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Pan W.,Shaoxing University | Huang S.,Zhejiang University | Zhang J.,Wenzhou Medical College | Zhao B.,Zhejiang University | And 5 more authors.
Hepato-Gastroenterology | Year: 2013

Background/Aims: Heterogeneity in primary tumor and related metastases may result in different response to anticancer therapy. Previous work revealed that there were heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases. Whether such heterogeneity in primary colon carcinoma and corresponding lymphatic and hepatic metastases would result in different response to anticancer therapy is unknown. Methodology: To investigate whether the heterogeneity in primary colon carcinoma and matched lymphatic and hepatic metastases would result in different response to anticancer therapy, patient-derived tumor tissue (PDTT) xenograft models of colon carcinoma with lymphatic and hepatic metastases were used to evaluate the response to VEGF-targeted therapy (bevacizumab) in combination with chemotherapy (capecitabine). Results: All xenografts of primary colon carcinoma and corresponding lymphatic and hepatic metastases in nude mice responded to VEGF-targeted therapy in combination with chemotherapy. However, chemotherapy alone resulted in significantly higher tumor growth inhibition rate in xenogfafts of primary colon carcinoma than that of corresponding lymphatic and hepatic metastasis (p <0.01). VEGF-targeted therapy in combination with chemotherapy resulted in significantly higher tumor growth inhibition rate in xenogfafts of colon carcinoma lymphatic metastasis than that of corresponding primary colon carcinoma and hepatic metastasis (p <0.001). Conclusions: Our results demonstrate that primary colon carcinoma and its corresponding lymphatic and hepatic metastases have different response rate to chemotherapy and to VEGF-targeted therapy in combination with chemotherapy. This study provides us new hints to tumor-site-based personalized cancer therapy in metastatic colon carcinoma. © H.G.E. Update Medical Publishing S.A. Source

Wu X.,Zhejiang University | Luo Y.,Zhejiang University | Chen J.,Zhejiang University | Pan R.,Zhejiang University | And 7 more authors.
Stem Cells and Development | Year: 2014

Recently, a unique population of progenitor cells was isolated from human menstrual blood. The human menstrual blood progenitor cells (MBPCs) possess many advantages, such as the noninvasive acquisition procedure, broad multipotency, a higher proliferative rate, and low immunogenicity, and have attracted extensive attention in regenerative medicine. Preclinical studies to test the safety and efficacy of MBPCs have been underway in several animal models. However, relevant studies in type 1 diabetes mellitus (T1DM) have not yet been proceeded. Herein, we studied the therapeutic effect of MBPCs and the mechanism of β-cell regeneration after MBPC transplantation in the T1DM model. Intravenous injection of MBPCs can reverse hyperglycemia and weight loss, prolong lifespan, and increase insulin production in diabetic mice. Histological and immunohistochemistry analyses indicated that T1DM mice with MBPC transplantation recovered islet structures and increased the β-cell number. We further analyzed in vivo distribution of MBPCs and discovered that a majority of MBPCs migrated into damaged pancreas and located at the islet, duct, and exocrine tissue. MBPCs did not differentiate into insulin-producing cells, but enhanced neurogenin3 (ngn3) expression, which represented endocrine progenitors that were activated. Ngn3+ cells were not only in the ductal epithelium, but also in the islet and exocrine tissue. We analyzed a series of genes associated with the embryonic mode of β-cell development by real-time polymerase chain reaction and the results showed that the levels of those gene expressions all increased after cell transplantation. According to the results, we concluded that MBPCs stimulated β-cell regeneration through promoting differentiation of endogenous progenitor cells. © Copyright 2014, Mary Ann Liebert, Inc. Source

Mou X.-Z.,Zhejiang University | Mou X.-Z.,Institute for Cell Based Drug Development of Zhejiang Province | Lin J.,Zhejiang University | Chen J.-Y.,Institute for Cell Based Drug Development of Zhejiang Province | And 8 more authors.
Journal of Zhejiang University: Science B | Year: 2013

Orthotopic liver transplantation (OLT) is the only proven effective treatment for both end-stage and metabolic liver diseases. Hepatocyte transplantation is a promising alternative for OLT, but the lack of available donor livers has hampered its clinical application. Hepatocyte-like cells (HLCs) differentiated from many multi-potential stem cells can help repair damaged liver tissue. Yet almost suitable cells currently identified for human use are difficult to harvest and involve invasive procedures. Recently, a novel mesenchymal stem cell derived from human menstrual blood (MenSC) has been discovered and obtained easily and repeatedly. In this study, we examined whether the MenSCs are able to differentiate into functional HLCs in vitro. After three weeks of incubation in hepatogenic differentiation medium containing hepatocyte growth factor (HGF), fibroblast growth factor-4 (FGF-4), and oncostain M (OSM), cuboidal HLCs were observed, and cells also expressed hepatocyte-specific marker genes including albumin (ALB), α-fetoprotein (AFP), cytokeratin 18/19 (CK18/19), and cytochrome P450 1A1/3A4 (CYP1A1/3A4). Differentiated cells further demonstrated in vitro mature hepatocyte functions such as urea synthesis, glycogen storage, and indocyanine green (ICG) uptake. After intrasplenic transplantation into mice with 2/3 partial hepatectomy, the MenSC-derived HLCs were detected in recipient livers and expressed human ALB protein. We also showed that MenSC-derived HLC transplantation could restore the serum ALB level and significantly suppressed transaminase activity of liver injury animals. In conclusion, MenSCs may serve as an ideal, easily accessible source of material for tissue engineering and cell therapy of liver tissues. © 2013 Zhejiang University and Springer-Verlag Berlin Heidelberg. Source

Fu C.-Y.,Zhejiang Sci-Tech University | Fu C.-Y.,Institute for Cell Based Drug Development of Zhejiang Province | Xia R.-L.,Zhejiang Sci-Tech University | Zhang T.-F.,Zhejiang Sci-Tech University | And 6 more authors.
PLoS ONE | Year: 2014

Our previous studies have shown that an active fragment of human tachykinins (hHK-1(4-11)) produced an opioidindependent analgesia after intracerebroventricular (i.c.v.) injection in mice, which has been markedly enhanced by a d OR antagonist, naltrindole hydrochloride (NTI). In this study, we have further characterized the in vivo analgesia after i.c.v. injection of hHK-1(4-11) in mouse model. Our qRT-PCR results showed that the mRNA levels of several ligands and receptors (e.g. PPT-A, PPT-C, KOR, PDYN and PENK) have not changed significantly. Furthermore, neither transcription nor expression of NK1 receptor, MOR and POMC have changed noticeably. In contrast, both mRNA and protein levels of DOR have been upregulated significantly, indicating that the enhanced expression of d opioid receptor negatively modulates the analgesia induced by i.c.v. injection of hHK-1(4-11). Additionally, the combinatorial data from our previous and present experiments strongly suggest that the discriminable distribution sites in the central nervous system between hHK-1(4-11) and r/mHK-1 may be attributed to their discriminable analgesic effects. Altogether, our findings will not only contribute to the understanding of the complicated mechanisms regarding the nociceptive modulation of hemokinin-1 as well as its active fragments at supraspinal level, but may also lead to novel pharmacological interventions. © 2014 Fu et al. Source

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