Development and external validation of a novel nomogram for predicting cancer-specific survival in patients with ascending colon adenocarcinoma after surgery: a population-based study.

BACKGROUND: This study aimed to develop and validate a novel nomogram to predict the cancer-specific survival (CSS) of patients with ascending colon adenocarcinoma after surgery. METHODS: Patients with ascending colon adenocarcinoma were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2015 and randomly divided into a training set (5930) and a validation set (2540). The cut-off values for age, tumour size and lymph node ratio (LNR) were calculated via X-tile software. In the training set, independent prognostic factors were identified using univariate and multivariate Cox analyses, and a nomogram incorporating these factors was subsequently built. Data from the validation set were used to assess the reliability and accuracy of the nomogram and then compared with the 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system. Furthermore, external validation was performed from a single institution in China. RESULTS: A total of 8470 patients were enrolled from the SEER database, 5930 patients were allocated to the training set, 2540 were allocated to the internal validation set and a separate set of 473 patients was allocated to the external validation set. The optimal cut-off values of age, tumour size and lymph node ratio were 73 and 85, 33 and 75 and 4.9 and 32.8, respectively. Univariate and multivariate Cox multivariate regression revealed that age, AJCC 8th edition T, N and M stage, carcinoembryonic antigen (CEA), tumour differentiation, chemotherapy, perineural invasion and LNR were independent risk factors for patient CSS. The nomogram showed good predictive ability, as indicated by discriminative ability and calibration, with C statistics of 0.835 (95% CI, 0.823-0.847) and 0.848 (95% CI, 0.830-0.866) in the training and validation sets and 0.732 (95% CI, 0.664-0.799) in the external validation set. The nomogram showed favourable discrimination and calibration abilities and performed better than the AJCC TNM staging system. CONCLUSIONS: A novel validated nomogram could effectively predict patients with ascending colon adenocarcinoma after surgery, and this predictive power may guide clinicians in accurate prognostic judgement.

USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling.

Ubiquitination and deubiquitination are important post-translational regulatory mechanisms responsible for fine tuning the antiviral signaling. In this study, we identified a deubiquitinase, the ubiquitin-specific peptidase 7/herpes virus associated ubiquitin-specific protease (USP7/HAUSP) as an important negative modulator of virus-induced signaling. Overexpression of USP7 suppressed Sendai virus and polyinosinic-polycytidylic acid and poly(deoxyadenylic-deoxythymidylic)-induced ISRE and IFN-ß activation, and enhanced virus replication. Knockdown or knockout of endogenous USP7 expression had the opposite effect. Coimmunoprecipitation assays showed that USP7 physically interacted with tripartite motif (TRIM)27. This interaction was enhanced after SeV infection. In addition, TNF receptor-associated factor family member-associated NF-kappa-B-binding kinase (TBK)-1 was pulled down in the TRIM27-USP7 complex. Overexpression of USP7 promoted the ubiquitination and degradation of TBK1 through promoting the stability of TRIM27. Knockout of endogenous USP7 led to enhanced TRIM27 degradation and reduced TBK1 ubiquitination and degradation, resulting in enhanced type I IFN signaling. Our findings suggest that USP7 acts as a negative regulator in antiviral signaling by stabilizing TRIM27 and promoting the degradation of TBK1.-Cai, J., Chen, H.-Y., Peng, S.-J., Meng, J.-L., Wang, Y., Zhou, Y., Qian, X.-P., Sun, X.-Y., Pang, X.-W., Zhang, Y., Zhang, J. USP7-TRIM27 axis negatively modulates antiviral type I IFN signaling.

Circulating tumour cells predict survival in gastric cancer patients: a meta-analysis.

AIM OF THE STUDY: The prognostic value of the detection of circulating tumour cells (CTCs) in gastric cancer has been studied intensely in recent years. However, the application of different technologies led to inconsistent results between the studies. Here, we performed a meta-analysis of published studies to summarise the evidence. MATERIAL AND METHODS: Medline and ISI Web of Knowledge were searched up to March 2013 using "circulating tumor cells" and "gastric cancer" as search terms. Hazard ratio (HR) with 95% confidence intervals (CIs) for prognostic outcomes and clinical characteristics were extracted from each study. Pooled hazard ratios (HR) and odds ratios (OR) were calculated using random or fixed-effects models. RESULTS: Twelve studies enrolling 774 patients were included. The combined HR estimate for overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were 1.41 (95% CI: 1.28-1.62), 2.99 (95% CI: 2.01-4.45) and 1.64 (95% CI: 1.02-2.62), respectively. Subgroup analysis concerning detection methods and sampling time showed that results of RT-PCR for the OS group and RT-PCR for the DFS group suggest a prognostic significance of CTC detection (pooled HR [95% CI]: 1.45 [1.28-1.65], I(2) = 38%, p = 0.13; 2.99 [2.01-4.45], I(2) = 0%, p = 0.32). In addition, results of the baseline CTC detection group also indicated a significant prognostic value to predict OS and DFS (pooled HR [95% CI]: 1.47 [1.19-1.82], I(2) = 38%, p = 0.14; 2.99 [2.01-4.45], I(2) = 0%, p = 0.32). We simultaneously found that the detection of CTCs correlated with pathological stage (pooled OR [95% CI]: 2.95 [1.65-5.28], I(2) = 56%, p = 0.03), lymph node status (pooled OR [95% CI]: 2.26 [1.50-3.41], I(2) = 37%, p = 0.09), the depth of invasion (pooled OR [95% CI]: 3.21 [1.38-7.43], I(2) = 72%, p = 0.002), and distant metastasis (pooled OR [95% CI]: 2.68 [1.25-5.73], I(2) = 43%, p = 0.15). CONCLUSIONS: Detection of CTCs is associated with poorer prognosis in gastric cancer patients.

An Analysis Regarding the Association Between DAZ Interacting Zinc Finger Protein 1 (DZIP1) and Colorectal Cancer (CRC).

Colorectal cancer (CRC) is the third most common malignant disease worldwide, and its incidence is increasing, but the molecular mechanisms of this disease are highly heterogeneous and still far from being fully understood. Increasing evidence suggests that fibrosis mediated by abnormal activation of fibroblasts based in the microenvironment is associated with a poor prognosis. However, the function and pathogenic mechanisms of fibroblasts in CRC remain unclear. Here, combining scrna-seq and clinical specimen data, DAZ Interacting Protein 1 (DZIP1) was found to be expressed on fibroblasts and cancer cells and positively correlated with stromal deposition. Importantly, pseudotime-series analysis showed that DZIP1 levels were up-regulated in malignant transformation of fibroblasts and experimentally confirmed that DZIP1 modulates activation of fibroblasts and promotes epithelial-mesenchymal transition (EMT) in tumor cells. Further studies showed that DZIP1 expressed by tumor cells also has a driving effect on EMT and contributes to the recruitment of more fibroblasts. A similar phenomenon was observed in xenografted nude mice. And it was confirmed in xenograft mice that downregulation of DZIP1 expression significantly delayed tumor formation and reduced tumor size in CRC cells. Taken together, our findings suggested that DZIP1 was a regulator of the CRC mesenchymal phenotype. The revelation of targeting DZIP1 provides a new avenue for CRC therapy.

Id1 expression promotes peripheral CD4+ T cell proliferation and survival upon TCR activation without co-stimulation.

Although the role of E proteins in the thymocyte development is well documented, much less is known about their function in peripheral T cells. Here we demonstrated that CD4 promoter-driven transgenic expression of Id1, a naturally occurring dominant-negative inhibitor of E proteins, can substitute for the co-stimulatory signal delivered by CD28 to facilitate the proliferation and survival of naïve CD4+ cells upon anti-CD3 stimulation. We next discovered that IL-2 production and NF-κB activity after anti-CD3 stimulation were significantly elevated in Id1-expressing cells, which may be, at least in part, responsible for the augmentation of their proliferation and survival. Taken together, results from this study suggest an important role of E and Id proteins in peripheral T cell activation. The ability of Id proteins to by-pass co-stimulatory signals to enable T cell activation has significant implications in regulating T cell immunity.

The expression of netrin-1 in the thymus and its effects on thymocyte adhesion and migration.

Netrin-1, a known axon guidance molecule, being a secreted laminin-related molecule, has been suggested to be involved in multiple physiological and pathological conditions, such as organogenesis, angiogenesis, tumorigenesis, and inflammation-mediated tissue injury. However, its function in thymocyte development is still unknown. Here, we demonstrate that Netrin-1 is expressed in mouse thymus tissue and is primarily expressed in thymic stromal cells, and the expression of Netrin-1 in thymocytes can be induced by anti-CD3 antibody or IL-7 treatment. Importantly, Netrin-1 mediates the adhesion of thymocytes, and this effect is comparable to or greater than that of fibronectin. Furthermore, Netrin-1 specifically promotes the chemotaxis of CXCL12. These suggest that Netrin-1 may play an important role in thymocyte development.

An Analysis Regarding the Association Between Proteasome (PSM) and Hepatocellular Carcinoma (HCC).

Background: The Proteasome (PSM) is a large multi-catalytic protease complex consisting of a 20S core particle and a 19S regulatory particle whose main function is to accept and degrade ubiquitinated substrates, are now considered as one of the potential regulators of tumor proliferation, and stemness maintenance. However, to date, studies on the relationship between PSM and hepatocellular carcinoma (HCC) are limited. Methods: This study used a bioinformatics approach combining validation experiments to investigate the biological mechanisms that may be related with PSM. A series of experiments in vivo and in vitro were performed to explore the function of the 26S proteasome non-ATPase regulatory subunit 13 (PSMD13) in HCC. Results: HCC patients can be divided into two clusters. Cluster 1 (C1) patients having a significantly worse prognosis than Cluster (C2). Two subtypes had significant differences in proliferation-related signaling. In particular, the frequency of TP53 mutation was significantly higher in C1 than in C2. In addition, PSM-associated genes were highly consistent with the expression of DNA repair-related signatures, suggesting a potential link between PSM and genomic instability. We also found that downregulation of PSMD13 expression significantly inhibited stemness of tumor cells and impaired the Epithelial mesenchymal transition (EMT) process. Finally, the correlation between the PSMD13 and Ki67 was found to be strong. Conclusion: PSM is a valid predictor of prognosis and therapeutic response in patients with HCC disease. Furthermore, PSMD13 may be a potential therapeutic target.

[Relationship between BRCA1 mRNA expression in tumor cells from malignant effusions and chemosensitivity to cisplatin in patients with metastatic malignant effusions].

OBJECTIVE: To explore the mRNA expression of breast cancer susceptibility gene 1 (BRCA1) in tumor cells isolated from malignant pleural and peritoneal effusions, and the predictive role of BRCA1 related to the efficacy of cisplatin-based chemotherapy. METHODS: Tumor cells were isolated from malignant pleural and peritoneal effusions of 31 cancer patients. The response of these tumor cells to cisplatin was determined by CCK8 assay. Real time quantitative RT-PCR was used to examine the BRCA1 mRNA level in the primary culture cancer cells. RESULTS: The expression level of BRCA1 mRNA was 0.618 (0.014 - 18.063) in primary culture tumor cells. The IC(50) of DDP was 2.809 µg/ml in the primary culture tumor cells (0.118 - 19.439 µg/ml). Both BRCA1 mRNA expression and the tumor cells IC(50) of DDP were not significantly related with patient age, gender, the type of primary tumor, whether to accept the chemotherapy and effusion type (P > 0.05). The level of BRCA1 mRNA was negatively correlated with the chemosensitivity in terms of IC(50) of cisplatin (P < 0.001). CONCLUSION: Assessment of expression level of BRCA1 mRNA may be useful in predicting the efficacy of cisplatin-based chemotherapy in patients with metastatic malignant effusions.

Developmental pathway of CD4+CD8- medullary thymocytes during mouse ontogeny and its defect in Aire-/- mice.

The newly generated single-positive (SP) thymocytes undergo further maturation in the thymic medulla before their emigration to the periphery. The present study was undertaken to validate a developmental program we proposed for CD4SP medullary thymocytes and to explore the mechanisms regulating this process. During mouse ontogeny, the emergence of different subsets of CD4SP thymocytes followed a strict temporal order from SP1 to SP4. Parallel to the transition in surface phenotype, a steady increase in function was observed. As further evidence, purified SP1 cells were able to sequentially give rise to SP2, SP3, and SP4 cells in intrathymic adoptive transfer and in culture. Notably, the development of CD4SP cells in the medulla seemed to be critically dependent on a functionally intact medullary epithelial cell compartment because Relb and Aire deficiency were found to cause severe blockage at the transition from SP3 to SP4. Taken together, this work establishes an ontogenetically and functionally relevant maturation program for CD4SP thymocytes. Precise dissection of this program should facilitate further inquiry into the molecular mechanisms governing normal thymocyte development and its disturbance in pathological conditions.

[Anti-angiogenic effect of vinorelbine in combination with cetuximab in vitro and in vivo].

OBJECTIVE: This experiment aims to study the anti-angiogenic ability of vinorelbine combined with cetuximab in vitro and in vivo. METHODS: Human lung adenocarcinoma A549 cells were used as control group. Proliferation of human umbilical vein endothelial cells (HUVEC) was assessed by MTT assay. Furthermore, we used Transwell chambers, capillary tube formation and flow cytometry to observe the effects of vinorelbine combined with cetuximab on HUVEC migration, tube formation and cell apoptosis, respectively. In addition, the anti-angiogenic ability of the drugs was checked using chicken chorioallantoic membrane (CAM) model. RESULTS: The inhibitory rate of HUVEC growth was 25.8%, 39.2%, 54.0% for vinorelbine at the concentration of 0.1 ng/ml, 0.4 ng/ml, and 0.8 ng/ml, respectively; that of 0.25 microg/ml cetuximab was 19.7%, and that of 0.1 ng/ml vinorelbine + 0.25 microg/ml cetuximab, 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab and 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 29.5%, 46.4%, 64.6%, respectively. The inhibitory rates of the drugs at the above mentioned combinations of migration and tube formation of HUVEC were 51.9%, 68.2%, 95.0%, respectively. The inhibitory rate of 0.1 ng/ml + 0.25 microg/ml cetuximab and 0.4 ng/ml vinorelbine + 0.25 microg/ml cetuximab on tube formation of HUVEC was 38.8% and 57.7%, respectively, showing a sub-additive effect, and that of combination of 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 78.9%, showing a synergistic effect. In addition, the apoptotic rate of HUVEC induced by 0.8 ng/ml vinorelbine + 0.25 microg/ml cetuximab was 59.9%, showing a synergistic effect. The in vivo experiment also showed that the combination of the two drugs had a synergistic anti-angiogenic effect. CONCLUSION: Both low dose vinorelbine and cetuximab have an anti-angiogenic effect in vitro and in vivo, and the combination of the two drugs has sub-additive or synergistic inhibitory effect on angiogenesis.

beta-Tubulin III mRNA expression and docetaxel sensitivity in non-small cell lung cancer.

PURPOSE: Despite the success of docetaxel as an anti-tumour agent, the inter-individual variability in drug response still poses a major impediment to further use of this agent in the treatment of cancer. Current knowledge about predictive biomarkers of docetaxel sensitivity in malignant effusions is poor. The aim of this study was to investigate the association between beta-tubulin III mRNA expression and chemosensitivity to docetaxel in metastatic malignant effusions. METHODS: Real-time quantitative PCR was used for analysis of beta-tubulin III mRNA expression in 37 malignant effusions collected prospectively. Viable tumour cells obtained from malignant effusions were tested for sensitivity to docetaxel using ATP-TCA assay. RESULTS: beta-tubulin III expression was inversely correlated with sensitivity to docetaxel in pleural effusions of NSCLC patients (P =0.022). The lower level of beta-tubulin III mRNA expression in malignant effusions was associated with higher chemosensitivity to docetaxel in NSCLC patients in vitro. No correlation was found between beta-tubulin III mRNA expression and docetaxel sensitivity in malignant effusions of gastric cancer patient. CONCLUSION: Our results demonstrated that beta-tubulin III mRNA expression level in malignant effusions, in which all cancer cells were metastatic, was correlated with docetaxel sensitivity in NSCLC. This highlights the potential role of biomarkers in malignant effusions in further customized chemotherapy.

[Prognostic significance of ERCC1 mRNA expression in patients with non-small cell lung cancer receiving platinum-based chemotherapy].

OBJECTIVE: To investigate the correlation of the mRNA expression level of excision repair cross-complementing group 1 (ERCC1) gene with clinicopathological parameters and clinical outcome in patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy. METHODS: The mRNA expression of ERCC1 in formalin-fixed paraffin-embedded primary tumor specimens was measured by real-time quantitative reverse transcriptase polymerase chain reaction. The association between ERCC1 expression levels and clinicopathological parameters in NSCLC patients was analyzed. RESULTS: The median value of ERCC1 mRNA expression level compared with beta-actin in tumor specimens of 61 NSCLC patients was 0.48. There was no correlation between ERCC1 expression and clinicopathological parameters. Patients with low expression of ERCC1 mRNA (less than 0.35, 0.28, respectively) had a significantly longer median time to progression (TTP) (14.3 vs. 8.0 months, P = 0.028) and overall survival (OS) (28.4 vs. 12.9 months, P = 0.0064) than those with high expression. Multivariate analysis showed that a low ERCC1 mRNA expression was an independent factor for OS. CONCLUSION: Our findings suggest that intratumoral ERCC1 mRNA expression level, although is uncorrelated with clinicopathological parameters, is an independent predictive marker for survival of the patients with NSCLC receiving platinum-based chemotherapy, and may provide critical information for personalized chemotherapy.

[Tumor associated antigen CHP2 promotes intraperitoneal metastasis of HEK293 cells in nude mice].

OBJECTIVE: To investigate the effect of tumor associate antigen of CHP2 on the metastatic potential of HEK293 cells in nude mice. METHODS: Matrigel testing by Boyden chamber and intraperitoneal inoculation of BALB/c nude mice were respectively performed to detect the metastatic potential of HEK293 transfectants in vitro and in vivo. HE staining was used to confirm the tumor metastasis in related organs. Molecules probably involved in metastasis of HEK293 cells were screened by RT-PCR. RESULTS: CHP2 significantly promoted the migration of HEK293 cells through matrigel in vitro. CHP2 accelerated the tumorigenesis of HEK293 cells in nude mice and tissue invasion was observed in spleen, kidney and liver. CHP2 up-regulated osteopontin (OPN) expression in HEK293 cells, but had no effect on MMP2 expression. CONCLUSION: CHP2 enhanced the migration and metastasis of HEK293 cells in vitro and in vivo. Up-regulated OPN expression might contribute to the invasive potential of HEK293 cells.

Tat-HA-NR2B9c attenuate oxaliplatin-induced neuropathic pain.

Oxaliplatin is a commonly used chemotherapy drug, which can produce acute and chronic peripheral neurotoxicity. Currently, there is no good therapeutic drug in clinic. Excessive stimulation of N-methyl-d-aspartate receptors (NMDARs) is crucial for the transmission of pain signals. However, directly inhibiting NMDARs can cause severe side effects because they have key physiological functions in the Central nervous system (CNS). Several years ago, we prepared a polypeptide Tat-HA-NR2B9c which can disturb NMDARs-postsynaptic density protein-95 (PSD-95) interaction. In this study, we studied whether Tat-HA-NR2B9c could be an effective treatment for oxaliplatin-induced neuropathic pain. To conform it, a rat model of oxaliplatin-induced neuropathic was established, and analgesic effect of Tat-HA-NR2B9c was studied. Here, we show that oxaliplatin induces the interaction of NMDARs with PSD-95. Uncoupling the complex by Tat-HA-NR2B9c has potent analgesic effect in oxaliplatin-induced cold hyperalgesia and mechanical allodynia without suppressing general behavioral. Tat-HA-NR2B9c neither inhibits NMDARs function nor impacts antitumor activity of oxaliplatin. Thus, this new drug may serve as a treatment for oxaliplatin-induced neuropathic pain, perhaps without major side effects.

Predictive value of thymidylate synthase expression in advanced colorectal cancer patients receiving fluoropyrimidine-based chemotherapy: evidence from 24 studies.

The published data about thymidylate synthase (TS) expression and its predictive value in advanced colorectal cancer (CRC) patients receiving fluoropyrimidine-based chemotherapy seemed inconclusive. To derive a more precise estimation of the relationship, a metaanalysis was performed. Studies have been identified by searching PubMed and Embase. Inclusion criteria were advanced CRC patients, received fluoropyrimidine-based chemotherapy and evaluation of TS expression and overall response rate (ORR). The relative ratio (RR) for ORR in patients with low-TS expression over those with high-TS expression with 95% confidence interval (CI) was calculated for each study as an estimation of the predictive effect of TS. A total of 24 studies including 1,112 patients were involved in this metaanalysis. The overall RR was 2.20 (95% CI, 1.82-2.66; p = 0.000). For studies evaluating TS expression in metastatic lesions, the pooled RR was 3.23 (95% CI, 2.27-4.59; p = 0.000); for studies testing TS expression in primary lesions, a pooled RR of 1.89 (95% CI, 1.45-2.48; p = 0.000) was estimated. Focusing the analysis on immunohistochemistry (IHC)-based or RTPCR-based assessments, the pooled RR was 1.83 (95% CI, 1.44-2.34; p = 0.000) and 2.96 (95% CI, 2.07-4.22; p = 0.000), respectively. The results indicated that low-TS expression tumors in advanced CRC patients were more sensitive to fluoropyrimidine-based chemotherapy. Subgroup analyses indicated that the predictive value of TS expression evaluated in metastases was more prominent than that of primary lesions, and that TS expression tested by RTPCR was also of greater predictive value than by IHC.

Proteomic analysis of anti-tumor effects by Rhizoma Paridis total saponin treatment in HepG2 cells.

Rhizoma Paridis total saponin (RPTS) had been identified as the major components responsible for the anti-tumor effects of the herb Rhizoma Paridis, which had been used in China for centuries to treat many diseases including tumor. To elucidate the anti-tumor mechanism of RPTS, a proteomic analysis was carried out with RPTS treatment in HepG2 cells. More than 50 proteins showed a significant change between control (0.01% DMSO) and RPTS (IC(50) approximately 10microg/ml) treated cells after 48h. Twelve proteins had been identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) using peptide fingerprinting from 15 protein spots (density difference >2 fold between the control and RPTS-treated group). Among them, six proteins were down-regulated (dUTPase, hnRNP K, GMP synthase, etc.) and six proteins were up-regulated (DNase gamma, Nucleoside diphosphate kinase A, Centrin-2, etc.) by RPTS treatment in HepG2 cells as determined by spot volume (p<0.05). Most of the identified proteins were associated with tumor initiation, promotion, and progression. These findings might offer valuable insights into the mechanism of anti-tumor effect affected by RPTS treatment in HepG2 cells.

[Differential gene expression of the inhibitor of apoptosis proteins in docetaxel-resistant gastric cancer cells].

OBJECTIVE: Resistance to chemotherapy may indicate an unfavorable outcome for patients with gastric cancer. The purpose of this study was to examine whether docetaxel-resistance could be due in part to the expression of the inhibitor of apoptosis proteins (IAP). METHODS: Docetaxel-resistant cells, BGC-823/R1, BGC-823/R2 and BGC-823/R3, were established from parent BGC-823 cells by stepwise increasing concentration of docetaxel. To characterize these cells, we examined the effects of docetaxel on cell growth and apoptosis by MTT assay and double staining with both annexin-V-FITC and PI, and analyzed the cross-resistance to various anticancer drugs. Expression of IAP compared with that in parental cells was evaluated by real-time quantitative PCR. RESULTS: The BGC-823 resistant cells, BGC-823/R1, R2 and R3 cells, were 10.2-, 24.5-, 56.3-fold more resistant to docetaxel than parental cells, respectively, and this resistance was paralleled with reduced induction of apoptosis. BGC-823/R3 cells showed cross-resistance to paclitaxel, whereas exhibited weak or no cross-resistance against 5-fluorouracil, cisplatin and oxaliplatin. The expressions of survivin and XIAP were gradually increased with the extent of docetaxel resistance (r = 0.909, P < 0.001 and r = 0.892, P < 0.001, respectively). CONCLUSION: IAP may make an important contribution to the resistance to the apoptotic effect of docetaxel in gastric cancer, and could be used as a potential therapeutic target.

Comparison of microsatellite status detection methods in colorectal carcinoma.

There are two commonly accepted methods for detecting microsatellite status. One is to detect amplified microsatellite loci by polymerase chain reaction (PCR) and the other is to detect mismatch repair gene (MMR) protein expression by immunohistochemistry (IHC). PCR detection is considered to be accurate in clinical operations while IHC is widely used due to ease of operation and lesser expense. In order to compare IHC with PCR in detecting microsatellite status in colorectal carcinoma, a total of 569 samples of colorectal carcinoma resection were collected in the Department of Pathology, Nanjing Drum Tower Hospital, between June 2014 and June 2017. In all samples, IHC and PCR was used to detect microsatellite status and the consistency of results between the two methods was compared. We found that 48 cases of microsatellite instability (MSI) were detected by PCR including 37 cases of microsatellite instability high (MSI-H), 11 cases of microsatellite instability low (MSI-L), and 521 cases of MSS. MSI accounted for 8.44% of all cases and MSI-H accounted for 6.50%. IHC results of the 569 patients showed that 69 cases were deficient mismatch repair (dMMR) and 500 cases were proficient mismatch repair (pMMR). dMMR accounted for 12.13% of all cases. Loss expression of PMS2 protein was the most common while MSH6 was rare. The coincidence rate of the two methods for detecting microsatellite states was 91.92%. IHC and the PCR method had high consistency in microsatellite status. Compared with PCR, the IHC method is more economical and more convenient for clinical operations. When the 4 repair proteins were without deficiency detected by IHC, it could be diagnosed as MSS/MSI-L and further PCR was not necessary. When any repair protein was found to be deficient, PCR detection was needed to determine whether MSI existed. Our conclusion will save a lot of time and costs in clinical work.

Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma.

PURPOSE: The most common genitourinary malignancy in China is bladder transitional cell carcinoma (TCC). Early diagnosis of new and recurrent bladder cancers, followed by timely treatment, will help decrease mortality. There are currently no satisfactory markers for bladder cancer available in clinics. Better diagnostic methods are highly demanded. EXPERIMENTAL DESIGN: In this research, we have used comprehensive expressed sequence tag analysis, serial analysis of gene expression, and microarray analysis and quickly discovered a candidate marker, urothelial carcinoma associated 1 (UCA1). The UCA1 gene was characterized and its performance as a urine marker was analyzed by reverse transcription-PCR with urine sediments. A total of 212 individuals were included in this study, 94 having bladder cancers, 33 ureter/pelvic cancers, and 85 normal and other urinary tract disease controls. RESULTS: UCA1 was identified as a novel noncoding RNA gene dramatically up-regulated in TCC and it is the most TCC-specific gene yet identified. The full-length cDNA was 1,439 bp, and sequence analysis showed that it belonged to the human endogenous retrovirus H family. Clinical tests showed that UCA1 assay was highly specific (91.8%, 78 of 85) and very sensitive (80.9%, 76 of 94) in the diagnosis of bladder cancer and was especially valuable for superficial G2-G3 patients (sensitivity 91.1%, 41 of 45). It showed excellent differential diagnostic performance in various urinary tract diseases without TCC. CONCLUSIONS: UCA1 is a very sensitive and specific unique marker for bladder cancer. It could have important implications in postoperative noninvasive follow-up. This research also highlights a shortcut to new cancer diagnostic assays through integration of in silico isolation methods with translational clinical tests based on RNA detection protocols.

Survivin: potential role in diagnosis, prognosis and targeted therapy of gastric cancer.

Survivin is a protein that is highly expressed in a vast number of malignancies, but is minimally expressed in normal tissues. It plays a role as an inhibitor of cell death in cancer cells, thus facilitating the growth of these cells. In the case of gastric cancer, survivin is over-expressed in tumor cells and plays a role in the carcinogenesis process. Several studies on gastric cancer have indicated that there is a relationship between survivin expression and the ultimate behavior of the carcinoma. Since the expression pattern of survivin is selective to cancer cells, it has been described as an "ideal target" for cancer therapy. Currently, several pre-clinical and clinical trials are on-going to investigate the effects of interfering with survivin function in cancer cells as a biologic therapy. Survivin is a potentially significant protein in the diagnosis, prognosis and treatment of gastric tumors.