<Emphasis Type="Italic">Metallothionien 3</Emphasis> expression is frequently down-regulated in oesophageal squamous cell carcinoma by DNA methylation

Background  

Metallothionein 3 (MT3) inhibits growth in a variety of cell types. We measured MT3 gene expression by RT-PCR, and DNA methylation in the MT3 promoter by combined bisulphite restriction analysis, in four oesophageal cancer cell lines and the resected oesophagus from 64 patients with oesophageal squamous cell carcinoma (SCC).     

O<Superscript><Emphasis Type="Italic">6</Emphasis></Superscript>-<Emphasis Type="Italic">methylguanine-DNA methyltransferase</Emphasis> is downregulated in transformed astrocyte cells: implications for anti-glioma therapies

Background  

A novel alkylating agent, temozolomide, has proven efficacious in the treatment of malignant gliomas. However, expression of O ⁶ -methylguanine-DNA methyltransferase (MGMT) renders glioma cells resistant to the treatment, indicating that identification of mechanisms underlying the gene regulation of MGMT is highly required. Although glioma-derived cell lines have been widely employed to understand such mechanisms, those models harbor numerous unidentified genetic lesions specific for individual cell lines, which complicates the study of specific molecules and pathways.     

Functional promoter upstream p53 regulatory sequence of <Emphasis Type="Italic">IGFBP3</Emphasis> that is silenced by tumor specific methylation

Background  

Insulin-like growth factor binding protein (IGFBP)-3 functions as a carrier of insulin-like growth factors (IGFs) in circulation and a mediator of the growth suppression signal in cells. There are two reported p53 regulatory regions in the IGFBP3 gene; one upstream of the promoter and one intronic. We previously reported a hot spot of promoter hypermethylation of IGFBP-3 in human hepatocellular carcinomas and derivative cell lines. As the hot spot locates at the putative upstream p53 consensus sequences, these p53 consensus sequences are really functional is a question to be answered.     

Epigenetic changes within the promoter region of the <Emphasis Type="Italic">HLA-G</Emphasis> gene in ovarian tumors

Background  

Previous findings have suggested that epigenetic-mediated HLA-G expression in tumor cells may be associated with resistance to host immunosurveillance. To explore the potential role of DNA methylation on HLA-G expression in ovarian cancer, we correlated differences in HLA-G expression with methylation changes within the HLA-G regulatory region in an ovarian cancer cell line treated with 5-aza-deoxycytidine (5-aza-dC) and in malignant and benign ovarian tumor samples and ovarian surface epithelial cells (OSE) isolated from patients with normal ovaries.     

<Emphasis Type="Italic">Tumor suppressor in lung cancer 1 (TSLC1)</Emphasis> alters tumorigenic growth properties and gene expression

Background  

Introduction of cDNA or genomic clones of the tumor suppressor in lung cancer 1 (TSLC1) gene into the non-small cell lung cancer line, A549, reverses tumorigenic growth properties of these cells. These results and the observation that TSLC1 is down-regulated in a number of tumors suggest that TSLC1 functions as a critical switch mediating repression of tumorigenesis.     

EBV-positive Hodgkin lymphoma is associated with suppression of p21<Superscript>cip1/waf1</Superscript> and a worse prognosis

Background  

About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV-encoded small RNAs (EBERs) are presented in all EBV-infected cells, but their functions are still less understood.     

Genetic and epigenetic silencing of the <Emphasis Type="Italic">beclin 1</Emphasis>gene in sporadic breast tumors

Background  

Beclin 1, an important autophagy-related protein in human cells, is involved in cell death and cell survival. Beclin 1 mapped to human chromosome 17q21. It is widely expressed in normal mammary epithelial cells. Although down-regulated expression with mono-allelic deletions of beclin 1 gene was frequently observed in breast tumors, whether there was other regulatory mechanism of beclin 1 was to be investigated. We studied the expression of beclin 1 and explored the possible regulatory mechanisms on its expression in breast tumors.     

Breast cancer oestrogen independence mediated by <Emphasis Type="Italic">BCAR1</Emphasis> or <Emphasis Type="Italic">BCAR3</Emphasis> genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

Introduction  

Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known. The aim of this study was to investigate the growth control mediated by these BCAR genes by gene expression profiling.     

Analysis of <Emphasis Type="Italic">CUL-5</Emphasis> expression in breast epithelial cells,breast cancer cell lines,normal tissues and tumor tissues

Background  

The chromosomal location of CUL-5 (11q 22-23) is associated with LOH in breast cancer, suggesting that CUL-5 may be a tumor suppressor. The purpose of this research was to determine if there is differential expression of CUL-5 in breast epithelial cells versus breast cancer cell lines, and normal human tissues versus human tumors. The expression of CUL-5 in breast epithelial cells (HMEC, MCF-10A), and breast cancer cells (MCF-7, MDA-MB-231) was examined using RT-PCR, Northern blot analysis, and Western blot analysis. The expression of mRNA for other CUL family members (CUL-1, -2, -3, -4A, and -4B) in these cells was evaluated by RT-PCR. A normal human tissue expression array and a cancer profiling array were used to examine CUL-5 expression in normal human tissues and matched normal tissues versus tumor tissues, respectively.     

The apoptotic response in HCT116<Superscript><Emphasis Type="Italic">BAX-/-</Emphasis></Superscript>cancer cells becomes rapidly saturated with increasing expression of a GFP-BAX fusion protein

Background  

Many chemotherapeutic agents promote tumor cell death by activating the intrinsic pathway of apoptosis. Intrinsic apoptosis involves permeabilization of the mitochondrial outer membrane and the release of cytochrome c, a process that is controlled by proteins of the BCL2 gene family. Chemoresistance is often associated with abnormalities in concentrations of BCL2 family proteins. Although stoichiometirc interactions between anti-apoptotic and BH3-only BCL2 family proteins have been well documented as affecting cell death, the association between changes in BAX concentration and intrinsic apoptosis are poorly understood.     

Simultaneous <Emphasis Type="Italic">CXCL12</Emphasis> and <Emphasis Type="Italic">ESR1</Emphasis> CpG island hypermethylation correlates with poor prognosis in sporadic breast cancer

Background  

CXCL12 is a chemokine that is constitutively expressed in many organs and tissues. CXCL12 promoter hypermethylation has been detected in primary breast tumours and contributes to their metastatic potential. It has been shown that the oestrogen receptor α (ESR1) gene can also be silenced by DNA methylation. In this study, we used methylation-specific PCR (MSP) to analyse the methylation status in two regions of the CXCL12 promoter and ESR1 in tumour cell lines and in primary breast tumour samples, and correlated our results with clinicopathological data.     

Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>

Background  

Uterine sarcomas are very rare malignancies with no approved chemotherapy protocols. Histone deacetylase (HDAC) inhibitors belong to the most promising groups of compounds for molecular targeting therapy. Here, we described the antitumor effects of suberoylanilide hydroxamic acid (SAHA; vorinostat) on MES-SA uterine sarcoma cells in vitro and in vivo. We investigated effects of vorinostat on growth and colony forming ability by using uterine sarcoma MES-SA cells. We analyzed the influence of vorinostat on expression of different HDACs, p21^WAF1 and activation of apoptosis. Finally, we examined the antitumor effects of vorinostat on uterine sarcoma in vivo.     

<Emphasis Type="Italic">FLT3</Emphasis>mutation incidence and timing of origin in a population case series of pediatric leukemia

Background  

Mutations in FLT3 result in activated tyrosine kinase activity, cell growth stimulation, and a poor prognosis among various subtypes of leukemia. The causes and timing of the mutations are not currently known. We evaluated the prevalence and timing of origin of FLT3 mutations in a population series of childhood leukemia patients from Northern California.     

Conjugation of chlorin <Emphasis Type="Italic">p</Emphasis><Subscript>6</Subscript> to histamine enhances its cellular uptake and phototoxicity in oral cancer cells

Purpose  

Our previous studies in hamster cheek pouch model have shown that chlorin p ₆ (Cp ₆), a chlorophyll derivative is a suitable photosensitizer for photodynamic treatment (PDT) of small tumors (<5 mm). However, for bigger tumors, the accumulation of Cp ₆ was inadequate, which compromised the effectiveness of PDT. The purpose of present study was to investigate the possibility of improving the cellular uptake of Cp ₆ by conjugating it to histamine, a biogenic amine that is known to modulate tumor growth and development via cell surface receptors.     

Anti-proliferative effects of <Emphasis Type="Italic">Bifidobacterium adolescentis</Emphasis> SPM0212 extract on human colon cancer cell lines

Background  

Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of Bifidobacterium adolescentis isolated from healthy young Koreans.     

Differential expression and role of p21<Superscript>cip/waf1</Superscript> and p27<Superscript>kip1</Superscript> in TNF-α-induced inhibition of proliferation in human glioma cells

Background  

The role of TNF-α in affecting the fate of tumors is controversial, while some studies have reported apoptotic or necrotic effects of TNF-α, others provide evidence that endogenous TNF-α promotes growth and development of tumors. Understanding the mechanism(s) of TNF-α mediated growth arrest will be important in unraveling the contribution of tissue associated macrophages in tumor resistance. The aim of this study was to investigate the role of Cyclin Dependent Kinase Inhibitors (CDKI) – p21^cip/waf1 and p27^kip1 in TNF-α mediated responses in context with p53 and activation of NF-κB and Akt pathways. The study was done with human glioma cell lines -LN-18 and LN-229 cells, using monolayer cultures and Multicellular Spheroids (MCS) as in vitro models.     

The -786T>C promoter polymorphism of the <Emphasis Type="Italic">NOS3</Emphasis>gene is associated with prostate cancer progression

Background  

There is no biological or epidemiological data on the association between NOS3 promoter polymorphisms and prostate cancer. The polymorphisms in the promoter region of NOS3 gene may be responsible for variations in the plasma NO, which may promote cancer progression by providing a selective growth advantage to tumor cells by angiogenic stimulus and by direct DNA damage.     

An experimental study on cervix cancer with combination of HSV-TK/GCV suicide gene therapy system and <Superscript>60</Superscript>Co radiotherapy

Background  

To evaluate the killing effect of HSV-TK/GCV suicide gene therapy system combined with ⁶⁰Co radiotherapy on human cervical cancer Hela cell line in vitro and in vivo, and to explore the radiosensitization by HSV-TK/GCV system.     

<Emphasis Type="Italic">In vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> anticancer properties of a <Emphasis Type="Italic">Calcarea carbonica</Emphasis> derivative complex (M8) treatment in a murine melanoma model

Background  

Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have had only marginal success. Previous studies in mice demonstrated that a high diluted complex derived from Calcarea carbonica (M8) stimulated the tumoricidal response of activated lymphocytes against B16F10 melanoma cells in vitro.