Bone marrow adipocytes is a new player in supporting myeloma cells proliferation and survival in myeloma microenvironment.

Multiple myeloma (MM) is a lethal B cell neoplasm characterized by clonal expansion of malignant plasma cells in the bone marrow and remains incurable due to disease relapse and drug resistance. Bone marrow adipocytes (BMAs) are emerging as playing active functions that can support myeloma cell growth and survival. The aim of this study is to investigate myeloma-mesenchymal stem cells (MSCs) interaction and the impact of such interactions on the pathogenesis of MM using in vitro co-culture assay.

Intratumoral expression of interleukin 23 variants using oncolytic vaccinia virus elicit potent antitumor effects on multiple tumor models via tumor microenvironment modulation.

Newly emerging cancer immunotherapy has led to significant progress in cancer treatment; however, its efficacy is limited in solid tumors since the majority of them are "cold" tumors. Oncolytic viruses, especially when properly armed, can directly target tumor cells and indirectly modulate the tumor microenvironment (TME), resulting in "hot" tumors. These viruses can be applied as a cancer immunotherapy approach either alone or in combination with other cancer immunotherapies.

CSN8 is a key regulator in hypoxia-induced epithelial-mesenchymal transition and dormancy of colorectal cancer cells.

Hypoxic stress plays a pivotal role in cancer progression; however, how hypoxia drives tumors to become more aggressive or metastatic and adaptive to adverse environmental stress is still poorly understood. In this study, we revealed that CSN8 might be a key regulatory switch controlling hypoxia-induced malignant tumor progression. We demonstrated that the expression of CSN8 increased significantly in colorectal cancerous tissues, which was correlated with lymph node metastasis and predicted poor patient survival.

Oncolytic vaccinia virus delivering tethered IL-12 enhances antitumor effects with improved safety.

Immune checkpoint blockade is arguably the most effective current cancer therapy approach; however, its efficacy is limited to patients with "hot" tumors, warranting an effective approach to transform "cold" tumors. Oncolytic viruses (especially properly armed ones) have positive effects on almost every aspect of the cancer-immunity cycle and can change the cancer-immune set point of a tumor. Here, we tested whether oncolytic vaccinia virus delivering tethered interleukin 12 (IL-12) could turn a "cold" tumor into a "hot" tumor while avoiding IL-12's systemic toxicity.

Nuclear-localized costimulatory molecule 4-1BBL promotes colon cancer cell proliferation and migration by regulating nuclear Gsk3β, and is linked to the poor outcomes associated with colon cancer.

Anti-tumor immune response and the prognosis of tumor are the results of competition between stimulatory and inhibitory checkpoints. Except for upregulating inhibitory checkpoints, lowering some immune accelerating molecules to convert an immunostimulatory microenvironment into an immunodormant one through "decelerating the accelerator" might be another effective immune escape pattern. 4-1BBL is a classical transmembrane costimulatory molecule involving in antitumor immune responses.

Modifying the cancer-immune set point using vaccinia virus expressing re-designed interleukin-2.

The complex immune tumour microenvironment requires an equally complex immunotherapy approach, especially when the cancer-immune set point is non-inflamed. Oncolytic viruses expressing immune activating cytokines might optimally modify the immune microenvironment and improve the antitumour effects. In this study, we have explored a variety of IL-2 constructs expressed by a tumour-selective oncolytic vaccinia virus, designed to maintain IL-2 in the tumour microenvironment to reduce systemic toxicity.

Impact of cell fusion in myeloma marrow microenvironment on tumor progression.

Background: Mesenchymal stem cells (MSCs) represent a subset of non-hematopoietic adult stem cells, which can also fuse with other cells spontaneously in bone marrow and capable of adopting the phenotype of other cells. The fusion of somatic cells with stem cells can reprogram somatic cells to a pluripotent state. Our research on the fusion of bone marrow mesenchymal stem cells(BM-MSCs) and MM cells demonstrate that the fused cells can exhibit stemness and cancer cell-like characteristics.

Impact of connexin 43 coupling on survival and migration of multiple myeloma cells.

Introduction: Gap junctions (GJs) represent the best known intercellular communication (IC) system and are membrane-spanning channels that facilitate intercellular communication by allowing small signaling molecules to pass from cell to cell. In this study, we constructed an amino terminus of human Cx43 (Cx43NT-GFP), verified the overexpression of Cx43-NT in HUVEC cells and explored the impact of gap junctions (GJs) on multiple myeloma (MM).

Material And Methods: The levels of phosphorylated Cx43(s368) and the change of MAPK pathway associated molecules (ERK1/2, JNK, p38, NFκB) were also investigated in our cell models.

Dietary quercetin ameliorates experimental colitis in mouse by remodeling the function of colonic macrophages via a heme oxygenase-1-dependent pathway.

Inflammatory bowel disease (IBD) results from a chronic intestinal inflammation and tissue destruction via an aberrant immune-driven inflammatory response towards an altered gut microbiota. Dietary intervention is becoming an attractive avenue for the therapy of colitis because diet is a key determinant of the mucosal immune response. Quercetin (QCN) is the most common in nature and the major representative of dietary antioxidant flavonoids, which has been demonstrated to influence the progression of colitis.

Immune checkpoint molecule PD-1 acts as a novel biomarker for the pathological process of gestational diabetes mellitus.

Aim: Accumulating evidence suggested that challenge of the maternal-fetal interaction during pregnancy might cause the impairment of immunological hemostasis and lead to gestational diabetes mellitus (GDM) pathological process. Immune checkpoint molecule PD-1 is one of the critical molecule balancing immune response and immunological tolerance.

Methods: PD-1 expressions on T-cell subsets of GDM patients and control groups were measured via flow cytometric analysis and followed up.

Directional delivery of RSPO1 by mesenchymal stem cells ameliorates radiation-induced intestinal injury.

Radiation-induced intestinal injury (RIII) commonly occurs in patients who received radiotherapy for pelvic or abdominal cancer, or who suffered from whole-body irradiation during a nuclear accident. RIII can lead to intestinal disorders and even death given its integrity damage that results from intestinal stem cell (ISC) loss. Recovery from RIII relies on the intensity of supportive treatment, which can attenuate lethal infection and give surviving stem cells an opportunity to regenerate.

Impact of Global and Gene-Specific DNA Methylation in de Novo or Relapsed Acute Myeloid Leukemia Patients Treated with Decitabine.

In this investigation, global DNA methylation patterns and the specific methylation status of 5 genes were studied in DNA from peripheral blood (PB) and impact on progression free survival (PFS) and overall-survival (OS) in patients with de novo or relapsed acute myeloid leukemia (AML) treated with decitabine-based regimens waas assessed. DNA was isolated from PB samples at the time of -1, 1, and 7 days of chemotherapy. Global methylation was determined by ELISA, and the CpG island DNA methylation profile of 5 genes using a DNA methylation PCR system.

[Sensitivity to bortezomib of RPIM8226 cells after co-cultured with down-regulated Cav-1 expression HUVECs].

Objective: To investigate the sensitivity to bortezomib of RPMI8226 cells after co-cultured with down-regulated Caveolin (Cav)-1 expression of HUVECs by transfection with Cav-1 shRNA (HUVECs(Cav-1 low)).

Methods: Exposure to bortezomib with or without 50 nmol/L dexamethasone at different concentration, the proliferation of RPMI8226 was analyzed by MTT assay when it was cultured alone or co-cultured with HUVECs(Cav-1 low). Cav-1 expression was detected by using of Western blot and cell cycle, apoptosis and the level of reactive oxygen species (ROS) were analyzed by flow cytometry.

An anti-human CD13 monoclonal antibody that suppresses the suppressive function of Treg cells.

CD13 (CD13/aminopeptidase N, APN, or CD13/APN) is a widely expressed type II membrane-bound metalloprotease. It is often overexpressed on cancer cells and expressed on CD4(+)CD25(hi) Treg cell subpopulation with higher suppressive ability. It has been determined to be a promising target in cancer diagnosis and therapy.

Blockade of PD-1/PD-L1 immune checkpoint during DC vaccination induces potent protective immunity against breast cancer in hu-SCID mice.

Immune checkpoints, such as the PD-1/PD-L1 pathway, negatively interfere in the efficiency of dendritic cell (DC) vaccination in cancer immunotherapy. In this study, we demonstrated that the blockade of PD-L1 signaling could promote DC maturation, proliferation, and IL-12 secretion, augment DC primed T cell response and reverse tumor cell dampened T cell impairment. Blockade of PD-L1 signaling during DC vaccination showed better therapeutic effects than classic DC vaccination by preventing tumor growth and prolonging survival times in a breast tumor-bearing hu-SCID model.

[Eukaryotic expression and biological activity of recombinant human IL-17B protein].

Aim: To construct pCEP4/hIL-17B recombinant expression vector and express it stably in eukaryotic cells and investigate the biological activity in vitro.

Methods: The CDS region of human IL-17B gene was cloned by RT-PCR. After identification by sequencing, the hIL-17B gene was inserted into expression vector of pCEP4 to construct the recombinant vector pCEP4/hIL-17B, then transfected into 293T cells.

Anti-human FLT3 monoclonal antibody that inhibits proliferation of monocytic leukemia cell line SHI-1.

FLT3, a transmembrane molecule, was found on hematopoietic stem/progenitor cells and leukemia cells and determined to be a promising target in leukemia diagnosis and therapy. In this study a functional anti-human FLT3, monoclonal antibody (MAb) 10G6, was obtained and the specificity of this MAb was verified by flow cytometry. This MAb effectively recognized the FLT3 molecule expressed on a series of malignant cell lines.

Functional expression of chimeric Fab of an anti-CD40L mAb: Vector design and culture condition optimization.

CD40L is an important costimulatory molecule in the induction of the humoral and cell-mediated immune responses. 4F1, a specific murine antagonistic monoclonal antibody against human CD40L molecule, is a promising candidate biomedicine for autoimmune diseases, transplantation rejection and anti-angiogenesis therapy of cancer. To avoid the mAb induced thromboembolism as a consequence of platelet surface FcγR activation, we attempted to construct a chimeric Fab of 4F1 to minimize its side effects for potential clinical use.

T-bet and eomesodermin are required for T cell-mediated antitumor immune responses.

Cell-mediated adaptive immunity is very important in tumor immune surveillance and tumor vaccination. However, the genetic program underlying an effective adaptive antitumor immunity is elusive. T-bet and Eomesodermin (Eomes) have been suggested to be master regulators of Th1 cells and CD8(+) T cells.

Gadd45b and Gadd45g are important for anti-tumor immune responses.

An effective Th1 type cell-mediated immune response against cancer cells is critical in limiting cancer progression. Gadd45b, a signaling molecule highly up-regulated during Th1 type responses, is studied for its role in limiting tumor growth. Mouse B16 melanoma cells implanted into Gadd45b(-/-) mice grew faster than those in WT or Gadd45b(+/-) littermate controls.

A novel approach to induce human DCs from monocytes by triggering 4-1BBL reverse signaling.

Dendritic cells (DCs) are responsible for the initiation of immune responses. Our study demonstrates a new pathway for generating a large quantity of stimulatory monocyte-derived DCs (Mo-DCs) from human monocytes using anti-4-1BB ligand (4-1BBL) mAb to trigger reverse signaling. The anti-4-1BBL-driven Mo-DCs (DCs(alpha-4-1BBL)) not only express higher levels of CD86, CD83 and HLA-DR, when compared with the Mo-DCs matured by tumor necrosis factor alpha, but also exhibit a unique phenotype that expresses lower levels of PD-L1.

CD13+CD4+CD25hi regulatory T cells exhibit higher suppressive function and increase with tumor stage in non-small cell lung cancer patients.

Regulatory T cells (Tregs) in peripheral blood and tumor infiltrating lymphocytes (TILs) play crucial roles in suppressing anti-tumor immune responses in cancer patients, and correlate with clinical outcomes. We identified an important subpopulation, CD13+CD4+CD25hiTreg cells, among CD4+CD25hiTreg cells in the peripheral blood of non-small cell lung cancer (NSCLC) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with NSCLC (n = 72) or from healthy donors (n = 30).

IL-17 signaling-independent central nervous system autoimmunity is negatively regulated by TGF-beta.

Recent studies have established an important role of Th17 in induction of autoimmune diseases. We have found that although IL-17 receptor A (IL-17RA)(-/-) mice were resistant to experimental autoimmune encephalomyelitis, a small number of them developed milder clinical signs of this autoimmune disease. In addition, blockade of TGF-beta in IL-17RA(-/-) mice resulted in much more severe clinical signs of experimental autoimmune encephalomyelitis and significantly increased parenchymal lymphocyte infiltration in the CNS.

[Preparation of three functional monoclonal antibodies against human FL molecule and analysis of their bioactivity].

Aim: To Prepare three functional monoclonal antibodies(mAbs) against human FL molecule and analyze their bioactivity.

Methods: The cell line L929-FL transfected with human FL gene was used as immunogen. The hybridomas secreting the antibodies against human FL were obtained by fusing splenoecytes from the immunized mice with murine myeloma cells(Sp2/0).