Dendritic cells (DC) are professional antigen-presenting cells that can be generated in vitro from CD34+ peripheral blood progenitor cells by recombinant cytokines. These cells have potential implications for immunotherapeutic approaches in the treatment of cancer and other diseases. Physiologically, immature DC in the periphery capture and process antigens, then mature to interdigitating DC and migrate to lymphoid organs, where they activate lymphocytes. However, it is not known if DC generated in vitro have the capacity to traffic in vivo to the lymphoid tissues, such as spleen and lymph nodes. We have investigated whether human radiolabeled DC differentiated in vitro migrate and localize to lymphoid tissues after intravenous and intralymphatic injection. The distribution and localization of the DC were evaluated in five patients with malignant melanoma using serial whole-body gamma camera imaging. Intravenously infused DC demonstrated transient lung uptake followed by localization in the spleen and liver for at least 7 days. DC injected into a lymphatic vessel at the dorsal foot were rapidly detected in the draining lymph nodes where they remained for more than 24 h. These data suggest that DC differentiated in vitro localize preferentially to lymphoid tissue, where they could induce specific immune responses.

Antigens, CD34↗

PubMedDate not supplied

Therapy of invasive aspergillosis with itraconazole: improvement of therapeutic efficacy by early diagnosis.

We report on the treatment of invasive aspergillosis with the new triazole antimycotic agent itraconazole. All 11 patients suffered from pulmonary invasive aspergillosis. Two patients also had cerebral aspergillosis; in one of these patients the paranasal sinuses were also invaded. Underlying diseases were acute lymphoblastic leukaemia (n = 3), acute myeloid leukaemia (n = 4); one patient underwent allogeneic bone marrow transplantation before he developed aspergillosis; another was transplanted after successful aspergillosis treatment, liver cirrhosis (n = 1), lung infarction after pulmonary embolism (n = 1), chronic bronchitis after pulmonary tuberculosis (n = 1) and AIDS (n = 1). In five cases initial diagnosis was established by means of mycological methods and clinical signs. In six patients invasive pulmonary aspergillosis was initially diagnosed due to the clinical criteria presented in this paper. Secondary mycological confirmation after onset of therapy was achieved in five out of these six patients. All of the patients initially responded to therapy. One female patient experienced a relapse of aspergillosis and died of cerebral involvement and relapsing leukaemia. Two further patients died due to underlying diseases (pulmonary embolism, relapsing leukaemia). Nine patients (82%) were cured of the mycosis, including the patient with cerebral involvement; two underwent surgical resection of residual pulmonary lesions. Itraconazole is a very effective drug for treatment of invasive aspergillosis. Therapeutic efficacy can be optimized by early diagnosis using clinical criteria and prompt start of treatment.

Adult↗

PubMedDate not supplied

Dacarbazine and interferon alpha for stage IV malignant melanoma.

Based on encouraging reports of improved response rates with the use of dacarbazine (DTIC) in combination with recombinant interferon alpha-2a (rIFN-alpha-2a) in patients with metastatic malignant melanoma, we conducted a phase II study to determine the efficacy and feasibility of this treatment regimen. 31 patients were treated with an induction dose of rIFN-alpha-2a at 15 MIU/ m2 intravenously (i.v.) daily for 5 days per week for 3 consecutive weeks followed by a continuous maintenance dose of 10 MIU/m2 subcutaneously (s.c.) given 3 days per week; starting on day 22, in conjunction with rIFN-alpha-2a s.c., DTIC was started at a dose of 200 mg/m2 i.v. for 5 continuous days completing a 28-day cycle. Therapy was continued until progression was evidenced. Of the 29 evaluable patients, 7 (24.1%) achieved an objective response (complete plus partial remission) with the highest responses occurring in those patients assessed with pulmonary metastases. The median duration to treatment failure was 2.6 months, while the median survival was 6.9 months. Our data reveal that using rIFN-alpha-2a plus DTIC in combination does not yield better results than those achieved when using DTIC alone. However, 3 of the 7 responders experienced long-term survival ranging up to 42 months. Whether this benefit is achieved by the addition of rIFN-alpha-2a can only be answered by large randomized clinical trials. Conflicting results with some of the current literature are discussed.

Adult↗

PubMedDate not supplied

Comparison of cytogenetics, cytokine secretion, and oncogene expression in primary cultures of renal carcinoma cells.

We compared the cytogenetic pattern of 20 different primary tumor cell cultures (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was correlated with the gain of an additional chromosome 7. Structural changes involving chromosome 5q22, the site of the GM-CSF gene, were matched with the high secretion of GM-CSF in PTCC. No such association was found for beta 2-microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc, and pan-ras. Our approach may be useful in simultaneously analyzing several factors contributing to tumor progression and may contribute to understanding the multistep development of RCC.

Adult↗

PubMedDate not supplied

In vivo administration of recombinant human interleukin-3 elicits an acute phase response involving endogenous synthesis of interleukin-6.

Interleukin-6 has been shown to stimulate in vitro synthesis of C-reactive protein (CCRP) in hepatocytes by enhancing the transcriptional rate of the CRP gene. It has also been demonstrated that IL-6 spurs the terminal differentiation of B-cells into immunoglobulin secreting cells when synergizing with IL-3. IL-6 may therefore act as a prime molecule in the acute phase and immune response. We have administered rh IL-3 to cancer patients in a phase I/II clinical trial. Endogenous IL-6 levels increased in a dose-dependent fashion upon i.v. bolus injection of rh IL-3 and continued to be significantly elevated above pretreatment levels when IL-3 was further administered by the s.c. route. Increases of IL-6 levels were associated with enhanced production of CRP in vivo detected after 24 h of injection. At day 14 of rh IL-3 treatment plasma immunoglobulin concentrations were measured and IgM was found to be increased by greater than 2.5 fold above starting levels. These results indicate that rh IL-3 also augments the acute phase response in vivo and contributes to increased synthesis of IgM and that induction of endogenous IL-6 is involved in these events.

Acute-Phase Proteins↗

PubMedDate not supplied

Monokines: stimulatory and inhibitory regulator molecules of myelopoiesis in vitro.

The conditions for monocytes to secrete molecules that are involved in myelopoiesis, i.e. Colony Stimulating Factors (CSFs), Interleukin-1 (IL-1) and Tumor Necrosis Factor-alpha (TNF-alpha) were investigated. Whereas secretion of these molecules by monocytes is negligible in a quiescent state, activation of monocytes with Interferon-gamma (IFN-gamma) results in mRNA accumulation and subsequent protein secretion of CSF for granulocytes (G-CSF) and for monocytes (M-CSF). Under identical conditions mRNA-transcripts of TNF-alpha, IL-1-alpha and IL-1-beta genes were induced. Whereas IFN-gamma induces secretion of TNF-alpha protein, protein secretion of IL-1 by monocytes failed to occur in response to an IFN-gamma stimulus. However, the presence in culture of IFN-gamma in combination with TNF-alpha induced secretion of IL-1. Although IL-1 regulates the production of CSF for granulocytes and monocytes (GM-CSF) by IL-1 receptive T-lymphocytes, and is therefore involved in upregulatory mechanisms of myeloid growth, it may be able to suppress growth of myelopoietic progenitor cells (MPC) as well, when hematopoietic cultures are depleted of cells, that have the potential to secrete CSFs. Similarly, IFN-gamma, although being a major inducer of CSF secretion by monocytes, was shown to inhibit myeloid colony growth when exposed to purified MPC and allowed to synergize with TNF-alpha.

Biological Factors↗

PubMedDate not supplied

[On the problem of short dosage in liver diseases].

Explore the source record for details and available documents.

Diathermy↗

PubMedDate not supplied

Oncogene and HSP-70 expression in primary tumor cell cultures of renal cell carcinoma compared to their corresponding cell line.

BACKGROUND: Tumor progression in renal cell carcinoma (RCC) can be explained by a multistep model, in which the activation of certain oncogenes such as c-neu and c-fos appear to be early events in tumorigenesis, while the expression of p53 and pan-ras are found in advanced stages. MATERIAL AND METHODS: The expression of oncogenes and growth factors was examined in 29 primary tumor cell cultures (PTCC) of RCC using immunocytochemistry. RESULTS: In PTCC high expression of c-neu and c-fos was present in all tumors, whereas mdr, TGF-alpha, EGF, c-myc, pan-ras, p53 and HSP-70 was detected at low expression levels. In 27% (8/29) of PTCC, cell lines (CL) were established. Oncogene expression was increased in CL compared to PTCC. CONCLUSION: The pattern of oncogene expressions found in CL is similar to findings described in highly malignant tumors in vivo. Therefore, the establishment of CL seems to depend on a selective recruitment of tumor cells with an upregulated oncogene expression.

Adenocarcinoma, Clear Cell↗