PubMed Health⌕ Search

Biomedical subjects

Wanjun Chen

Publications and source records attributed to Wanjun Chen.

10 recordsLinked to original sources
PubMed2006

Dendritic cells and (CD4+)CD25+ T regulatory cells: crosstalk between two professionals in immunity versus tolerance.

Dendritic cells (DCs) are professional antigen presenting cells (APCs). (CD4+)CD25+ T regulatory cells (T regs) are recognized as professional regulatory cells. DCs not only initiate T cell immunity by uptake, processing and presentation of specific antigens, but also induce immune tolerance by deletion of T cells and/or induction of regulatory T cells. (CD4+)CD25+ T regs maintain immune tolerance by suppressing the function of CD4+ and CD8+ T cells, B cells, macrophages, DCs and NK cells. It would be inconceivable that the delicate balance between immunity and tolerance could be kept impeccable without the crosstalk between DCs and (CD4+)CD25+ T regs. This review focuses on the recent development in our understanding of DCs and (CD4+)CD25+ T regs in immune tolerance, with transforming growth factor-beta (TGF-beta) serving as a potential link between these two professionals.

Animals↗
PubMed2005

Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation.

Despite recent emerging evidence suggesting that cancer stem cells subsist in a variety of tumors, it is not yet fully elucidated whether postnatal stem cells are directly involved in tumorigenesis. We used murine bone marrow-derived mesenchymal stem cells (BMMSCs) as a model to test a hypothesis that tumorigenesis may originate from spontaneous mutation of stem cells. In this study, we demonstrated that murine BMMSCs, after numerous passages, obtained unlimited population doublings and proceeded to a malignant transformation state, resulting in fibrosarcoma formation in vivo. Transformed BMMSCs colonized to multiple organs when delivered systemically through the tail vein. Fibrosarcoma cells formed by transformed BMMSCs contained cancer progenitors, which were capable of generating colony clusters in vitro and fibrosarcoma in vivo by the second administration. The mechanism by which BMMSCs transformed to malignant cells was associated with accumulated chromosomal abnormalities, gradual elevation in telomerase activity, and increased c-myc expression. Moreover, BMMSCs and their transformed counterpart, fibrosarcoma-forming cells, demonstrated different sensitivity to anti-cancer drugs. BMMSCs/fibrosarcoma transformation system may provide an ideal system to elucidate the mechanism of how stem cells become cancer cells and to screen anti-sarcoma drugs.

Animals↗
PubMed2005

Transforming growth factor-beta-induced regulatory T cells referee inflammatory and autoimmune diseases.

Naturally occurring CD4+CD25+ regulatory T cells mediate immune suppression to limit immunopathogenesis associated with chronic inflammation, persistent infections and autoimmune diseases. Their mode of suppression is contact-dependent, antigen-nonspecific and involves a nonredundant contribution from the cytokine transforming growth factor (TGF)-beta. Not only can TGF-beta mediate cell-cell suppression between the regulatory T cells and CD4+CD25- or CD8+ T cells, but new evidence also reveals its role in the conversion of CD4+CD25- T cells, together with TCR antigen stimulation, into the regulatory phenotype. Elemental to this conversion process is induction of expression of the forkhead transcription factor, Foxp3. This context-dependent coercion of naive CD4+ T cells into a powerful subset of regulatory cells provides a window into potential manipulation of these cells to orchestrate therapeutic intervention in diseases characterized by inadequate suppression, as well as a promising means of controlling pathologic situations in which excessive suppression dominates.

Animals↗
PubMed2005

[The relationship between cyclin D1 and hypopharyngeal carcinoma].

OBJECTIVE: To study the relation ship between Cyclin expression and the biological behavior in 53 cases of hypopharyngeal squamous cell carcinoma. METHOD: Immunohistochemical (sp). method was used to detect the expression of cyclin D in 53 cases of hypopharyngeal squamous cell carcinoma and 11 cases of normal adjacent epithelium. RESULT: Positive expression for Cyclin D1 in hypopharyngeal squamous cell carcinoma was found in nuclear. The expression of cyclin D1 in the tumorous cell was significant hig her than in normal epithelium. Cyclin D1 expression was related to T grade and primary site, which correlation coefficient were 0.345 and -0.386 respectively. The highest positive rate of Cyclin D1 expression was in pyriform sinus. CONCLUSION: Cyclin D1 expression was related to T grade and primary site positively.

Adult↗
PubMed2004

TGF-beta: the perpetrator of immune suppression by regulatory T cells and suicidal T cells.

Innate and adaptive immunity function to eliminate foreign invaders and respond to injury while enabling coexistence with commensal microbes and tolerance against self and innocuous agents. Although most often effective in accomplishing these objectives, immunologic processes are not fail-safe and may underserve or be excessive in protecting the host. Checks and balances to maintain control of the immune system are in place and are becoming increasingly appreciated as targets for manipulating immunopathologic responses. One of the most recognized mediators of immune regulation is the cytokine transforming growth factor-beta (TGF-beta), a product of immune and nonimmune cells. Emerging data have unveiled a pivotal role for TGF-beta as a perpetrator of suppression by CD4(+)CD25(+) regulatory T (Treg) cells and in apoptotic sequelae. Through its immunosuppressive prowess, TGF-beta effectively orchestrates resolution of inflammation and control of autoaggressive immune reactions by managing T cell anergy, defining unique populations of Treg cells, regulating T cell death, and influencing the host response to infections.

Animals↗
PubMed2004

Regulatory T cells and transcription factors: gatekeepers in allergic inflammation.

Antigen-provoked polarization of CD4+ T cells along the Th1 pathway is often associated with autoimmune and chronic inflammatory diseases, whereas extreme skewing of the response toward a Th2 phenotype has been linked to atopy and allergic diseases. Intense interest in the underlying molecular mechanisms that control polarization has revealed a contingent of regulatory transcription factors, which not only help to define these pathways but also suggest potential sites for interventional tactics. Moreover, the recent identification of transcription factors specifically associated with CD4(+)CD25+ regulatory T-cells provides new clues regarding manipulation of this population in pursuit of directed immune regulation. Continued unraveling of the pathways underlying the development of deleterious immune responses and their control will guide new avenues of investigation and intervention.

Animals↗
PubMed2003

Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence.

Our previous work demonstrated that cytotoxic T lymphocyte (CTL)-mediated tumor immunosurveillance of the 15-12RM tumor could be suppressed by a CD1d-restricted lymphocyte, most likely a natural killer (NK) T cell, which produces interleukin (IL)-13. Here we present evidence for the effector elements in this suppressive pathway. T cell-reconstituted recombination activating gene (RAG)2 knockout (KO) and RAG2/IL-4 receptor alpha double KO mice showed that inhibition of immunosurveillance requires IL-13 responsiveness by a non-T non-B cell. Such nonlymphoid splenocytes from tumor-bearing mice produced more transforming growth factor (TGF)-beta, a potent inhibitor of CTL, ex vivo than such cells from naive mice, and this TGF-beta production was dependent on the presence in vivo of both IL-13 and CD1d-restricted T cells. Ex vivo TGF-beta production was also abrogated by depleting either CD11b+ or Gr-1+ cells from the nonlymphoid cells of tumor-bearing mice. Further, blocking TGF-beta or depleting Gr-1+ cells in vivo prevented the tumor recurrence, implying that TGF-beta made by a CD11b+ Gr-1+ myeloid cell, in an IL-13 and CD1d-restricted T cell-dependent mechanism, is necessary for down-regulation of tumor immunosurveillance. Identification of this stepwise regulation of immunosurveillance, involving CD1-restricted T cells, IL-13, myeloid cells, and TGF-beta, explains previous observations on myeloid suppressor cells or TGF-beta and provides insights for targeted approaches for cancer immunotherapy, including synergistic blockade of TGF-beta and IL-13.

Animals↗
PubMed2003

TGF-beta: how tolerant can it be?

A balance between an adequate immune response to an antigen or pathogen and tolerance is a prerequisite for normal immune homeostasis and the well-being of the host. In this complex self-regulation, multiple mechanisms have been implicated as contributing to the immune tolerance network, including apoptosis, anergy, and active suppression. Current excitement focuses on active suppression and new regulatory T cell-mediated pathways of immunosuppression that are being unraveled. Central to several of these pathways is transforming growth factor-beta (TGF-beta), a potent immunoregulatory cytokine that contributes to the function and generation of regulatory T cells.

Animals↗
PubMed2002

[Surgical approaches to the skull and near skull base neoplasms].

OBJECTIVE: To seek for the best surgical approaches to the skull and near-skull base neoplasms. METHOD: 161 patients with skull or near-skull base tumors were surgically treated. The surgical approaches were craniofacial approach in 6 cases, total maxillectomy or/with orbital exenteration in 5 cases, lateral rhinotomy in 7 cases, frontorbital approach in 1 cases, maxillary swing or extended maxillary swing approach in 21 cases, mandibular swing approach in 30 cases, cervical approach in 48 cases, postaurical large C incision approach in 19 cases, transparotid approach in 8 cases, transoral approach in 6 cases, temporofrontal approach in 8 cases, subtemporal preauricular approach in 2 cases. RESULT: Of the 98 benign tumors cases, 2 recurred postoperatively. Of the 63 malignant tumors, 1 case had cerebrospinal fluid leakage and died of intracranial infection 1.5 months postoperatively. In the follow up period, the longest one survival was over 8 years, and 10 over 5 years, 19 over 3 years, 16 over 2 years, 16 over 1 year. Survival rates of 3 and 5 years were 59.18% and 38.46% respectively. CONCLUSION: According to the site, range and pathology of the skull base neoplasmas, surgical approaches were designed and selected rationally and the effects better.

Adolescent↗