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.     

Antitumor activity and mechanisms of action of total glycosides from aerial part of <Emphasis Type="Italic">Cimicifuga dahurica</Emphasis> targeted against hepatoma

Background  

Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of Cimicifuga dahurica showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of C. dahurica and therefore might eventually be useful in the prevention or treatment of Hepatoma.     

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.     

<Emphasis Type="Italic">BRAF</Emphasis>/K-<Emphasis Type="Italic">ras</Emphasis> mutation,microsatellite instability,and promoter hypermethylation of <Emphasis Type="Italic">hMLH1</Emphasis>/<Emphasis Type="Italic">MGMT</Emphasis> in human gastric carcinomas

Background The BRAF and K-ras genes are the most frequently mutated oncogenes in various human malignancies. We examined BRAF and K-ras mutations in human gastric cancer, and investigated their relationship with microsatellite instability (MSI) and the hypermethylation of promoter regions in hMLH1 and O ⁶ -methylguanine DNA methyltransferase (MGMT).Methods Sixteen gastric cancer cell lines and 62 gastric cancer tissue samples were screened for BRAF and K-ras mutations by direct sequencing. We also performed a microsatellite assay and investigated methylation status in the promoter regions of hMLH1 and MGMT.Results mutation was not found in any of the cancer cell lines examined. One (1.6%) cancer tissue sample showed a point mutation in the BRAF gene (GT_G GA_G; V599E). K-ras mutation (GG_T GA_T, G12D) was detected in five (31%) gastric cancer cell lines and in 1 (1.6%) gastric cancer tissue sample. In the gastric cancer tissue samples examined, MSI was detected in 23 (37%) samples. Hypermethylated promoter regions in hMLH1 and MGMT, respectively, were detected in 6 (10%) and 13 (21%) gastric cancer tissue samples. Microsatellite stable (MSS) tumors showed frequent lymphatic invasion (P = 0.050).Conclusion Although BRAF mutation has been reported in a variety of other human cancers, it is a rare event in the carcinogenesis and progression/development of gastric cancer.     

<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.     

<Emphasis Type="Italic">MGMT</Emphasis> promoter methylation,loss of expression and prognosis in 855 colorectal cancers

Objective  

O ⁶-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme. MGMT promoter hypermethylation and epigenetic silencing often occur as early events in carcinogenesis. However, prognostic significance of MGMT alterations in colorectal cancer remains uncertain.     

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.     

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">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.     

<Emphasis Type="Italic">CDKN1C</Emphasis>/p57<Superscript>kip2</Superscript>is a candidate tumor suppressor gene in human breast cancer

Background  

CDKN1C (also known as p57^KIP2) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21^CIP1 and B/p27^KIP1) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo.     

Phosphorylation of Ser<Superscript>78</Superscript> of Hsp27 correlated with HER-2/<Emphasis Type="Italic">neu</Emphasis> status and lymph node positivity in breast cancer

Background  

Abnormal amplification/expression of HER-2/neu oncogene has been causally linked with tumorigenesis and metastasis in breast cancer and associated with shortened overall survival of patients. Recently, heat shock protein 27 (Hsp27) was reported to be highly expressed in HER-2/neu positive tumors and cell lines. However, putative functional links between phosphorylation of Hsp27 with HER-2/neu status and other clinicopathological features remain to be elucidated.     

<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.     

<Emphasis Type="Italic">In vitro</Emphasis> cytotoxicity of novel platinum-based drugs and dichloroacetate against lung carcinoid cell lines

Introduction  

Chemotherapy for advanced well-differentiated carcinoids is characterised by low response rates and short duration of responses. The present study aimed to assess the in vitro activity of novel platinum-based chemotherapeutic drugs in combination with dichloroacetate (DCA), a sensitiser to apoptosis, against lung carcinoid cell lines.     

Impact of <Emphasis Type="Italic">UGT2B7</Emphasis><Superscript><Emphasis Type="Italic">His268Tyr</Emphasis></Superscript> polymorphism on the outcome of adjuvant epirubicin treatment in breast cancer

Introduction  

Epirubicin is a common adjuvant treatment for breast cancer. It is mainly eliminated after glucuronidation through uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7). The present study aimed to describe the impact of the UGT2B7 ^His268Tyr polymorphism on invasive disease-free survival in breast cancer patients after epirubicin treatment.     

Methylation screening of the <Emphasis Type="Italic">TGFBI</Emphasis> promoter in human lung and prostate cancer by methylation-specific PCR

Background  

Hypermethylation of the TGFBI promoter has been shown to correlate with decreased expression of this gene in human tumor cell lines. In this study, we optimized a methylation-specific polymerase chain reaction (MSP) method and investigated the methylation status of the TGFBI promoter in human lung and prostate cancer specimens.     

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.     

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.     

Silencing of the <Emphasis Type="Italic">XAF1</Emphasis> gene by promoter hypermethylation in cancer cells and reactivation to TRAIL-sensitization by IFN-β

Background  

XIAP-associated factor 1 (XAF1) is a putative tumor suppressor that exerts its proapoptotic effects through both caspase-dependent and – independent means. Loss of XAF1 expression through promoter methylation has been implicated in the process of tumorigenesis in a variety of cancers. In this report, we investigated the role of basal xaf1 promoter methylation in xaf1 expression and assessed the responsiveness of cancer cell lines to XAF1 induction by IFN-β.     

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.