p21(Waf1/Cip1/Sdi1) is best known as a broad-specificity inhibitor of cyclin/cyclin-dependent kinase complexes, but p21 also interacts with many other regulators of transcription or signal transduction. p21 induction, which is mediated by p53 and by p53-independent mechanisms, is essential for the onset of cell cycle arrest in damage response and cell ...

The transcription factor AP-1 (activator protein-1) is involved in cellular proliferation, transformation and death. Using mice and cells lacking AP-1 components, the target-genes and molecular mechanisms mediating these processes were recently identified. Interestingly, the growth-promoting activity of c-Jun is mediated by repression of tumour suppressors, as well as upregulation of ...

Immunotherapy could have a role in the therapy of colorectal cancer as there is now convincing evidence that the immune system can specifically recognize and destroy malignant cells. The MAb 17-1A has been used in advanced and primary disease, along with newer agents such as anti-epidermal growth factor receptor (EGFR) ...

The epithelial tumour microenvironment is a complex tissue comprising variable numbers of tumour cells, fibroblasts, endothelial cells and infiltrating leucocytes. Cytokines are key molecules controlling autocrine or paracrine communications within and between these individual cell types. Under some circumstances, endogenous cytokines may orchestrate host responses against the tumour, but there ...

The mechanisms by which tumour cells escape recognition by the immune system or subvert antitumour effector responses remain poorly understood. In the course of investigating the potential of costimulatory signals in anticancer immunotherapy strategies, we have observed that HeLa cells (a human cervical carcinoma cell line) cocultured with peripheral blood ...

Survivin is a structurally unique member of the inhibitors of apoptosis protein (IAP) family that is involved in both control of cell division and inhibition of apoptosis. Its anti-apoptotic function seems to be related to its ability to directly or indirectly inhibit caspases, although the precise role of survivin in ...

Angiogenesis is central to both the growth and metastasis of solid tumours. Anti-angiogenic strategies result in blood vessel regression accompanied by tumour cell apoptosis. Radiotherapy and many chemotherapeutic agents kill tumours by inducing apoptotic cell death. We propose that, in addition to its role as an angiogenic factor, vascular endothelial ...

Cell-based therapies are promising approaches to treat uncontrolled pathologies, such as tumours. Apoptotic tumour cells have recently been proposed as a source of tumour-associated antigens to stimulate an efficient immune response. However, a complex relationship exists between apoptosis and the immune system. In this review, the different factors that may ...

The role of macrophages in tumour growth and development is complex and multifaceted. Whilst there is limited evidence that tumour-associated macrophages (TAMs) can be directly tumouricidal and stimulate the anti-tumour activity of T cells, there is now contrasting evidence that tumour cells are able to block or evade the activity ...

Standard of care for non-small cell lung cancer (NSCLC) (surgery, chemotherapy and radiation) may enhance patient survival but the enhancement is typically transient and quite uncommon with advanced disease. Researchers and medical professionals are using new approaches to improve patient mortality and morbidity. One of these approaches, immunotherapy, seeks to ...

Treatment with monoclonal antibodies (mAbs) specific for CD25 (anti-CD25 mAb) has been shown to suppress growth of a variety of different tumours in mice. These studies did not however determine whether or not anti-CD25 mAbs facilitate tumour rejection by depletion of regulatory T cells or by binding to tumour-specific effector ...

Nitric oxide (NO) is a potent bioactive molecule produced in the presence of NO synthase (NOS) enzymes, which mediates numerous physiological functions under constitutive conditions. Sustained overproduction of NO (and NO-reaction products), typically under inductive conditions, can lead to cell cycle arrest and cellular apoptosis. Furthermore, carcinogenesis may result from ...

Gap junctional intercellular communication has been implicated in growth control and differentiation. The mechanisms by which connexins, the gap junction proteins, act as tumor suppressors are unclear. In this review, several different mechanisms are considered. Since transformation results in a loss of the differentiated state, one mechanism by which gap ...

We have investigated the role of HIF-1 in the cellular response to redox modulation via the inhibition of oxidative phosphorylation. We demonstrate that manipulation of redox in air, achieved by inhibiting cytochrome oxidase with cyanide, induces HIF-1 mediated transcription in wild-type CHO and HT1080 human tumour cells but not in ...

Interleukin 2 (IL-2) and interleukin 12 (IL-12) have potent anti-tumour activity as single agent therapy against several different murine and human tumours. Combining these cytokines may result in improved therapeutic effectiveness, however, the toxicity associated with simultaneous administration is prohibitive. This study was designed to determine the specific histopathologic changes ...

Cells undergo a variety of biological responses when placed in hypoxic conditions, including activation of signalling pathways that regulate proliferation, angiogenesis and death. Cancer cells have adapted these pathways, allowing tumours to survive and even grow under hypoxic conditions, and tumour hypoxia is associated with poor prognosis and resistance to ...

In lymphomas an innate defect in the T-cell repertoire could account for the impaired tumour-specific immune response; alternatively, the tumour itself could exert an inhibitory effect on the immune system. To address this issue we analysed the T-cell responses against follicular lymphoma (FL) in identical twins as it can be ...

In the course of anthracyclin administration, melatonin acts as an effective scavenger of oxygen free radicals and exerts cardio- and nephroprotective effects. The present study aimed at corroborating cytostatic effectiveness of daunorubicin, applied in parallel with melatonin, in rats with transplanted Morris hepatoma. The percentage of tumour cells, which manifested ...

Tea has received a great deal of attention because tea polyphenols are strong antioxidants, and tea preparations have inhibitory activity against tumorigenesis. The bioavailability and biotransformation of tea polyphenols, however, are key factors limiting these activities in vivo. The inhibition of tumorigenesis by green or black tea preparations has been ...

Acute and chronic graft versus host disease (GVHD) remain the major barriers to successful hematopoietic cell transplantation. The induction of GVHD may be divided into three phases: recipient conditioning;donor T-cell activation; andeffector cells mediating GVHD. This review examines GVHD prevention and treatment using this conceptual model as framework. The various ...

Cancers appear to escape surveillance by the immune system at least in part because they fail to induce a protective immune response. Therapeutic vaccines based on specific tumour antigens and tumour cells modified ex vivo by genetic techniques are but two strategies being used to circumvent this problem. In this ...

Cepharanthin is one of the biscoclaurine alkaloids widely used for treatment of many acute and chronic diseases; snakebite, bronchial asthma, alopecia areata, leukopenia during radiation therapy or anticancer treatment. Recently, it has been reported that cepharanthin exerts antitumour effects by increasing immunological competence of the host or apoptosis-inducing activity. In ...

Cord blood T cells are much more likely to be induced to apoptosis in vitro than adult T cells. Nevertheless, the expression of Fas is markedly lower on cord blood lymphocytes than on peripheral blood lymphocytes. In the current investigation, we determined the capacity of tumour necrosis factor-alpha (TNF-alpha) to ...

The relation between tumour metabolism and induction of apoptosis by gene therapy was investigated in a rat Morris hepatoma (MH3924A) model expressing the HSV thymidine kinase (HSVtk) gene. In vivo the amount of glucose transporter (GLUT1 and GLUT3 isoforms) expressing cells was determined in tumours of untreated and treated animals ...

BACKGROUND: Despite the increasing incidence of basal cell carcinoma (BCC), its pathogenesis has remained largely unknown. Recently, it was reported that genes involved in tissue morphogenesis, such as sonic hedgehog or patched, were found to be mutated in BCC, suggesting the involvement of those molecules in the pathogenesis of this ...

Human T-cell leukaemia virus type I (HTLV-I) associated adult T-cell leukaemia/lymphoma (ATL) carries a very poor prognosis due to an intrinsic resistance of leukaemic cells to conventional or even high doses of chemotherapy and to an associated severe immunosuppression. Therefore, the potential role of conventional chemotherapy, high dose chemotherapy with ...

Recent developments in both molecular and cellular biology have improved the understanding of the tumorigenesis of laryngeal squamous cell carcinoma. Loco-regional recurrence of this condition still poses a significant oncological management dilemma for a subset of these tumours. Therefore, the possibility that specific tumour characteristics (demonstrable by immunohistochemical and molecular ...

The prospect of developing 'magic bullets' to attack tumour cells has been a goal of biologists for decades. Abundant experimental and clinical observations demonstrating that an effective specific immune response may engender tumour regression has prompted efforts to find an immunotherapeutic approach to this problem. The most important arm of ...

Haematology represents a prime example of how rapidly immunology is moving towards the bedside. The diagnosis of blood disease has been modified by the "cluster of differentiation" (CD) nomenclature of leucocyte surface antigens, and the molecular genetics of the immune system has had a major effect on the diagnosis and ...

Chemokines are small, chemotactic cytokines that direct migration of leukocytes, activate inflammatory responses and participate in many other pleiotropic functions, including regulation of tumour growth. Chemokines modulate tumour behaviour by three important mechanisms: regulation of tumour-associated angiogenesis, activation of a host tumour-specific immunological response, and direct stimulation of tumour cell ...

Nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD) are characterized by their association with Epstein-Barr virus (EBV) and the presence of an intense lymphoid stroma, consisting of T lymphocytes and other reactive cells. In both entities, the tumour cells express viral proteins known to provide target epitopes for cytotoxic T-cells (CTLs), ...

The biological activities of nitric oxide (NO) include vasodilatation, inhibition of platelet aggregation, neurotransmission, neural plasticity, and modulation of inflammatory and immunological functions. NO synthase (NOS), which is the enzyme that produces NO, has been detected in resected human glioma specimens, and both human and rodent glioma cell lines. NO ...

Angiogenesis is essential for tumour growth and metastasis. The induction of tumour vascularization is mediated by the release of angiogenic peptides. Among these factors, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are thought to be the most important. Previous experimental studies indicate that ...

HSPPC-96 is a protein peptide complex consisting of a 96 kDa heat shock protein (Hsp), gp96, and an array of gp96-associated cellular peptides. Immunisation with HSPPC-96 induces T-cell specific immunity against these peptides; gp96 is not immunogenic per se. The non-covalent binding of gp96 to peptides is neither selective nor ...

Lymphocytes were originally thought to form the basis of a 'cancer immunosurveillance' process that protects immunocompetent hosts against primary tumour development, but this idea was largely abandoned when no differences in primary tumour development were found between athymic nude mice and syngeneic wild-type mice. However, subsequent observations that nude mice ...

Treatment of hormone refractory prostate cancer requires new treatment strategies. Genetic prodrug activation therapy (GPAT) may provide a new therapeutic avenue. In this study the antitumour efficacy of the gene encoding herpes simplex virus thymidine kinase (HSVtk) activating the prodrug ganciclovir (GCV) was compared in two models of ectopic (subcutaneous) ...

Chemicals with the potential to cause cancer through damaging DNA can be readily identified in a range of in vitro screens that detect genotoxicity. However, many carcinogens are non-genotoxic yet cause rodent tumours, particularly in the liver. Some non-genotoxic carcinogens such as the peroxisome proliferators (PPs) act directly to cause ...

Epidemiological evidence suggests protective effects of dietary flavonoids against cardiovascular disease. Tea provides a major source of dietary flavonoids in many countries and its polyphenolic components have well-recognised antioxidant properties. However, scavenging of free radicals may not be the sole mechanism by which tea-derived polyphenols exert their protective effects. This ...

Vitiligo is a skin disease in which melanocytes (MCs) are eradicated from lesional epidermis, resulting in disfiguring loss of pigment. MCs are destroyed by MC-reactive T cells, as well as other non-immune and immune components. Similarities exist between the autoimmunity observed in vitiligo and the tumour immunity observed in melanoma ...

The development of genetically modified tumour vaccines (GMTV) has been prompted by a better understanding of antitumour immune responses and genetic engineering technologies, as well as the identification of numerous tumour antigens (TA) in several malignancies which occasionally induce spontaneous tumour regressions. Cellular vaccines are based on autologous or allogeneic ...

This study investigated the endogenous production of the pro-inflammatory and angiogenic cytokine IL-8 by human colorectal cancer cells. We describe substantial (>0.5 ng/ml) constitutive production of IL-8 by certain human colorectal cancer cell lines without the requirement for exogenous stimulation. Tumour cell-derived IL-8 production was upregulated by the addition of ...

There is little evidence that cutaneous dendritic cells (DC), including epidermal Langerhans cells (LC), can induce immunity to UV radiation (UVR)-induced skin tumours. Here, it is shown that cells within skin can induce protective antitumour immunity against a UVR-induced fibrosarcoma. Transplantation of the skin overlying subcutaneous tumours onto naïve recipients ...

Cellular response to treatment is dependent on the metabolic preconditioning of individual cells, which is a reflection of environmental conditions. Within solid tumours there are areas of different oxygen tension, which, we hypothesise, may indicate that cells are exposed to conditions that change continually. Other characteristics of the solid-tumour microenvironment ...

Viral oncogenes, mutated cellular oncogenes, or other adventitious agents that might contaminate vaccine preparations on inoculation of the host will encounter a T cell-mediated immune response which will play a determining role in the progression of neoplastic events or replication of contaminating viral agents. Using SV40 T antigen tumour systems ...

Expression of the E1A oncogene of adenovirus serotype 5 (Ad5) sensitizes neoplastic cells from different species, including human, to apoptosis triggered by components of the innate mmune response. This E1A activity causes a marked reduction in the tumorigenicities of sarcoma cells in a manner that is directly linked to the ...

It is commonly accepted that moderate intensity exercise is beneficial to the immune system. We tested the influence of a moderate intensity training protocol (8 weeks) upon immune system function in Wistar tumour-bearing (TB) rats. The metabolism of glucose and glutamine in lymphocytes and macrophages was assessed, together with some ...

The macrophage theory of depression proposes that an excessive secretion of monocyte/macrophage cytokines causes symptoms of depression. It has been suggested that changes in immune function that accompany pregnancy and childbirth could contribute to the affective symptoms suffered by many puerperal women. Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory ...

BACKGROUND: Heat shock proteins (HSP) are cytoprotective, antiapoptotic proteins which may predict clinical prognosis in various types of cancer. Here, we asked whether the differential response to radiochemotherapy and different overall prognosis for astrocytic and oligodendroglial tumours can be accounted for by differences in HSP expression. MATERIAL AND METHODS: We ...

OBJECTIVE: To define the cellular basis for immune enhancement by a probiotic lactic acid bacteria strain (Bifidobacterium lactis HN019); and to determine whether immune enhancement can be optimized by delivery in oligosaccharide-enriched low-fat milk. DESIGN: A double-blind, three-stage before-and-after intervention trial. SETTING: Taipei Medical College Hospital, Taipei, Taiwan. SUBJECTS: Fifty ...

Interleukin 1alpha (IL-1alpha), a pleiotropic cytokine with multiple anti-tumour activities, has been investigated in our laboratory for its potential to serve as an immunotherapeutic agent. In the present study, an attempt was made to direct IL-1alpha to macrophages, in order to induce their immunoregulatory activities. For that purpose, IL-1alpha was ...