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Cytokine Therapy (cytokine + therapy)
Selected AbstractsCytokine therapy in dermatologyEXPERIMENTAL DERMATOLOGY, Issue 2 2002K. Asadullah Abstract: Cytokines have been in the focus of scientific interest for some years now. Analysing their expression permitted a better understanding of the pathogenesis of various diseases, including in dermatology. Moreover, they are now far beyond the stage when they were of interest only to the pathophysiological research sector: some cytokine therapies are already being employed as part of the clinical practice. In fact, several cytokines are used for the treatment of malignant, inflammatory and infectious skin diseases. Their stage of development ranges from advanced, already approved and well established therapies (e.g. IFN-, and IL-2 for melanoma) to early explorative trials (e.g. IL-4 and IL-10 for psoriasis). Some of the new approaches currently under investigation will actually lead to registration of new drugs for dermatological treatment and to supplement existing therapeutic options. Beside this, the results of clinical trials with cytokines are significantly contributing to our understanding of the pathophysiology of diseases. They will give a better insight into which mechanisms play a greater or lesser part in their development and may generate momentum for still better targeted pharmacological approaches. Here we would like to give an overview about the current stage of cytokine therapy and the prospects for dermatological indications. The terminology and immunobiology of cytokines are also briefly discussed, since for a sensible interpretation of the relevant findings a basic knowledge of these biologically highly active messenger substances is essential. [source] Cytokine therapy in melanomaJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2010Ryan J. Sullivan First page of article [source] Cytokine therapy in dermatologyEXPERIMENTAL DERMATOLOGY, Issue 2 2002K. Asadullah Abstract: Cytokines have been in the focus of scientific interest for some years now. Analysing their expression permitted a better understanding of the pathogenesis of various diseases, including in dermatology. Moreover, they are now far beyond the stage when they were of interest only to the pathophysiological research sector: some cytokine therapies are already being employed as part of the clinical practice. In fact, several cytokines are used for the treatment of malignant, inflammatory and infectious skin diseases. Their stage of development ranges from advanced, already approved and well established therapies (e.g. IFN-, and IL-2 for melanoma) to early explorative trials (e.g. IL-4 and IL-10 for psoriasis). Some of the new approaches currently under investigation will actually lead to registration of new drugs for dermatological treatment and to supplement existing therapeutic options. Beside this, the results of clinical trials with cytokines are significantly contributing to our understanding of the pathophysiology of diseases. They will give a better insight into which mechanisms play a greater or lesser part in their development and may generate momentum for still better targeted pharmacological approaches. Here we would like to give an overview about the current stage of cytokine therapy and the prospects for dermatological indications. The terminology and immunobiology of cytokines are also briefly discussed, since for a sensible interpretation of the relevant findings a basic knowledge of these biologically highly active messenger substances is essential. [source] New systemic treatment options for metastatic renal-cell carcinoma in the era of targeted therapiesASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010Thean Hsiang TAN Abstract Advances in understanding the biology and genetics of renal-cell carcinomas have led to the development of novel targeted therapies for the treatment of metastatic renal-cell cancer. Previously the systemic approaches were limited to cytokine therapies that were modest in their clinical benefits and at the expense of significant toxicities. Investigational treatments with allogeneic bone marrow transplantation were equally toxic and resulted in significant morbidity and mortality. The development of targeted therapy has revolutionized the treatment of metastatic renal-cell cancer with more meaningful outcomes. This review aims to provide a detailed discussion of the clinical benefits of targeted therapies such as sunitinib, sorafenib, temsirolimus, everolimus, bevacizumab, and some of the newer agents in clinical trial development. The efficacy of these compounds in terms of response, survival and clinical benefit are explored as well as their toxicities. The role of surgery in metastatic renal-cell carcinoma is reviewed in the context of cytoreductive therapy and resection of solitary and oligometastatic disease. Ongoing studies in the adjuvant setting following curative resection are also reviewed. The availability of targeted therapies has led to their rapid adoption as frontline therapy over traditional cytokine therapy, thus bringing more optimistic and hopeful therapeutic options in a condition where historically, systemic treatments have been relatively unsatisfactory and disappointing. [source] Cytokine therapy in dermatologyEXPERIMENTAL DERMATOLOGY, Issue 2 2002K. Asadullah Abstract: Cytokines have been in the focus of scientific interest for some years now. Analysing their expression permitted a better understanding of the pathogenesis of various diseases, including in dermatology. Moreover, they are now far beyond the stage when they were of interest only to the pathophysiological research sector: some cytokine therapies are already being employed as part of the clinical practice. In fact, several cytokines are used for the treatment of malignant, inflammatory and infectious skin diseases. Their stage of development ranges from advanced, already approved and well established therapies (e.g. IFN-, and IL-2 for melanoma) to early explorative trials (e.g. IL-4 and IL-10 for psoriasis). Some of the new approaches currently under investigation will actually lead to registration of new drugs for dermatological treatment and to supplement existing therapeutic options. Beside this, the results of clinical trials with cytokines are significantly contributing to our understanding of the pathophysiology of diseases. They will give a better insight into which mechanisms play a greater or lesser part in their development and may generate momentum for still better targeted pharmacological approaches. Here we would like to give an overview about the current stage of cytokine therapy and the prospects for dermatological indications. The terminology and immunobiology of cytokines are also briefly discussed, since for a sensible interpretation of the relevant findings a basic knowledge of these biologically highly active messenger substances is essential. [source] Granulocyte/macrophage-colony stimulating factor and interleukin-4 expand and activate type-1 dendritic cells (DC1) when administered in vivo to cancer patientsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2003Sylvia M. Kiertscher Abstract Two rare populations of cells with the features of dendritic cell precursors (preDC) can be identified in human peripheral blood. PreDC1 are HLA-DR+/CD11c+ cells which mature into DC1 capable of stimulating Th1 responses. In contrast, preDC2 are HLA-DR+/CD11c,/CD123+ cells that promote Th2 responses when matured into DC2. We hypothesized that administration of GM-CSF and IL-4, growth factors for DC1, would specifically augment the number and function of circulating DC1 in vivo. Patients with advanced metastatic cancer were treated with GM-CSF (2.5 ,g/kg/day) and IL-4 (4 or 6 ,g/kg/day) for 7 days. Cytokine administration at the highest IL-4 dose produced an average 2.3-fold increase in preDC2 number, but a 6.5-fold increase in preDC1, resulting in an increased ratio of circulating preDC1:preDC2 from 1.4:1 pre-treatment to 4.3:1 after cytokine therapy. DC1 precursors identified after in vivo therapy were larger, more complex and expressed higher levels of HLA-DR, CD11c and CD80 than pre-treatment cells. DC1 isolated from the peripheral blood of patients receiving GM-CSF/IL-4 therapy demonstrated MLR activity comparable to that of monocyte-derived DC generated in vitro from the patients' pre-treatment blood using GM-CSF and IL-4. We conclude that systemic administration of GM-CSF and IL-4 preferentially expands and matures the preDC1 population in vivo. These effects correlate with antigen-presenting activity, providing a mechanism by which systemic GM-CSF and IL-4 might stimulate anti-tumor immunity in vivo. © 2003 Wiley-Liss, Inc. [source] Quantitative Analysis of Cytokine mRNA Expression in Hearts from Patients with Nonischemic Dilated Cardiomyopathy (DCM)JOURNAL OF CARDIAC SURGERY, Issue 2003Akira Ukimura To evaluate the role of cytokines in nonischemic DCM, we analyzed the relative quantity of cytokine mRNA expression in the hearts from DCM patients with refractory heart failure, using the ABI PRISM7700 real-time PCR system. We used heart tissues resected from 32 DCM patients at the time of elective partial ventriculectomy (PLV), and five biopsy specimens with normal histological findings as control. Results and Discussion: Interleukin (IL)-1,, IL-10, and Tumor Necrosis Factor (TNF)-, mRNA were expressed at low levels in all normal hearts. The number of IL-10-positive DCM cases was significantly smaller than normal controls (P = 0.0036). One (10%) of 10 DCM patients with IL-10 mRNA expression died after PLV, and 10 (45%) of 22 DCM patients without IL-10 mRNA expression died. IL-1, mRNA was overexpressed (over twice the mean of control subjects) in 15 of 32, and TNF-, mRNA in 10 of 32 patients. We propose the classification of DCM patients into subgroups on the basis of cytokine mRNA expression. Anticytokine therapy or cytokine therapy may have potential in improving the condition of heart failure in certain subgroups of DCM patients. Conclusions: We suggest that DCM patients with heart failure deteriorate without IL-10 mRNA expression in the myocardium. The classification of DCM patients into subgroups on the basis of cytokine mRNA expression may have great value in considering the treatment of this heterogeneous disease state. (J CARD SURG 2003;18 (Suppl 2):S101-S108) [source] Granulocyte-macrophage colony stimulating factor and immunosuppression in the treatment of pediatric acquired severe aplastic anemiaPEDIATRIC BLOOD & CANCER, Issue 2 2005Michael R. Jeng MD Abstract Background Immunosuppressive therapy (IS) is effective in the treatment of patients with acquired severe aplastic anemia (SAA). An enhanced myeloid response and decreased infection risk may be possible with the addition of a hematopoietic cytokine. Published data on the combination of cytokines and IS in patients with SAA are limited. The addition of G-CSF to IS shortens the time to neutrophil count recovery, but may not improve overall survival. Because GM-CSF acts differently than G-CSF, its use in combination with IS may be different. Procedure A retrospective chart review was performed on patients diagnosed with SAA and treated with IS and GM-CSF at St. Jude Children's Research Hospital. Hematologic recovery, prognostic factors, and infection data were collected. Results Eighteen patients were included in this study. The median age at diagnosis was 7.2 years (range 1.8,17.0). Ten patients (56%) had a complete response, four (22%) a partial response, and four (22%) no response. Median time to erythrocyte and platelet transfusion independence were 90 (18,243) and 64 days (18,243), and to discontinuation of treatment 287 days (90,730). Median time to partial (ANC,>,500) and full (ANC,>,1,500) neutrophil recovery were 41 and 51 days, respectively. Seventeen documented discrete infections occurred in six patients over 36 patient years. Conclusions GM-CSF, in addition to IS, may shorten time to neutrophil count recovery, may be beneficial in decreasing infection rates, and may improve platelet response in patients with SAA. However, consistent with studies utilizing G-CSF, GM-CSF probably does not affect overall response rate. To fully answer whether or not cytokine therapy is of added value to IS in pediatric patients, a multi-institutional randomized trial is needed. © 2004 Wiley-Liss, Inc. [source] Laparoscopic cytoreductive nephrectomy with cytokine therapy for metastatic renal cell carcinomas compared with open nephrectomyASIAN JOURNAL OF ENDOSCOPIC SURGERY, Issue 3 2010T Fujita Abstract Introduction: We retrospectively reviewed and compared the operation records and long-term results of patients with metastatic renal cell carcinoma (mRCC) who underwent laparoscopic cytoreductive nephrectomy and those who underwent open procedure. Methods: A total of 75 patients with mRCC who underwent cytoreductive nephrectomy between 1997 and 2007 were studied: 23 patients in the laparoscopy group (LCN group) and 52 in the open group (OCN group). Most patients received interferon-based cytokine therapy after surgery. Patients with tumor thrombus in the inferior vena cava were excluded from this study. Results: Operating time in the LCN group was significantly longer than in the OCN group (320.3 min vs 269.6 min, P=0.049). Blood loss was less in the LCN group (527.8 ml) than in the OCN group (1372.3 ml, P=0.072). Convalescence was shorter in the LCN group (18.1 d) than in the OCN group (32.9 d, P<0.0001). Median follow-up periods were 15 months (range 2,110 months) and 17 months (range 1,103 months) in the LCN group and OCN group, respectively. There was no statistically significant difference between the two groups with regard to disease-specific patient survival and progression-free survival. Conclusions: Laparoscopic cytoreductive nephrectomy is a feasible alternative for patients with mRCC because its benefits include less blood loss and shorter convalescence. In addition, the long-term oncological results of laparoscopic cytoreductive nephrectomy are comparable to those of the open procedure. [source] New systemic treatment options for metastatic renal-cell carcinoma in the era of targeted therapiesASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010Thean Hsiang TAN Abstract Advances in understanding the biology and genetics of renal-cell carcinomas have led to the development of novel targeted therapies for the treatment of metastatic renal-cell cancer. Previously the systemic approaches were limited to cytokine therapies that were modest in their clinical benefits and at the expense of significant toxicities. Investigational treatments with allogeneic bone marrow transplantation were equally toxic and resulted in significant morbidity and mortality. The development of targeted therapy has revolutionized the treatment of metastatic renal-cell cancer with more meaningful outcomes. This review aims to provide a detailed discussion of the clinical benefits of targeted therapies such as sunitinib, sorafenib, temsirolimus, everolimus, bevacizumab, and some of the newer agents in clinical trial development. The efficacy of these compounds in terms of response, survival and clinical benefit are explored as well as their toxicities. The role of surgery in metastatic renal-cell carcinoma is reviewed in the context of cytoreductive therapy and resection of solitary and oligometastatic disease. Ongoing studies in the adjuvant setting following curative resection are also reviewed. The availability of targeted therapies has led to their rapid adoption as frontline therapy over traditional cytokine therapy, thus bringing more optimistic and hopeful therapeutic options in a condition where historically, systemic treatments have been relatively unsatisfactory and disappointing. [source] Interferon, tryptophan and depressionACTA NEUROPSYCHIATRICA, Issue 1 2003D. Fekkes Depression is a frequent comorbid disorder of many inflammatory diseases and it is suggested that brain inflammatory processes have a pathogenic role in mood dysregulation. Several immunocompromised patients have been treated with cytokines and long-term treatments have resulted in a variety of neuropsychiatric side-effects. The objective of the study was to present evidence for an association between the induction of neuropsychiatric side-effects during treatment with interferon-, (IFN-,) and changes in serotonergic and immunological parameters. Moreover, the use of IFN-,-induced depression as a paradigm for research into the pathophysiology of depressive disorders in general will be discussed. This literature review focused on the relationships between tryptophan, serotonin, cytokines and depression associated with interferon treatment. Immunotherapy with IFN-, influences several immunological and serotonergic parameters, and induces in most patients neurovegetative, somatic and depressive symptoms. Literature findings indicate that the development of depressive symptoms in patients undergoing cytokine therapy are secondary to cytokine induction and could be mediated by a reduced availability of tryptophan to the brain, resulting ultimately in decreased serotonergic activity. Changes in the metabolism of tryptophan and consequently of serotonin may play a role in the pathophysiology of interferon-induced depression. Studies on interferon-induced neuropsychiatric side-effects may be a promising research paradigm and shed light on the role of immunological and serotonergic factors in the pathogenesis of depressive disorders in general. However, first the appropriate symptomatology of the interferon-induced depressive states has to be documented. [source] | |||||||||||||||||||