Theranostic signature of tumor-derived exosomes in cancer.

Cancer is the most challenging global health crisis. In the recent times, studies on extracellular vesicles (EVs) are adding a new chapter to cancer research and reports on EVs explores cancer in a new dimension. Exosomes are a group of subpopulations of EVs.

Role of exosomes and its emerging therapeutic applications in the pathophysiology of non-infectious diseases.

Exosomes are a type of small extracellular vesicles (EVs) which play a crucial role in various diseases. These micro molecules have a macro impact in the pathophysiology of non-infectious diseases. Exosomes involvement in the different diseases has been studied as they regulate intercellular communications and can be derived from various sources.

Modulation of the contact hypersensitivity response by AE-941 (Neovastat), a novel antiangiogenic agent.

Background: AE-941 (Neovastat) is an angiogenesis inhibitor noted to have antiinflammatory properties.

Objective: We tested Neovastat in a contact hypersensitivity (CHS) model to determine the mechanism of action of its antiinflammatory effects.

Methods: Neovastat was orally administered (200 mg/kg/day) during the sensitization and challenge phases of a murine CHS assay and inflammatory responses were measured.

Low-dose ultraviolet B rays alter the mRNA expression of the circadian clock genes in cultured human keratinocytes.

Current understanding of mammalian circadian rhythms suggests that they are regulated by light targeting signaling pathways in the hypothalamic suprachiasmatic nuclei. Recently, investigators have identified the existence of extraretinal photoreceptors and a potential role for the skin in this regulatory process has been implied. We demonstrated that mRNA of the circadian clock genes Per1, Clock, and bmal1/mop3 are expressed in normal human cultured keratinocytes.

Impaired ultraviolet-B-induced cytokine induction in xeroderma pigmentosum fibroblasts.

Xeroderma pigmentosum is a rare, autosomal recessive disease in which patients develop excessive solar damage at an early age and have a 1000-fold increased risk of developing cutaneous neoplasms. Xeroderma pigmentosum can be classified into seven complementation groups (A-G) with defects in different DNA nucleotide excision repair genes. Xeroderma pigmentosum patients also have impaired immune function including reduced natural killer cell activity and impaired induction of interferon-gamma.

Role of Th2 cytokines, RANTES and eotaxin in AIDS-associated eosinophilic folliculitis.

The pathogenesis of AIDS-associated eosinophilic folliculitis is still unknown. The expression of chemokines and Th2-type cytokines is increased in other conditions associated with tissue eosinophilia and in allergic reactions. We evaluated the mRNA expression by reverse transcriptase polymerase chain reaction of two Th2 cytokines (interleukin-4 and interleukin-5) and of two chemokines (RANTES and eotaxin) in the skin of 6 patients with AIDS-associated eosinophilic folliculitis; the tissue localization of eotaxin was shown by immunohistochemistry.

Rethinking the role of tumour necrosis factor-alpha in ultraviolet (UV) B-induced immunosuppression: altered immune response in UV-irradiated TNFR1R2 gene-targeted mutant mice.

Background: Ultraviolet (UV) B-induced immunosuppression, implicated in the pathogenesis of skin cancers, is postulated to be mediated in part by cis-urocanic acid (cis-UCA) via tumour necrosis factor (TNF)-alpha. TNF-alpha produces morphological changes in Langerhans cells indistinguishable from those induced by UVB exposure and antibodies against TNF-alpha have been demonstrated to inhibit UVB-induced immunosuppression in vivo.

Objectives: To clarify further the role of TNF-alpha in UVB-induced immunosuppression and in cis-UCA immunosuppression.

CD4+ Th1 and CD8+ type 1 cytotoxic T cells both play a crucial role in the full development of contact hypersensitivity.

The role of CD4(+) vs CD8(+) T cells in contact hypersensitivity (CHS) remains controversial. In this study, we used gene knockout (KO) mice deficient in CD4(+) or CD8(+) T cells to directly address this issue. Mice lacking either CD4(+) or CD8(+) T cells demonstrated depressed CHS responses to dinitrofluorobenzene and oxazolone compared with wild-type C57BL/6 mice.

The effect of VAS972 on allergic contact hypersensitivity.

Background: Contact hypersensitivity (CHS) is a Th1-mediated immune response that can be down-regulated by immunosuppressive agents such as cyclosporine and environmental stimuli such as ultraviolet light. Recently, an immunomodulation therapy, VAS972, has been developed which is believed to down-regulate the Th1 arm of the immune response. This VAS972 involves modifying autologous blood by controlled exposure to the oxidizing agent ozone and UVC light, at an elevated temperature ex vivo.

Synthetic peptide immunogens elicit polyclonal and monoclonal antibodies specific for linear epitopes in the D motifs of Staphylococcus aureus fibronectin-binding protein, which are composed of amino acids that are essential for fibronectin binding.

A fibronectin (Fn)-binding adhesin of Staphylococcus aureus contains three tandem 37- or 38-amino-acid motifs (D1, D2, and D3), which function to bind Fn. Plasma from patients with S. aureus infections contain antibodies that preferentially recognize ligand induced binding sites in the D motifs and do not inhibit Fn binding (F.

Imiquimod, a topical immune response modifier, induces migration of Langerhans cells.

Langerhans cells are bone marrow derived dendritic cells that represent the major antigen-presenting cells in the skin. Langerhans cells take up and process antigen within the epidermis and present processed antigen to T lymphocyte in the regional lymph nodes and thus form an integral part of the cutaneous immune response. The cutaneous immune response can be modified by a number of pharmacologic agents, including corticosteroids, cyclosporine, and retinoids as well as physical agents, such as ultraviolet light.

In vitro and in vivo expression of interleukin-1alpha and tumor necrosis factor-alpha mRNA in pemphigus vulgaris: interleukin-1alpha and tumor necrosis factor-alpha are involved in acantholysis.

Keratinocyte-derived cytokines have been implicated in the pathogenesis of a number of skin diseases. In this study we examined the possible role of keratinocyte-derived cytokines in the development of acantholysis in pemphigus vulgaris. Nineteen patients with pemphigus vulgaris, demonstrating the characteristic clinical, pathologic, and immunopathologic findings were studied.

Immune modulation in pemphigus vulgaris: role of CD28 and IL-10.

Pemphigus vulgaris (PV) is an autoimmune bullous skin disease characterized by Abs to the desmosomal cadherin desmoglein-3. Although the autoantibodies have been shown to be pathogenic, the role of the cellular immune system in the pathology of pemphigus-induced acantholysis is unclear. To further delineate the potential role of T cell-signaling pathways in the pathogenesis of PV, we performed passive transfer experiments with PV IgG in gene-targeted mutant mice.

TNF receptor p55 plays a pivotal role in murine keratinocyte apoptosis induced by ultraviolet B irradiation.

Excess exposure of skin to ultraviolet B (UVB) results in the appearance of so-called sunburn cells. Although it has been demonstrated that sunburn cells represent apoptotic keratinocytes, the molecular mechanisms for UVB-induced apoptosis in keratinocytes have not been fully elucidated. The cytokine, TNF-alpha, has been shown to induce apoptosis in a variety of cell types.

Enhanced epidermal Langerhans cell migration in IL-10 knockout mice.

The migration of epidermal Langerhans cells (LC) to lymph nodes (LN) is critical in the initiation of contact hypersensitivity (CHS) responses. Studies suggest that contact allergen-induced epidermal proinflammatory cytokines, including IL-1 and TNF-alpha, play important roles in promoting LC migration. Contact allergens also induce epidermal anti-inflammatory cytokines such as IL-10.

Depressed Langerhans cell migration and reduced contact hypersensitivity response in mice lacking TNF receptor p75.

Epidermal Langerhans cells (LC) belong to the dendritic cell family and represent the major APC within the skin. LC capture epicutaneous Ag, migrate into regional lymph nodes, and present Ag to T cells, thereby initiating primary immune response. The migratory properties of LC are an essential component of their function.

The expression and modulation of IFN-alpha and IFN-beta in human keratinocytes.

In addition to leukocytes and fibroblasts, the classic sources of human interferons (IFN), many other human cells are now known to be capable of producing IFN. Keratinocytes (KC) are abundant in the skin and provide the first line of defense against viruses and other noxious agents. Human KC are a potent source of cytokines and were implicated as forming IFN-like protein(s).

Costimulation with ultraviolet B and interleukin-1 alpha dramatically increase tumor necrosis factor-alpha production in human dermal fibroblasts.

Ultraviolet light, particularly in wavelengths of 290-320 nm (UVB), is known to induce cytokine synthesis in the skin. Cytokines act in a cascade fashion and can have synergistic or antagonistic actions on regulation of other cytokines. In this study, we sought to determine whether cotreatment with UVB and interleukin-1 alpha (IL-1 alpha) induces tumor necrosis factor-alpha (TNF-alpha) production synergistically by human dermal fibroblasts.

CD45 molecule in gammadelta T-cell generation: disruption of CD45 exon 6 does not affect Vgamma3 dendritic epidermal T-cell development.

There are two distinct lineages of T cells: T-cell receptor (TCR) alphabeta-bearing cells (alphabeta T cells) and TCR gammadelta-bearing cells (gammadelta T cells). All of the alphabeta T cells and most subsets of gammadelta T cells develop in the thymus. It has been demonstrated that the protein tyrosine phosphatase CD45 plays a pivotal role in the intrathymic development of alphabeta T cells.

The role of CD4 molecules in the induction phase of contact hypersensitivity cytokine profiles in the skin and lymph nodes.

We have previously demonstrated that CD4 gene-targeted mutant mice (CD4- mice) demonstrate hyporesposiveness in contact hypersensitivity (CHS) suggesting that CD4 molecules are required for optimal induction of CHS. In the present study, we wished to examine the mechanisms of this hyporesponsiveness, in particular, we examined whether cytokines were altered in the skin and lymph nodes of CD4- mice following exposure to the contact allergen dinitrofluorobenzene (DNFB). Cytokine mRNA in the ear skin and draining lymph nodes (DLN) were examined by reverse transcription-polymerase chain reaction (RT-PCR) at various times after sensitization.

Effect of a novel topical immunomodulator, S-28463, on keratinocyte cytokine gene expression and production.

A new immunomodulating agent, imiquimod, has been reported to have antiviral and antitumor activities in animal models. S-28463 (4-amino-2-ethoxymethyl-alpha, alpha-dimethyl-1H-imidazo[4, 5-c]quinoline-1-ethanol), an analog of imiquimod, has more potent antiviral activity in animals than imiquimod. It has also been shown to be more potent at inducing cytokines in human blood in vitro.

Tumour necrosis factor receptor II (p75) signalling is required for the migration of Langerhans' cells.

Langerhans' cells (LC) represent the major antigen-presenting cells within the epidermis. Following exposure of the skin to antigen, LC take up antigen, migrate into draining lymph nodes (DLN) and present processed antigen to T lymphocytes, thereby initiating an immune response. The molecular mechanisms responsible for LC migration remain unclear.

Ultrasound backscatter microscope analysis of mouse melanoma progression.

The incidence and mortality rate of cutaneous melanoma continue to increase throughout the world, making the study of melanoma biology an important area of current research. While recent breakthroughs in transgenic mouse technology have led to promising mouse skin models of melanoma, there is presently no technique available for quantitatively studying subsurface melanoma progression, in vivo. We demonstrate the first application of an imaging method called ultrasound backscatter microscopy (UBM) for imaging early murine melanomas with spatial resolution of 30 microns axial and 60 microns lateral.

The role of cis-urocanic acid in UVB-induced suppression of contact hypersensitivity.

Ultraviolet light B (UVB) is well recognized to suppress the contact hypersensitivity (CHS) response and it has been postulated that cis-urocanic acid (UCA) is a mediator of the immunosuppression. This study was designed to examine the effect of UCA on CHS and to clarify its role in UVB-induced immunosuppression in C57BL/6 mice. Intradermal injection of 0.

Effect of gene-targeted mutation in TNF receptor (p55) on contact hypersensitivity and ultraviolet B-induced immunosuppression.

Tumor necrosis factor alpha (TNF-alpha) is a pleiotropic proinflammatory cytokine. TNF-alpha has been implicated in the pathogenesis of delayed-type hypersensitivity reactions such as allergic contact hypersensitivity and has been suggested as a mediator of ultraviolet B (UVB)-induced immunosuppression. Conflicting reports, however, exist concerning the effects of TNF-alpha on contact hypersensitivity (CHS).