A multi-targeting natural product, aiphanol, inhibits tumor growth and metastasis.

Cancer is one of the main causes of death in humans worldwide, the development of more effective anticancer drugs that can inhibit the malignant progression of cancer cells is of great significance. Aiphanol is a natural product identified from the seeds of and the rhizome of . Our preliminary studies revealed that it had potential antiangiogenic and antilymphangiogenic activity by directly targeting VEGFR2/3 and COX2 in endothelial cells.

Aiphanol, a multi-targeting stilbenolignan, potently suppresses mouse lymphangiogenesis and lymphatic metastasis.

The high incidence of lymphatic metastasis is closely related to poor prognosis and mortality in cancers. Potent inhibitors to prevent pathological lymphangiogenesis and lymphatic spread are urgently needed. The VEGF-C-VEGFR3 pathway plays a vital role in driving lymphangiogenesis and lymph node metastasis.

Combined expression of metastasis related markers Naa10p, SNCG and PRL-3 and its prognostic value in breast cancer patients.

Combinations of multiple biomarkers representing distinct aspects of metastasis may have better prognostic value for breast cancer patients, especially those in late stages. In this study, we evaluated the protein levels of N-α-acetyltransferase 10 protein (Naa10p), synuclein-γ (SNCG), and phosphatase of regenerating liver-3 (PRL-3) in 365 patients with breast cancer by immunohistochemistry. Distinct prognostic subgroups of breast cancer were identified by combination of the three biomarkers.

[Establishment of drug resistant cell line of MGC-803 and analysis of differential secretome].

Objective: To identify chemoresistance-associated secretory proteins by proteomic approaches, and to provide the basis for selecting suitable chemotherapy in gastric cancer treatment.

Methods: Drug resistant cell lines were established by gradient drug treatment with MGC-803 gastric cancer cells. The secreted proteins of MGC-803 parental and resistant cells were collected from the conditional medium without serum and separated by two-dimensional gel electrophoresis (2-DE).

HIWI expression profile in cancer cells and its prognostic value for patients with colorectal cancer.

Background: HIWI is a member of PIWI gene family and its expression is found in various tumors, indicating that it may play a pivotal role in tumor development. This study was designated to examine HIWI protein expression profile in several cancer cell lines and its prognostic value for patients with colorectal cancer.

Methods: Totally 270 patients who underwent surgical resection of primary colorectal cancer between January 1999 and December 2002 with a median follow-up time of 33 months were registered in the study.

[Construction and expression of PRL-3 plasmid with C104S point mutation and CAAX deletion].

Objective: To construct PRL-3 gene C104S point mutation and CAAX deletion mutants: pcDNA3-myc-PRL-3 (C104S), pEGFP-PRL-3 (C104S), pcDNA3-myc-PRL-3 (DeltaCAAX) and pEGFP-PRL-3 (DeltaCAAX), and express these plasmids in eukaryotic cells.

Methods: Recombinant plasmids were mutated with pcDNA3-myc-PRL-3 plasmid as template and specific primers. Mutants were identified by restriction enzyme digestion and DNA sequencing.

The eIF2alpha kinases PERK and PKR activate glycogen synthase kinase 3 to promote the proteasomal degradation of p53.

Phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) is mediated by a family of kinases that respond to various forms of environmental stress. The eIF2alpha kinases are critical for mRNA translation, cell proliferation, and apoptosis. Activation of the tumor suppressor p53 results in cell cycle arrest and apoptosis in response to various types of stress.

Interferons induce tyrosine phosphorylation of the eIF2alpha kinase PKR through activation of Jak1 and Tyk2.

The interferon (IFN)-inducible, double-stranded RNA activated protein kinase (PKR) is a dual-specificity kinase, which has an essential role in the regulation of protein synthesis by phosphorylating the translation eukaryotic initiation factor 2 (eIF2). Here, we show the tyrosine (Tyr) phosphorylation of PKR in response to type I or type II IFNs. We show that PKR physically interacts with either Jak1 or Tyk2 in unstimulated cells and that these interactions are increased in IFN-treated cells.

Critical role for Daxx in regulating Mdm2.

The tumour suppressor p53 induces apoptosis or cell-cycle arrest in response to genotoxic and other stresses. In unstressed cells, the anti-proliferative effects of p53 are restrained by mouse double minute 2 (Mdm2), a ubiquitin ligase (E3) that promotes p53 ubiquitination and degradation. Mdm2 also mediates its own degradation through auto-ubiquitination.

Tyrosine phosphorylation acts as a molecular switch to full-scale activation of the eIF2alpha RNA-dependent protein kinase.

Phosphorylation of the alpha-subunit of translation eukaryotic initiation factor-2 (eIF2) leads to the inhibition of protein synthesis in response to diverse conditions of stress. Serine/threonine RNA-dependent protein kinase (PKR) is an eIF2alpha kinase family member induced by type I IFN and activated in response to dsRNA or virus infection. Herein, we demonstrate that human PKR is a dual specificity kinase phosphorylated at Y101, Y162 and Y293 in vitro and in vivo.

Endoplasmic reticulum stress accelerates p53 degradation by the cooperative actions of Hdm2 and glycogen synthase kinase 3beta.

Inactivation of the tumor suppressor p53 by degradation is a mechanism utilized by cells to adapt to endoplasmic reticulum (ER) stress. However, the mechanisms of p53 destabilization by ER stress are not known. We demonstrate here that the E3 ubiquitin-ligase Hdm2 is essential for the nucleocytoplasmic transport and proteasome-dependent degradation of p53 in ER-stressed cells.

Resistance to vesicular stomatitis virus infection requires a functional cross talk between the eukaryotic translation initiation factor 2alpha kinases PERK and PKR.

Phosphorylation of the alpha (alpha) subunit of the eukaryotic translation initiation factor 2 (eIF2) leads to the inhibition of protein synthesis in response to diverse stress conditions, including viral infection. The eIF2alpha kinase PKR has been shown to play an essential role against vesicular stomatitis virus (VSV) infection. We demonstrate here that another eIF2alpha kinase, the endoplasmic reticulum-resident protein kinase PERK, contributes to cellular resistance to VSV infection.

Induction of p53-dependent apoptosis in HCT116 tumor cells by RNA viruses and possible implications in virus-mediated oncolysis.

Recent findings showed that type I interferons (IFN-alpha/beta) induce the transcription of tumor suppressor p53 and sensitize primary mouse embryonic fibroblasts (MEFs) to p53-mediated apoptosis by oncolytic viruses. However, the ability of RNA viruses to induce a p53-mediated apoptotic response may differ between primary and tumor cells and may be dependent upon the virus type. We have investigated this hypothesis by analyzing the apoptotic effects of various oncolytic viruses on the human colon carcinoma HCT116 cells and their derivatives lacking either p53 or bax gene.

Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta.

The tumor suppressor p53, a sensor of multiple forms of cellular stress, is regulated by post-translational mechanisms to induce cell-cycle arrest, senescence, or apoptosis. We demonstrate that endoplasmic reticulum (ER) stress inhibits p53-mediated apoptosis. The mechanism of inhibition involves the increased cytoplasmic localization of p53 due to phosphorylation at serine 315 and serine 376, which is mediated by glycogen synthase kinase-3 beta (GSK-3beta).

Studies on specific interaction of beta-2-glycoprotein I with HBsAg.

Aim: To observe the binding activity of beta-2-glycoprotein I(beta(2)GPI) to hepatitis B surface antigen (HBsAg) and the possible roles of beta(2)GPI in hepatitis B virus (HBV) infection.

Methods: The rationale of ELISA methods and ELISA-based research method and ligand-blotting technique were used to detect the specific interaction of beta(2)GPI with HBsAg.

Results: With the increase of rHBsAg, the binding of beta(2)GPI to rHBsAg elevated, and these changes had statistic significance.

Protein kinase inhibitor 2-aminopurine overrides multiple genotoxic stress-induced cellular pathways to promote cell survival.

2-Aminopurine (2-AP) is an adenine analog shown to cause cells to bypass chemical- and radiation-induced cell cycle arrest through as-yet unidentified mechanisms. 2-AP has also been shown to act as a kinase inhibitor. Tumor suppressor p53 plays an important role in the control of cell cycle and apoptosis in response to genotoxic stress.