Magnolol inhibits growth of gallbladder cancer cells through the p53 pathway.

Magnolol, the major active compound found in Magnolia officinalis has a wide range of clinical applications due to its anti-inflammation and anti-oxidation effects. This study investigated the effects of magnolol on the growth of human gallbladder carcinoma (GBC) cell lines. The results indicated that magnolol could significantly inhibit the growth of GBC cell lines in a dose- and time-dependent manner. Magnolol also blocked cell cycle progression at G0 /G1 phase and induced mitochondrial-related apoptosis by upregulating p53 and p21 protein levels and by downregulating cyclin D1, CDC25A, and Cdk2 protein levels. When cells were pretreated with a p53 inhibitor (pifithrin-a), followed by magnolol treatment, pifithrin-a blocked magnolol-induced apoptosis and G0 /G1 arrest. In vivo, magnolol suppressed tumor growth and activated the same mechanisms as were activated in vitro. In conclusion, our study is the first to report that magnolol has an inhibitory effect on the growth of GBC cells and that this compound may have potential as a novel therapeutic agent for the treatment of GBC.

Japonicone A inhibits the growth of non-small cell lung cancer cells via mitochondria-mediated pathways.

Japonicone A, which is a natural product isolated from the aerial part of Inula japonica Thunb., has a wide range of clinical applications, including anti-inflammation and anti-oxidation. This study investigated the effects of japonicone A on the growth of non-small cell lung cancer (NSCLC) cell lines. The results showed that japonicone A significantly inhibited the growth of NSCLC cell lines in a dose- and time-dependent manner. This product also blocked cell cycle progression at S phase and induced mitochondrial-related apoptosis by upregulating Bax, cleaved caspase-9, cleaved caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP) protein levels and by downregulating Bcl-2, cyclin D1, CDC25A, and CDK2 protein levels. In vivo, japonicone A suppressed tumor growth via the same mechanism as that observed in vitro. In conclusion, our study is the first to report that japonicone A has an inhibitory effect on the growth of NSCLC cells, indicating that japonicone A administration is a potential therapeutic approach for future NSCLC treatments.

Prognostic significance of nemo-like kinase (NLK) expression in patients with gallbladder cancer.

Nemo-like kinase (NLK), a serine/threonine protein kinase, has been implicated in tumor development and progression, and plays an important role in diverse signaling pathways by phosphorylating a variety of transcription factors. Recent studies demonstrated that altered expression of NLK was observed in various types of human cancers. However, the clinical significance of NLK expression in gallbladder cancer (GBC) remains largely unknown. In this study, we focused on the clinical significance of NLK in GBC, and found that nuclear NLK protein overexpression was frequently detected in GBC tissues. The overexpression of NLK was significantly correlated with histological grade, TNM stage, and perineural invasion. The results of Kaplan-Meier analysis indicated that a high expression level of NLK resulted in a significantly poorer prognosis of GBC patients (P = 0.002). Furthermore, multivariate Cox regression analysis showed that high NLK expression was an independent prognostic factor for GBC patients (HR = 3.077). In conclusion, overexpression of NLK is closely related to progression of GBC, and NLK could be used as a potential prognostic marker for GBC patients.

Preparation and study on the solid inclusion complex of cloxacillin sodium with beta-cyclodextrin.

The interaction of cloxacillin sodium with beta-cyclodextrin (beta-CD) has been studied by several analytical techniques, including (1)H NMR, fluorescence spectroscopy, infrared spectroscopy. In this paper, solid inclusion complex of cloxacillin sodium with beta-CD was synthesized by the coprecipitation method. In addition, the characterization of the inclusion complex has been proved by fluorimetry, infrared spectroscopy and 1D, 2D NMR. The experimental results confirmed the existence of 1:1 inclusion complex of cloxacillin sodium with beta-CD. The formation constant of complex was determined by fluorescence method and (1)H NMR. Spacial configuration of complex has been proposed on 2D NMR technique.

Chloride intracellular channel 1 (CLIC1) is activated and functions as an oncogene in pancreatic cancer.

Chloride intracellular channel 1 (CLIC1), a newly discovered member of the chloride channel protein family, has been implicated in multiple human cancers. However, little is known with regard to its expression and biological functions in pancreatic cancer. In this study, we focused on the clinical significance and biological functions of CLIC1 in pancreatic cancer and found that this protein was overexpressed in pancreatic cancer tissues. Patients with CLIC1-positive tumours had worse overall survival than those with CLIC1-negative tumours. Furthermore, the treatment of pancreatic cancer cell lines with CLIC1-targeting siRNA oligonucleotides significantly reduced cell proliferation and diminished anchorage-independent growth on both soft agar and cell migration. These data indicate that CLIC1 acts as a putative oncogene in pancreatic cancer and may represent a novel diagnostic and therapeutic target for pancreatic cancer.

Survey on the complexation character of p-sulfonatocalix[n]arenes and Caffeic acid.

In this work the inclusion complex formation of Caffeic acid (CA) with p-sulfonatocalix[n]arenes (SCXn, n=4, 6, 8) is reported aiming to improve the antioxidant activity, thermal stability and photostability properties of CA. Evidence for the formation was obtained using fluorescence spectroscopy, nuclear magnetic resonance spectroscopy (NMR), pulsed field gradient NMR (PFG-NMR), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and scanning electron microphotographs (SEM). Experimental conditions including concentrations of SCXn and pH were investigated for the inclusion formation in detail. The results showed that CA was able to form inclusion complexes with SCXn in a molar ratio of 1:1, and the formation constants were varied with the pH conditions. NMR spectroscopy indicated that both the aromatic ring and the vinyl group of CA were partially covered by SCXn.

Prognostic significance of metastasis associated in colon cancer 1 (MACC1) expression in patients with gallbladder cancer.

BACKGROUND: The clinical significance of metastasis associated in colon cancer 1 (MACC1), in human gallbladder cancer, is not yet established. This study was performed to assess the expression of MACC1 in benign and malignant gallbladder lesions, and to assess its clinicopathological significance. MATERIALS AND METHODS: Tissue samples from resected gallbladder cancer (n=70) and cholelithiasis (n=70) were evaluated for MACC1 expression by immunohistochemical staining. Their expression was correlated with different clinicopathological parameters. RESULTS: Cytoplasmic MACC1 expression was significantly higher (58.6%) in gallbladder cancer than in chronic cholecystitis (27.1%, P<0.001). High MACC1 levels were associated with lymph node metastasis (P<0.05), tumor node metastasis (TNM) stage (P<0.01), and perineural invasion (P<0.01), but not with sex, age, history of gallstones or histological grade (P>0.05). The univariate Kaplan-Meier analysis showed that a positive MACC1 expression was associated with decreased overall survival (P<0.001). The multivariate Cox regression analysis showed that MACC1 expression and the histopathological subtypes were independent risk factors for disease-free survival. CONCLUSION: The expression of MACC1 might be closely related to carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.

Yes-associated protein 1 (YAP1) promotes human gallbladder tumor growth via activation of the AXL/MAPK pathway.

The transcriptional coactivator Yes-associated protein 1 (YAP1), a key regulator of cell proliferation and organ size in vertebrates, has been implicated in various malignancies. However, little is known about the expression and biological function of YAP1 in human gallbladder cancer (GBC). In this study we examined the clinical significance and biological functions of YAP1 in GBC and found that nuclear YAP1 and its target gene AXL were overexpressed in GBC tissues. We also observed a significant correlation between high YAP1 and AXL expression levels and worse prognosis. The depletion of YAP1 using lentivirus shRNAs significantly inhibited cell proliferation by inducing cell cycle arrest in S phase in concordance with the decrease of CDK2, CDC25A, and cyclin A, and resulted in increased cell apoptosis and invasive repression in GBC cell lines in vitro. Furthermore, knockdown of YAP1 also inhibited tumor growth in vivo. Additionally, we demonstrated that the activation of the AXL/MAPK pathway was involved in the oncogenic functions of YAP1 in GBC. These results demonstrated that YAP1 is a putative oncogene and represents a prognostic marker and potentially a novel therapeutic target for GBC.

Downregulated expression of hepatoma-derived growth factor (HDGF) reduces gallbladder cancer cell proliferation and invasion.

Hepatoma-derived growth factor (HDGF), a heparin-binding growth factor, has a wide range of biological functions, including mitogenic activity and vascular development. Recent studies demonstrated that HDGF also acted as an oncogene with aberrantly increased activity in multiple human cancers; however, little is known about the biological function of HDGF in gallbladder cancer (GBC). In this study, we focused on the clinical significance and biological functions of HDGF in GBC and found that Nuclear HDGF protein overexpression was frequently detected in GBC tissues. Patients with nuclear HDGF-positive tumors had worse overall survival than patients with HDGF-negative tumors. Furthermore, treatment of GBC lines with HDGF-targeting siRNA oligonucleotides (HDGF-siRNA) significantly reduced the proliferation of GBC-SD and SGC-996 cell lines and diminished both anchorage-independent growth on soft agar and cell migration. These data indicate that HDGF acts as a putative oncogene in GBC and could be a novel diagnostic and therapeutic target for GBC.