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Various Human Cancers (various + human_cancers)
Selected AbstractsOsteoprotegerin (OPG),a potential new role in the regulation of endothelialcell phenotype and tumour angiogenesis?INTERNATIONAL JOURNAL OF CANCER, Issue 8 2006Simon S. Cross Abstract The progression of cancer depends on the establishment of a tumour blood supply, and therefore tumour angiogenesis has been identified as a major target for new anticancer agents. Recent reports have suggested that osteoprotegerin (OPG) is involved in the control of endothelial cell survival through the inhibition of the activity of tumour necrosis factor- (TNF) related apoptosis-inducing ligand (TRAIL). The role of OPG in human tumour development and angiogenesis is currently unknown. In the present study we demonstrate the ability of OPG to support endothelial cell survival, as well as the formation of cord-like structures in vitro using a matrigel tubule formation assay. Investigation of various human cancers demonstrated endothelial OPG expression in 59% of malignant tumours (n = 512), but in contrast, OPG was absent in endothelial cells associated with benign tumours and normal tissues (n = 178). In a series of 400 breast tumours, endothelial OPG expression was associated with high tumour grade and certain histological types. Our data show a clear separation in endothelial OPG expression between malignant tumours and nonmalignant tissues, supporting a potential biological role for this molecule in the development and/or maintenance of the tumour vasculature. This is the first study to report the proangiogenic effects of OPG in vitro, as well as correlating expression of OPG by tumour endothelial cells with clinicopathological data in human tumours. © 2005 Wiley-Liss, Inc. [source] Sodium 1, 4-dihydroxy-9, 10-anthraquinone- 2-sulphonate interacts with calf thymus DNA in a way that mimics anthracycline antibiotics: an electrochemical and spectroscopic studyJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 6 2010Partha Sarathi Guin Abstract The anthracycline drugs, adriamycin and daunorubicin, efficient in the treatment of various human cancers, form strong intercalation complexes with DNA. The therapeutic efficiency and toxic properties of the drugs are associated with electron transfer processes, which correlate well with the redox behaviour of the compounds. Sodium 1,4-dihydroxy 9,10-anthraquinone-2-sulphonate (sodium quinizarin-2-sulphonate, NaLH2) (Na-Qz-2S) is a molecule that resembles anthracycline drugs and has a simpler structure in comparison to these drugs. Two electrons in the course of chemical action reduce this molecule like the anthracyclines. Electrochemical methods were used to identify this process. UV-Vis and fluorescence spectroscopy were used to analyse binding of the compound to calf thymus DNA. The binding constant and site size were evaluated for Na-Qz-2S and the same compared to that of the anthracyclines. Such comparisons are essential in order to understand whether the simpler hydroxy-anthraquinones can be a substitute for anthracycline drugs in cancer chemotherapy. Copyright © 2009 John Wiley & Sons, Ltd. [source] The tumor suppressor NPRL2 in hepatocellular carcinoma plays an important role in progression and can be served as an independent prognostic factorJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2009Satoshi Otani MD Abstract Background/Aims Hepatocarcinogenesis is a multifactorial, multistep process that involves the activation of oncogenes or the inactivation of tumor suppressor genes throughout the different stages of hepatocellular carcinoma (HCC) progression. NPRL2 is one of the candidate tumor suppressor genes identified on chromosome 3p21.3, a region which frequently contains genetic abnormalities found in the early stages of the development of various human cancers. In the current study, we aimed to evaluate NPRL2 expression in HCC and to explore the prognostic significance of NPRL2. Method We investigated NPRL2 mRNA expression in 70 HCC specimens, using quantitative real-time reverse transcription polymerase chain reaction analysis, and the correlation between NPRL2 expression and clinicopathologic parameters. Results NPRL2 mRNA was found to be expressed equally in both HCC tissues and corresponding non-cancerous liver tissues. However, higher NPRL2 expression correlated significantly with tumor size (P,=,0.0062) and serum PIVKA-II levels (P,=,0.0002). Univariate and multivariate analyses revealed that higher NPRL2 mRNA expression was an independent prognostic factor for overall survival (risk ratio 0.39; P,<,0.0001). Conclusion Our results suggest that NPRL2 mRNA expression has prognostic significance for the survival of patients with HCC. J. Surg. Oncol. 2009;100:358,363. © 2009 Wiley-Liss, Inc. [source] Identification of the H2-Kd -restricted cytotoxic T lymphocyte epitopes of a tumor-associated antigen, SPARC, which can stimulate antitumor immunity without causing autoimmune disease in miceCANCER SCIENCE, Issue 1 2009Yoshiaki Ikuta We previously reported that the secreted protein acidic and rich in cystein (SPARC) was overexpressed in melanoma in humans, and the serum SPARC level was useful as a novel tumor marker for melanoma. SPARC was also reported to be overexpressed in various human cancers. In this study, we asked whether SPARC-specific cytotoxic T lymphocytes (CTL) could induce antitumor immunity to SPARC-expressing tumor in mice or not as a preclinical study of SPARC-directed anticancer immunotherapy. Because of similarities in the structural motifs of major histocompatibility complex-binding peptides between H2-Kd and HLA-A24 (A*2402), the most common human leukocyte antigen class I allele in the Japanese population, we attempted to identify the H2-Kd -restricted SPARC epitope for CTL in BALB/c mice and we found that the mouse SPARC143,151 (DYIGPCKYI) and SPARC225,234 (MYIFPVHWQF) peptides could induce peptide-reactive CTL in BALB/c mice without causing autoimmune diseases. The immunization of mice with SPARC225,234 peptide-pulsed bone marrow-derived dendritic cells (BMDC) inhibited the growth of s.c. inoculated mouse mammary cancer cell line, N2C, expressing SPARC and these mice lived longer than the mice immunized with peptide-unpulsed BMDC. In conclusion, our study indicated that SPARC peptide-based cancer immunotherapy was effective and safe at least in a mouse tumor prevention model. (Cancer Sci 2009; 100: 132,137) [source] PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinomaCANCER SCIENCE, Issue 12 2006Ken-ichi Kozaki Phosphatidylinositol 3-kinases (PI3K) are a group of heterodimeric lipid kinases that regulate many cellular processes. Gene amplification and somatic mutations mainly within the helical (exon 9) and kinase (exon 20) domains of PIK3CA, which encode the 110-kDa catalytic subunit of PI3K and are mapped to 3q26, have been reported in various human cancers. Herein, 14 human oral squamous cell carcinoma (OSCC) cell lines and 108 primary OSCC tumors were investigated for activating mutations at exons 9 and 20 as well as amplifications in PIK3CA. PIK3CA missense mutations in exons 9 and 20 were identified in 21.4% (3/14) of OSCC cell lines and 7.4% (8/108) of OSCC tumors by genomic DNA sequencing. An increase in the copy number of PIK3CA, although small, was detected in 57.1% (8/14) of OSCC lines and 16.7% (18/108) of OSCC tumors using quantitative real-time PCR. A significant correlation between somatic mutations of PIK3CA and disease stage was observed: the frequency of mutations was higher in stage IV (16.1%, 5/31) than in a subset of early stages (stages I,III) (3.9%, 3/77; P = 0.042, Fisher's extract test). In contrast, the amplification of PIK3CA was observed at a similar frequency among all stages. AKT was highly phosphorylated in OSCC cell lines with PIK3CA mutations compared to those without mutations, despite the amplification. The results suggest that somatic mutations of the PIK3CA gene are likely to occur late in the development of OSCC, and play a crucial role through the PI3K,AKT signaling pathway in cancer progression. (Cancer Sci 2006; 97: 1351,1358) [source] Overexpression of Human Telomerase RNA in Helicobacter pylori -infected Human Gastric MucosaCANCER SCIENCE, Issue 11 2000Kwon Hur Telomerase, an enzyme associated with cellular immortality and malignancy, plays an important role in cellular immortalization and tumorigenesis. Furthermore, overexpression of the RNA component of the telomerase, called human telomerase RNA (hTR), has been demonstrated in various human cancers as an early event. The pattern of hTR expression following Helicobacter pylori (H. pylori) infection in human gastric mucosa was investigated by a radioactive in situ hybridization (ISH) assay. Paraffin-embedded sections of 50 biopsy specimens taken from the gastric antrum of individual patients infected to different extents with H. pylori, as well as normal gastric mucosa, were studied. In normal gastric mucosa, only weak hTR expression was noted and the expression was limited to basal cells of the gastric glands. However, the degree of hTR expression gradually increased in parallel with the degree of H. pylori infection. The mean scores of gastric mucosa with mild, moderate and severe degrees of H. pylori infection were 2.3, 2.8, and 3.7 times higher than that of normal gastric mucosa, respectively. The results of this study suggested that up-regulation of hTR expression is a frequent and early event associated with H. pylori infection in the gastric mucosa and may play some role in gastric carcinogenesis. Sufficient synthesis of hTR during this early stage may be a prerequisite for telomerase reactivation to occur in gastric cancer. [source] | ||||||||||