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OBJECTIVE@#To investigate the potential mechanisms that curcumin reverses 5-fluorouracil (5-FU) multidrug resistance (MDR).@*METHODS@#Cell growth and the inhibitory rate of curcumin (2-25 μg/mL) and/or 5-FU (0.05-1000 μg/mL) on human colon cancer HCT-8 and HCT-8/5-FU (5-FU-resistant cell line) were determined using cell counting kit-8 (CCK-8) assay. Apoptosis and cell cycle after 5-FU and/or curcumin treatment were detected by flow cytometry (FCM) and transmission electron microscopy (TEM). The expression of the multidrug resistance related factors p-glycoprotein (P-gp) and heat shock protein 27 (HSP-27) genes and proteins were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting (WB), respectively.@*RESULTS@#The inhibitory rate of curcumin or 5-FU on HCT-8 and HCT-8/5-FU cells proliferation at exponential phase were in a dosedependent manner, HCT-8 cell line was more sensitive to curcumin or 5-FU when compared the inhibitory rate of HCT-8/5-FU. The 50% inhibitory concentration (IC) of combination 5-FU and curcumin (4.0 μg/mL) in HCT-8/5-FU was calculated as 179.26 μg/mL, with reversal fold of 1.85. Another IC of combination 5-FU and curcumin (5.5 μg/mL) in HCT-8/5-FU was calculated as 89.25 μg/mL, with reversal fold of 3.71. Synergistic effect of 5-FU and curcumin on HCT-8 and HCT-8/5-FU cells were found. The cell cycle analysis performed by FCM showed that HCT-8 and HCT-8/5-FU cells mostly accumulated at G/G phase, which suggested a synergistic effect of curcumin and 5-FU to induce apoptosis. FCM analysis found that the percentage of apoptosis of cells treated with curcumin, 5-FU and their combination were significantly increased compared to the control group (P<0.05), and the percentage of apoptosis of the combination groups were slightly higher than other groups (P<0.05). The mRNA levels of P-gp (0.28±0.02) and HSP-27 (0.28±0.09) in HCT-8/5-FU cells treated with combination drugs were lower than cells treated with 5-FU alone (P-gp, 0.48±0.07, P=0.009; HSP-27, 0.57±0.10, P=0.007). The protein levels of P-gp (0.25±0.06) and HSP-27 (0.09±0.02) in HCT-8/5-FU cells treated with combination drugs were decreased when compared to 5-FU alone (P-gp, 0.46±0.02, P=0.005; HSP-27, 0.43±0.01, P=0.000).@*CONCLUSIONS@#Curcumin can inhibit the proliferation of human colon cancer cells. Curcumin has the ability of reversal effects on the multidrug resistance of human colon cancer cells lines HCT-8/5-FU. Down-regulation of P-gp and HSP-27 may be the mechanism of curcumin reversing the drug resistance of HCT-8/5-FU to 5-FU.
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Objective To investigate the characteristics of sleep patterns and their effects on the risk of diabetes mellitus (DM) among adults in Guangzhou. Methods A retrospective study was conducted using data collected by the lifestyle survey and health outcomes of 5 666 employees from Guangzhou who underwent physical examination between November 2012 and October 2013 at Guangdong Provincial People's Hospital. Sleep patterns and their distribution profiles were analysed using latent class analysis (LCA). Multiple logistic regression models were performed to investigate the association between sleep patterns and DM. Results LCA identified five sleep patterns: “very short sleep duration with insomnia” (class 1, 5.6%), “sleep insufficiency with mild daytime dysfunction” (class 2, 20.4%), “normal sleep” (class 3, 47.7%), “sleep insufficiency with daytime functioning complaints” (class 4, 4.7%) and “sleep insufficiency with poor nocturnal sleep” (class 5, 21.6%). After adjustment for the confounding factors, subjects of class 1 (OR=2.28, 95% CI: 1.51-3.43, <0.001), class 4 (OR=2.48, 95% CI: 1.54-4.00, P<0.001) and class 5 (OR=1.31, 95% CI: 1.01-1.71, P=0.045) had a higher risk of DM when compared with those of class 3. Conclusions There were significant associations between various sleep-related factors, leading to distinct sleep behavioral patterns among adults. Poor sleep patterns could increase the risk of DM.
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Purpose To investigate the pathological features and prognostic value of tertiary lymphoid structure (TLS) formation in gastric cancer (GC) . Methods HE staining slides were reviewed to evaluate the TLS in 163 specimens from patients with GC in the Third Affiliated Hospital of Soochow University from 2006 to 2008. The validation cohort contained 63 randomly selected cases and immunohistochemical staining of MECA-79 was used to verify the accuracy of pathological assessment of TLS. Results TLS score and MECA-79 immunohistochemical staining showed significant correlation (P = 0. 002) and agreement (P = 0. 024) . The TLS was not significantly correlated to clinical pathological parameters. The patients with high level of TLS had better prognosis (P = 0. 025) with the mean survival time of 48. 54 months. In multivariate Cox regression analysis, TLS was an independent prognostic factor (P = 0. 031) . Conclusion The pathological evaluation of TLS is accurate. The formation of TLS is an important positive prognostic factor for GC patients.
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<p><b>OBJECTIVE</b>To investigate the efficacy of integrated Chinese and Western medicine (IM) in the treatment of metastatic colorectal cancer (mCRC) in a cohort study.</p><p><b>METHODS</b>The survival outcome of patients receiving IM was compared with that of patients receiving Western medicine alone. The study design was adopted with "continuous administration of Chinese medicine for ⩾ 3 months" as the exposure factor. Patients who met this exposure factor were assigned to the IM cohort (Group A, 110 patients). Patients who did not meet this exposure factor were assigned to the Western medicine cohort (Group B, 225 patients). The overall survival (OS), progression-free survival (PFS), and 1st year, 2nd year, and 3rd year survival in the two cohorts were compared.</p><p><b>RESULTS</b>The median OS in Group A and B were 18 months [95% confidence interval (CI) 15-21] and 16 months (95% CI 14-18), respectively, and the median PFS in Group A and B were 6 months (95% CI 4-7) and 5 months (95% CI 4-6), respectively. No statistically significant differences were observed between the groups (P=0.186, P=0.223). Group A demonstrated significantly longer OS and PFS than Group B in the following subgroups: female patients, patients with lesions in the right half of the colon, and those who received first-line treatment (P<0.05). In the subgroup of elderly patients (age>65 years), the OS in Group A was longer than that in Group B (P<0.05).</p><p><b>CONCLUSION</b>IM could prolong the survival of patients with mCRC. (Registry No. ChiCTR-IOR-17010497).</p>
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<p><b>OBJECTIVE</b>To evaluate the prognostic value of metastatic lymph node ratio (MLR) for patients with gastric cancer.</p><p><b>METHODS</b>Data collected from 1247 patients with gastric cancer who underwent radical surgery (pT4 cases were excluded) at the First Affiliated Hospital of Nanjing Medical University between 2005 and 2009 were analyzed retrospectively. MLR was compared to pathological N staging (pN) in terms of prognostic accuracy, homogenicity, and applicability.</p><p><b>RESULTS</b>MLR and pN were both positively correlated with the number of retrieved lymph nodes(both P<0.01). Significant differences were found in 5-year cumulative survival rate (5-YCSR) among different pN stages and MLR classification(all P<0.01). Multivariable analysis showed that both pN and MLR were independent prognostic factors(both P<0.01). The area under ROC curve(AUC) of MLR was larger than pN, however the difference was not statistically significant(P>0.05). There were significant differences in 5-YCSR among different MLR stages within the same pN stages(P<0.05), but not among different pN stages within the same MLR stage(P>0.05). Significant differences in 5-YCSR were also found among different retrieved-node groups within the same pN stage (P<0.05), but not within the same MLR stages (P>0.05).</p><p><b>CONCLUSIONS</b>MLR is an independent prognostic factor for patients with gastric cancer. The prognostic homogenicity and applicability of MLR are better than those of pN, however the prediction accuracy is not favorable.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Follow-Up Studies , Lymph Nodes , Pathology , Lymphatic Metastasis , Pathology , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms , Diagnosis , PathologyABSTRACT
<p><b>BACKGROUND</b>Hepatitis B virus infection is closely related to hepatocellular carcinoma (HCC). Cyclooxygenase-2 (COX-2) is overexpressed in HCC and considered to play a role in hepatic carcinogenesis. In this study, we analyzed the polymorphism of COX-2 promoter -899G/C in healthy controls, chronic hepatitis B (CHB) patients, liver cirrhosis patients, and hepatocellular carcinoma (HCC) patients, to investigate the relationship between COX-2 -899G/C polymorphism and the risk for hepatitis B-related liver cancer in a Chinese population from Gansu province.</p><p><b>METHODS</b>Patients were divided into four groups: 300 patients with CHB, 300 patients with liver cirrhosis, 300 patients with HCC, and 300 healthy controls. The polymorphism of COX-2 -899G/C was detected by PCR-TaqMan probes. The results were analyzed by SPSS 17.0.</p><p><b>RESULTS</b>The COX-2 -899G/C genotypes were GG, GC, and CC. Frequencies in CHB were 87.00%, 12.67%, 0.33%; in liver cirrhosis were 85.33%, 14.00%, 0.67%; in HCC were 77.00%, 21.67%, 1.33%; and in healthy controls were 90.67%, 9.00%, 0.33%, respectively. COX-2 -899C carriers may have an increased risk for hepatitis B-related liver cancer. Compared with the frequency of GG genotype, there were significant differences in the frequency of GC genotype between HCC and healthy control groups (OR = 2.835, 95%CI: 1.751 - 4.589); HCC and CHB groups (OR = 1.933, 95%CI: 1.248 - 2.994); and HCC and liver cirrhosis groups (OR = 1.175, 95%CI: 1.119 - 2.628). Stratification analyses showed that COX-2 -899C allele carriers with a drinking history are more susceptible to develop HCC.</p><p><b>CONCLUSION</b>COX-2 -899C genotype may increase the susceptibility of individuals to hepatitis B-related liver cancer in Gansu province, China.</p>