Study of the radiotherapy sensitization effects and mechanism of capecitabine (Xeloda) against non-small-cell lung cancer cell line A549.

The purpose of this study was to explore the radiotherapy sensitization effects and the mechanism of capecitabine (Xeloda) against the non-small-cell lung cancer cell line, A549. γ-[(60)Co] radiation was used as the intervention method. Proliferative inhibition of capecitabine on A549 cells was determined by the CCK-8 method. The effects of capecitabine on the apoptosis rate and cell cycle distribution of A549 were detected with the flow cytometric method. We found that capecitabine inhibited the proliferation of A549 in a dose-dependent manner, notably increased the cell apoptosis rate and blocked the cellular G0/G1 phase after radiotherapy by γ-[(60)Co]. Therefore, capecitabine can significantly increase the radiosensitivity of A549; its mechanism may be related to cell cycle arrest and induction of apoptosis.

MiR-1298 expression correlates with prognosis and inhibits cell proliferation and invasion of gastric cancer.

OBJECTIVE: To explore the association between miR-1298 expression and clinicopathological factors, prognosis of gastric cancer (GC) patients and biological functions underlying the GC progression. PATIENTS AND METHODS: Expression of miR-1298 was examined by qRT-PCR in GC tissues and cells, the adjacent normal tissues and normal gastric cell line GES-1 cells were used as controls. Association of disease-free survival (DFS) and overall survival (OS) time with miR-1298 expression was analyzed by Kaplan-Meier analysis and log-rank test. Univariate and multivariate analysis were also performed to analyze relative prognostic risk factors of GC patients. Cell proliferation and invasion assays were used to examine cell proliferation and invasion capacities in vitro. The relative protein expression was analyzed by Western blot analysis. RESULTS: MiR-1298 expression was lower in GC tissues and cells, compared to adjacent normal tissues and GES-1 cells, respectively. Lower miR-1298 expression levels were associated with lymph node metastasis and TNM stage. Kaplan-Meier analysis showed that lower miR-1298 expression predicted poor DFS and OS of GC patients. Furthermore, we demonstrated that lymph node metastasis, TNM stage, and lower miR-1298 expression were independent risk factors for DFS and OS in GC patients. In vitro, miR-1298 overexpression inhibited cell proliferation and invasion abilities. Additionally, our results revealed that miR-1298 overexpression suppressed PI3K/AKT signaling pathway in GC cells. CONCLUSIONS: Our evidence indicated that miR-1298 may provide a specifically promising target for therapy of GC patients.

Effects of selective brain cooling in patients with severe traumatic brain injury: a preliminary study.

We prospectively investigated non-invasive selective brain cooling (SBC) in patients with severe traumatic brain injury. Sixty-six in-patients were randomized into three groups. In one group, brain temperature was maintained at 33 - 35 degrees C by cooling the head and neck (SBC); in a second group, mild systemic hypothermia (MSH; rectal temperature 33 - 35 degrees C) was produced with a cooling blanket; and a control group was not exposed to hypothermia. Natural rewarming began after 3 days. Mean intracranial pressure 24, 48 or 72 h after injury was significantly lower in the SBC group than in the control group. Mean serum superoxide dismutase levels on Days 3 and 7 after injury in the SBC and MSH groups were significantly higher than in the control group. The percentage of patients with a good neurological outcome 2 years after injury was 72.7%, 57.1% and 34.8% in the SBC, MSH and control groups, respectively. Complications were managed without severe sequelae. Non-invasive SBC was safe and effective.

Thyroid-stimulating hormone receptor affects metastasis and prognosis in papillary thyroid carcinoma.

OBJECTIVE: Although endocrine therapy of papillary thyroid carcinoma (PTC) by inhibiting thyroid-stimulating hormone (TSH) has been used for many years, its mechanism of action is not clear. This study aimed to explore the expression and role of TSH receptor (TSHR) in PTC, to provide a theoretical basis for optimization of endocrine treatment options in PTC. PATIENTS AND METHODS: Expression of TSHR was tested by immunohistochemistry of tissues from 150 cases of PTC and 21 normal thyroid tissues. Survival analysis was performed by Kaplan-Meier and log-rank analyses, and multivariate analysis was done using a Cox model. The regulatory effects of the TSH-TSHR signal transduction pathway on differentiated thyroid carcinoma cells were explored in vitro. RESULTS: The positive expression rate of TSHR in PTC was 68% (102/150). TSHR expression was an independent factor affecting the prognosis of PTC patients aged > 45 years (p = 0.006), and TSHR might have a role in decreasing distant metastasis (p = 0.024). In vitro experiments showed that up-regulation of TSHR promoted apoptosis of thyroid cancer cells and inhibited metastasis significantly. There was no significant regulatory effect of the TSH-TSHR signal transduction pathway on the proliferation of thyroid carcinoma cells. CONCLUSIONS: TSHR expression is an independent factor that affects the prognosis of PTC patients, and might decrease distant metastasis in patient aged > 45 years. Up-regulation of TSHR could inhibit metastasis and promote apoptosis in PTC cells.

RTN4/Nogo is an independent prognostic marker for gastric cancer: preliminary results.

OBJECTIVE: Gastric cancer is the fourth most common malignant cancer and is the second leading cause of cancer death worldwide. We evaluated the association of the immunohistochemical RTN4 expression with clinicopathological variables and patient outcome, and to evaluate its prognostic value. PATIENTS AND METHODS: Histological samples from 95 primary gastric carcinoma patients were retrospectively studied with monoclonal antibody to RTN4. RESULTS: Tumors with high RTN4 expression were found in 57.9% of patients. High RTN4 were associated with advanced stages (p = 0.0377) and different histology (p = 0.0030). In the overall population (median follow-up 42 months), patients with high RTN4 had shorter survival time than those with low RTN4 expression (p = 0.0119). In Cox multivariate analysis, high RTN4 (p = 0.0160) is an independent prognostic factor for overall survival of gastric cancer patients. CONCLUSIONS: Our data suggest that RTN4 may contribute to the malignant progression of gastric cancer and serve as a novel prognostic indicator for gastric cancer patients.

[Evaluation of glycated hemoglobin in the early diagnosis of diabetes mellitus].

Although oral glucose tolerance test (OGTT) has been the key examination in early diagnosis of diabetes mellitus, but it still has some problems. It may be affected by some physiological or pathological changes and also requires frequent blood sampling. We investigated the usefulness of measuring the level of glycated hemoglobin (GHb) or HbA1 and HbA1c in screening or early diagnosis of diabetes mellitus. OGTT was performed and fasting levels of HbA1 and HbA1c were measured in 168 subjects. According to the diagnostic criteria of WHO for 75g OGTT, 31 subjects were classified as normal, 35 as having impaired glucose tolerance test (IGT) and 102 as diabetics. The method used for determination of HbA1 and HbA1c was high pressure liquid chromatography (HPLC). The total discovery rate for GHb in diabetic patients was 87%. In patients with fasting level of plasma glucose (FPG) greater than or equal to 8 mmol/L the discovery rate was 100%, while in those with level of FPG less than or equal to 7.94 mmol/L the rate was 80%. Thus, GHb is very useful in screening and early diagnosis of NIDDM (type II), especially diabetes mellitus of the elderly.

The exponential function transforms the Abbreviated Injury Scale, which both improves accuracy and simplifies scoring.

PURPOSE: We present here the exponential function which transforms the Abbreviated Injury Scale (AIS). It is called the Exponential Injury Severity Score (EISS), and significantly outperforms the venerable but dated New Injury Severity Score (NISS) and Injury Severity Score (ISS) as a predictor of mortality. METHODS: The EISS is defined as a change of AIS values by raising each AIS severity score (1-6) by 3 taking a power of AIS minus 2 and then summing the three most severe injuries (i.e., highest AIS), regardless of body regions. EISS values were calculated for every patient in two large independent data sets: 3,911 and 4,129 patients treated during a 6-year period at the Class A tertiary hospitals in China. The power of the EISS to predict mortality was then compared with previously calculated NISS values for the same patients in each of the two data sets. RESULTS: We found that the EISS is more predictive of survival [Zhejiang: area under the receiver operating characteristic curve (AUC): NISS = 0.932, EISS = 0.949, P = 0.0115; Liaoning: AUC: NISS = 0.924, EISS = 0.942, P = 0.0139]. Moreover, the EISS provides a better fit throughout its entire range of prediction (Hosmer-Lemeshow statistic for Zhejiang: NISS = 21.86, P = 0.0027, EISS = 13.52, P = 0.0604; Liaoning: NISS = 23.27, P = 0.0015, EISS = 15.55, P = 0.0164). CONCLUSIONS: The EISS may be used as the standard summary measure of human trauma.

Serum vascular endothelial growth factor and angiogenesis are related to the prognosis of patients with gastrointestinal stromal tumors.

AIM: To investigate if serum vascular endothelial growth factor (SVEGF), tissue VEGF and microvessel density (MVD) have any relation to progress and prognosis in gastrointestinal stromal tumors (GIST). METHODS: SVEGF was examined using ELISA. VEGF and MVD were examined using immunohistochemical staining. RESULTS: The median level of SVEGF was higher in GIST than in controls. A higher level of SVEGF and a positive expression rate of VEGF were obtained in diameter >or=5 cm, mitotic count >or=2/10 high power fields (HPF), recurrence and high risk groups. The MVD of experimental was higher than that of controls. A higher MVD was observed in mitotic count >or=2/10HPF and recurrence groups. The median level of SVEGF was higher in the VEGF positive group than in the controls. The SVEGF presented a relationship with MVD. Factors predicating poor prognosis were SVEGF and VEGF. CONCLUSIONS: SVEGF and VEGF show a correlation with poor prognosis of GIST.

Monoamine-activated alpha 2-macroglobulin binds trk receptor and inhibits nerve growth factor-stimulated trk phosphorylation and signal transduction.

Monoamine-activated alpha 2-macroglobulin (alpha 2M) has been shown to inhibit beta-nerve growth factor (NGF)-promoted neurite outgrowth and the survival of embryonic sensory and forebrain neurons, whereas normal alpha 2M has little or no such activity. The objective of this study is to elucidate the mechanism of inhibition by monoamine-activated alpha 2M. Methylamine-activated alpha 2M (MA-alpha 2M) and serotonin-activated alpha 2M (5HT-alpha 2M) dose dependently inhibit NGF-promoted neurite outgrowth of the pheochromocytoma PC12 cell and its subline PC12(6-24) which overexpresses human trk protooncogene product, but have no effect on their viability, and this inhibition can be blocked by high concentrations of NGF. The binding of MA-alpha 2M to trk, which is a part of high-affinity NGF receptor, was studied with PC12(6-24) cells and NIH-3T3 fibroblasts expressing trk (trk-3T3). In each case MA-alpha 2M readily forms stable complexes with trk in vivo, whereas normal alpha 2M does not. Both 5HT-alpha 2M and MA-alpha 2M also dose dependently block NGF-promoted autophosphorylation of trk in vivo, whereas normal alpha 2M and plasmin-reacted alpha 2M are inactive or much less active. MA-alpha 2M also blocks NGF-promoted incorporation of 32P from [32P]ATP into trk receptors in vitro. Neither MA-alpha 2M, 5HT-alpha 2M, nor normal alpha 2M, however, blocks either platelet-derived growth factor-stimulated or epidermal growth factor-stimulated tyrosine phosphorylation of the respective receptors. Tyrosine phosphorylation of two of the intracellular substrates, phospholipase C-gamma 1 and extracellular signal-regulated kinase-2, in the NGF-promoted pathways is also dose dependently blocked by MA-alpha 2M. However, by comparison MA-alpha 2M is more effective in inhibiting the activation of phospholipase C-gamma 1 than trk. We conclude that monoamine-activated alpha 2M may block neurite outgrowth and neuronal survival by its specific binding to NGF receptors, thus inhibiting the NGF-promoted activation of intracellular second messenger pathways.

[Hyperlipidemia treated with xiaobu jianfei pian].

A total of 51 cases with hyperlipidemia, who were defined deficiency symptom-complex complicated by symptoms of excessiveness in TCM were studied clinically. The patients were divided into two groups at random. One group was treated with Xiaobu Jianfei Pian (XJP) as treated group, another with Fangfeng Tongsheng San as a control. It was found that XJP was able to lower total serum cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (apo) B significantly (P less than 0.001, 0.001, 0.001) while it had markedly improved clinical symptoms. It was also observed that XJP had good effects on the ratios of apoA1/B and TC/HDL-C, and was able to reduce body weight index. All of these were better than those of the control group statistically. These evidences indicate that XJP possesses clinical therapeutic effects on both lipid-lowering and lipid-adjusting, which suggest that XJP may be an effective anti-hyperlipidemia medicine.