Animals ; Humans ; MicroRNAs ; genetics ; Neoplasms ; genetics ; pathology ; RNA Interference ; RNA, Neoplasm ; genetics ; RNA, Small Interfering ; genetics

Alternative splicing of pre-mRNA is an important mechanism for regulating gene function at the post-transcription level and for producing proteomic diversity in higher eukaryotes. The alternative splicing is regulated by the interaction between diverse cis-acting elements and trans-acting factors. Alternative splicing events of oncogenes, tumor suppressor genes and metastasis suppressor genes are associated with the initiation and development of human neoplasms. The protein isoforms sourced from alternative splicing take part in regulating the gene transcription, cell cycle, apoptosis of cells, and playing a role in tumor growth. It is possible for molecular therapy to target directly isoforms of protein produced by alternative splicing or to interfere with the process of alternative splicing.
Alternative Splicing ; genetics ; Humans ; Neoplasms ; genetics ; RNA Precursors ; metabolism ; RNA, Neoplasm ; analysis ; Transcription, Genetic

OBJECTIVE: This study was to determine the expression of Toll-like receptor 4 (TLR-4) in ovarian serous adenocarcinoma tissues. METHODS: TLR-4 expression was evaluated at the RNA level by real-time quantitative RT-PCR, in 24 fresh frozen ovarian serous adenocarcinoma tissues and 9 normal ovarian tissues. TLR-4 expression was also evaluated by immunohistochemistry (IHC) in each three ovarian carcinoma tissues and normal ovarian tissues. RESULTS: Positive immunoreactivity for TLR-4 was observed in the normal ovarian tissues but not in the ovarian carcinoma tissues. The staining was localized in the cytoplasm as well as on the cell surface. Real-time quantitative RT-PCR revealed that TLR-4 expression was significantly lower in tumors than in normal ovarian tissues (p=0.0003). There were no significant correlations between clinical parameters and the expression level of TLR-4 mRNA in ovarian serous adenocarcinomas. However, tumors without LN metastasis (p=0.068) and lower grade (p=0.075) showed trends of higher TLR-4 mRNA expression. CONCLUSION: TLR-4 expression was significantly lower in ovarian serous adenocarcinoma tissues than in normal ovarian tissues, and further studies on TLR-4 signaling pathway in ovarian carcinoma are needed.
Adenocarcinoma ; Cytoplasm ; Immunohistochemistry ; Neoplasm Metastasis ; Ovarian Neoplasms* ; RNA ; RNA, Messenger ; Toll-Like Receptor 4

Actinomyces meyeri is rarely isolated in cases of actinomycosis. The identification of A. meyeri had historically been difficult and unreliable. With the recent development of 16S ribosomal RNA (16S rRNA) sequencing, Actinomyces species such as A. meyeri can be isolated much more reliably. A. meyeri often causes disseminated disease, which can be secondary to frequent pulmonary infections. A penicillin-based regimen is the mainstay of A. meyeri treatment, with a prolonged course usually required. Here, we report a case of pulmonary actinomycosis with brain abscess caused by A. meyeri that was initially thought to represent lung cancer with brain metastasis.
Actinomyces* ; Actinomycosis ; Brain Abscess ; Brain* ; Lung Neoplasms ; Lung* ; Neoplasm Metastasis ; RNA ; RNA, Ribosomal, 16S ; Sequence Analysis

PURPOSE: Despite advances in the treatment of cancer, recurrence and metastasis continue to pose major problems in clinical mamagement. Recently, molecular based peripheral blood assay using the reverse transcriptase-polymerase chain reaction(RT-PCR) has been shown to be highly sensitive molecular staging modality for detecting extraprostatic disease pre-and post-operatively. The assay uses primers those are specific for prostate specific antigen(PSA) and prostate specific membrane antigen(PSMA). MATERIALS AND METHODS: We compared the application of RT-PCR assay for PSA versus PSMA. These assays were applied to ribonucleic acids extracts from the peripheral blood lymphocyte fraction of 29 patients with metastaic prostate cancer, in which, 13 cases were non neoadjuvant hormonal therapy(NHT) group. In addition, blood specimens from 5 clinically localized cancer were tested. RESULTS: Of 13 metastatic untreated patients 6 had positive for PSA, while 10 cases had positive results for PSMA. Among the 16 patients with hormone treated metastatic cancer patients, 8 (50%) had positive for PSMA while only 1 had positive for PSA. Of 5 localized prostatic cancer, only 1 had positive result just for PSMA. In neoadjuvant hormone treated group, marked reduction in incidence of positive RT-PCR for PSA was noted. An additional explanation is that PSMA may be expressed in hormone refractory cancer. CONCLUSIONS: Presently RT-PCR assay using PSMA is highly sensitive and more accurate than PSA RT-PCR for predicting micrometastasis. We are continuing to increase our patient number and may increase our ability to detect early localized cancer using a molecular approach.
Humans ; Incidence ; Lymphocytes ; Membranes ; Neoplasm Metastasis ; Neoplasm Micrometastasis* ; Prostate ; Prostatic Neoplasms* ; Recurrence ; RNA

OBJECTIVETo investigate the expression of prostaglandin transporter (PGT) in colorectal cancer (CRC) tissues and its relationship with clinicopathological features.

METHODSThe mRNA and protein levels of PGT were determined by real-time PCR, Western blot and immunohistochemical methods in cancer tissues and adjacent normal tissue from 80 patients with colorectal cancer and their relationship with clinicopathological features was analyzed.

RESULTSCompared with the adjacent normal tissue of colorectal cancer, the PGT mRNA relative expression (0.57 ± 0.33 vs. 2.33 ± 1.20) and the PGT protein expression in cancer tissues decreased significantly [PGT/GAPDH 0.45 ± 0.16 vs. 0.78 ± 0.23, integral A 718.7 ± 359.4 vs. 10412.0 ± 6423.3, average A 0.03 ± 0.01 vs. 0.12 ± 0.09, all P<0.01]. Lower mRNA and protein expressions of PGT in colorectal cancer were associated with depth of invasion T3 to T4 and TNM stage III( to IIII( (P<0.01), while not associated with gender, age, tumor location and differentiation degree (all P>0.05).

CONCLUSIONExpression levels of PGT mRNA and protein in colorectal cancer tissue are significantly down-regulation. PGT expression is associated with invasion depth and late stages.

OBJECTIVEThe aim of this review was to assess RNA interference (RNAi) and its possibility as a potential and powerful tool to develop highly specific double-stranded RNA (dsRNA) or small interfering RNA (siRNA) based gene-silencing therapeutics.

DATA SOURCESThe data used in this review were obtained from the current RNAi-related research reports.

STUDY SELECTIONdsRNA-mediated RNAi has recently emerged as a powerful reverse genetic tool to silence gene expression in multiple organisms. The discovery that synthetic duplexes of 21 nucleotides siRNAs trigger gene-specific silencing in mammalian cells has further expanded the utility of RNAi in to the mammalian system.

DATA EXTRACTIONThe currently published papers reporting the discovery and mechanism of RNAi phenomena and application of RNAi on gene function in mammalian cells were included.

DATA SYNTHESISSince the recent development of RNAi technology in the mammalian system, investigators have used RNAi to elucidate gene function, and to develop gene-based therapeutics by delivery exogenous siRNA or siRNA expressing vector. The general and sequence-specific inhibitory effects of RNAi that will be selective, long-term, and systemic to modulate gene targets mentioned in similar reports have caused much concern about its effectiveness in mammals and its eventual use as a therapeutic mordality.

CONCLUSIONSIt is certain that the ability of RNAi in mammals to silence specific genes, either when transfected directly as siRNAs or when generated from DNA vectors, will undoubtedly accelerate the study of gene function and might also be used as a potentially useful method to develop highly gene-specific therapeutic methods. It is also expected that RNAi might one day be used to treat human diseases.

PURPOSE: The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility. MATERIALS AND METHODS: We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical. RESULTS: Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41–2.72; P < 0.001) and 2.54 (95% CI, 1.84–3.50; P < 0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P < 0.001). CONCLUSIONS: The pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.
Biology ; Classification ; Cohort Studies ; Gastrectomy ; Humans ; Neoplasm Metastasis ; Neoplasm Staging* ; Pliability ; Prognosis ; RNA, Messenger ; Stomach Neoplasms*

After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis. To develop therapeutic strategies targeting RBPs, RNA interference-based oligonucleotides or small molecule inhibitors have been screened based on reduced RBP-RNA interaction and changed level of target RNAs. Identification of binding RNAs with high-throughput techniques and integral analysis of multiple datasets will help us develop new therapeutic drugs or prognostic biomarkers for human cancers.
Apoptosis ; Biomarkers ; Carcinogenesis ; Cell Proliferation ; Chemoprevention ; Dataset ; Epigenomics ; Humans ; Neoplasm Metastasis ; Oligonucleotides ; Protein Processing, Post-Translational ; RNA* ; RNA-Binding Proteins*

MicroRNAs (miRNAs) are small non-coding RNAs that mediate gene expression at the post-transcriptional level by degrading or repressing targeted mRNAs. These molecules are about 21-25 nucleotides in length and exert their effects by binding to partially complementary sites in mRNAs, predominantly in the 3'-untranslated region (3'-UTR). Recent evidence has demonstrated that miRNAs can function as oncogenes or tumor suppressors through the modulation of multiple oncogenic cellular processes in cancer development, including initiation, cell proliferation, apoptosis, invasion and metastasis. In our present study, we examined the expression profile of miRNAs related to oral cancer cell growth inhibition using normal human oral keratinocytes (NHOK) and YD-38 human oral cancer cells. By miRNA microassay analysis, 40 and 31 miRNAs among the 1,769 examined were found to be up- and down-regulated in YD-38 cells compared with NHOK cells, respectively. Using qRT-PCR analysis, the expression levels of miR-30a and miR-1246 were found to be increased in YD-38 cells compared with NHOK cells, whereas miR-203 and miR-125a were observed to be decreased. Importantly, the overexpression of miR-203 and miR-125a significantly inhibited the growth of YD-38 cells. This finding and the microarray data indicate the involvement of specific miRNAs in the development and progression of oral cancer.
Apoptosis ; Cell Proliferation ; Gene Expression ; Humans ; Keratinocytes ; MicroRNAs ; Mouth Neoplasms ; Neoplasm Metastasis ; Nucleotides ; Oncogenes ; RNA, Messenger ; RNA, Small Untranslated