Diffuse-type gastric cancer (DGC) exhibits rapid disease progression and a poor prognosis. There are no effective serum biomarkers for early detection of DGC. We have established an E-cadherin/p53 ...double conditional knockout (DCKO) mouse line that recapitulates human DGC morphologically and molecularly. In this study we tried to identify circulating microRNAs (miRNAs) as non-invasive biomarkers for DGC diagnosis using DCKO mice.
We performed miRNA microarray and quantitative reverse transcription-PCR analyses of tissue and serum samples from DCKO mice with DGC and age-matched littermate controls.
Comparative analyses showed that mouse and human primary gastric cancers have similar miRNA expression patterns. Next, we selected some candidate miRNAs highly expressed in sera and cancer tissues of DCKO mice for further evaluation. TaqMan quantitative RT-PCR analyses indicated that four of them, miR-103, miR-107, miR-194 and miR-210, were significantly upregulated in sera of both early and advanced-stage DGC-bearing mice compared with in corresponding controls. Receiver-operating characteristic curve analyses demonstrated that these four miRNAs can discriminate DGC-positive cases from normal ones with high sensitivity and specificity.
These observations suggest that this mouse model of DGC is useful for identifying serum biomarkers, and we found circulating miRNAs that can accurately detect DGC at an early stage.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Tongue squamous cell carcinoma (TSCC) is highly diverse, even in its early stages. This cancer is classified into three subtypes (superficial, exophytic, and endophytic) based on macroscopic ...appearance. Of these subtypes, the endophytic tumours have the worst prognosis because of their invasiveness and higher frequency of metastasis.
To understand the molecular mechanism underlying the endophytic subtype and to identify biomarkers, we performed a comprehensive gene expression microarray analysis of clinical biopsy samples and also confirmed the clinical relevance of differential gene expression.
Expression of the parvin-beta (PARVB) gene and its encoded protein was significantly upregulated in endophytic-type TSCC. PARVB is known to play a critical role in actin reorganization and focal adhesions. Knockdown of PARVB expression in vitro caused apparent decreases in cell migration and wound healing, implying that PARVB has a crucial role in cell motility. Moreover, metastasis-free survival was significantly lower in patients with higher tumour expression of PARVB.
These findings suggest that PARVB overexpression is a candidate biomarker for endophytic tumours and metastasis. This protein may be a clinically useful target for adjuvant TSCC therapy.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Intracellular phosphoprotein activation significantly regulates cancer progression. However, the significance of circulating phosphoproteins in the blood remains unknown. We investigated the serum ...phosphoprotein profile involved in pancreatic cancer (PaCa) by a novel approach that comprehensively measured serum phosphoproteins levels, and clinically applied this method to the detection of PaCa.
We analysed the serum phosphoproteins that comprised cancer cellular signal pathways by comparing sera from PaCa patients and benign controls including healthy volunteers (HVs) and pancreatitis patients.
Hierarchical clustering analysis between PaCa patients and HVs revealed differential pathway-specific profiles. In particular, the components of the extracellular signal-regulated kinase (ERK) signalling pathway were significantly increased in the sera of PaCa patients compared with HVs. The positive rate of p-ERK1/2 (82%) was found to be superior to that of CA19-9 (53%) for early stage PaCa. For the combination of these serum levels, the area under the receiver-operator characteristics curves was showing significant ability to distinguish between the two populations in independent validation set, and between cancer and non-cancer populations in another validation set.
The comprehensive measurement of serum cell signal phosphoproteins is useful for the detection of PaCa. Further investigations will lead to the implementation of tailor-made molecular-targeted therapeutics.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Advanced LIGO detectors have recently completed their second observation run successfully. The run lasted for approximately 10 months and led to multiple new discoveries. The sensitivity to ...gravitational waves was partially limited by laser noise. Here, we utilize auxiliary sensors that witness these correlated noise sources, and use them for noise subtraction in the time domain data. This noise and line removal is particularly significant for the LIGO Hanford Observatory, where the improvement in sensitivity is greater than 20%. Consequently, we were also able to improve the astrophysical estimation for the location, masses, spins, and orbital parameters of the gravitational wave progenitors.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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