Clinicopathological characteristics and prognostic analysis of Lauren classification in gastric adenocarcinoma in China

BACKGROUND: According to the Lauren classification, gastric adenocarcinomas are divided into diffuse and intestinal types. The causative attribution explaining the dismal prognosis of diffuse-type remains unknown. METHODS: We examined the archive of 1000 patients with gastric adenocarcinomas who received radical gastrectomy in our center and assessed the effect of the Lauren classification on survival in a multivariate approach. Moreover we compared the variation of clinical features between the diffuse-type and intestinal-type and explored the contributing factors for the prognostic difference. RESULTS: There were 805 resectable patients for the final analysis. Diffuse-type comprised of 48.7% in the gastric carcinoma in our group and showed poorer prognosis than intestinal-type (P=0.013). Multivariate analysis revealed that independent prognostic factors for gastric carcinoma patients were T stage (P<0.001), N stage (P<0.001) tumor size (P<0.001) and Lauren classification (P=0.003). For the clinical features, diffuse-type was significantly associated with younger age (p<0.001), female preponderance (p <0.001), distal location (P<0.001), advanced pT (p < 0.001), advanced pN (p < 0.001) and advanced TNM stage (p = 0.027). CONCLUSIONS: Diffuse type adenocarcinoma carries a worse prognosis that may be partially explained by the tendency of this subtype to present at more advanced T and N stage. However, Lauren classification has prognostic significance that is independent of T and N stage as well as other prognostic variables based on the multivariate cox analysis

DNA polymeraseη protein expression predicts treatment response and survival of metastatic gastric adenocarcinoma patients treated with oxaliplatin-based chemotherapy

<p>Abstract</p> <p>Background</p> <p>DNA polymerase η (pol η) is capable of bypassing DNA adducts produced by cisplatin or oxaliplatin and is associated with cellular tolerance to platinum. Previous studies showed that defective pol η resulted in enhanced cisplatin or oxaliplatin sensitivity in some cell lines. The purpose of the present study was to investigate the role of pol η protein expression in metastatic gastric adenocarcinoma.</p> <p>Methods</p> <p>Four gastric adenocarcinoma cell lines were chosen to explore the relationship between pol η protein expression and oxaliplatin sensitivity by western blotting and MTT assay. Eighty metastatic gastric adenocarcinoma patients treated with FOLFOX or XELOX regimen as first-line chemotherapy were analyzed, corresponding pretreatment formalin-fixed paraffin-embedded tumor tissues were used to detect pol η protein expression by immunohistochemistry. Relationship between pol η protein expression and clinical features and outcome of these patients was analyzed.</p> <p>Results</p> <p>A positive linear relationship between pol η protein expression and 48 h IC50 values of oxaliplatin in four gastric cancer cell lines was observed. Positivity of pol η protein expression was strongly associated with poor treatment response, as well as shorter survival at both univariate (8 versus 14 months; P < 0.001) and multivariate (hazard ratio, 4.555; 95% confidence interval, 2.461-8.429; P < 0.001) analysis in eighty metastatic gastric adenocarcinoma patients.</p> <p>Conclusions</p> <p>Our study indicates that polη is a predictive factor of treatment response and survival of metastatic gastric adenocarcinoma patients treated with FOLFOX or XELOX as first-line chemotherapy. Therefore confirming the value of polη in studies with prospective design is mandatory.</p

Down-regulation of Toll-like receptor 4 gene expression by short interfering RNA attenuates bone cancer pain in a rat model

<p>Abstract</p> <p>Background</p> <p>This study demonstrates a critical role in CNS innate immunity of the microglial Toll-like receptor 4 (TLR4) in the induction and maintenance of behavioral hypersensitivity in a rat model of bone cancer pain with the technique of RNA interference (RNAi). We hypothesized that after intramedullary injection of Walker 256 cells (a breast cancer cell line) into the tibia, CNS neuroimmune activation and subsequent cytokine expression are triggered by the stimulation of microglial membrane-bound TLR4.</p> <p>Results</p> <p>We assessed tactile allodynia and spontaneous pain in female Sprague-Dawley (SD) rats after intramedullary injection of Walker 256 cells into the tibia. In a complementary study, TLR4 small interfering RNA(siRNA) was administered intrathecally to bone cancer pain rats to reduce the expression of spinal TLR4. The bone cancer pain rats treated with TLR4 siRNA displayed significantly attenuated behavioral hypersensitivity and decreased expression of spinal microglial markers and proinflammatory cytokines compared with controls. Only intrathecal injection of TRL4 siRNA at post-inoculation day 4 could prevent initial development of bone cancer pain; intrathecal injection of TRL4 siRNA at post-inoculation day 9 could attenuate, but not completely block, well-established bone cancer pain.</p> <p>Conclusions</p> <p>TLR4 might be the main mediator in the induction of bone cancer pain. Further study of this early, specific, and innate CNS/microglial response, and how it leads to sustained glial/neuronal hypersensitivity, might lead to new therapies for the prevention and treatment of bone cancer pain syndromes.</p

Prognostic effects of 25-hydroxyvitamin D levels in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Results from large epidemiologic studies on the association between vitamin D and gastric cancer are controversial. Vitamin D significantly promotes apoptosis in the undifferentiated gastric cancer cell, but the prognostic effects of its levels are unknown.</p> <p>Methods</p> <p>197 gastric carcinoma patients who received treatment in the cancer centre of Sun Yat-sen University from January 2002 to January 2006 were involved in the study. The stored blood drawn before any treatment was assayed for 25-hydroxyvitamin D levels. The clinicopathologic data were collected to examine the prognostic effects of vitamin D.</p> <p>Results</p> <p>The mean vitamin D levels of the 197 gastric patients was 49.85 ± 23.68 nmol/L, among whom 114(57.9%) were deficient in Vitamin D(< 50 nmol/L), 67(34%) were insufficient (50-75 nmol/L) and 16(8.1%) were sufficient (> 75 nmol/L). Clinical stage (<it>P </it>= 0.004) and lymph node metastasis classification (<it>P </it>= 0.009) were inversely associated with vitamin D levels. The patients with high vitamin D levels group (≥ 50 nmol/L) had a higher overall survival compared with the low vitamin D levels group (< 50 nmol/L)(<it>P </it>= 0.018). Multivariate analysis indicated that vitamin D levels were an independent prognostic factor of gastric cancer (<it>P </it>= 0.019).</p> <p>Conclusions</p> <p>Vitamin D deficiency may be associated with poor prognosis in gastric cancer.</p

Copper-transporting P-type adenosine triphosphatase (ATP7A) is associated with platinum-resistance in non-small cell lung cancer (NSCLC)

<p>Abstract</p> <p>Background</p> <p>Copper export protein ATP7A is important for maintaining copper homeostasis. Recent studies have shown that copper transporters are also involved in the transport of platinum. The goal of this study was to determine the role of ATP7A in the platinum-resistance of non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Sensitivities to platinums were detected by MTT assay and drug-resistance related genes were analyzed by real-time PCR and immunoblotting between DDP-sensitive A549 and the corresponding DDP-resistant cell subline (A549/DDP). ATP7A expression was evaluated by immunohistochemistry in tumor tissues of unresectable NSCLC patients who received cisplatin-basing chemotherapy.</p> <p>Results</p> <p>The expression of ATP7A was significantly higher in A549/DDP cell subline than in A549 cells at both mRNA and protein levels. The silencing of ATP7A expression in A549/DDP by siRNA partially reversed DDP-resistance (29.62%) and increased cell apoptosis. ATP7A expression was detected in 41.6%of NSCLC patients, but not in adjacent stroma nor normal lung tissues. ATP7A-positive patients had a significantly poorer histological grade (p = 0.039) and poorer response to platinum-basing chemotherapy (p = 0.001) compared with ATP7A-negative patients. Cox's proportional hazards analysis showed that ATP7A expression was an independent prognostic factor for overall survival (p = 0.045).</p> <p>Conclusions</p> <p>ATP7A overexpression played an important role in platinum-resistance of NSCLC, and was a negative prognostic factor of NSCLC patients treated with platinum-based chemotherapy.</p

Association of sleep behaviors, insulin resistance surrogates, and the risk of hypertension in Chinese adults with type 2 diabetes mellitus

ObjectiveOur aim was to evaluate the association between midday napping, combined sleep quality, and insulin resistance surrogates and the risk of hypertension in patients with type 2 diabetes mellitus (T2DM).MethodsData were collected using a standardized questionnaire. Binary logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the risk of hypertension. Systolic and diastolic blood pressure were grouped as categorical variables and unpaired two-sided Student’s t-test and Spearman correlation analysis were performed to estimate the association between different blood pressure levels and insulin resistance surrogates.ResultsThe overall prevalence rate of hypertension was 50%. Age (OR = 1.056, 95% CI:1.044–1.068), poor sleep quality (OR = 1.959, 95% CI:1.393–2.755), hyperlipidemia (OR = 1.821, 95% CI:1.462–2.369), family history of hypertension (OR = 2.811, 95% CI:2.261–3.495), and obesity (OR = 5.515, 95% CI:1.384–21.971) were significantly associated with an increased risk of hypertension. Midday napping for 1–30 min was negatively correlated with the risk of hypertension (OR = 0.534, 95% CI:0.305–0.936, P &lt;0.05).ConclusionPoor sleep quality and obesity are independent risk factors for hypertension. Midday napping (1–30 min) is associated with a decreased risk of hypertension in patients with T2DM