutes (ICGR15) was measured in both group A and group B before 1st, 2nd TACE and one month after 2nd TACE respectively. RESULTS: Hepatic functional reserve before 1st TACE was 11.18% +/- 7.30% in group A and 11.83 +/- 7.18% in group B, (P > 0.05). Hepatic functional reserve before 2nd TACE was 11.69% +/- 5.13% in group A and 16.64 +/- 10.15% in group B, (P < 0.05). Hepatic functional reserve one month after 2nd TACE was 11.53% +/- 5.30% in group A and 19.80 +/- 11.26% in group B, (P < 0.05). CONCLUSIONS: Invigorating the spleen and activating blood circulation Chinese herbal medicine can prevent hepatic functional reserve injury after TACE.