Cystatin A promotes the antitumor activity of T helper type 1 cells and dendritic cells in murine models of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a disease with poor prognosis due to diagnostic and therapeutic limitations. We previously identified cystatin A (CSTA) as a PDAC biomarker and have conducted the present study to investigate the antitumor effects of CSTA. PDAC murine models were established with genetically modified PAN02 tumor cell lines to evaluate the antitumor immune response.

The declining insulinogenic index correlates with inflammation and metabolic dysregulation in non-obese individuals assessed by blood gene expression.

Aims: Diabetes onset is difficult to predict. Since decreased insulinogenic index (IGI) is observed in prediabetes, and blood gene expression correlates with insulin secretion, candidate biomarkers can be identified.

Methods: We collected blood from 96 participants (54 males, 42 females) in 2008 (age: 52.

Characterization of adipose tissue-derived stromal cells of mice with nonalcoholic fatty liver disease and their use for liver repair.

Introduction: Freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs), containing miscellaneous cells like the relatively abundant mesenchymal stem cells, are attractive for repair and regenerative therapy. However, the detailed characteristics and therapeutic efficacy of u-ADSCs obtained from disease-affected hosts are unknown. We compared the properties of u-ADSCs obtained from wild-type mice and from a mouse model of non-alcoholic steatohepatitis (NASH).

Eight-year longitudinal study of whole blood gene expression profiles in individuals undergoing long-term medical follow-up.

Blood circulates throughout the body via the peripheral tissues, contributes to host homeostasis and maintains normal physiological functions, in addition to responding to lesions. Previously, we revealed that gene expression analysis of peripheral blood cells is a useful approach for assessing diseases such as diabetes mellitus and cancer because the altered gene expression profiles of peripheral blood cells can reflect the presence and state of diseases. However, no chronological assessment of whole gene expression profiles has been conducted.

Restorative effect of adipose tissue-derived stem cells on impaired hepatocytes through Notch signaling in non-alcoholic steatohepatitis mice.

Adipose tissue-derived stem cells (ADSCs) have been suggested as a novel treatment for non-alcoholic steatohepatitis (NASH); however, the mechanisms underlying their therapeutic effect remain poorly understood. In this study, we aimed to investigate the association of Notch signaling, which is crucial for cellular proliferation and differentiation in ADSC-mediated treatment of NASH. Flow cytometry analysis of ADSCs showed that they expressed the Notch ligands JAG1, DLL1, and DLL4.

Clinical trial of autologous adipose tissue-derived regenerative (stem) cells therapy for exploration of its safety and efficacy.

Introduction: Liver cirrhosis is the ultimate condition of chronic liver diseases. Non-alcoholic steatohepatitis and fatty liver diseases are emerging in association with metabolic syndrome largely due to excess nutrition. Stromal cells of adipose tissue are enriched mesenchymal stem cells which are pluripotent and immunomodulatory, which are expected to be applied for repairing/regenerative therapy of the impaired organs.

Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis.

Background: Pancreatic ductular adenocarcinoma (PDAC) is among the most dreadful of malignancies, in part due to the lack of efficacious chemotherapy. Immune checkpoint inhibitors, including anti-programmed cell death 1 (anti-PD-1) antibodies, are novel promising forms of systemic immunotherapy. In the current study, we assessed whether gemcitabine (GEM) combined with anti-PD-1 antibody treatment was efficacious as immunochemotherapy for advanced PDAC using a murine model of liver metastasis.

Regenerative Therapy for Liver Cirrhosis Based on Intrahepatic Arterial Infusion of Autologous Subcutaneous Adipose Tissue-Derived Regenerative (Stem) Cells: Protocol for a Confirmatory Multicenter Uncontrolled Clinical Trial.

Background: Liver cirrhosis results from chronic hepatitis, and is characterized by advanced fibrosis due to long-term hepatic inflammation. Cirrhosis ultimately leads to manifestations of jaundice, ascites, and encephalopathy, and increases the risk of hepatocellular carcinoma. Once cirrhosis is established, resulting in hepatic failure, no effective treatment is available.

Adipose tissue-derived stem cells prevent fibrosis in murine steatohepatitis by suppressing IL-17-mediated inflammation.

Background And Aim: The pathological features of non-alcoholic steatohepatitis (NASH) have not been determined, so fundamental treatment has not been established. Adipose-tissue-derived stromal/stem cells (ADSCs) are beneficial for repair/regenerative therapy of impaired organs because of their immuno-modulatory capability. In this study, we assessed how liver damage progresses during the early development phase of the murine NASH model and investigated whether ADSCs are preventatively efficacious against the fibrosis progression of NASH.

Development of novel diagnostic system for pancreatic cancer, including early stages, measuring mRNA of whole blood cells.

Pancreatic ductal adenocarcinoma (PDAC) is the most life-threating disease among all digestive system malignancies. We developed a blood mRNA PDAC screening system using real-time detection PCR to detect the expression of 56 genes, to discriminate PDAC from noncancer subjects. We undertook a clinical study to assess the performance of the developed system.

Distinct chemotherapy-associated anti-cancer immunity by myeloid cells inhibition in murine pancreatic cancer models.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy associated with an extremely poor prognosis. Chemotherapy, such as gemcitabine (GEM), is the only treatment for PDAC patients who are not suitable for radical surgical treatment; however, its anti-tumor efficacy is limited. In this study, we investigated the host immune system response in murine PDAC models undergoing GEM treatment.

Biological characteristics of gene expression features in pancreatic cancer cells induced by proton and X-ray irradiation.

Background: Radiation therapy is an important alternative treatment for advanced cancer. The aim of the current study was to disclose distinct alterations of the biological characteristics of gene expression features in pancreatic cancer cells, MIAPaCa-2, following proton and X-ray irradiation.

Materials And Methods: Using cDNA microarray, we examined the gene expression alterations of MIAPaCa-2 cells following proton or X-ray irradiation.

The CD45 fraction in murine adipose tissue derived stromal cells harbors immune-inhibitory inflammatory cells.

Stromal cells in adipose tissue are useful for repair/regenerative therapy as they harbor a substantial number of mesenchymal stem cells; therefore, freshly isolated autologous uncultured adipose tissue derived stromal cells (u-ADSCs) are useful for regenerative therapy, and obviate the need for mesenchymal stem cells. We evaluated the therapeutic effect of murine u-ADSCs and sorted subsets of u-ADSCs in a concanavalin A (ConA) induced murine model of hepatitis, as well as their characteristics. We found that 10-20% of u-ADSCs expressed the CD45 leukocyte-related antigen.

Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell.

Introduction: Adipose tissue stromal cells contain a substantial number of mesenchymal stem cells. As such, their application to regeneration of miscellaneous impaired organs has attracted much attention.

Methods: We designed a clinical study to investigate freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell (ADRC) therapy for liver cirrhosis and conducted treatment in four cirrhotic patients.

Adipose tissue derived stromal stem cell therapy in murine ConA-derived hepatitis is dependent on myeloid-lineage and CD4+ T-cell suppression.

Mesenchymal stromal stem cells (MSCs) are an attractive therapeutic model for regenerative medicine due to their pluripotency. MSCs are used as a treatment for several inflammatory diseases, including hepatitis. However, the detailed immunopathological impact of MSC treatment on liver disease, particularly for adipose tissue derived stromal stem cells (ADSCs), has not been described.

Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model.

Unlabelled: Cirrhosis is a chronic liver disease that impairs hepatic function and causes advanced fibrosis. Mesenchymal stem cells have gained recent popularity as a regenerative therapy since they possess immunomodulatory functions. We found that injected adipose tissue-derived stem cells (ADSCs) reside in the liver.

Utilisation of nanoparticle technology in cancer chemoresistance.

The implementation of cytotoxic chemotherapeutic drugs in the fight against cancer has played an invariably essential role for minimizing the extent of tumour progression and/or metastases in the patient and thus allowing for longer event free survival periods following chemotherapy. However, such therapeutics are nonspecific and bring with them dose-dependent cumulative adverse effects which can severely exacerbate patient suffering. In addition, the emergence of innate and/or acquired chemoresistance to the exposed cytotoxic agents undoubtedly serves to thwart effective clinical efficacy of chemotherapy in the cancer patient.

Association of changes in the gene expression profile of blood cells with the local tumor inflammatory response in a murine tumor model.

Cancer tissue is frequently associated with the host inflammatory response, which involves blood cells. Using DNA microarrays, we examined the gene expression profiles of blood and tumors in a murine subcutaneous hepatocellular carcinoma model, in which tumors develop during the initial 10 days and then diminish and disappear by day 25 after implantation. Immunohistochemical and gene expression analysis indicated that tumor tissues were associated with an active immune response, particularly the CD4+ T cell-mediated immune response, on day 10.

Nanocarriers for cytoplasmic delivery: cellular uptake and intracellular fate of chitosan and hyaluronic acid-coated chitosan nanoparticles in a phagocytic cell model.

The cellular uptake of hyaluronic-acid-coated, negatively charged chitosan/triphosphate nanoparticles and that of uncoated, positively charged ones is investigated by studying cellular localization, uptake kinetics and mechanism of internalization in J774.2 macrophages, using non-phagocytic L929 fibroblasts as a control for uncoated nanoparticles. Both kinds of nanoparticles undergo endosomal escape and adopt a similar clathrin-based endocytic mechanism.

Chitosan/TPP and chitosan/TPP-hyaluronic acid nanoparticles: systematic optimisation of the preparative process and preliminary biological evaluation.

Purpose: Chitosan is one of the most sought-after components for designing nanoparticles for drug delivery applications. However, despite the large number of studies, reproducibility is often an issue; generally more attention should be focused on purity and precise characterization of the starting material, as well as on the development of robust preparative procedures.

Methods: Using a rational experimental design, we have studied the influence of a number of orthogonal factors (pH, concentrations, ratios of components, different methods of mixing) in the preparation of chitosan/triphosphate (TPP) nanoparticles and in their coating with hyaluronic acid (HA), aiming at the minimisation of size polydispersity, the maximisation of zeta potential and long-term stability, and at the control over average nanoparticle size.