Exosomes as potential sources of biomarkers in colorectal cancer.

Colorectal cancer (CRC), a common malignancy, is among the leading causes of cancer-related deaths worldwide. Developing novel biomarkers is an important public health strategy to effectively reduce the mortality of this disease. Recent studies have found that exosomes may be important sources of biomarkers in CRC. Exosomes are nanometer-sized membrane vesicles (30-200 nm) secreted by normal or cancer cells, which participate in intercellular communication by transporting RNAs and proteins. Accumulating evidence has shown that some differentially expressed RNAs and proteins in exosomes play key roles in the initiation and development of CRC and are potential candidates for malignancy detection. Accordingly, exploring the correlation between these exosomes and CRC may be beneficial for the development of novel biomarkers in this disease. Here, we summarize the important roles of exosomes as biomarkers in CRC diagnosis, as well as the application in the metastasis, chemoresistance, and recrudescence of CRC. In particular, we discuss the prospects and limitations of exosomes as tumor markers.

Matrine Ameliorates Colorectal Cancer in Rats via Inhibition of HMGB1 Signaling and Downregulation of IL-6, TNF-α, and HMGB1.

Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-ß1) and p53, and corresponding high-mobility group box 1 (HMGB1) signaling and T helper cell differentiation were thought to be associated with matrine's mechanism. Expression of predicted serum targets were verified in a 1,2-dimethylhydrazine dihydrochloride-induced CRC model rats that were treated with matrine (ip) for 18 weeks. Data show that matrine suppressed CRC growth and decreased previously elevated expression of IL-6, TNF-α, p53, and HMGB1. Matrine may have had a therapeutic effect on CRC via inhibition of HMGB1 signaling, and this occurred through downregulation of IL-6, TNF-α, and HMGB1.

Associations between NBS1 Polymorphisms and Colorectal Cancer in Chinese Population.

As the central protein of the double strand breaks (DSB)-induced DNA repair pathway, NBS1 participates in detecting the DSBs and plays an essential role in maintaining genomic stability. Single nucleotide polymorphisms (SNPs) in NBS1 gene were commonly tested that associated with the susceptibility to multiple cancers, but the results remained controversial. Thus, we conducted two independent hospital-based case-control studies comprising 1,072 colorectal cancer patients and 1,263 controls to evaluate the association between four NBS1 SNPs and colorectal cancer risk. The result showed that rs2735383C/G polymorphism in the 3'-untranslated region (UTR) of NBS1 was significantly associated with risk of colorectal cancer using logistic regression (P<10(-4)). Furthermore, we observed that rs2735383CC genotype was associated with substantially increased risk of colorectal cancer (odds ratio=1.55, 95% confidence interval=1.27-1.94), compared with the rs2735383GC+GG genotypes. Further functional experiments demonstrated that the rs2735383C allele in the NBS1 disrupted the binding affinity of has-miR-509-5p to the NBS1 3'-UTR in colorectal cancer cells, affecting the NBS1 transcriptional activity and expression level. In conclusion, current evidence suggests that the rs2735383C/G polymorphism might contribute to the risk for colorectal cancer.

[Expressions of STAT3, p-STAT3 and E-cadherin in colorectal cancer and clinical implications].

OBJECTIVE: To investigate the correlation of expressions of STAT3 and p-STAT3 with epithelial mesenchymal transition(EMT)-associated protein E-cadherin in colorectal cancer, and to examine the association of above expressions with tumor invasion and metastasis of colorectal cancer. METHODS: Immunohistochemistry assay ElivisionTM plus was used to detect the expressions of STAT3, p-STAT3 and E-cadherin protein in colorectal cancer tissue samples of 50 cases and their corresponding adjacent non-tumor tissues. Association of these protein expressions with tumor invasion and metastasis was analyzed with χ(2) test. Correlation of STAT3 and p-STAT3 with E-cadherin was analyzed with Spearman method. RESULTS: Positive expression rates of STAT3, p-STAT3 and E-cadherin protein in colorectal cancer tissues were 72%(36/50), 76%(38/50) and 26%(13/50), which were significantly higher compared to adjacent normal intestinal mucosa tissues [24%(12/50), 26%(13/50) and 68%(34/50), all P<0.05]. STAT3, p-STAT3 and E-cadherin expressions were associated with tumor differentiation, tumor invasion depth, tumor size, lymph node metastasis, TNM staging (all P<0.05). In colorectal cancer tissues, STAT3 protein expression was positively correlated with p-STAT3 expression. STAT3 and p-STAT3 expressions in colorectal cancer tissues were negatively correlated with E-cadherin expression(P<0.05). CONCLUSION: STAT3 and p-STAT3 may be involved in tumor EMT through inhibition of E-cadherin expression, leading to the development of colorectal cancer.

[Clinical value of 64-slice spiral 3-phase CT enhanced scanning for preoperative TNM staging assessment of gastric carcinoma].

OBJECTIVE: To explore the clinical value of 64-slice spiral 3-phase CT enhanced scanning for preoperative TNM staging assessment of gastric carcinoma. METHODS: A retrospective study was performed to review the 64-slice spiral 3-phase CT enhanced scanning of 120 patients with gastric cancer diagnosed by biopsy prior to operation and postoperative pathological reports. All the findings were reviewed by two senior radiologic diagnosticians separately and compared with pathological findings. RESULTS: The accuracy of 64-slice spiral CT enhanced scan was 79.2%(95/120) for T staging, 66.7%(10/15) for T1, 66.7%(14/21) for T2, 84.0%(42/50) for T3, and 85.3%(29/34) for T4. For gastric wall with single layer and multiple layers, the accuracy of CT enhanced scanning was 59.4%(19/32) and 81.8%(72/88) for T staging, and the difference was statistically significant(P<0.05). The accuracy of 64-slice spiral CT enhanced scan was 73.9%(85/115) for N staging, 75.5%(37/49) for N0, 70.3%(26/37) for N1, 75.9%(22/29) for N2. The accuracy of 64-slice spiral CT enhanced scanning was 89.2% for M staging. CONCLUSION: 64-slice spiral CT 3-phase enhanced scanning can monitor the invasion, lymphatic metastasis, and distant metastasis of gastric cancer dynamically, which may become an important examination item for the preoperative evaluation of gastric cancer.