ObjectiveTo detect the aberrant expression of circulating miRNAs and explore the potential early diagnostic biomarkers in patients with Parkinson's disease (PD).MethodsPlasma samples were collected from 25 treatment‐naïve PD‐diagnosed patients and 25 healthy controls followed by a real‐time PCR‐based miRNA screening analysis of neuron disease‐related miRNAs.ResultsA subset of miRNAs with aberrant expression levels in the plasma of PD‐diagnosed patients were identified including upregulation of miR‐27a and downregulation of let‐7a, let‐7f, miR‐142‐3p, and miR‐222 with the AUC values more than 0.8 derived from the receiver operating characteristic curves.ConclusionsThe high sensitivity and specificity of the circulating miRNAs may enable early diagnosis of PD. The study provides a group of novel miRNA candidates for detecting PD.

Here, we investigated the role of zinc ribbon domaincontaining 1 (ZNRD1) in multidrug resistance (MDR) of leukemia cells and the possible underlying mechanisms. ZNRD1 was found overexpressed in the vincristineinduced MDR leukemia cell HL-60/vincristine moreso than its parental cell HL-60. Up-regulation of ZNRD1 expression could confer resistance of both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs on HL-60 cells and suppress Adriamycin-induced apoptosis accompanied by decreased accumulation and increased releasing amount of Adriamycin. ZNRD1 could significantly upregulate the expression of P-gp, Bcl-2, and the transcription of the MDR1 gene but not alter the expression of MDR-associated protein, glutathione S-transferase activity, or intracellular glutathione content in leukemia cells. In addition, inhibition of ZNRD1 expression by RNA interference or P-gp inhibitor could partially reverse ZNRD1-mediated MDR. The further study of the biological functions of ZNRD1 may be helpful for understanding the mechanisms of MDR of leukemia and developing possible strategies to treat leukemia. [Mol Cancer Ther 2005;4(12):1936 -42]

Background: The discovery of the importance of angiogenesis in tumor growth has emphasized the need to find specific vascular targets for tumor-targeted therapies. Previously, using phage display technology, we identified the peptide GX1 as having the ability to target the gastric cancer vasculature. The present study investigated the bioactivities of GX1, as well as its potential ability to cooperate with recombinant mutant human tumor necrosis factor alpha (rmhTNFα), in gastric cancer therapy.

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Quantification of single-cell proteomics provides key insights into cellular heterogeneity while conventional flow cytometry cannot provide absolute quantification of intracellular proteins of single cells due to the lack of calibration approaches. This paper presents a constriction channel (with a cross sectional area smaller than cells) based microfluidic flow cytometer, capable of collecting copy numbers of specific intracellular proteins. In this platform, single cells stained with fluorescence labelled antibodies were forced to squeeze through the constriction channel with the fluorescence intensities quantified and since cells fully filled the constriction channel during the squeezing process, solutions with fluorescence labelled antibodies were flushed into the constriction channel to obtain calibration curves. By combining raw fluorescence data and calibration curves, absolute quantification of intracellular proteins was realized. As a demonstration, copy numbers of beta-actin of single tumour cells were quantified to be 0.90 ± 0.30 μM (A549, n = 14 228), 2.34 ± 0.70 μM (MCF 10A, n = 2455), and 0.98 ± 0.65 μM (Hep G2, n = 6945). The travelling time for individual cells was quantified to be roughly 10 ms and thus a throughput of 100 cells per s can be achieved. This microfluidic system can be used to quantify the copy numbers of intracellular proteins in a high-throughput manner, which may function as an enabling technique in the field of single-cell proteomics.

Gastric cancer is an aggressive cancer with poor prognosis. Identification of precise prognostic marker and effective therapeutic target is important in the treatment of gastric cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple functions including tumorigenic suppression, apoptosis induction and diminishing angiogenic properties. Here, the level of TIP30 expression was determined in gastric cancer, and the impact of its alteration on cancer biology and clinical outcome was investigated. We found that TIP30 protein was absent or reduced in gastric cancer cell lines. There was also a loss or substantial decrease of TIP30 expression in 106 cases of gastric tumors as compared with that in normal gastric mucosa (p < 0.05), which was significantly associated with inferior survival duration. In a Cox proportional hazards model, TIP30 expression independently predicted better survival (p < 0.05). We also restored TIP30 protein expression in human gastric cancer-derived cells AGS and MKN28 lacking endogenous TIP30 protein to study the effects of TIP30 expression on cell proliferation, cell kinetics, tumorigenicity and metastasis in BALB/c nude mice and found that adenoviralmediated restoration of TIP30 expression led to downregulation of cyclin D1, Bcl-2, Bcl-xl, but to upregulation of p27, Bax, p53, caspase 3 and 9 expression, cell cycle G0/G1 arrest and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Taken together, the present work revealed a novel function of TIP30, which can possibly be used as an independent prognostic factor and a potential therapeutic target for gastric cancer. ' 2008 Wiley-Liss, Inc.Key words: TIP30; prognosis; tumorigenesis; metastasis; gastric cancer Although the incidence of gastric cancer declined in the West from the 1940s to the 1980s, it remains a major public health problem throughout the world.1 Higher incidences are observed in Japan, China, Eastern Europe and South America. In Asia and parts of South America, in particular, gastric cancer is the most common epithelial malignancy and leading cause of cancerrelated death. Moreover, gastric cancer remains the second most frequently diagnosed malignancy worldwide and is the cause of 12% of all cancer-related deaths each year.1,2 Advances in the treatment of this disease are likely to come from a fuller understanding of its biology and behavior. The aggressive nature of human metastatic gastric carcinoma is related to mutations of various oncogenes and tumor suppressor genes 3-7 and abnormalities in several growth factors and their receptors.5 These abnormalities affect the downstream signal transduction pathways involved in the control of cell growth and differentiation. Specifically, they confer a tremendous survival and growth advantage to gastric cancer cells. Previous studies indicated the role of several tumor suppressor genes in gastric cancer development and progression, including the E-cadherin/CDH1 gene, TP53 and p16. 3,6,[8][9][10][...

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ABBREVIATIONS Research PaperThe Effect of Somatostatin and SSTR3 on Proliferation and Apoptosis of Gastric Cancer Cells ABSTRACTIn the present study, we detected the expression of SSTR3 protein in 40 patients with gastric adenocarcinoma and 40 cases of normal gastric mucosa by immunoperoxidased staining. SSTR3 mRNA and protein were also examined in gastric cancer cell lines and eternal gastric epithelial cell line by RT-PCR, immunofluorescence and Western blot. The effect of octreotide on the growth of gastric cancer cells was examined by MTT test, and the apoptosis by flow cytometry. Competitive protein binding method was also used to evaluate the role of SSTR3. The results were: (1) SSTR3 protein existed in the membrane of gastric cancer cells. In normal gastric mucosa, SSTR3 protein distributed to the cellular membrane and cytoplasm or interstitial tissue in submucosa. The expression of SSTR3 protein was significantly lower in gastric cancer compared with normal mucosa. Moreover, the poor-differentiated adenocarcinoma was lower than the well-differentiated adenocarcinoma, and the similar result in cell lines. (2) Octreotide could inhibit the growth and induce the apoptosis of gastric cancer and normal epithelial cells that expressed SSTR3, but didn't affect the cells with no or weakly expression of SSTR3. (3) When the cells were administrated octreotide in combination of SSTR3 antibody, the effect of octreotide decreased dramatically. The preliminary study suggested that SSTR3 might play a role in the growth and apoptosis of gastric cancer. In those gastric cancers that expressed SSTR3, octreotide could be effective in inhibiting cell growth and inducing cell apoptosis through mediation of SSTR3.