Publications by authors named "Jingkun Zhao"

29 Publications

  • Page 1 of 1

High versus low ligation of the inferior mesenteric artery during laparoscopic rectal cancer surgery: A prospective study of surgical and oncological outcomes.

J Surg Oncol 2021 Mar 2. Epub 2021 Mar 2.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background And Objectives: There is controversy regarding whether the inferior mesenteric artery (IMA) should be ligated at its origin from the aorta (high ligation, HL) or below the branch of the left colic artery (low ligation, LL) during surgery for rectal cancer.

Methods: This prospective study randomized 95 patients with histologically proven rectal cancer (clinical stages I-III based on the 8th American Joint Committee on Cancer guidelines) to undergo HL (n = 47) or LL with lymph node dissection at the root of the IMA (n = 48).

Results: Only two intraoperative adverse events were observed (two HL patients experienced anastomotic ischemia and underwent extended bowel excision and splenic flexure mobilization). The LL group had a significantly shorter time to first flatus (p < .0001). No significant differences were observed in operative time (p = .14), intraoperative blood loss (p = .21), distance from the upper margin (p = .77), distance from the lower margin (p = .35), harvested lymph nodes (p = .33), or anastomotic leakage (p = .44), 2-year overall survival (p = .97), or 2-year disease-free survival (p = .42).

Conclusion: During laparoscopic low anterior resection, a combination of LL at the IMA and vascular root lymph node dissection may help protect the blood supply of the anastomosis, reduce postoperative complications, and enhance recovery, without compromising radical excision.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jso.26362DOI Listing
March 2021

Studies on the physicochemical properties, gelling behavior and drug release performance of agar/κ-carrageenan mixed hydrogels.

Int J Biol Macromol 2020 Jul 12;154:878-887. Epub 2020 Mar 12.

College of chemistry and chemical engineering, Qingdao University, Qingdao 266071, China. Electronic address:

A series of agar/κ-carrageenan mixed hydrogels with different mass ratios were prepared, and their physicochemical properties, gelling behavior and drug release performance were determined and analyzed. The results showed that the gel strength, the gelling temperature and the gel melting temperature decreased with the increase of κ-carrageenan, while the apparent viscosities increased. Optical rotation and differential scanning calorimetry (DSC) indicated that there did exist intermolecular interactions between agar and κ-carrageenan, and the detailed gelling mechanism of the mixed hydrogels was proposed, which was different from that of the previous research. Besides, agar/κ-carrageenan mixed hydrogels were used as carriers for the delivery of metformin hydrochloride (MET). The results showed that the drug loading efficiency and the sustained release capacity of agar hydrogels could be enhanced by the addition of κ-carrageenan, and the release profile was mainly dominated by the electrostatic interaction between the MET and the polysaccharides. These results indicated that κ-carrageenan had the potential to improve the physicochemical properties and drug release performance of agar hydrogel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2020.03.087DOI Listing
July 2020

Polo-like kinase 3 inhibits glucose metabolism in colorectal cancer by targeting HSP90/STAT3/HK2 signaling.

J Exp Clin Cancer Res 2019 Oct 26;38(1):426. Epub 2019 Oct 26.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, China.

Background: Polo-like kinase 3 (PLK3) has been documented as a tumor suppressor in several types of malignancies. However, the role of PLK3 in colorectal cancer (CRC) progression and glucose metabolism remains to be known.

Methods: The expression of PLK3 in CRC tissues was determined by immunohistochemistry. Cells proliferation was examined by EdU, CCK-8 and in vivo analyses. Glucose metabolism was assessed by detecting lactate production, glucose uptake, mitochondrial respiration, extracellular acidification rate, oxygen consumption rate and ATP production. Chromatin immunoprecipitation, luciferase reporter assays and co-immunoprecipitation were performed to explore the signaling pathway. Specific targeting by miRNAs was determined by luciferase reporter assays and correlation with target protein expression.

Results: PLK3 was significantly downregulated in CRC tissues and its low expression was correlated with worse prognosis of patients. In vitro and in vivo experiments revealed that PLK3 contributed to growth inhibition of CRC cells. Furthermore, we demonstrated that PLK3 impeded glucose metabolism via targeting Hexokinase 2 (HK2) expression. Mechanically, PLK3 bound to Heat shock protein 90 (HSP90) and facilitated its degradation, which led to a significant decrease of phosphorylated STAT3. The downregulation of p-STAT3 further suppressed the transcriptional activation of HK2. Moreover, our investigations showed that PLK3 was directly targeted by miR-106b at post-transcriptional level in CRC cells.

Conclusion: This study suggests that PLK3 inhibits glucose metabolism by targeting HSP90/STAT3/HK2 signaling and PLK3 may serve as a potential therapeutic target in colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-019-1418-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815449PMC
October 2019

A positive feedback loop of β-catenin/CCR2 axis promotes regorafenib resistance in colorectal cancer.

Cell Death Dis 2019 09 9;10(9):643. Epub 2019 Sep 9.

Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200008, China.

Resistance to molecular targeted therapies is a significant challenge for advanced colorectal cancer (CRC). Understanding the underlying mechanisms and developing effective strategies against regorafenib resistance are highly desired in the clinic. Here, we screened the expression of chemokine receptors and identified CC chemokine receptor 2 (CCR2) as a top upregulated gene in regorafenib-resistant cells. CCR2 silencing alleviated drug tolerance in regorafenib-resistant cells, while overexpression of CCR2 enhanced CRC cells resistance to regorafenib. Moreover, CCR2-mediated regorafenib tolerance was demonstrated to be associated with AKT/GSK3β-regulated β-catenin stabilization. In turn, β-catenin modulation is sufficient to trigger the transcriptional activation of CCR2 expression. Clinically, high-CCR2 expression was correlated to shorter overall survival and disease-free survival of patients. A positive correlation between CCR2 and nuclear β-catenin expression was observed in a cohort of CRC tissues. Altogether, these findings suggest β-catenin and CCR2 are part of a positive-feedback loop, which sustains a high CCR2 expression level, conferring CRC cells resistance to regorafenib. Thus, targeting CCR2 may be a useful therapeutic strategy to alleviate regorafenib tolerance to increase the efficacy of CRC treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-019-1906-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733926PMC
September 2019

Preparation of methyl alginate and its application in acidified milk drinks.

Int J Biol Macromol 2019 Jul 1;132:651-657. Epub 2019 Apr 1.

College of Chemical Science and Engineering, Qingdao University, Qingdao 266071, China. Electronic address:

A series of methyl alginate with different degree of esterification (DE) were prepared with low cost, and its application in acidified milk drinks (AMDs) was investigated. The gel strength, molecular weight, solution apparent viscosity and optical rotation value of methyl alginate all decreased with the increase of DE. Methyl alginate with DE equal or larger than 60.7% was more effective in stabilizing AMDs than high-methoxyl pectin (HMP) under the same conditions, and the higher the DE, the better its stabilizing ability. The methyl alginate had better synergistic action for stabilizing AMDs with propylene glycol alginate (PGA) than HMP. The reason for this could be attributed to that methyl alginate and PGA had the same main chain structure, and the same levorotatory optical activity. The results indicated that the methyl alginate had a potential industry application prospect for stabilizing AMDs as an alternative to HMP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2019.03.243DOI Listing
July 2019

CCL19 suppresses angiogenesis through promoting miR-206 and inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in colorectal cancer.

Cell Death Dis 2018 09 24;9(10):974. Epub 2018 Sep 24.

Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.

The mechanisms underlying the role of chemokines in tumor angiogenesis is still not fully understood. In this study, we detected the influence of CCL19 on colorectal cancer (CRC) angiogenesis. The expression of CCL19 and CD31 in CRC tissues were detected by immunohistochemistry. Human CRC cell lines SW1116 and SW620 stably transfected with CCL19 lentivirus and CCL19 shRNA, and HUVEC stably transfected with CCR7 shRNA were used in our study. Our study showed that CCL19 was significantly low-expressed in CRC tissues and positively related to highly tumor microvessel density. In vitro, we observed that CCL19 high-expressed SW1116 supernatant was able to inhibit proliferation, migration, and sprouting responses of HUVEC, whereas CCL19 low-expressed SW620 supernatant can promote HUVEC angiogenesis. Additionally, we further demonstrated that these functions maybe achieved through promoting miR-206 thus inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in a CCR7-dependent manner. Mice angiogenesis model also confirmed that elevated expression of CCL19 inhibit the angiogenesis of CRC in vivo. In summary, our results supported that CCL19 can inhibit CRC angiogenesis through promoting miR-206 thus inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway. This may be a novel therapeutic option for anti-vascular treatment in CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-018-1010-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155262PMC
September 2018

Baicalin and ginsenoside Rb1 promote the proliferation and differentiation of neural stem cells in Alzheimer's disease model rats.

Brain Res 2018 Jan 14;1678:187-194. Epub 2017 Oct 14.

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China. Electronic address:

Background: This study aimed to explore the effects of ginsenoside Rb1 and baicalin on the proliferation and differentiation of neural stem cells (NSC) in Alzheimer's disease model rats.

Method: The healthy Sprague Dawley male rats were randomly divided into 4 groups: control group, model group, ginsenoside Rb1 group and baicalin group. Besides, the animal model of dementia was induced by the injection of Aβ1-40. 2 weeks later, the rats in the baicalin and ginsenoside Rb1 groups were injected with baicalin and ginsenoside Rb1, respectively. The contents, expression sites of Nestin, GFAP and NSE and the percentage of viable cells were detected by immunohistochemistry. In addition, the expression levels of Nestin, GFAP and NSE in hippocampus of rats were detected by western-blot and metrology analysis was performed using quantity.

Results: Injection of Aβ1-40 significantly reduced the number of neuronal cells (p < .05). In addition, compared with the control group, the percentages of positive cells of NSCs, astrocytes and neuronal were increased. Besides, compared with the model group, the percentage of positive neural cells was improved by ginsenoside Rb1 (p < .05), and the percentages of astrocytes and neuronal were increased by ginsenoside Rb1 and baicalin (p < .05). Moreover, the expressions of Nestin and NSE were enhanced by ginsenoside Rb1 and baicalin (p < .05), while the GFAP level was only affected by ginsenoside Rb1 (p < .05) when compared with the model group.

Conclusion: Ginsenoside Rb1 and baicalin might promote the proliferation and differentiation of endogenous NSCs in AD rat model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2017.10.003DOI Listing
January 2018

Overexpression of CXCR2 predicts poor prognosis in patients with colorectal cancer.

Oncotarget 2017 Apr;8(17):28442-28454

Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.

Colorectal cancer is a heterogeneous disease. Although many risk factors are used to predict colorectal cancer patients' prognosis after surgical resection, new prognostic factors are still needed to be defined to promote predictive efficacy of prognosis and further guide therapies. Herein, we identified the prognostic significance of CXCR2 in colorectal cancer patients. We retrospectively analysed 134 patients with colorectal cancer who underwent minimally invasive surgery between 2010 and 2011. The overall cohort was divided into a training set (n = 78) and a validation set (n = 56). We detected CXCR2 expression using immunohistochemical staining and defined the cut-off value using X-tile program. Next, we analysed the association between CXCR2 expression and clinicopathologic features in training and validation sets. High expression of CXCR2 was associated with Dukes stage (P = 0.018), tumor invasion (P = 0.018) and liver metastasis (P = 0.047). Multivariate COX regression analyses confirmed that high CXCR2 level was an independent prognostic risk factor for both overall survival and disease free survival. Kaplan-Meier survival analysis demonstrated that patients with high expression of CXCR2 had a poor overall survival and disease free survival even in low-risk group (I + II). This indicated that CXCR2 can help to refine individual risk stratification. In addition, we established Nomograms of all significant factors to predict 3- or 5-years overall survival and disease free survival. Moreover, we found the combination of CXCR2 and its ligand CXCL5 had more significant value in predicting the prognosis than single CXCR2 factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.16086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438662PMC
April 2017

Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways.

Mol Cancer 2017 03 29;16(1):70. Epub 2017 Mar 29.

Shanghai Minimally Invasive Surgery Center, Ruijin hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

Background: Metastasis is a major cause of death in human colorectal cancer patients. However, the contribution of chemokines in the tumor microenvironment to tumor metastasis is not fully understood.

Methods: Herein, we examinined several chemokines in colorectal cancer patients using chemokine ELISA array. Immunohistochemistry was used to detect expression of CXCL5 in colorectal cancer patients tissues. Human HCT116 and SW480 cell lines stably transfected with CXCL5, shCXCL5 and shCXCR2 lentivirus plasmids were used in our in vitro study. Immunoblot, immunofluorescence and transwell assay were used to examine the molecular biology and morphological changes in these cells. In addition, we used nude mice to detect the influence of CXCL5 on tumor metastasis in vivo.

Results: We found that CXCL5 was overexpressed in tumor tissues and associated with advanced tumor stage as well as poor prognosis in colorectal cancer patients. We also demonstrated that CXCL5 was primarily expressed in the tumor cell cytoplasm and cell membranes, which may indicate that the CXCL5 was predominantly produced by cancer epithelial cells instead of fibroblasts in the tumor mesenchyme. Additionally, overexpression of CXCL5 enhanced the migration and invasion of colorectal cancer cells by inducing the epithelial-mesenchymal transition (EMT) through activation of the ERK/Elk-1/Snail pathway and the AKT/GSK3β/β-catenin pathway in a CXCR2-dependent manner. The silencing of Snail and β-catenin attenuated CXCL5/CXCR2-enhanced cell migration and invasion in vitro. The elevated expression of CXCL5 can also potentiate the metastasis of colorectal cancer cells to the liver in vivo in nude mice intrasplenic injection model.

Conclusion: In conclusion, our findings support CXCL5 as a promoter of colorectal cancer metastasis and a predictor of poor clinical outcomes in colorectal cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12943-017-0629-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372323PMC
March 2017

Long-term outcomes and propensity score matching analysis: rectal cancer resection for patients with elevated preoperative risk.

Oncotarget 2017 Apr;8(15):25679-25690

Department of General and Visceral Surgery, Red Cross Hospital of Munich, Munich, Germany.

Background: It is still controversial about the treatment strategy for rectal cancer patients with elevated operative risk and elder rectal cancer patients.

Methods: This study presented a retrospective single center experience in rectal cancer proctectomy for high operative risk patients. High operative risk patient was defined as Cr-POSSUM > 5% combined with associated risk factors. 220 in 1477 consecutive patients met the inclusion criteria.

Results: 132 patients were selected (66:66) after propensity score matching. The total complication rate between conventional open rectal resection (71 %) and laparoscopic surgery (41%) was significantly different (p = 0.0005). There is a significantly positive correlation between open surgery and advanced Dindo Classification (p = 0.02). Cr-POSSUM is positively correlated with Dindo Classification (p = 0.01). There was no significant difference in survival rate among stage I~II, different age groups or different Cr-POSSUM score sub-groups. However, stage III-IV tumor patients in laparoscopic group experienced improved overall survival rate. (p < 0.0001). For patients with preoperative pulmonary or renal disease, patients in laparoscopic group also had better long term prognosis (p = 0.03, p = 0.049).

Conclusions: The results demonstrate the potential advantages of laparoscopic rectal cancer resection for high operative risk patients, especially for the patients with preoperative respiratory or renal disease and stage III cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.13827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421961PMC
April 2017

An efficient and simple co-culture method for isolating primary human hepatic cells: Potential application for tumor microenvironment research.

Oncol Rep 2016 Oct 28;36(4):2126-34. Epub 2016 Jul 28.

Heart Center, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China.

Co-cultivation of non-parenchymal cells (NPCs) and tumor cells from the same donor is important for metastatic cancer research. This study aimed to optimize a protocol for liver NPC isolation. Two novel 3D organotypic co‑culture models for hepatocyte, endothelial cell (EC) and Kupffer cell (KC) isolation were used. Long‑term cell co‑culture, density gradient centrifugation and magnetic‑activated cell sorting (MACS) were established. ECs were isolated from the co‑culture system; the purity of the ECs was 92±1.2%. The island‑like shape of hepatocytes was noted in the 3D co‑culture system, and spindle cells were found in the rest space. Immunofluorescence analysis showed a net structure; the connective tissue was positively stained with VE‑cadherin or CD68, which were ECs and KCs/macrophages. KCs were enriched in this system and separated by using selective adherence to plastic. Clec4f+ KCs consisted of 87±6.3% of these cells. Heterogeneous endothelium populations were detected, including sinusoid ECs, microvascular ECs and hepatic lymphatic vessel epithelial cells. In addition, hepatic progenitor cells were isolated and differentiated into hepatoblasts. Dendritic cells (DCs), invariant natural killer T (iNKT) cells were further separated by density gradient centrifugation and magnetic bead sorting. In the present study, high protein expression levels of desmin and GFAP were observed in the hepatic stellate cells (HSCs). Most of the HSCs were α‑SMA‑positive cells, which underlined the identity of activated HSCs. Intrahepatic human biliary epithelial cells (hBECs) were semi‑purified by centrifugation on a Percoll gradient and were further immunopurified. In conclusion, we provide an efficient long‑term culture method to obtain liver NPCs in sufficient number and purity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2016.4979DOI Listing
October 2016

Plk2 promotes tumor growth and inhibits apoptosis by targeting Fbxw7/Cyclin E in colorectal cancer.

Cancer Lett 2016 10 14;380(2):457-466. Epub 2016 Jul 14.

Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

Polo-like kinase 2 (Plk2) and Polo-like kinase 3 (Plk3) have been documented as a tumor suppressor and are lowly expressed in several types of cancer. However, our results showed that Plk3 was lowly expressed, whereas Plk2 expressed highly in tumor tissues. We therefore aimed to explore the mechanisms governing the role of Plk2 in colorectal cancer (CRC). Our investigation demonstrated that Plk2 was an independent prognostic marker in CRC patients. Plk2 promotes tumor growth and inhibits apoptosis of CRC cells in vitro and in vivo. Moreover, Plk2 binds to Fbxw7 and results in its subsequent degradation, which in turn leads to the stabilization of Cyclin E. The pro-tumor activity of Plk2 could be inverted by restoring Fbxw7 expression and depletion of Cyclin E. In addition, the expressions of Fbxw7 and Cyclin E were significantly associated with Plk2 protein levels in CRC tissues. In conclusion, our data show that Plk2 represents an independent prognostic marker and regulates tumor growth and apoptosis by targeting Fbxw7/Cyclin E pathway in CRC, suggesting Plk2 as a potential therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2016.07.004DOI Listing
October 2016

CCR4 promotes metastasis via ERK/NF-κB/MMP13 pathway and acts downstream of TNF-α in colorectal cancer.

Oncotarget 2016 Jul;7(30):47637-47649

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Chemokines and chemokine receptors are causally involved in the metastasis of human malignancies. As a crucial chemokine receptor for mediating immune homeostasis, however, the role of CCR4 in colorectal cancer (CRC) remains unknown. In this study, we found that high expression of CCR4 in CRC tissues was correlated with shorter overall survival and disease free survival. In vitro and in vivo experiments revealed that silencing CCR4 attenuated the invasion and metastasis of CRC cells, whereas ectopic overexpression of CCR4 contributed to the forced metastasis of these cells. We further demonstrated that matrix metalloproteinase 13 (MMP13) played an important role in CCR4-mediated cancer cell invasion, which is up-regulated by ERK/NF-κB signaling. Positive correlation between CCR4 and MMP13 expression was also observed in CRC tissues. Moreover, our investigations showed that the level of CCR4 could be induced by TNF-α dependent of NF-κB activation in CRC cells. CCR4 might be implicated in TNF-α-regulated cancer cells metastasis. Combination of CCR4 and TNF-α is a more powerful prognostic marker for CRC patients. These findings suggest that CCR4 facilitates metastasis through ERK/NF-κB/MMP13 signaling and acts as a downstream target of TNF-α. CCR4 inhibition may be a promising therapeutic option for suppressing CRC metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.10256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216967PMC
July 2016

Cadherin-12 enhances proliferation in colorectal cancer cells and increases progression by promoting EMT.

Tumour Biol 2016 Jul 14;37(7):9077-88. Epub 2016 Jan 14.

Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

Cadherin-12 (CDH12) is a subtype of N-cadherin family. In this study, we investigated the expression of CDH12 and the role of CDH12 in prognosis of colorectal cancer (CRC) patients. In addition, we observed the influence of CDH12 on proliferation and progression of CRC cell lines. By using immunohistochemical staining, we analyzed CRC samples and adjacent non-tumor tissues collected from 78 patients who underwent laparoscopic surgery in Shanghai Minimally Invasive Center, China. Statistical analyses were used to analyze relationship between CDH12 and tumor features. Kaplan-Meier method was used to analyze patients' survival. Proliferation ability of CRC cells was tested by CCK-8 assay, and transwell assays were performed to detect migration and invasion ability. Western blot assay was performed to investigate epithelial-mesenchymal transition (EMT) variants. We found that expression of CDH12 in tumor tissue was higher than in adjacent normal tissue. High expression of CDH12 was associated with tumor invasion depth and predicts poor prognosis of CRC patients. Ectopic/repressing expression of CDH12 increased/decreased the proliferation and migration ability of CRC cells. CDH12 is able to increase cancer cell migration and invasion via promoting EMT by targeting transcriptional factor Snail. These findings may conclude that CDH12 may act as a predictor in CRC patients' prognosis and an oncogene in CRC cell proliferation and migration. CDH12 may influence CRC cell progression through promoting EMT by targeting Snail. In addition, CDH12 is promoted by MCP1 through induction of MCPIP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13277-015-4555-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990612PMC
July 2016

PFDN1, an indicator for colorectal cancer prognosis, enhances tumor cell proliferation and motility through cytoskeletal reorganization.

Med Oncol 2015 Dec 9;32(12):264. Epub 2015 Nov 9.

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Prefoldin (PFDN) subunits have been reported upregulated in various tumor types, while the expression and functions of PFDN1 (PFDN subunit 1) in colorectal cancer (CRC) are not well elucidated. The aim of this study was to investigate the use of PFDN1 as a poor prognosis indicator for CRC and explore the functions of PFDN1 in CRC. The relationship between PFDN1 expression and CRC clinical-pathological statistics was detected on the tissue microarray containing 145 cases of CRC. ShRNA was used to silence PFDN1 expression in SW480 and RKO CRC cells, and these transfected cells were analyzed for changes in proliferation, colony formation, cell cycle, migration, and invasion. Immunofluorescence and immunoblot were used to determine the remodeling of the F-actin and α-tubulin. Finally, tumor growth on nude mice was observed and measured. In this study, we found PFDN1 was upregulated in CRC tissues compared with adjacent normal tissues. Also, PFDN1 expression positively correlated with tumor size and tumor invasion. Moreover, after silencing PFDN1 in SW480 and RKO cells, the proliferation and motility of CRC cells were significantly suppressed. The inhibitory effect of PFDN1 on tumor cell growth and motility was partially due to G2/M cell cycle blockage and cytoskeletal deficiency. Finally, in vivo assay showed that downregulation of PFDN1 inhibited tumor growth on nude mice and PFDN1 expression correlated with higher levels of Ki-67 staining. These findings indicate that PFDN1 was involved in the progression of CRC, and provide new insights into PFDN1 as a potential therapeutic target for CRC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12032-015-0710-zDOI Listing
December 2015

Survival of Colorectal Cancer in Patients With or Without Inflammatory Bowel Disease: A Meta-Analysis.

Dig Dis Sci 2016 Mar 30;61(3):881-9. Epub 2015 Oct 30.

Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC), but little is known about the influence of IBD on CRC prognosis.

Aims: The aim of this study was to perform a meta-analysis to compare survival in CRC patients with IBD (IBD-CRC) and without IBD.

Methods: An electronic search was conducted via PubMed, Embase, and the Cochrane Library to identify eligible trials until July 2015. We pooled the hazard ratios (HRs) and their 95% confidence intervals (CIs) to quantitatively assess the survival of CRC in patients with or without IBD. In addition, clinicopathological parameters of IBD-CRC versus non-IBD CRC were evaluated.

Results: Twelve studies containing a total of 3472 IBD-CRC patients were eligible according to our selection criteria. Our analysis indicated that CRC patients with IBD had shorter overall survival than those without IBD (HR 1.24, 95% CI 1.19-1.29). IBD-CRC showed a propensity to develop in proximal colon [odds ratio (OR) 2.52, 95% CI 1.35-4.72] and correlated with worse differentiation of tumor (OR 1.59, 95% CI 1.26-1.99) compared to non-IBD CRC. Meta-regression analysis showed that sample size (P = 0.002) could explain 99.01% inter-study heterogeneity.

Conclusion: This meta-analysis found poorer overall survival in CRC patients with IBD than CRC patients without IBD, and further prospective research to confirm these findings is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-015-3940-1DOI Listing
March 2016

The metastasis suppressor, NDRG1, inhibits "stemness" of colorectal cancer via down-regulation of nuclear β-catenin and CD44.

Oncotarget 2015 Oct;6(32):33893-911

Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

N-myc downstream-regulated gene 1 (NDRG1), has been identified as an important metastasis suppressor for colorectal cancer (CRC). In this study, we investigated: (1) the effects of NDRG1 on CRC stemness and tumorigenesis; (2) the molecular mechanisms involved; and (3) the relationship between NDRG1 expression and colorectal cancer prognosis. Our investigation demonstrated that CRC cells with silenced NDRG1 showed more tumorigenic ability and stem cell-like properties, such as: colony and sphere formation, chemoresistance, cell invasion, high expression of CD44, and tumorigenicity in vivo. Moreover, NDRG1 silencing reduced β-catenin expression on the cell membrane, while increasing its nuclear expression. The anti-tumor activity of NDRG1 was demonstrated to be mediated by preventing β-catenin nuclear translocation, as silencing of this latter molecule could reverse the effects of silencing NDRG1 expression. NDRG1 expression was also demonstrated to be negatively correlated to CRC prognosis. In addition, there was a negative correlation between NDRG1 and nuclear β-catenin and also NDRG1 and CD44 expression in clinical CRC specimens. Taken together, our investigation demonstrates that the anti-metastatic activity of NDRG1 in CRC occurs through the down-regulation of nuclear β-catenin and suggests that NDRG1 is a significant therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.5294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741810PMC
October 2015

Identification of pivotal markers in vascular dementia based on proteomics data.

Dement Geriatr Cogn Disord 2015 19;39(5-6):312-20. Epub 2015 Mar 19.

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, PR China.

Objective: The aim of this study was to analyze protein expression profiles of vascular dementia (VaD) subjects for investigating the underlying therapeutic markers.

Methods: Protein expression profile data were acquired from a quantitative clinical proteomic study, including 10 nondemented elderly controls and 10 age-matched VaD subjects. Differentially expressed proteins (DEPs) were identified between VaD subjects and controls, followed by function prediction using DAVID (Database for Annotation, Visualization, and Integrated Discovery). Then, a protein-protein interaction (PPI) network was constructed by comparing it with the STRING (Search Tool for the Retrieval of Interacting Genes) database, and the pathway crosstalk analysis was conducted based on overlapping PPI network and enriched pathways. Furthermore, the subpathway was screened and analyzed by the iSubpathwayMiner package in R.

Results: A total of 144 DEPs were screened from VaD subjects and the controls. They were significantly enriched in many pathways. High-degree proteins were detected in the PPI network, such as ATP5B (ATP synthase subunit β). Furthermore, 'metabolic pathways' and 'Alzheimer's disease' were the significant pathways screened in the crosstalk analysis. At last, upregulated proteins were enriched in 2 subpathways of 1 pathway, while downregulated proteins were enriched in 162 subpathways of 36 pathways.

Conclusion: By analyzing the differential expressions of proteins, the potential underlying therapeutic markers and mechanism of VaD might be elucidated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000375296DOI Listing
October 2015

Plasma 25-hydroxyvitamin D levels and survival of colorectal cancer patients: a meta-analysis.

Eur J Cancer 2015 Apr 4;51(6):786-8. Epub 2015 Mar 4.

Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejca.2015.01.010DOI Listing
April 2015

CC motif chemokine ligand 19 suppressed colorectal cancer in vivo accompanied by an increase in IL-12 and IFN-γ.

Biomed Pharmacother 2015 Feb 24;69:374-9. Epub 2014 Dec 24.

Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Second Ruijin Road, Shanghai, China. Electronic address:

In this study we investigate the role of CC motif chemokine ligand 19 (CCL19) to colorectal cancer (CRC) in vivo. We injected different dose of recombinant mouse CCL19 (rmCCL19) in the tumor site of the model of transplanted tumor. Result shows that rmCCL19 can suppress CRC tumorigenesis and growth in vivo, and it can also prolong overall survival of mice. Quantitative reverse transcription-polymerase chain reaction and enzyme linked immunosorbent assay results showed that the interferon-γ (IFN-γ) and interleukin-12 (IL-12) levels in the tumors and plasma were significantly enhanced after processing with rmCCL19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2014.12.032DOI Listing
February 2015

Mild hypothermia reduces expression of Fas/FasL and MMP-3 after cerebral ischemia-reperfusion in rats.

Iran J Basic Med Sci 2014 Jun;17(6):454-9

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Objectives: To investigate the effects of local mild hypothermia on the expression of Fas, FasL and MMP-3 after cerebral ischemia-reperfusion in rats.

Materials And Methods: Male Wistar rats were divided into sham-operated group (Sham), normothermia group (NT), and hypothermia group (HT). MCAO/R model was established by Longa's method, and reperfusion was allowed after 2 hr occlusion. Mild hypothermia (33±0.5°C) for 6 hr was initiated at the start of reperfusion. Immunohistochemistry was performed to determine expression Fas, FasL, and MMP-3.

Results: Infarct volume was reduced in the hypothermia group (18.43±4.23%) compared with the normothermia group (24.76±5.76%) (P<0.05). In mild hypothermia group, numbers of Fas-positive and MMP-3 positive cells were significantly less than those of normothermia group (P<0.05). Neurological functional scores of mild hypothermia were significantly improved (P<0.05).

Conclusion: Mild hypothermia decreases infarct volume after cerebral ischemia-reperfusion, reduces Fas and MMP-3 expression, but increases FasL in cerebral ischemia-reperfusion rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137946PMC
June 2014

The physicochemical property characterization of agar acetate.

Carbohydr Polym 2014 Sep 27;110:32-7. Epub 2014 Mar 27.

College of Chemical Science and Engineering, Qingdao University, Qingdao 266071, China. Electronic address:

A series of agar acetates with different degree of substitution (DS) were prepared, and their properties were determined and analyzed. The results showed that the gelling temperature, the gel melting temperature, the gel strength, the gel hardness, the gel fracturability, the gel springiness and the solution apparent viscosity of agar acetates all decreased except that their gel cohesiveness increased with the increase of DS. The variation process of agar molecules in solution from coil to helix could be also observed by measuring solution optical rotation in a lower concentration at which even the solution could not form a gel. The gel skeleton structures of agar acetates were of porous network structures, and the pores became smaller and denser with the increase of DS. After acetylation, the water holding capacity of the agar was improved, but its thermal stability was lowered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2014.03.036DOI Listing
September 2014

Antitumor efficacy of CC motif chemokine ligand 19 in colorectal cancer.

Dig Dis Sci 2014 Sep 5;59(9):2153-62. Epub 2014 Apr 5.

Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Second Ruijin Road, Shanghai, China.

Objectives: To investigate the function of CC motif chemokine ligand 19 (CCL19) in colorectal cancer (CRC).

Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry were performed separately to detect the expression of CCL19 in colorectal carcinoma tissues. The expression of CCL19 and its receptor (CCR7) in CRC cell lines were screened by Western blot. SW620, SW1116 and LoVo cell lines were screened and processed with recombinant human CCL19 (rhCCL19) or si-CCL19 RNA. Cell proliferation assay and transwell assay were performed to evaluate the proliferation, migration and invasion of CRC cells, respectively. And the role of proangiogenesis was checked by endothelial tube formation assay.

Results: qRT-PCR, Western blot and immunohistochemistry revealed that both CCL19 mRNA and protein were obviously expressed in a lower degree in CRC tissues than normal tissues (P < 0.01). The CCL19 expression correlated with tumor size (P = 0.03) and invasion depth (P = 0.04) in a negative manner and CCL19-positive patients had longer lifespans (P < 0.05). SW620 and SW1116 cells were screened as CCL19/CCR7 high-expression cells, while LoVo was selected as CCL19/CCR7 low-expression cell among seven CRC cell lines by Western blot. The proliferation, migration, invasion and proangiogenesis of SW620 and SW1116 cells were distinctly suppressed after they were stimulated by rhCCL19 (P < 0.05), and the data presented dose-dependency. Oppositely, these abilities were significantly enhanced after CCL19 gene was silenced (P < 0.05). However, the effects of rhCCL19 and si-CCL19 RNA on LoVo were not significant (P > 0.05).

Conclusion: Our research findings indicate that CCL19 may play a suppressive role in colorectal tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-014-3138-yDOI Listing
September 2014

Cadherin-12 contributes to tumorigenicity in colorectal cancer by promoting migration, invasion, adhersion and angiogenesis.

J Transl Med 2013 Nov 15;11:288. Epub 2013 Nov 15.

Shanghai Minimally Invasive Surgery Center, Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Rd, Shanghai 200025, People's Republic of China.

Background: Cadherin 12 (CDH12), which encodes a type II classical cadherin from the cadherin superfamily, may mediate calcium-dependent cell adhesion. It has been demonstrated that CDH12 could play an important role in the invasion and metastasis of salivary adenoid cystic carcinoma. We decided to investigate the relationship between CDH12 expression level and clinicopathologic variables in colorectal carcinoma (CRC) patients and to explore the functions of CDH12 in tumorigenesis in CRC.

Methods: The expression levels of CDH12 in colorectal carcinoma tissues were detected by immunohistochemistry. Real-time PCR and Western Blot were used to screen CDH12 high-expression cell lines. CCK-8 assay was used to detect the proliferation ability of CRC cells being transfected by shRNAs against CDH12. The wound assay and transwell assay were performed to test migration and invasion ability. The importance of CDH12 in cell-cell junctions was detected by cell adhesion assay and cell aggregation assay. Endothelial tube formation assay was used to test the influence of CDH12 on angiogenesis.

Results: Statistical analysis of clinical cases revealed that the positive rate of CDH12 was higher in the CRC tumor tissues compared with the adjacent non-tumor tissues. The expression levels of CDH12 in CRC patients are significantly correlated with invasion depth. Consistently, the ability of proliferation, migration and invasion were suppressed when CDH12 was decreased in CRC cells transfected with shRNAs. Cell adhesion assay and cell aggregation assay presented that tumor cells tend to disperse with the lack of CDH12. Endothelial tube formation assay showed that down-regulation of CDH12 could obviously inhibit the process of angiogenesis, implying that CDH12 may play an important role in tumor metastasis

Conclusion: Our results showed that CDH12 promotes proliferation, migration, invasion, adhesion and angiogenesis, suggesting that CDH12 may be an oncogene in colorectal cancer. CDH12 is expected to become a new diagnostic and prognostic marker and a novel target of the treatment of colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1479-5876-11-288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879717PMC
November 2013

TXNDC9 expression in colorectal cancer cells and its influence on colorectal cancer prognosis.

Cancer Invest 2012 Dec;30(10):721-6

Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai, China.

In this study, we analyzed the protein expression of thioredoxin domain containing 9 (TXNDC9) in 116 colorectal cancer (CRC) cases. Among them, 97 were positive in CRC tissues and 60 were positive in normal mucosa. TXNDC9 expression in CRC was correlated with the extent of tumor invasion and the tumor size. TXNDC9-negative patients had longer lifespans. In vitro assays showed the significant suppression of CRC cell proliferation (P < .01) compared with two control groups; the number of invaded cells also decreased (P < .01). These findings suggest that TXNDC9 gene may function in cancer development and may be an effective target for inhibiting the growth and metastasis of CRC cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/07357907.2012.732160DOI Listing
December 2012

Acute disseminated encephalomyelitis associated with Influenza A H1N1 infection.

Neurol Sci 2011 Oct 8;32(5):907-9. Epub 2011 Mar 8.

Department of Neurology, The First Clinical College of Harbin Medical University, Harbin, 150001 Heilongjiang, People's Republic of China.

Previous studies had not suggested acute disseminated encephalomyelitis (ADEM) during Influenza A H1N1 infection. We report the case of patient who had predominant neurological complication following Influenza A H1N1 infection. The patient, who showed clinical and MRI evidence of ADEM, had significant recovery, which in part, may be related to early treatment. The patient demonstrated that the prognosis of Influenza A H1N1-associated ADEM may not be poor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-011-0500-0DOI Listing
October 2011

A novel lectin with highly potent antiproliferative and HIV-1 reverse transcriptase inhibitory activities from the edible wild mushroom Russula delica.

Glycoconj J 2010 Feb;27(2):259-65

State Key Laboratory for Agrobiotechnology and Department of Microbiology, China Agricultural University, Beijing 100094, China.

A dimeric lectin with a molecular weight of 60 kDa and high hemagglutinating activity was isolated from fresh fruiting bodies of the wild mushroom Russula delica. The lectin was composed of two identical subunits, each with a molecular weight of 30 kDa. It was adsorbed on both SP-Sepharose and Q-Sepharose and unadsorbed on DEAE-cellulose. Its hemagglutinating activity was stable up to 70 degrees C, and in HCl and NaOH solutions of concentrations up to 25 and 12.5 mM, respectively. The activity was inhibited by inulin and o-nitrophenyl-beta-D-galactopyranoside. Al3+, Fe3+ and Zn2+ ions, but not by Ca2+, Mg2+ and Mn2+ ions. Mg2+ ions at 10 mM concentration potentiated the hemagglutinating activity of the lectin. Russula delica lectin was devoid of mitogenic activity toward mouse splenocytes, but potently inhibited proliferation of HepG2 hepatoma and MCF 7 breast cancer cells, with an IC50 value of 0.88 microM and 0.52 microM, respectively. It potently inhibited HIV-1 reverse transcriptase activity with an IC50 of 0.26 microM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10719-009-9274-5DOI Listing
February 2010

Analysis of fuzhisan and quantitation of baicalin and ginsenoside Rb(1) by HPLC-DAD-ELSD.

Arch Pharm Res 2009 Jul 31;32(7):989-96. Epub 2009 Jul 31.

Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, P. R. China.

Fuzhisan (FZS) is a traditional Chinese medicine composed of Radix Ginseng Rubra (Araliaceae family), Scutellaria baicalensis Georgi (Labiatae family), Angelica sinensis (Oliv) Diels (Umbelliferae family), Anemone altaica Fisch. Ex C.A. Mey (Araceae family) and Glycyrrhiza uralensis (Leguminosae family). To establish the chemical fingerprint of the components of FZS and quantify the components, baicalin and ginsenoside Rb(1), a high performance liquid chromatography method coupled with diode array and evaporative light scattering detectors (DAD-ELSD) was developed. Separation of 36 components from 12 batches of FZS was performed on a C(18) column, with a mobile phase consisting of acetonitrile and 0.1% acetic acid-water, with gradient elution at a column temperature of 30 degrees C. The optimum detection wavelength was set at 335 nm, the drift tube temperature of ELSD was set at 80 degrees C, the carrier gas pressure was 25 psi, and the gain = 10. The similarity among 12 batches of FZS was over 0.95. Five constituents of FZS, namely baicalin, ferulic acid, and ginsenosides Rg(1), Re, and Rb(1), were identified based on their retention times (RT). Calibration curves for baicalin and ginsenoside Rb1 showed good linearity (r (2) > 0.9992); recoveries ranged from 95% to 99%. This quantification method is reproducible and simple, and may provide a tool to assess the quality of FZS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12272-009-1703-2DOI Listing
July 2009