Relationship Between Infiltration of CD163+ TAMs, FoxP3+ Tregs, or CD66b+ TANs and Cell Differentiation in Colorectal Cancer Tissues.

BACKGROUND/AIMS: There are many studies on immune cell infiltration in colorectal cancer, including FoxP3+-regulatory T cells, CD66b+ tumorassociated neutrophils, and CD163+ tumor-associated macrophages. These studies mainly focus on the relationship between cell infiltration and tumor progression, prognosis, and so on, while the relationship between tumor cell differentiation and cell infiltration is poorly understood. We aimed to explore the relationship between cell infiltration and tumor cell differentiation. MATERIALS AND METHODS: The tissue microarray and immunohistochemistry were used to determine the infiltration of FoxP3+-regulatory T cells, CD66b+ tumor-associated neutrophils, and CD163+ tumor-associated macrophages in 673 colorectal cancer samples from the Second Affiliated Hospital, Wenzhou Medical University (2001-2009). Kruskal-Wallis test was used to assess the positive cell infiltration in colorectal cancer tissues with tumor cells of varying degrees of differentiation. RESULTS: The number of CD163+ tumor-associated macrophages, FoxP3+-regulatory T cells, and CD66b+ tumor-associated neutrophils in colorectal cancer tissues was different, and the level of CD163+ tumor-associated macrophages was the highest while the level of FoxP3+-regulatory T cells was the least. There were significant differences in the cell infiltration of colorectal cancer tissue cells with different levels of differentiation (P < .05). The highest infiltration of CD163+ tumor-associated macrophages (154.07 ± 6.95) and FoxP3+-regulatory T cells (20.14 ± 2.07) were in the poorly differentiated colorectal cancer tissues, while the higher infiltration of CD66b+ tumor-associated neutrophils was in the moderately or well-differentiated colorectal cancer tissues (36.70 ± 1.10 and 36.09 ± 1.06, respectively). CONCLUSION: Infiltration of CD163+ tumor-associated macrophages, FoxP3+-regulatory T cells, and CD66b+ tumor-associated neutrophils in colorectal cancer tissues may be related to the differentiation of tumor cells.

Construction of a Metabolism-Related Long Non-Coding RNAs-Based Risk Score Model of Hepatocellular Carcinoma for Prognosis and Personalized Treatment Prediction.

Background: Long non-coding RNAs (lncRNAs) play a key regulatory role in tumor metabolism. Although hepatocellular carcinoma (HCC) is a metabolic disease, there have been few systematic reports on the association between lncRNA expression and metabolism in HCC. Results: In this study, we screened 557 metabolism-related lncRNAs in HCC. A risk score model based on 13 metabolism-related lncRNA pairs was constructed to predict the outcome and drug response in HCC. The risk score model presented a better prediction of the outcomes than that with common clinicopathological characteristics, such as tumor stage, grade, and status and aneuploidy score in both training and testing cohorts. In addition, patients in the high-risk group exhibited higher responses to gemcitabine and epothilone, whereas those in the low-risk group were more sensitive to metformin and nilotinib. Conclusion: The metabolism-related lncRNAs-based risk score model and the other findings of this study may be helpful for HCC prognosis and personalized treatment prediction.

Preparation of Biodegradable Polymeric Nanocapsules for Treatment of Malignant Tumor Using Coaxial Capillary Microfluidic Device.

Objective: Nanocapsules play a role in the targeted delivery of chemotherapy drugs. However, the traditional technology for preparation of nanocapsules is relatively complex with poor controllability, leading to large differences batch to batch. This study aimed to evaluate the quality of drugs-loaded nanocapsules (Drugs-NCs) fabricated by coaxial capillary microfluidic device, and inhibitory effect on malignant tumors. Materials and Methods: In this study, oxaliplatin, irinotecan, and 5-fluorouracil were selected as chemotherapy drugs, and Drugs-NCs were prepared by coaxial glass capillary microfluidic device. Next, transmission electron microscope was utilized to characterize surface morphology and particle size distribution of Drugs-NCs. Then, high performance liquid chromatography was used to determine the drug loading and encapsulation efficiency. Dialysis method was performed to measure the drug release of Drugs-NCs in vitro. To study the effects of Drugs + NCs on tumor growth in vivo, BALB/c (nu/nu) nude mice were used in vivo experiments. Results: The Drugs-NCs were spherical and uniform in size (103.4 nm). Besides, the encapsulation efficiencies of oxaliplatin, irinotecan, and 5-fluorouracil were 97.0%, 95.7%, and 15.6%, respectively. Moreover, drugs encapsulated in the nanocapsules released less and was pH-dependent, with more rapid release being observed at pH 5.5 group compared with pH 7.4 group. MTT assay and in vivo experiments indicated the inhibitory effect of Drugs-NCs on malignant tumors. Conclusion: The prepared nanocapsules had potential tumor targeting. Furthermore, coaxial capillary microfluidic device could be used as a promising microfluidic technology to fabricate multiple Drug-NCs.

Ileal transposition rapidly improves glucose tolerance and gradually improves insulin resistance in non-obese type 2 diabetic rats.

BACKGROUND: Many studies have confirmed that ileal transposition can improve type 2 diabetes mellitus (T2DM), accompanied by increased glucagon-like peptide-1 (GLP-1). We performed the experiment on diabetic rats to evaluate the effects and mechanisms of ileal transposition on the glycemic metabolism. METHODS: Twenty Goto-Kakizaki (GK) rats were randomly divided into the ileal transposition group (IT group) and the sham operation group (Sham group). Weight, food intake, fasting plasma glucose (FPG), fasting insulin (F-ins), oral glucose tolerance test (OGTT) and GLP-1 were determined at baseline and 1, 4, 8, 16 and 24 weeks post-operatively. The homeostasis model assessment-insulin resistance (HOMA-IR) index and the area under the curve (AUC) during OGTT were measured. Histological determination of the GLP-1 receptor (GLP-1R) was performed on the pancreas and ileum 24 weeks post-operatively. RESULTS: In comparison with the Sham group, the IT group showed a higher GLP-1 level and lower AUC at 4, 8, 16 and 24 weeks post-operatively (all P < 0.05) and a lower FPG, F-ins levels and HOMA-IR at 8, 16 and 24 weeks post-operatively (all P < 0.05). Compared with baseline levels, the plasma GLP-1, AUC and FPG levels decreased significantly at each post-operative time point in the IT group (all P < 0.05), but not in the Sham group (all P > 0.05); F-ins and HOMA-IR significantly decreased at 8, 16 and 24 weeks post-operatively in the IT group (all P < 0.05). GLP-1R expression in the IT group was significantly higher than that of the Sham group in both the pancreas and the ileum at 24 weeks post-operatively (P < 0.05). CONCLUSIONS: Ileal transposition ameliorated glucose metabolism without reduction in weight or food intake in GK rats, which may be induced by the increased GLP-1 expression. However, the delayed improvement of insulin resistance, accompanied by decreased plasma insulin levels, might not directly result from the increased GLP-1.

CircRNA_100290 promotes colorectal cancer progression through miR-516b-induced downregulation of FZD4 expression and Wnt/ß-catenin signaling.

Accumulating evidence indicates that circular RNAs (circRNA) exert crucial functions in the development and advance of cancers. CircRNA_100290 has been reported to promote proliferation in oral cancer. However, whether it participates in colorectal cancer (CRC) remains unclear. Here, our report showed that circRNA_100290 level was significantly increased in CRC tissues and cell lines. Besides, circRNA_100290 expression was positively correlated with tumor metastasis while inversely correlated with prognosis. Silencing circRNA_100290 markedly reduced cell proliferation rate, inhibited migration and invasion abilities, but promoted apoptosis in vitro. Mechanistically, our data revealed circRNA_100290 was a competing endogenous RNA (ceRNA) of FZD4 by sponging miR-516b, leading to activation of Wnt/ß-catenin pathway. Rescue assay indicated that FZD4-induced activation of ß-catenin pathway is indispensable for the function of circRNA_100290 in CRC. In summary, our study for the first time revealed a novel regulatory loop of circRNA_100290/miR-516b/FZD4/Wnt/ß-catenin implicated in CRC progression.

Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway.

BACKGROUND: Nano-particles have been widely used in target-specific drug delivery system and showed advantages in cancers treatment. This study aims to evaluate the effect of chitosan coated doxorubicin nano-particles drug delivery system in liver cancer. METHODS: The chitosan nano-particles were prepared by using the ionic gelation method. The characterizations of the nano-particles were determined by transmission electron microscopy. The cytotoxicity was detected by MTT assay, and the endocytosis, cell apoptosis and cell cycle were examined by flow cytometry. The protein level was analyzed with western blot. The dual luciferase reporter assay was performed to assess the interaction between p53 and the promoter of PRC1, and chromatin immune-precipitation was used to verify the binding between them. RESULTS: The FA-CS-DOX nano-particles were irregular and spherical particles around 30-40 nm, with uniform size and no adhesion. No significant difference was noted in doxorubicin release rate between CS-DOX and FA-CS-DOX. FA-CS-DOX nano-particles showed stronger cytotoxicity than CS-DOX. FA-CS-DOX nano-particles promoted the apoptosis and arrested cell cycle at G2/M phase, and they up-regulated p53. FA-CS-DOX nano-particles inhibited cell survival through p53/PRC1 pathway. CONCLUSION: Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer by promoting apoptosis and arresting cell cycle at G2/M phase through p53/PRC1 pathway.

The long non-coding RNA AK023948 enhances tumor progression in hepatocellular carcinoma.

The long non-coding RNAs (lncRNAs) have been demonstrated to play pivotal roles in a broad range of processes including tumor biology. However, the exact contributions of lncRNAs to hepatocellular carcinoma (HCC) remain poorly defined. In current study, we have unraveled a novel function of AK023948 in HCC. We found that AK023948 was substantially upregulated in tumor tissues. Meanwhile, higher AK023948 expression correlated with poor survival. Upregulation of AK023948 expression can promote HepG2 and Hep3B proliferation and invasion in in vitro experiments. Furthermore, AK023948 also decreased tumor growth in vivo. The tumorigenic role of AK023948 was partially ascribed to PI3K/Akt/mTOR signaling and AK023948 knockdown decreased pathway activation and tumor growth. These data collectively suggest an oncogenic role for AK023948 and may provide potential insight into therapeutic intervention.

Laparoscopic surgery assisted by colonoscopy for a submucosal cecal fecalith presenting as acute appendicitis: A case report.

RATIONALE: A cecal submucosal fecalith is extremely rare and is likely to be misdiagnosed as appendicitis with an incarcerated fecalith. PATIENT CONCERNS: This review presents the case of a female patient complaining of recurrent abdominal pain in the right lower quadrant, similar to the clinical symptoms of appendicitis. Physical examination revealed an abdominal tenderness in the right lower quadrant without rebound tenderness or muscular tension. An ultrasound examination found a mass located in the right lower abdomen. Computed tomography showed a high-density shadow in the cecal cavity. DIAGNOSES: A fecalith was detected in the submucosal cecal wall. The postoperative pathologic examination showed that the fecalith was located in the submucosa. INTERVENTIONS: A partial cecal excision was performed under laparoscopic surgery assisted by colonoscopy. OUTCOMES: The patient was discharged 1 week after surgery without postoperative complications. LESSONS: Fecaliths should be considered in the differential diagnosis of submucosal occupying lesions of the cecum.

Efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a meta-analysis.

BACKGROUND: What benefits and toxicities patients acquire from the use of bevacizumab combined with firstline chemotherapy remains controversial. This study was performed to evaluate the efficacy and safety of first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer (mCRC). METHODS: Several databases, including PubMed, Embase, and Cochrane Library, were searched up to April 30, 2013. Eligible studies were only randomized, controlled trials (RCTs) with a direct comparison between mCRC patients treated with and without bevacizumab. Overall risk ratio (RR), hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CI) were calculated employing fixed or random-effects models depending on the heterogeneity of the included trials. RESULTS: Six RCTs, including 1582 patients in chemotherapy plus bevacizumab group and 1484 patients in chemotherapyalone group, were included. Overall, the addition of bevacizumab to first-line chemotherapy increased overall response rate (ORR) by 4.5%, prolonged both progression-free survival (PFS) and overall survival (OS), and increased the rate of total Grades 3 or 4 adverse events (G3/4AEs) by 6.9%. Significant differences were found in ORR (RR = 1.22 (95% CI 1.01-1.46), P = 0.03), PFS (HR = 0.60 (95% CI 0.47-0.77), P < 0.0001), OS (HR = 0.83 (95% CI 0.70-0.97), P = 0.02), and any G3/4AEs (OR = 1.56 (95% CI 1.29-1.89), P < 0.00001). CONCLUSION: Bevacizumab is a valuable addition to the current first-line chemotherapy regimens used in patients with mCRC, because of conferring a significant improvement in ORR, PFS, and OS, even though it increased adverse events.

[Factors influencing the long-term survival in pancreatic carcinoma patients after radical resection].

OBJECTIVE: To investigate the factors influencing the long-term survival of pancreatic carcinoma patients after radical resection. METHODS: The data of 184 pancreatic carcinoma patients with radical resection were analyzed retrospectively. Analysis of the prognostic factors influencing the long-term survival was performed using Cox proportional hazard regression model. RESULTS: The overall 1-, 3- and 5-year survival rates in this group were 61.7%, 29.0% and 14.3%, respectively. They were 78.0%, 38.4% and 25.7%, respectively, for the patients with a tumor < 3 cm in diameter, significantly better than those with a tumor >or= 3 cm (52.8%, 22.7% and 7.2%, respectively, P < 0.05). Moreover, the 1-, 3- and 5-year survival rates were 67.6%, 30.5% and 17.4%, respectively, in the patients without lymph node involvement, much longer than that in those with lymph node metastasis (37.1%, 20.6% and 0, respectively, P < 0.05). Multivariate analysis by Cox proportional hazard regression model revealed that the tumor size (P < 0.05) and lymph node metastasis (P < 0.01) significantly influenced the long-term survival of the patients. CONCLUSION: Tumor size and lymph node metastasis are significant factors influencing the long-term survival of pancreatic carcinoma patients with radical resection. Therefore, early diagnosis and radical resection are the key points to improve treatment outcome.