The rate of morbidity and mortality of hepatocellular carcinoma (HCC) in Taiwan has not lessened because of difficulty in treating tumor metastasis. Norcantharidin (NCTD) is currently used as an anticancer drug for hepatoma, breast cancer, and colorectal adenocarcinoma. NCTD possesses various biological anticancer activities, including apoptosis. However, detailed effects and molecular mechanisms of NCTD on metastasis are unclear. Thus, HCC cells were subjected to treatment with NCTD and then analyzed to determine the effects of NCTD on cell metastasis. Modified Boyden chamber assays revealed that NCTD treatment inhibited cell migration and invasion capacities of HCC cells substantially. Results of zymography and western blotting showed that activities and protein levels of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (u-PA) were inhibited by NCTD. Western blot analysis showed that NCTD inhibits phosphorylation of ERK1/2. Testing of mRNA level, quantitative real-time PCR, and promoter assays evaluated the inhibitory effects of NCTD on MMP-9 and u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay for analyzing the genomic DNA sequences bound to these proteins was reactive to the transcription protein nuclear factor (NF)-kappaB, which was inhibited by NCTD. The expression of NF-kappa B was measured by western blot analysis, which revealed decreased nuclear-factor DNA-binding activity after NCTD treatment. NCTD inhibited MMP-9 and u-PA expression through the phosphorylation of ERK1/2 and NF-kappaB signaling pathway which serves as a powerful chemopreventive agent in HCC cell metastasis.

The mortality and morbidity rates from cancer metastasis have not declined in Taiwan, especially because of hepatocellular carcinoma (HCC). Resveratrol has been shown to have benefits such as cardioprotection, providing antioxidative, anti-inflammatory, anti-cancer properties in previous studies. Therefore, HCC cells were subjected to treatment with resveratrol and then analyzed to determine the effects of resveratrol on the migration and invasion. Modified Boyden chamber assays revealed that resveratrol treatment significantly inhibited cell migration and invasion capacities of Huh7 cell lines that have low cytotoxicity in vitro, even at a high concentration of 100 µM. The results of casein zymography and western blotting revealed that the activities and protein levels of the urokinase-type plasminogen activator (u-PA) were inhibited by resveratrol. Western blot analysis also showed that resveratrol inhibits phosphorylation of JNK1/2. Tests of the mRNA level, real-time PCR, and promoter assays evaluated the inhibitory effects of resveratrol on u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay showed that reactive in transcription protein of nuclear factor SP-1 was inhibited by resveratrol. Resveratrol inhibits u-PA expression and the metastasis of HCC cells and is a powerful chemopreventive agent. The inhibitory effects were associated with the downregulation of the transcription factors of SP-1 signaling pathways.

Objectives Isolated minor rib fractures (IMRFs) after blunt chest traumas are commonly observed in emergency departments. However, the relationship between IMRFs and subsequent pneumonia remains controversial. This nationwide cohort study investigated the association between IMRFs and the risk of pneumonia in patients with blunt chest traumas. Design Nationwide population-based cohort study. Setting Patients with IMRFs were identified between 2010 and 2011 from the Taiwan National Health Insurance Research Database. Participants Non-traumatic patients were matched through 1:8 propensity-score matching according to age, sex, and comorbidities (namely diabetes, hypertension, cardiovascular disease, asthma and chronic obstructive pulmonary disease (COPD)) with the comparison cohort. We estimated the adjusted HRs (aHRs) by using the Cox proportional hazard model. A total of 709 patients with IMRFs and 5672 non-traumatic patients were included. Main outcome measure The primary end point was the occurrence of pneumonia within 30 days. Results The incidence of pneumonia following IMRFs was 1.6% (11/709). The aHR for the risk of pneumonia after IMRFs was 8.94 (95% CI=3.79 to 21.09, p<0.001). Furthermore, old age (≥65 years; aHR=5.60, 95% CI 1.97 to 15.89, p<0.001) and COPD (aHR=5.41, 95% CI 1.02 to 3.59, p<0.001) were risk factors for pneumonia following IMRFs. In the IMRF group, presence of single or two isolated rib fractures was associated with an increased risk of pneumonia with aHRs of 3.97 (95% CI 1.09 to 14.44, p<0.001) and 17.13 (95% CI 6.66 to 44.04, p<0.001), respectively. Conclusions Although the incidence of pneumonia following IMRFs is low, patients with two isolated rib fractures were particularly susceptible to pneumonia. Physicians should focus on this complication, particularly in elderly patients and those with COPD.

Hepatocellular carcinoma (HCC) is a malignancy of liver and a leading cause of cancer mortality worldwide. Its management is compounded by biological and clinical heterogeneity. These interindividual genetic variations can modulate the effects of HCC treatment. High-mobility group box protein 1 (HMGB1) is a well investigated, ubiquitous nuclear protein found in eukaryotic cells that plays a multiple biological roles such as DNA stability, program cell death, immune response, and furthermore in cancer progression. In this report, we examined HMGB1 single nucleotide polymorphisms (SNPs) with multiple risk factors related to HCC susceptibility and clinicopathological characteristics. Four HMGB1 SNPs (rs1412125, rs2249825, rs1045411, and rs1360485) were assessed by using a TaqMan SNPs Genotyping in 324 patients with HCC and in 695 cancer-free controls. The results showed that HMGB1 SNP rs1045411 with CT or at least one T alleles has lower risk of HCC than wild-type (CC) carriers. Moreover, HMGB1 SNP rs1412125 with TT allele has a higher risk of distant metastasis compared with patients carrying at least one C allele. The present study is the first report to discuss the risk factors associated with HMGB1 SNPs in HCC progression in Taiwan.