Analysis of large deletions in <Emphasis Type="Italic">BRCA1</Emphasis>, <Emphasis Type="Italic">BRCA2</Emphasis> and <Emphasis Type="Italic">PALB2</Emphasis> genes in Finnish breast and ovarian cancer families

Background  

BRCA1 and BRCA2 are the two most important genes associated with familial breast and ovarian cancer susceptibility. In addition, PALB2 has recently been identified as a breast cancer susceptibility gene in several populations. Here we have evaluated whether large genomic rearrangement in these genes could explain some of Finnish breast and/or ovarian cancer families.     

<Emphasis Type="Italic">BRAF</Emphasis>, <Emphasis Type="Italic">KRAS</Emphasis> and <Emphasis Type="Italic">PIK3CA</Emphasis> mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?

Background  

BRAF, KRAS and PIK3CA mutations are frequently found in sporadic colorectal cancer (CRC). In contrast to KRAS and PIK3CA mutations, BRAF mutations are associated with tumours harbouring CpG Island methylation phenotype (CIMP), MLH1 methylation and microsatellite instability (MSI). We aimed at determine the frequency of KRAS, BRAF and PIK3CA mutations in the process of colorectal tumourigenesis using a series of colorectal polyps and carcinomas. In the series of polyps CIMP, MLH1 methylation and MSI were also studied.     

Role of nitric oxide in <Emphasis Type="Italic">Salmonella typhimurium</Emphasis>-mediated cancer cell killing

Background  

Bacterial targeting of tumours is an important anti-cancer strategy. We previously showed that strain SL7838 of Salmonella typhimurium targets and kills cancer cells. Whether NO generation by the bacteria has a role in SL7838 lethality to cancer cells is explored. This bacterium has the mechanism for generating NO, but also for decomposing it.     

<Emphasis Type="Italic">LIMD1</Emphasis> is more frequently altered than <Emphasis Type="Italic">RB1</Emphasis> in head and neck squamous cell carcinoma: clinical and prognostic implications

Introduction  

To understand the role of two interacting proteins LIMD1 and pRB in development of head and neck squamous cell carcinoma (HNSCC), alterations of these genes were analyzed in 25 dysplastic head and neck lesions, 58 primary HNSCC samples and two HNSCC cell lines.     

Cathepsin B inhibition interferes with metastatic potential of human melanoma: an <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis> study

Background  

Cathepsins represent a group of proteases involved in determining the metastatic potential of cancer cells. Among these are cysteinyl- (e.g. cathepsin B and cathepsin L) and aspartyl-proteases (e.g. cathepsin D), normally present inside the lysosomes as inactive proenzymes. Once released in the extracellular space, cathepsins contribute to metastatic potential by facilitating cell migration and invasiveness.     

Genetic polymorphisms of <Emphasis Type="Italic">RANTES,IL1-A,MCP-1</Emphasis> and <Emphasis Type="Italic">TNF-A</Emphasis> genes in patients with prostate cancer

Background  

Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk.     

Comprehensive analysis of <Emphasis Type="Italic">NuMA</Emphasis>variation in breast cancer

Background  

A recent genome wide case-control association study identified NuMA region on 11q13 as a candidate locus for breast cancer susceptibility. Specifically, the variant Ala794Gly was suggested to be associated with increased risk of breast cancer.     

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.     

Genetic variability in <Emphasis Type="Italic">CYP3A4</Emphasis> and <Emphasis Type="Italic">CYP3A5</Emphasis>in primary liver,gastric and colorectal cancer patients

Background  

Drug-metabolizing enzymes play a role in chemical carcinogenesis through enzymatic activation of procarcinogens to biologically reactive metabolites. The role of gene polymorphisms of several cytochrome P450 enzymes in digestive cancer risk has been extensively investigated. However, the drug-metabolizing enzymes with the broader substrate specificity, CYP3A4 and CYP3A5, have not been analyzed so far. This study aims to examine associations between common CYP3A4 and CYP3A5 polymorphisms and digestive cancer risk.     

High resolution melting analysis for rapid and sensitive <Emphasis Type="Italic">EGFR</Emphasis> and <Emphasis Type="Italic">KRAS</Emphasis> mutation detection in formalin fixed paraffin embedded biopsies

Background  

Epithelial growth factor receptor (EGFR) and KRAS mutation status have been reported as predictive markers of tumour response to EGFR inhibitors. High resolution melting (HRM) analysis is an attractive screening method for the detection of both known and unknown mutations as it is rapid to set up and inexpensive to operate. However, up to now it has not been fully validated for clinical samples when formalin-fixed paraffin-embedded (FFPE) sections are the only material available for analysis as is often the case.     

<Emphasis Type="Italic">GSTT2</Emphasis> promoter polymorphisms and colorectal cancer risk

Background  

Glutathione S -transferases are a group of enzymes that participate in detoxification and defense mechanisms against toxic carcinogens and other compounds. These enzymes play an important role in human carcinogenesis. In the present study, we sought to determine whether GSTT2 promoter single nucleotide polymorphisms (SNPs) are associated with colorectal cancer risk.     

The immunomodulator PSK induces <Emphasis Type="Italic">in vitro</Emphasis> cytotoxic activity in tumour cell lines <Emphasis Type="Italic">via</Emphasis> arrest of cell cycle and induction of apoptosis

Background  

Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated.     

A novel circular invasion assay mimics <Emphasis Type="Italic">in vivo</Emphasis> invasive behavior of cancer cell lines and distinguishes single-cell motility <Emphasis Type="Italic">in vitro</Emphasis>

Background  

Classical in vitro wound-healing assays and other techniques designed to study cell migration and invasion have been used for many years to elucidate the various mechanisms associated with metastasis. However, many of these methods are limited in their ability to achieve reproducible, quantitative results that translate well in vivo. Such techniques are also commonly unable to elucidate single-cell motility mechanisms, an important factor to be considered when studying dissemination. Therefore, we developed and applied a novel in vitro circular invasion assay (CIA) in order to bridge the translational gap between in vitro and in vivo findings, and to distinguish between different modes of invasion.     

Mutation analysis of the <Emphasis Type="Italic">MDM4</Emphasis>gene in German breast cancer patients

Background  

MDM4 is a negative regulator of p53 and cooperates with MDM2 in the cellular response to DNA damage. It is unknown, however, whether MDM4 gene alterations play some role in the inherited component of breast cancer susceptibility.     

Prodrug converting enzyme gene delivery by <Emphasis Type="Italic">L. monocytogenes</Emphasis>

Background  

Listeria monocytogenes is a highly versatile bacterial carrier system for introducing protein, DNA and RNA into mammalian cells. The delivery of tumor antigens with the help of this carrier into tumor-bearing animals has been successfully carried out previously and it was recently reported that L. monocytogenes is able to colonize and replicate within solid tumors after local or even systemic injection.     

No influence of the polymorphisms <Emphasis Type="Italic">CYP2C19</Emphasis> and <Emphasis Type="Italic">CYP2D6</Emphasis> on the efficacy of cyclophosphamide,thalidomide, and bortezomib in patients with Multiple Myeloma

Background  

The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment.     

Mouse <Emphasis Type="Italic">Rad1</Emphasis> deletion enhances susceptibility for skin tumor development

Background  

Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. The Rad1 protein, evolutionarily conserved from yeast to humans, exists in cells as monomer as well as a component in the 9-1-1 protein complex. Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown.     

Gene expression deregulation by <Emphasis Type="Italic">KRAS</Emphasis> G12D and G12V in a <Emphasis Type="Italic">BRAF</Emphasis> V600E context

Background  

KRAS and BRAF mutations appear of relevance in the genesis and progression of several solid tumor types but the co-occurrence and interaction of these mutations have not yet been fully elucidated. Using a microsatellite stable (MSS) colorectal cancer (CRC) cell line (Colo741) having mutated BRAF and KRAS ^WT , we also aimed to investigate the KRAS-BRAF interaction. Gene expression profiles for control KRAS ^WT , KRAS ^G12V and KRAS ^G12D transfected cells were obtained after cell clone selection and RT-PCR screening. Extensive qPCR was performed to confirm microarray data.     

Polymorphisms in the cytochrome <Emphasis Type="Italic">P</Emphasis>450 genes <Emphasis Type="Italic">CYP1A2, CYP1B1, CYP3A4, CYP3A5, CYP11A1, CYP17A1</Emphasis>, <Emphasis Type="Italic">CYP19A1</Emphasis>and colorectal cancer risk

Background  

Cytochrome P 450 (CYP) enzymes have the potential to affect colorectal cancer (CRC) risk by determining the genotoxic impact of exogenous carcinogens and levels of sex hormones.