Inflammation has been found to be associated with many neurodegenerative diseases, including Parkinson’s and dementia. Attenuation of microglia-induced inflammation is a strategy that impedes the progression of neurodegenerative diseases. We used lipopolysaccharide (LPS) to simulate murine microglia cells (BV2 cells) as an experimental model to mimic the inflammatory environment in the brain. In addition, we examined the anti-inflammatory ability of corylin, a main compound isolated from Psoralea corylifolia L. that is commonly used in Chinese herbal medicine. The production of nitric oxide (NO) by LPS-activated BV2 cells was measured using Griess reaction. The secretion of proinflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) by LPS-activated BV2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA). The expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, IL-1β and mitogen-activated protein kinases (MAPKs) in LPS-activated BV2 cells was examined by Western blot. Our experimental results demonstrated that corylin suppressed the production of NO and proinflammatory cytokines by LPS-activated BV2 cells. In addition, corylin inhibited the expression of iNOS and COX-2, attenuated the phosphorylation of ERK, JNK and p38, decreased the expression of NLRP3 and ASC, and repressed the activation of caspase-1 and IL-1β by LPS-activated BV2 cells. Our results indicate the anti-inflammatory effects of corylin acted through attenuating LPS-induced inflammation and inhibiting the activation of NLRP3 inflammasome in LPS-activated BV2 cells. These results suggest that corylin might have potential in treating brain inflammation and attenuating the progression of neurodegeneration diseases.

Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-β-d-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial–mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-β-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.

Background: Tumor hypoxia is an important factor related to tumor resistance to radiotherapy and chemotherapy. This study investigated molecules synthesized in colorectal cancer cells during hypoxia to explore the possibility of developing molecular probes capable of detecting cell death and/or the efficiency of radiotherapy and chemotherapy. Methods: At first, we incubated two human colorectal adenocarcinoma cell lines SW480 (UICC stage II) and SW620 (UICC stage III) cells in hypoxic (≤2% O₂, 93% N₂, and 5% CO₂) and normoxic conditions (20% O₂, 75% N₂, and 5% CO₂) for 24 h and 48 h. The relative expression ratio of GLUT1 mRNA in hypoxic conditions was analyzed by RT-PCR. Ten cancerous tissues collected from human colorectal cancer patients were examined. HIF-1α and HIF-2α levels were measured to indicate the degree of hypoxia, and gene expression under hypoxic conditions was determined. As a comparison, HIF-1α, HIF-2α, and GLUT1 levels were measured in the peripheral blood of 100 CRC patients. Results: Hypoxia-induced lactate was found to be elevated 3.24- to 3.36-fold in SW480 cells, and 3.06- to 3.17-fold in SW620 cells. The increased relative expression ratio of GLUT1 mRNA, under hypoxic conditions was higher in SW620 cells (1.39- to 1.72-fold elevation) than in SW480 cells (1.24- to 1.66-fold elevation). HIF-1α and HIF-2α levels were elevated and GLUT1 genes were significantly overexpressed in CRC tissue specimens. The elevated ratio of GLUT1 was higher in stage III and IV CRC tissue specimens than in the stage I and II (2.97–4.73 versus 1.44–2.11). GLUT1 mRNA was also increased in the peripheral blood of stage II and III CRC patients as compared to stage I patients, suggesting that GLUT1 may serve as a hypoxic indicator in CRC patients. Conclusion: In conclusion, this study demonstrated that GLUT1 has the potential to be employed as a molecular marker to indicate the degree of hypoxia experienced by tumors circulating in the blood of cancer patients.

After a low anterior resection, creating a defunctioning stoma is vital for securing the anastomosis in low-lying rectal cancer patients receiving concurrent chemoradiotherapy. Although it decreases the complication and reoperation rates associated with anastomotic leakage, the complications that arise before and after stoma closure should be carefully evaluated and managed. This study enrolled 95 rectal cancer patients who received neoadjuvant concurrent chemoradiotherapy and low anterior resection with anastomosis of the bowel between July 2010 and November 2012. A defunctioning stoma was created in 63 patients during low anterior resection and in another three patients after anastomotic leakage. The total complication rate from stoma creation to closure was 36.4%. Ileostomy led to greater renal insufficiency than colostomy did and significantly increased the readmission rate (all p < 0.05). The complication rate related to stoma closure was 36.0%. Patients with ileostomy had an increased risk of developing complications (p = 0.017), and early closure of the defunctioning stoma yielded a higher incidence of morbidity (p = 0.006). Multivariate analysis revealed that a time to closure of ≤109 days was an independent risk factor for developing complications (p = 0.007). The optimal timing of stoma reversal is at least 109 days after stoma construction in rectal cancer patients receiving concurrent chemoradiotherapy and low anterior resection.

We evaluated the clinicopathologic features and outcomes of Taiwanese patients with right-sided versus left-sided colon cancer according to various cancer stages. A total of 1095 patients with primary colorectal cancer (CRC) undergoing surgery at a single-institution were enrolled. We analyzed patient differences in terms of clinicopathologic features, overall survival (OS) and cancer-specific survival (CSS) of right- versus left-sided colon cancer. Right-sided colon cancers were noted in 249 (22.7 %) patients, and left-sided colon cancers were noted in 846 (77.3 %) patients. Right-sided colon cancers were found to be significantly larger (P = 0.003) and poorly differentiated (P < 0.001), while also exhibiting advanced depth of tumor invasion (P = 0.002) and advanced UICC/AJCC stage (P = 0.016). Patients with right-sided colon cancers had both poorer OS and CSS than those with left-sided colon cancers (P = 0.021 and 0.023, respectively). However, analysis by various stages revealed significant OS and CSS differences (P = 0.002 and 0.002, respectively) between right-sided and left-sided colon cancers only in stage III patients. This study demonstrated poorer OS and CSS in patients with right-sided versus those with left-sided colon cancers, but significant differences were noted only in stage III patients.

Early relapse in colorectal cancer (CRC) patients is attributed mainly to the higher malignant entity (such as an unfavorable genotype, deeper tumor invasion, lymph node metastasis and advance cancer stage) and poor response to chemotherapy. Several investigations have demonstrated that genetic polymorphisms in drug-targeted genes, metabolizing enzymes, and DNA-repairing enzymes are all strongly correlated with inter-individual differences in the efficacy and toxicity of many treatment regimens. This preliminary study attempts to identify the correlation between genetic polymorphisms and clinicopathological features of CRC, and evaluates the relationship between genetic polymorphisms and chemotherapeutic susceptibility of Taiwanese CRC patients. To our knowledge, this study discusses, for the first time, early cancer relapse and its indication by multiple genes.