Complex in vitro 3D models of digestive system tumors to advance precision medicine and drug testing: Progress, challenges, and trends.

Digestive system cancers account for nearly half of all cancers around the world and have a high mortality rate. Cell culture and animal models represent cornerstones of digestive cancer research. However, their ability to enable cancer precision medicine is limited.

Clinical significance of exosomes as potential biomarkers in cancer.

Background: Exosomes are microvesicles, measuring 30-100 nm in diameter. They are widely distributed in body fluids, including blood, bile, urine and saliva. Cancer-derived exosomes carry a wide variety of DNA, RNA, proteins and lipids, and may serve as novel biomarkers in cancer.

Author Correction: TRPC5 channels participate in pressure-sensing in aortic baroreceptors.

This corrects the article DOI: 10.1038/ncomms11947.

Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective.

The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors.

Therapeutic potential of targeting acinar cell reprogramming in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC.

In Vivo Metabolite Profiling of a Purified Ellagitannin Isolated from Polygonum capitatum in Rats.

Ellagitannin is a common compound in food and herbs, but there are few detailed studies on the metabolism of purified ellagitannins. FR429 is a purified ellagitannin with antitumor potential, which is from Polygonum capitatum Buch.-Ham.

TRPC5 channels participate in pressure-sensing in aortic baroreceptors.

Blood pressure is maintained within a normal physiological range by a sophisticated regulatory mechanism. Baroreceptors serve as a frontline sensor to detect the change in blood pressure. Nerve signals are then sent to the cardiovascular control centre in the brain in order to stimulate baroreflex responses.

Novel therapeutic targets for pancreatic cancer.

Pancreatic cancer has become the fourth leading cause of cancer death in the last two decades. Only 3%-15% of patients diagnosed with pancreatic cancer had 5 year survival rate. Drug resistance, high metastasis, poor prognosis and tumour relapse contributed to the malignancies and difficulties in treating pancreatic cancer.

Ubiquitous expression of MAKORIN-2 in normal and malignant hematopoietic cells and its growth promoting activity.

Makorin-2 (MKRN2) is a highly conserved protein and yet its functions are largely unknown. We investigated the expression levels of MKRN2 and RAF1 in normal and malignant hematopoietic cells, and leukemia cell lines. We also attempted to delineate the role of MKRN2 in umbilical cord blood CD34+ stem/progenitor cells and K562 cell line by over-expression and inhibition of MKRN2 through lentivirus transduction and shRNA nucleofection, respectively.

Identification of metabolites of FR429, a potential antitumor ellagitannin, transformed by rat intestinal bacteria in vitro, based on liquid chromatography-ion trap-time of flight mass spectrometry analysis.

FR429 is an ellagitannin with a potential antitumor activity, isolated and purified from Polygonum capitatum Buch.-Ham.ex D.

STK31 maintains the undifferentiated state of colon cancer cells.

The expression of serine/threonine kinase (STK) family is frequently altered in human cancers. However, the functions of these kinases in cancer development remain elusive. Here, we report that STK31 is robustly and heterogeneously expressed in colon cancer tissues and plays a critical role in determining the differentiation state of colon cancer cells.

Protective effects of cathelicidin-encoding Lactococcus lactis in murine ulcerative colitis.

Background And Aim: Intrarectal administration of mouse cathelin-related antimicrobial peptide (mCRAMP) reduced intestinal inflammation in mice. In the current study, we examined whether mCRAMP-transformed Lactococcus lactis given orally attained similar protective effects.

Method: mCRAMP was produced and secreted from the transformed L.

EZH2 protein: a promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies.

Background And Aims: A previous study of ours indicated that enhancer of zeste homologue 2 (EZH2) plays an important role in hepatocellular carcinoma (HCC) tumorigenesis. The aim of the present study was to investigate the potential diagnostic utility of EZH2 in HCC.

Methods: Immunohistochemistry was performed to examine the expression dynamics of EZH2 in two independent surgical cohorts of HCC and non-malignant liver tissues to develop a diagnostic yield of EZH2, HSP70 and GPC3 for HCC detection.

MiR-26a inhibits cell growth and tumorigenesis of nasopharyngeal carcinoma through repression of EZH2.

Several microRNAs (miRNA) have been implicated in nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in southern China. In this study, we report that microRNA miR-26a is commonly downregulated in NPC specimens and NPC cell lines with important functional consequences. Ectopic expression of miR-26a dramatically suppressed cell proliferation and colony formation by inducing G(1)-phase cell-cycle arrest.

Aqueous extracts of Fructus Ligustri Lucidi enhance the sensitivity of human colorectal carcinoma DLD-1 cells to doxorubicin-induced apoptosis via Tbx3 suppression.

Chemoresistance has imposed a great challenge for cancer therapy. Fructus Ligustri Lucidi (FLL) is one of the commonest Chinese herbs that has been used for thousand years. This study shows that the aqueous extract of FLL (AFLL) enhanced the sensitivity of DLD-1 colon cancer cells to doxorubicin-induced apoptosis.

EZH2 supports ovarian carcinoma cell invasion and/or metastasis via regulation of TGF-beta1 and is a predictor of outcome in ovarian carcinoma patients.

It was suggested that the enhancer of zeste homolog 2 (EZH2) gene is a putative candidate oncogene in several types of human cancer. The potential oncogenic role of EZH2 and its clinical/prognostic significance, however, in ovarian carcinoma are unclear. In this study, EZH2 expression was examined by immunohistochemistry (IHC) in cohorts of normal and tumorous ovarian tissues.

Overexpression of Bax inhibitor-1 (BI-1) induces cell transformation in NIH3T3 cells.

BI-1 (Bax inhibitor-1), an apoptosis-inhibiting gene belonging to the Bcl-2 protein family, plays an important role in mitochondrial apoptosis pathway to suppress Bax-induced apoptosis. To investigate the potential role of BI-1 in promoting cell growth and tumorigenesis, in the present study we overexpressed the BI-1 gene in NIH3T3 cells using the lentivirus-mediated gene expression system. Our in vitro studies showed that NIH3T3 cells overexpressing BI-1 displayed a significantly higher growth rate and formed more and larger colonies than the control cells.

Functional characterisation of cell cycle-related kinase (CCRK) in colorectal cancer carcinogenesis.

Cell cycle-related kinase (CCRK) is a newly identified protein kinase homologous to Cdk7. We have previously shown that CCRK is a candidate oncogene in human glioblastoma. However, whether CCRK is a bona fide oncogene remains to be tested.

PYRIN domain of NALP2 inhibits cell proliferation and tumor growth of human glioblastoma.

NACHT leucine-rich domain and pyrin-containing protein 2 (NALP2) plays a crucial role in inflammation through regulation of NF-kappaB activity. The N-terminal PRYIN domain of NALP2 (PYD) functions similarly in inhibiting NF-kappaB activity. To investigate if NALP2 or PYD regulates cell proliferation or tumor growth of glioblastoma, lentiviruses carrying PYD (Lenti-PYD-Flag) was successfully packaged.

Curcumin induces down-regulation of EZH2 expression through the MAPK pathway in MDA-MB-435 human breast cancer cells.

Curcumin, a natural compound isolated from turmeric, may inhibit cell proliferation in various tumor cells through a mechanism that is not fully understood. The enhancer of zeste homolog 2 (EZH2) gene is overexpressed in human breast cancers with poor prognosis. In this study, we observed a dose- and time-dependent down-regulation of expression of EZH2 by curcumin that correlates with decreased proliferation in the MDA-MB-435 breast cancer cell line.

Hsa-let-7g inhibits proliferation of hepatocellular carcinoma cells by downregulation of c-Myc and upregulation of p16(INK4A).

zMicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs that regulate approximately one-third of human genes at post-transcription level. Previous studies have shown that miRNAs were implicated in many cellular processes and participated in the progress of various tumors including hepatocellular carcinoma (HCC). Among all miRNAs, the let-7 family is well recognized to play pivotal roles in tumorigenesis by functioning as potential growth suppressor.

High expression of EZH2 is associated with tumor aggressiveness and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.

The enhancer of zeste homolog 2 (EZH2), a known repressor of gene transcription, has been reported to be associated with biological malignancy in several cancers. The potential oncogenic role of EZH2 and its clinical/prognostic significance, however, in esophageal squamous cell carcinoma (ESCC) are unclear. In this study, the methods of immunohistochemistry and fluorescence in-situ hybridization were used to examine protein expression and amplification of EZH2 in 98 pretreatment biopsy specimens of ESCC who received definitive chemoradiotherapy (CRT).

Flavonoids of Herba Epimedii regulate osteogenesis of human mesenchymal stem cells through BMP and Wnt/beta-catenin signaling pathway.

Herba Epimedii is one of the most commonly used Chinese herbs for treating osteoporosis. In the present study, the flavonoids of Herba Epimedii (HEF) have shown to promote the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. They were noted to enhance the mRNA expression of BMP-2, BMP-4, Runx2, beta-catenin and cyclinD1, all of which are BMP or Wnt-signaling pathway related regulators.

Glucose-regulated protein 78 is an intracellular antiviral factor against hepatitis B virus.

Hepatitis B virus (HBV) infection is a global public health problem that plays a crucial role in the pathogenesis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. However, the pathogenesis of HBV infection and the mechanisms of host-virus interactions are still elusive. In this study, two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics were applied to analyze the host response to HBV using an inducible HBV-producing cell line, HepAD38.

The use of folate-PEG-grafted-hybranched-PEI nonviral vector for the inhibition of glioma growth in the rat.

Combined treatment using nonviral agent-mediated enzyme/prodrug therapy and immunotherapy had been proposed as a powerful alternative method of cancer therapy. The present study was aimed to evaluate the cytotoxicity in vitro and the therapeutic efficacy in vivo when the cytosine deaminase/5-fluorocytosine (CD/5-FC) and TNF-related apoptosis-inducing ligand (TRAIL) genes were jointly used against rat C6 glioma cells. The potency of the FA-PEG-PEI used as a nonviral vector was tested in the FR-expressed C6 glioma cells and Wistar rats.