No abstract

A nanorobot is used to realize deep penetration of drugs in atherosclerotic plaque, photothermal ablation of inflammatory macrophages and long-term anti-proliferation effects.

Under malignant circumstances, PaSCs express and secret galectin-1, which could further promote the proliferation and invasion of cancer cells.

Identification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non-smallcell lung cancer (NSCLC) cell line, NCI-H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed RhoB expression in 112 primary NSCLCs with immunohistochemistry and found no or a weak RhoB expression in 33 (42%) of 78 adenocarcinomas, whereas we found it in 29 (94%) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly-or moderately-differentiated adenocarcinomas than in well-differentiated ones (p 5 0.0014). Furthermore, no or a weak expression of RhoB indicated a tendency to poor patient prognosis. Although hypermethylation was not found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG for NSCLC. ' 2006 Wiley-Liss, Inc.Key words: RhoB; lung cancer; immunohistochemistry; homozygous deletion; chromosome 2pNon-small-cell lung cancer (NSCLC) is a leading cause of cancer death in both Western countries and Japan, and genetic and epigenetic alterations in proto-oncogenes and tumor suppressor genes (TSGs) are implicated in the development of lung tumors. Genetic changes affecting TSGs usually involve 2 events, with one hit being a loss of large chromosomal DNA regions of 1 parental allele and the other hit a smaller mutational event (e.g. point mutation, smaller deletion/insertion) or promoter hypermethylation affecting the other allele. Cytogenetic and allelotyping studies have revealed many nonrandom chromosomal alteration regions showing a loss of heterozygosity (LOH) and/or occasional homozygous deletions in lung cancer, with each targeted TSG subsequently identified, including 17p13 for p53, 9p21 for p16 INK4a /p14 ARF , 13q14 for RB, and multiple loci of 3p for FHIT, RASSF1A, and/or other unidentified genes.1-4 A high-resolution genome-wide allelotyping analysis of 36 lung cancer cell lines with matched B lymphoblastoid cell lines was performed in which 22 different regions with more than 60% LOH were identified. 5Chromosomal arms with the most frequent LOH were 1p, 3p, 4p, 4q, 5q, 8p, 9p, 9q, 10p, 10q, 13q, 15q, 17p, 18q, 19p, Xp and Xq. Noticeably, new homozygous deletions at 2p23, 8q24, 18q11 and Xq22, in NCI-H2882, NCI-H2122, NCI-H2887 and NCI-...

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality worldwide. Various imaging modalities provide important information about HCC for its clinical management. Since positron-emission tomography (PET) or PET-computed tomography was introduced to the oncologic setting, it has played crucial roles in detecting, distinguishing, accurately staging, and evaluating local, residual, and recurrent HCC. PET imaging visualizes tissue metabolic information that is closely associated with treatment. Dynamic PET imaging and dual-tracer have emerged as complementary techniques that aid in various aspects of HCC diagnosis. The advent of new radiotracers and the development of immuno-PET and PET-magnetic resonance imaging have improved the ability to detect lesions and have made great progress in treatment surveillance. The current PET diagnostic capabilities for HCC and the supplementary techniques are reviewed herein.

Abstract. We investigated the relationship of ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression and promoter methylation with pancreatic cancer tumorigenesis and drug resistance. Gemcitabine-resistant pancreatic cancer cells, SW1990/ GZ (33.3-fold increased resistance), were obtained by treating SW1990 cells with gemcitabine. The expression of ABCB1/ MDR1, ABCC1/MRP1 and ABCG2/BCRP was determined by quantitative real-time RT-PCR in the cell lines, 3 normal pancreatic tissues, 15 human pancreatic cancer samples and 15 adjacent tissues. Promoter methylation was determined in cell lines by bisulfite genomic sequencing. ABCB1/MDR1, ABCC1/ MRP1 and ABCG2/BCRP were upregulated in SW1990 and SW1990/GZ compared with normal pancreatic tissue, and expression in SW1990/GZ was significantly higher than in SW1990 cells. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/ BCRP were upregulated in pancreatic cancer tissues, compared to adjacent tissues. The ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP promoter were hypomethylated in all the cell lines. ABCB1/MDR1, ABCC1/MRP1 and ABCG2/BCRP expression correlated with pancreatic cancer tumorigenesis and drug resistance in a mechanism that is independent of promoter methylation. IntroductionPancreatic cancer is among the 10 leading causes of cancerrelated deaths, with a 5-year survival <5% (1). Most patients have advanced stage disease at diagnosis. One fifth of pancreatic cancer patients present in the early stage and are eligible for surgical resection (2), which is a complex operation that is associated with high rates of operative morbidity. Pancreatic cancer also shows resistance to chemotherapy. Gemcitabine, the standard treatment in advanced disease, prolongs survival by 5-6 months. Chemotherapy is largely ineffective for patients with metastases as disease frequently redevelops even after surgery; therefore, there is an urgent need to understand the molecular mechanism of chemoresistance in pancreatic cancer.One well-known mechanism of chemoresistance is the overexpression of energy-dependent pumps, such as adenosine triphosphate-binding cassette (ABC) transporters, which lead to the extrusion of drugs and their metabolites (3). P-gp, a 170,000-Da phosphoglycoprotein that consists of two ATP binding cassettes and two transmembrane regions, which is associated with chemoresistance in cancers of the gastrointestinal tract, liver and kidneys (4). The breast cancer resistance protein (ABCG2/BCRP) is a 655-amino-acid polypeptide transporter with a wide range of substrates associated with breast cancer resistance (5). Additionally, ABCC1/MRP1 is correlated with differentiation grade and tumor size in primary hepatocellular carcinoma and breast cancer (6,7).DNA methylation of CpG dinucleotides is the predominant epigenetic gene expression modification. More than 40% of protein coding genes have 5' CpG rich segments, termed CpG islands (8). The aberrant methylation of gene promoters is frequently observed in human cancers and correlates with carcinogenesis, tumor progression and chemosensitivity (9,10). M...

In the treatment of coronary artery disease (CAD), the use of stent implantation often leads to clinical complications such as restenosis, delayed endothelial healing, and thrombosis. Here, we develop a double drug sustained-release coating for the stent surface by grafting heparin/NONOate nanoparticles (Hep/NONOates). The Hep/NONOates and surface modification of the stent were characterized by X-ray photoelectron spectroscopy, attenuated total reflection Fourier-transform infrared spectroscopy, static water contact angle, and scanning electron microscopy (SEM), and the release behaviors of the anticoagulant, heparin (Hep) and the bioactive molecule, nitric oxide (NO) were studied. Furthermore, the blood compatibility and cytotoxicity of the modified stent were evaluated by whole blood adhesion and platelet adhesion tests, hemolysis assay, morphological changes of red blood cells, plasma recalcification time assay, in vitro coagulation time tests, and MTT assay. Finally, the results of a rabbit carotid artery stent implantation experiment showed that the double drug sustained-release coating for the stent can accelerate regeneration of endothelial cells and keep good anticoagulant activity. This study can provide new design ideas based on nanotechnology for improving the safety and effectiveness of drug-eluting stents.

MicroRNAs (miRNAs) are small non-coding RNAs of 20-22 nucleotides (nts) and constitute a novel class of gene regulators that negatively regulate gene expression at the post-transcriptional level. The expression of miRNA is deregulated in many types of cancers. Alterations in miRNA expression may be an important contributor to the development of pancreatic carcinoma. We hypothesized that genetic variations in miRNA genes were associated with pancreatic carcinoma and analyzed genomic sequences coding for the precursors of eight miRNA genes in both pancreatic carcinoma tissues and cancer cell lines. Four novel mutations in primary miRNA transcripts were identified. TaqMan miRNA assays showed that miR-21 was significantly overexpressed in 20 pancreatic carcinomas and 6 cancer cell lines compared with paired benign tissues and normal pancreas. Two mutations of miR-21 did not notably alter the activity of the promoter of the miRNA gene. Although most of these mutations seem to have no effect on miRNA processing, an A-G mutation at 29-nt downstream of pre-miR-21 led to a conformational change of the secondary structure close to the stem reaching into the pre-miR-21 and a relative reduction of the mature miR-21 expression in vivo. These results suggested that miRNA might play an important role in pancreatic tumorigenesis, but the molecular mechanism underlying the particular sequence variations in miRNA that can cause aberrant expression remains to be determined.