MedWorm: Cytokine Therapy

Intraarticular Treatments for Osteoarthritis: New Perspectives.

Current Drug Targets — Thu, 04 Mar 2010 00:00:00 +0100

Authors: Chevalier X To date, no targeted treatments for osteoarthritis have been developed. Therefore the challenge for the next years is to find a treatment that may slow down the progression of the disease. Osteoarthritis of the weight-bearing joints, such as knee OA, is more a local mechanical driven disease than a generalized one. To reach a non-vascularised tissue such as the cartilage, local intra-articular administration of drugs should be considered. The purpose of this review is to evaluate the advantages of local intra-articular drug administration compared with a systemic one in patients with osteoarthritis of weight-bearing joints. New perspectives of such strategy are reviewed, including anti-cytokine therapy, gene therapy, delivery of growth factors, stem cells therapy a...

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mTOR pathway inhibition in renal cell carcinoma.

Urologic Oncology — Thu, 04 Mar 2010 00:00:00 +0100

Authors: Pinto Marín A, Redondo Sánchez A, Espinosa Arranz E, Zamora Auñón P, Castelo Fernández B, González Barón M Renal cell carcinoma therapy has changed in a very significant way in the last few years. Up to 5 new agents have been developed, improving the results previously achieved with cytokine therapy. Bevacizumab, sorafenib, sunitinib, temsirolimus, and everolimus are now part of the therapeutic arsenal for this illness. Particularly, this has been the first tumoral type in which inhibition of mammalian target of rapamycin (mTOR) has proved its efficacy in phase III trials, either as first-line therapy for poor prognosis patients (temsirolimus, CCI-779) or as second-line therapy after failure of tyrosine-kinase inhibitors (everolimus, RAD001)....

Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model

BMC Cancer — Thu, 18 Feb 2010 00:00:00 +0100

Background: The treatment paradigm in advanced renal cell carcinoma (RCC) has changed in the recent years. Sunitinib has been established as a new standard for first-line therapy. We studied the prognostic significance of baseline characteristics and we compared the risk stratification with the established Memorial Sloan Kettering Cancer Center (MSKCC) model. Methods: This is a retrospective analysis of patients treated in six Greek Oncology Units of HECOG. Inclusion criteria were: advanced renal cell carcinoma not amenable to surgery and treatment with Sunitinib. Previous cytokine therapy but no targeted agents was allowed. Overall survival (OS) was the major end point. Significance of prognostic factors was evaluated with multivariate cox regression analysis. A model was developed to str...

Molecular basis for the treatment of renal cell carcinoma

Clinical and Translational Oncology — Fri, 29 Jan 2010 17:53:04 +0100

Abstract Renal cell carcinoma (RCC) is a heterogeneous malignancy whose incidence rate has notably increased in recent years without any evident reason. Traditionally, RCC has been resistant to classic treatments (chemotherapy, radiotherapy and hormonal therapy), with only a small percentage of patients benefiting from cytokine therapy. Different hereditary syndromes have been associated with RCC, Von Hippel Lindau (VHL) being the most important syndrome. Understanding key molecular pathways implicated in the tumorigenesis of RCC has crystallised in the development of more effective therapies. Specifically, drugs targeting VEGF (bevacizumab, sunitinib, sorafenib, axitinib, pazopanib) and PI3K-mTOR (temsirolimus and everolimus) have become the cornerstone of renal cancer tr...

Osteoarthritis: can anti-cytokine therapy play a role in treatment?

Clinical Rheumatology — Wed, 27 Jan 2010 20:28:54 +0100

Abstract Osteoarthritis (OA) is the most common joint disorder worldwide, and it has an enormous socioeconomic impact both in the United States and throughout the world. The degree of articular inflammation is usually associated with the disease’s progression, indicating that this process could contribute to articular damage. IL-1 beta and anti-TNF alpha are the two major cytokines players in the physiopathology of OA. Hence, we aimed to review the current literature on the effects of IL-1 and TNF-alpha neutralization as a new OA therapy. In vitro and experimental models showed a reduction in cartilage destruction with IL-1 inhibition therapy by IL-1 receptor antagonists (IL-1Ra). Despite this favorable evidence in animal models, studies on the inhibition of IL-1R in hum...

Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model.

Cytokine — Thu, 07 Jan 2010 00:00:00 +0100

Authors: Kalaaji AN, Lu J, Markovic SN, Celis E, Pittelkow MR Various cytokines, including interferon alpha (IFNalpha), tumor necrosis factor alpha (TNFalpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been used as adjuvant therapy for advanced-stage melanoma with some success but with marked toxicity, which appears to be related to higher doses. We investigated the efficacy of IFNalpha, GM-CSF, and TNFalpha in various combinations to induce antitumor and immune responses in a B16F10 murine melanoma model. These studies showed that GM-CSF, IFNalpha, and TNFalpha, when injected together intratumorally, mediated significant inhibition of tumor growth. Tumor regression correlated with local tumor necrosis and significant infiltration of T cells. In addition, this...

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Passive Antibody-Mediated Immunotherapy for the Treatment of Malignant Gliomas

Neurosurgery Clinics of North America — Mon, 30 Nov 2009 16:46:13 +0100

Despite advances in understanding the molecular mechanisms of brain cancer, the outcome of patients with malignant gliomas treated according to the current standard of care remains poor. Novel therapies are needed, and immunotherapy has emerged with great promise. The diffuse infiltration of malignant gliomas is a major challenge to effective treatment; immunotherapy has the advantage of accessing the entire brain with specificity for tumor cells. Therapeutic immune approaches include cytokine therapy, passive immunotherapy, and active immunotherapy. Cytokine therapy involves the administration of immunomodulatory cytokines to activate the immune system. Active immunotherapy is the generation or augmentation of an immune response, typically by vaccination against tumor antigens. Passive im...

Relationship Between Tumor-infiltrating T Lymphocytes and Clinical Response After Reduced-intensity Allogeneic Hematopoietic Stem Cell Transplantation for Advanced Renal Cell Carcinoma: A Single Center Prospective Study

Japanese Journal of Clinical Oncology — Thu, 26 Nov 2009 16:16:47 +0100

Conclusions Our results demonstrate the efficacy of HSCT for RCC and suggest that the graft-versus-tumor effect elicited by CTLs is induced in vivo. HSCT should be further explored as a potential curative treatment for RCC. (Source: Japanese Journal of Clinical Oncology)

Stage migration and increasing proportion of favorable-prognosis metastatic renal cell carcinoma patients

Cancer — Tue, 17 Nov 2009 00:00:00 +0100

The Memorial Sloan-Kettering Cancer Center risk model classifies patients with metastatic renal cell carcinoma (RCC) by 5 pretreatment features as favorable, intermediate, and poor risk. The number of Memorial Sloan-Kettering Cancer Center patients in each risk group was examined by year of treatment to analyze stage migration.The distribution of risk groups was examined retrospectively in 789 Memorial Sloan-Kettering Cancer Center patients with metastatic RCC treated in a first-line therapy clinical trial from 1975 to 2007. Date of treatment onset was divided into 6 cohorts between 1975 and 2007 (1975-1980, 1981-1985, 1986-1990, 1991-1995, 1996-2001, and 2001-2007).The median age of the first-line metastatic RCC clinical trial patients was 59 years (range, 20-82 years). Most patients rece...

Abnormalities of thyroid function in Japanese patients with metastatic renal cell carcinoma treated with sorafenib: A prospective evaluation.

Urologic Oncology — Thu, 12 Nov 2009 00:00:00 +0100

The objective of this study was to characterize features of thyroid dysfunction in Japanese patients with metastatic renal cell carcinoma (RCC) who were treated with sorafenib. We performed a prospective observational study including 69 Japanese patients who were diagnosed as having metastatic RCC refractory to cytokine therapy and subsequently treated with sorafenib for at least 12 weeks. Thyroid function was assessed before and every 4 weeks after the initiation of sorafenib treatment. Of the 69 patients, 23 (33.3%) did not show any biochemical thyroid abnormality, while the remaining 46 (67.7%) developed hypothyroidism. However, 11 (23.9%) of these 46 hypothyroid patients initially had a suppressed thyroid-stimulating hormone (TSH) value accompanying the increase in free triiodothyronin...

NCCN Guidelines for Kidney Cancer Updated

Kidney Cancer Association — Tue, 03 Nov 2009 16:43:09 +0100

to Include Pazopanib for Advanced Disease; Free Webinar Discusses Updates The NCCN Guidelines for Kidney Cancer have been updated to incorporate the recently approved therapy pazopanib as a treatment option for patients with advanced renal cell carcinoma. In conjunction with this update, NCCN presents a series of free webinars scheduled for the week of November 9, 2009, hosted by an NCCN Guidelines Panel Member to review the information that supported modification of the NCCN Guidelines. FORT WASHINGTON, PA — Following the recent FDA approval of pazopanib (Votrient™, GlaxoSmithKline) for advanced renal cell carcinoma, the National Comprehensive Cancer Network (NCCN) has updated the NCCN Clinical Practice Guidelines in Oncology™ for Kidney Cancer to include pazopanib as...

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General Model of Inflammation.

Bulletin of Mathematical Biology — Fri, 23 Oct 2009 00:00:00 +0100

Authors: Herald MC Dysfunctions in the immune system, due to genetics, disease or environmental factors, can cause bacterial colonization and chronic inflammation. In cystic fibrosis and chronic obstructive pulmonary disease, respiratory infections can initiate inflammation of the airway. We propose a system of nonlinear ordinary differential equations to describe interactions between macrophages, both inflammatory and anti-inflammatory cytokines, and bacteria. Small changes in parameters governing inflammatory cytokine production and macrophage sensitivity to cytokines result in dramatically different model behaviors. When the immune system is functioning properly, a non-aggressive pathogen will not provide a sufficient trigger to initiate chronic inflammation, however, in disease pos...

Notes from the 8th International Symposium

Kidney Cancer Association — Wed, 14 Oct 2009 19:57:52 +0100

Patient advocates generously volunteered their time to take notes at the recent 8th International Kidney Cancer Symposium, in Chicago. These notes are intended to capture the essence of this important medical meeting and convey it in a way that is useful to patients, survivors, and their families. The first installment sumarizes the Saturday morning session. Integration of Surgical and Systemic Therapy in Metastatic RCC This session was opened by Dr. Bradley Leibovich who presented two cases on which the audience voted on methods to integrate surgery with systemic treatment interventions. The diversity of responses opened the way to consideration of the three discussions that followed. Dr. Jorge Garcia discussed the role of neoadju...

The role of interleukin-17 in the pathogenesis of rheumatoid arthritis

Current Rheumatology Reports — Tue, 06 Oct 2009 12:59:24 +0100

This article discusses the history of the discovery of Th17 cells, the potential mechanisms of action of IL-17 in autoimmunity, and perspectives for IL-17-targeted cytokine therapy. Content Type Journal ArticleDOI 10.1007/s11926-009-0052-yAuthors Sarah L. Gaffen, University of Pittsburgh Department of Medicine, Division of Rheumatology and Clinical Immunology Pittsburgh PA 15261 USA Journal Current Rheumatology ReportsOnline ISSN 1534-6307Print ISSN 1523-3774 Journal Volume Volume 11 Journal Issue Volume 11, Number 5 / October, 2009 (Source: Current Rheumatology Reports)

Interleukin -6 subfamily cytokines and rheumatoid arthritis: Role of antagonists.

International Immunopharmacology — Thu, 01 Oct 2009 23:00:00 +0100

Authors: Jazayeri JA, Carroll GJ, Vernallis AB Many cytokines have been implicated in the inflammatory pathways that characterise rheumatoid arthritis (RA) and related inflammatory diseases of the joints. These include members of the interleukin-6 (IL-6) family of cytokines, several of which have been detected in excess in the synovial fluid from RA patients. What makes the IL-6 group of cytokines a family is their common use of the glycoprotein 130 (gp130) receptor subunit, to which they bind with different affinities. Several strategies have been developed to block the pro-inflammatory activities of IL-6 subfamily cytokines. These include the application of monoclonal antibodies, the creation of mutant form(s) of the cytokine with enhanced binding affinity to gp130 receptor and the g...

Lack of specific {gamma}-retroviral vector long terminal repeat promoter silencing in patients receiving genetically engineered lymphocytes and activation upon lymphocyte restimulation

Blood — Thu, 01 Oct 2009 16:03:26 +0100

Retroviral transduction of tumor antigen-specific T-cell receptor (TCR) genes into lymphocytes redirects T cells to lyse tumors. Furthermore, adoptive transfer of these lymphocytes has mediated objective responses in patients with metastatic cancer. From 2004 to 2006, more than 40 patients were treated with autologous gene-modified lymphocytes expressing a melanoma antigen-specific TCR at the National Cancer Institute. Eighteen such patients were analyzed for persistence and gene expression in vivo. In addition, the impact of epigenetic silencing and of lymphocyte restimulation was studied. Although gene-modified lymphocytes persisted in vivo, the shutdown of TCR transgene expression was observed. Bisulfite sequencing analysis and ex vivo DNA methyltransferase inhibition demonstrated that ...

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Efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with and without prior cytokine therapy, a subanalysis of TARGET

Medical Oncology — Wed, 16 Sep 2009 18:45:51 +0100

Abstract Before the development of targeted therapies, administration of cytokines (e.g., interleukin-2, interferon-α) was the primary systemic treatment option for advanced renal cell carcinoma. Sorafenib, an oral targeted, multikinase inhibitor, significantly prolonged progression-free survival and overall survival in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET), a large (N = 903) phase III, double-blind, randomised, placebo-controlled study of patients with advanced renal cell carcinoma resistant to standard therapy. This analysis of a patient subgroup from TARGET evaluated the safety and efficacy of sorafenib in patients who had received prior cytokine therapy (sorafenib: n = 374; placebo: n = 368) and in patie...

Cytokine and anti-cytokine therapy in asthma: ready for the clinic?

Clinical and Developmental Immunology — Fri, 11 Sep 2009 09:00:46 +0100

Authors: Desai D, Brightling C Asthma is a common disease with an increasing prevalence worldwide. Up to 10% of these patients have asthma that is refractory to current therapy. This group have a disproportionate use of health care resources attributed to asthma, have significant morbidity and mortality and therefore represent an unmet clinical need. Asthma is a complex heterogeneous condition that is characterized by typical symptoms and disordered airway physiology set against a background of airway inflammation and remodelling. The inflammatory process underlying asthma is co-ordinated by a cytokine network. Modulating this network with biological therapy presents a new paradigm for asthma treatment. Clinical trials undertaken to date have underscored the complexity of the inflammat...

Steering orally induced deviation of xenogeneic immunity with exogenous cytokines in rats fed porcine proteins.

Transplant Immunology — Thu, 10 Sep 2009 23:00:00 +0100

The objective of this study was to determine if rat cell-mediated immunity (CMI) and antibody (Ab) to discordant porcine xenoantigens could be suppressed by oral administration of porcine protein with adjunct systemic cytokine therapy. Based on principles of oral tolerance, it was hypothesized that: a. Feeding proteins from porcine blood mononuclear cells (PBMC) would induce a type 2 response, inhibiting CMI and type 1 Ab (associated with xenograft rejection) but increasing the amount of type 2 Ab. b. IL-4, a type 2 cytokine would exaggerate type 2 bias, enhancing immune deviation. c. IFN-gamma, a type 1 cytokine was expected to down-regulate overall Ab production, but increase CMI and type 1 Ab. DA rats fed porcine proteins with or without subcutaneous and intraperitoneal injections of IF...

Successful structure-based design of recent p38 MAP kinase inhibitors.

Current Topics in Medicinal Chemistry — Fri, 21 Aug 2009 12:34:02 +0100

Authors: Karcher SC, Laufer SA Inflammation is a complex immune response to cellular and tissue damage caused by physical, chemical, immunological, or microbial stimuli [1]. Prior to the successful launch of the anti-cytokine biologics [2-4], therapeutic approaches for the treatment of chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease were associated with severe side effects. Although biological agents have revolutionized the treatment of inflammatory disorders, the high costs and inconvenient dosing regimens would greatly benefit from novel safe and effective orally active inhibitors of tumor necrosis factor (TNF) alpha and interleukin (IL) 1beta. The clinical benefit of anti-cytokine therapy [5] and the central role of the p38 mitogen-activated...

Clinical and Immunologic Effects of Intranodal Autologous Tumor Lysate-Dendritic Cell Vaccine with Aldesleukin (Interleukin 2) and IFN-{alpha}2a Therapy in Metastatic Renal Cell Carcinoma Patients.

Clinical Cancer Research — Mon, 20 Jul 2009 23:00:00 +0100

CONCLUSIONS: The clinical and immunologic responses observed in this trial suggest an interaction between DC vaccination and cytokine therapy. Our data support the hypothesis that modulation of inflammatory, regulatory, and angiogenic pathways are necessary to optimize therapeutic benefit in renal cell carcinoma patients. Further exploration of this approach is warranted. PMID: 19622576 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

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Cytokine and anti-cytokine therapy in asthma: ready for the clinic?

Clinical and Experimental Immunology — Tue, 14 Jul 2009 23:00:00 +0100

Asthma is a common disease with an increasing prevalence worldwide. Up to 10% of these patients have asthma that is refractory to current therapy. This group have a disproportionate use of health care resources attributed to asthma, have significant morbidity and mortality and therefore represent an unmet clinical need. Asthma is a complex heterogeneous condition that is characterized by typical symptoms and disordered airway physiology set against a background of airway inflammation and remodelling. The inflammatory process underlying asthma is co-ordinated by a cytokine network. Modulating this network with biological therapy presents a new paradigm for asthma treatment. Clinical trials undertaken to date have underscored the complexity of the inflammatory profile and its relationship to...

How Can Second-Line Therapy for Metastatic Renal Cell Carcinoma Help to Define an Overall Management Strategy?

Oncology — Sun, 12 Jul 2009 23:00:00 +0100

Authors: Melichar B For many years, therapy for metastatic renal cell carcinoma (mRCC) was limited to a single line of cytokine therapy with either interferon or interleukin-2. Relatively recently, the novel targeted agents bevacizumab, sorafenib, sunitinib and temsirolimus have each demonstrated activity in patients with mRCC that is refractory to cytokine therapy. Based on phase III trial data of patients who have received no prior therapy for mRCC, targeted agents have now rapidly replaced cytokines or, in the case of bevacizumab, are used in combination with interferon as first-line therapy for mRCC. Thus, second-line therapy for mRCC needs to be re-evaluated. Available data indicate that patients whose disease is refractory to a targeted agent may obtain, in some cases, benefit fr...

Anti-cytokine therapeutics: history and update.

Current Pharmaceutical Design — Sat, 27 Jun 2009 15:42:04 +0100

Authors: Ratsimandresy RA, Rappaport J, Zagury JF Anti-cytokine therapy has promoted a revolution in the treatment of several inflammatory disorders during the past 10 years. Despite their medical and commercial success, they exhibit several drawbacks: difficulties of production, excessive costs, and a few side-effects. A promising alternative to the passive infusion of monoclonal antibodies or soluble cytokine receptors is the use of the active anti-cytokine immune therapy (ACIT). Surprisingly, clinical studies suggested the interest of this approach during the late 1980's, even before the advent of anti-cytokine passive immunotherapy. In this review, we first explain the involvement of several cytokines in many common diseases involving cytokine overproduction, and identify key targe...

Hope for rosacea: Cytokinin treatment offers patients a new therapeutic option

Modern Medicine — Tue, 02 Jun 2009 04:00:00 +0100

A novel therapeutic approach with Pyratine-XR appears to be a helpful adjunct in the treatment of rosacea. This topical cytokine therapy offers patients another effective option for rosacea and is a much welcomed addition in the dermatologic armamentarium. (Source: Modern Medicine)

Use of Cytokine Therapy in Primary Immunodeficiency

Clinical Reviews in Allergy and Immunology — Sat, 16 May 2009 05:38:02 +0100

Abstract Of the six cytokine therapies approved by the US Food and Drug Administration, five of them have been used in patients with primary immunodeficiency (PID). In some applications, clear benefits have been demonstrated, while in others, effects have been more marginal. The most compelling current applications of cytokine therapy in PID are those of granulocyte colony stimulating factor in severe congenital neutropenia and interferon gamma in chronic granulomatous disease. Despite encouraging results with interleukin-2 in common variable immunodeficiency and select other indications, its use in PID is not widespread. Content Type Journal ArticleDOI 10.1007/s12016-009-8131-4Authors Sumita Roy-Ghanta, Children’s Hospital of Philadelphia Division of Allergy and Immu...

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Interferon-alpha treatment may negatively influence disease progression in melanoma patients by hyperactivation of STAT3 protein

European Journal of Cancer — Tue, 21 Apr 2009 06:16:09 +0100

In this study, we have investigated the possibility that a growth-promoting STAT3 protein might be activated by interferon-alpha in melanoma cells. We examined 24 primary cultures established from node metastases of melanoma patients who were monitored in a 5-year clinical follow-up. The patients differed in the course of disease and survival end-points. Using Western blot analyses, we show that interferon-alpha stimulated STAT3 phosphorylation at tyrosine (Y705) residue in 17% of cases. These over-reactive cell populations originated from patients who had the shortest disease-free intervals. A significant correlation was obtained between the length of survival end-points and a lack of STAT3 activation by IFN-alpha. No STAT3 induction was observed in normal melanocytes. The STAT1 activatio...

Optimal management of metastatic renal cell carcinoma: an algorithm for treatment

BJU International — Tue, 21 Apr 2009 04:00:00 +0100

The treatment of metastatic renal cell carcinoma (mRCC) has been changed by the introduction of targeted agents. Consideration of individual patient factors, such as previous treatment and prognostic risk, e.g. according to the Memorial Sloan-Kettering Cancer Center (MSKCC) risk criteria), can assist in ensuring that patients receive appropriate targeted therapies. Available clinical evidence shows sunitinib to be the reference standard of care for the first-line treatment of mRCC in patients at favourable or intermediate prognostic risk according to MSKCC criteria. Combined treatment with bevacizumab plus interferon-[alpha] can also be considered for the first-line treatment of mRCC in this setting. For the first-line treatment of poor-risk patients, temsirolimus has shown benefit in a ph...

Harnessing innate and adaptive immunity for adoptive cell therapy of renal cell carcinoma

Journal of Molecular Medicine — Sat, 07 Mar 2009 12:01:44 +0100

Abstract The development of immunotherapies for renal cell carcinoma (RCC) has been the subject of research for several decades. In addition to cytokine therapy, the benefit of various adoptive cell therapies has again come into focus in the past several years. Nevertheless, success in fighting this immunogenic tumor is still disappointing. RCC can attract a multitude of different effector cells of both the innate and adaptive immune system, including natural killer (NK) cells, γδ T cells, NK-like T cells, peptide-specific T cells, dendritic cells (DC), and regulatory T cells (Tregs). Based on intensive research on the biology and function of different immune cells, we now understand that individual cell types do not act in isolation but function within a complex network...

Serum sickness, encephalitis and other complications of anti-cytokine therapy.

Best Practice & Research. Clinical Gastroenterology — Sat, 07 Mar 2009 02:49:59 +0100

Authors: Vermeire S, Van Assche G, Rutgeerts P The introduction of biological therapies has greatly advanced the therapeutic armamentarium of the inflammatory bowel diseases Crohn's disease and ulcerative colitis. At present, three anti-tumour necrosis factor (TNF) agents (infliximab, adalimumab and certolizumab pegol) and one anti-adhesion cytokine (natalizumab) have been approved and have shown efficacy in luminal and/or fistulizing Crohn's disease and/or in ulcerative colitis. Although the overall benefit/risk ratio for the anti-TNF agents is positive, of particular concern has been the problem of immunogenicity ascribed to the formation of antibodies to these molecules. Antibody formation is associated with allergic reactions and loss of response through decreased trough serum conc...

Interferon-alpha treatment may negatively influence disease progression in melanoma patients by hyperactivation of STAT3 protein.

European Journal of Cancer — Sat, 14 Feb 2009 05:00:00 +0100

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Genetic Deficiency of Complement Isoforms C4A or C4B Predicts Improved Survival of Metastatic Renal Cell Carcinoma

The Journal of Urology — Mon, 09 Feb 2009 15:43:21 +0100

Conclusions: Improved survival is seen in patients with C4A or C4B deficiency and renal cell carcinoma treated with cytokine therapy with or without surgery. These data support our hypothesis that patients with renal cell carcinoma who have autoimmune genotypes have favorable outcomes resulting from autoimmune mechanisms directed to the tumor. (Source: The Journal of Urology)

Targeting the immune system in cancer.

Current Pharmaceutical Biotechnology — Sun, 01 Feb 2009 05:00:00 +0100

Authors: Chaudhuri D, Suriano R, Mittelman A, Tiwari RK The concept of cancer immunotherapy provides a fresh perspective as it is not associated with many of the drawbacks of conventional therapies such as chemotherapy, radiotherapy and surgery. When fully activated the immune system has immense potential as is evident from mis-matched transplanted organs undergoing rapid immunological attack and rejection. However, the development of immune strategies for cancer therapy has been associated with challenges of their own. Early attempts at cancer vaccination were carried out in an empirical manner that did not always lead to reproducibility. This led to a search of tumor associated antigens with the belief that specific targeting of these antigens would lead to successful tumor eliminati...

Sorafenib induces therapeutic response in a patient with metastatic collecting duct carcinoma of kidney.

Onkologie — Sun, 01 Feb 2009 05:00:00 +0100

CONCLUSIONS: This is the first reported case of a patient with CDC responding to sorafenib treatment. Therefore, the role of sorafenib in the management of metastatic CDC needs prospective evaluation. PMID: 19209019 [PubMed - in process] (Source: Onkologie)

Granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and other immunomodulatory therapies for the treatment of infectious diseases in solid organ transplant recipients.

Current Opinion in Organ Transplantation — Mon, 01 Dec 2008 05:00:00 +0100

Authors: Page AV, Liles WC PURPOSE OF REVIEW: Infections continue to cause significant morbidity and mortality in SOT recipients despite major advances in immunosuppressive and antimicrobial regimens. Immunomodulatory cytokines provide a potential means to augment the host immune response to infection. This review will focus on cytokine therapy for the prophylaxis and treatment of infections in solid organ transplant recipients, and will speculate on the potential for further advances in the field. RECENT FINDINGS: In kidney and liver transplant recipients, granulocyte colony-stimulating factor (G-CSF) has been used successfully to reverse ganciclovir-induced neutropenia or cytomegalovirus-induced neutropenia. Although G-CSF also reversed corticosteroid-induced suppression of the neutr...

Comprehensive biomarker monitoring in cytokine therapy: heterogeneous, time-dependent, and persisting immune effects of interleukin-10 application in psoriasis.

Journal of Leukocyte Biology — Wed, 26 Nov 2008 05:00:00 +0100

We report systemic immunological effects of IL-10 therapy in 10 psoriasis patients during a 7-week treatment period followed by a 7-week observation period. IL-10 was given s.c. at 8 microg/kg/day or 20 microg/kg/3x/week, and a broad range of immunological biomarkers was analyzed in an extended kinetics (17 time-points) before, during, and after IL-10 therapy. Besides the expected anti-inflammatory effects (e.g., inhibition of LPS-induced cytokine secretion), we found unexpected effects, such as activation of NK cells and an increase in parameters, indicating proinflammatory activity (C-reactive protein and soluble IL-2R). Furthermore, cumulative effects (IgE and IgA), loss of effect (IL-1R antagonist and IFN-gamma secretion), or counter-regulation during and rebound after IL-10 therapy (T...

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Molecular biomarkers for advanced renal cell carcinoma: Implications for prognosis and therapy

Urologic Oncology: Seminars and Original Investigations — Mon, 03 Nov 2008 00:00:00 +0100

Conclusions: Thus, COX-2 and CAIX seem to be important predictors of outcome in patients with metastatic RCCs and might enhance the prognostic information obtained from pathology specimens. (Source: Urologic Oncology: Seminars and Original Investigations)

Molecular biomarkers for advanced renal cell carcinoma: Implications for prognosis and therapy.

Urologic Oncology — Wed, 29 Oct 2008 04:00:00 +0100

CONCLUSIONS: Thus, COX-2 and CAIX seem to be important predictors of outcome in patients with metastatic RCCs and might enhance the prognostic information obtained from pathology specimens. PMID: 18976937 [PubMed - as supplied by publisher] (Source: Urologic Oncology)

Targeted therapy for advanced renal cell cancer: cytokines and beyond.

Current Pharmaceutical Design — Thu, 11 Sep 2008 16:03:02 +0100

Authors: Papaetis GS, Karapanagiotou LM, Pandha H, Syrigos KN For the past 20 years cytokines have been the mainstay of treatment for advanced renal cell cancer (RCC), despite low response rates achieved and the high toxicity profile observed. The recent advances in molecular biology and the greater understanding of the von Hippel-Lindau (VHL) hypoxia-inducible factor (HIF)-hypoxia-induced gene pathway have paved the way for a plethora of novel agents that selectively inhibit key molecular events which allow the malignant process to continue. The high specificity of targeted agents should allow sparing of healthy cells thereby making them less toxic and well tolerated. However, new and unanticipated toxicities have been described with virtually all new agents, some of which may even be...

Cytokine therapy in cancer

Expert Opinion: Expert Opinion on Biological Therapy: Table of Contents — Mon, 08 Sep 2008 05:01:19 +0100

Expert Opinion on Biological Therapy , October 2008, Vol. 8, No. 10, Pages 1495-1505. Background: Cytokines provide important intercellular signals in inflammation, immunity and tumor and endothelial cell biology. Several cytokines have therapeutic potential when delivered exogenously alone or in combinations with chemotherapy or other ... (Source: Expert Opinion: Expert Opinion on Biological Therapy: Table of Contents)

Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: A randomized Phase III clinical trial Ravaud A, Hawkins R, Gardner JP, von der Maase H, Zantl N, Harper P, Rolland F, Audhuy B, Machiels JP, Pétavy F, Gore M, Schöffski P, El-Hariry I, Department of Medical Oncology, Hôpital Saint André, Bordeaux, France.

Urologic Oncology — Mon, 01 Sep 2008 04:00:00 +0100

CONCLUSION: Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC. PMID: 18774480 [PubMed - in process] (Source: Urologic Oncology)

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Immunotherapy of metastatic renal cell carcinoma.

Cancer Journal — Mon, 01 Sep 2008 04:00:00 +0100

Authors: McDermott DF, Atkins MB In 1992, high-dose bolus interleukin (IL)-2 was granted Food and Drug Administration approval based on its ability to produce durable complete responses in a small number of patients with metastatic renal cell carcinoma (RCC). However, the substantial toxicity and limited efficacy that is associated with IL-2 has narrowed its application to highly selected patients treated at specialized centers. In recent years, the relative merits of low- and high-dose cytokine regimens have been clarified by the results of 4 randomized trials. Taken together, these studies suggest that high-dose IV bolus IL-2 is superior in terms of response rate and possibly response quality to regimens that involve either low-dose IL-2 and interferon-alpha, intermediate- or low-dos...

Prospective Comparison of Sorafenib and Sunitinib for Second-Line Treatment of Cytokine-Refractory Kidney Cancer Patients.

Oncology — Wed, 20 Aug 2008 04:00:00 +0100

Conclusions: Both TKIs showed comparable clinical benefits. The Eastern Cooperative Oncology Group performance status and the Memorial Sloan-Kettering Cancer Center risk groups can help determine which patients might benefit from alternative drug treatments. PMID: 18714170 [PubMed - as supplied by publisher] (Source: Oncology)

MIF in autoimmunity and novel therapeutic approaches.

Autoimmunity Reviews — Tue, 19 Aug 2008 04:00:00 +0100

Authors: Stosic-Grujicic S, Stojanovic I, Nicoletti F Macrophage migration inhibitory factor (MIF) is a multipotent cytokine implicated in the pathogenesis of numerous inflammatory and autoimmune disorders. Since anti-cytokine therapy is considered to be a promising therapeutic strategy, selective targeting of MIF with either anti-MIF antibody or specific chemical MIF inhibitors might offer new therapeutic avenues for these disorders. Considering the unique relationship between MIF and glucocorticoids, therapeutic antagonism of MIF could also represent an effective approach for steroid-sparing therapies in patients with refractory autoimmune diseases. PMID: 18721909 [PubMed - as supplied by publisher] (Source: Autoimmunity Reviews)

Renal cell carcinoma: the translation of molecular biology into new treatments, new patient outcomes, and nursing implications.

Oncology Nursing Forum — Tue, 01 Jul 2008 04:00:00 +0100

CONCLUSIONS: Understanding the biologic basis of RCC has led to therapies that are transforming the goals for treatment outcomes in patients with metastatic disease and increasing time to progression with manageable side effects. IMPLICATIONS FOR NURSING: Counseling patients and managing treatment-related side effects of therapy are critical interventions for healthcare professionals caring for patients with RCC. Evolving treatments for metastatic disease are providing better options for patients and changing disease management. PMID: 18591174 [PubMed - in process] (Source: Oncology Nursing Forum)

Current status of debulking nephrectomy in the era of tyrosine kinase inhibitors

Current Oncology Reports — Tue, 24 Jun 2008 07:14:16 +0100

Abstract Cytoreductive nephrectomy (CN) has an established role against metastatic renal cell carcinoma (mRCC) in properly selected patients and offers a survival advantage when performed prior to cytokine therapy. With the emergence of new, effective targeted molecular therapies for mRCC, well-designed prospective trials are needed to clarify the biologic effects of CN to determine when and for whom CN should be performed in the context of targeted systemic therapy. Consequently, a thorough characterization of the systemic effects afforded by CN is imperative for developing individualized treatment strategies that effectively address the underlying biology of mRCC while maximizing patient quality of life during therapy. Until then, debulking surgery, which provides a surv...

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The current role of immunotherapy for renal cell carcinoma in the era of targeted therapeutics

Current Oncology Reports — Tue, 24 Jun 2008 07:14:15 +0100

Abstract The migration from cytokine therapy to the use of recently approved tyrosine kinase inhibitors and targeted therapeutic strategies may deprive some patients of a chance for long-term survival, as many clinicians now see these new agents as “easy fixes’ for treating renal cell carcinoma (RCC). New developments pertaining to the mechanism, patient selection, predictive biomarkers, and administration of interleukin-2 mandate a reassessment of the clinical landscape and the clinical trial information upon which our current practices are based. Recalibration of the scales that we use to weigh the various possible therapies for advanced kidney cancer is also needed. Despite the shift away from cytokine therapy in the current treatment paradigm, new therapeutic appro...

The future of tyrosine kinase inhibitors: Single agent or combination?

Current Oncology Reports — Tue, 24 Jun 2008 07:14:13 +0100

Abstract The past 3 years have delivered positive phase 3 trial results for sorafenib, sunitinib, temsirolimus, and bevacizumab in renal cell carcinoma (RCC). The benefit of these therapies has been best defined as either first-line therapy or following cytokine therapy in patients with clear cell RCC. In light of the differences in the molecular targets of each agent, there is reason to believe that sequential single-agent therapy or regimens combining these agents could extend the benefits observed in the reported randomized trials. However, to date, few data have been reported supporting either strategy. A careful consideration of the specific mechanism of action of each agent provides a basis for considering the optimal therapeutic strategies for incorporating each of ...

Conference report: Lapatinib demonstrates equivalent efficacy to hormone therapy in patients with advanced renal cell carcinoma?

NeLM news - Cancer — Wed, 11 Jun 2008 00:00:00 +0100

In this study 416 patients with advanced RCC who had experienced disease progression after first-line cytokine therapy were randomised to lapatinib 1,250 mg daily or HT with megestrol acetate or tamoxifen. The primary end point, median time to progression (TTP) was 15.3 weeks for lapatinib and 15.4 weeks for HT (HR= 0.94; P = 0 .60). Median OS was 46.9 weeks for lapatinib and 43.1 weeks for HT (HR = 0.88; P = 0.29). In a biomarker analysis of patients with EGFR-over expressed tumours (n = 241) median TTP was 15.1 weeks for lapatinib and 10.9 weeks for HT (HR = 0.76; P =0 .06), and median OS was 46.0 weeks for lapatinib and 37.9 weeks for HT (HR = 0.69; P = 0.02). The most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhoea (40%). (So...

Physiological functions of tumor necrosis factor and the consequences of its pathologic overexpression or blockade: Mouse models.

Cytokine and Growth Factor Reviews — Fri, 23 May 2008 04:00:00 +0100

Authors: Kruglov AA, Kuchmiy A, Grivennikov SI, Tumanov AV, Kuprash DV, Nedospasov SA TNF is an exciting cytokine which has helped to establish many paradigms in immunology. Although TNF itself has found only very limited use in the clinic, anti-cytokine therapy, which targets this single molecule, has enjoyed astounding success in treatment of a growing number of human diseases. However, since TNF mediates unique physiologic functions, in particular those related to host defense, TNF blockade may result in unwanted consequences. Much of our understanding about TNF intrinsic functions in the body, as well as about consequences of its overexpression and ablation, is based on studying phenotypes of various genetically engineered mice. Here we review mouse studies aimed at understanding T...

[Genitourinary Cancer] Lapatinib Versus Hormone Therapy in Patients With Advanced Renal Cell Carcinoma: A Randomized Phase III Clinical Trial

Journal of Clinical Oncology — Thu, 08 May 2008 04:00:00 +0100

Conclusion Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC. (Source: Journal of Clinical Oncology)

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[General Thoracic Surgery] Extension of survival by resection of asynchronous renal cell carcinoma metastases to mediastinal lymph nodes

The Journal of Thoracic and Cardiovascular Surgery — Thu, 01 May 2008 04:00:00 +0100

Conclusions Resection of renal cell carcinoma mediastinal lymph node metastases is safe, appears to extend survival, and should be considered an important component of treating patients with renal cell carcinoma who have asynchronous mediastinal lymph node metastases. (Source: The Journal of Thoracic and Cardiovascular Surgery)

A Large Open Label, Non-Comparative, Phase III Study Of The Multi-Targeted Kinase Inhibitor Sorafenib In European Patients

Cancer / Oncology News From Medical News Today — Sun, 06 Apr 2008 07:00:00 +0100

UroToday.com - Dr. Verzoni presented a trial to collect safety and efficacy data on sorafenib from a large and broad study population reflecting clinical practice. This nonrandomized, open-label study included male and female patients, aged â¥18, with an ECOG PS 0 2 and a life expectancy >2 months. Patients had to be unsuitable for or have failed prior cytokine therapy. Controlled, asymptomatic brain metastases were allowed. (Source: Cancer / Oncology News From Medical News Today)

The role and target potential of protein tyrosine phosphatases in cancer

Current Oncology Reports — Sat, 29 Mar 2008 09:11:06 +0100

Abstract Protein tyrosine phosphatases (PTPases) are attractive targets for developing novel cancer therapeutics. Activated via gain-of-function point mutations or overexpression, several PTPases have been identified as critical oncogenic molecules in human malignancies that may be targeted with small chemical inhibitors as a therapeutic strategy. Tumor suppressor PTPases have also been discovered as contributing factors in cancer development that may be targeted via intervention of downstream signaling events for therapeutic purposes. In addition, PTPases have been identified as key negative regulators of cytokines or immune cells. Targeting these negative PTPases may improve the efficacy of cytokine therapy and immunotherapy, which currently have modest response rates an...

An Antibiotic-Responsive Mouse Model of Fulminant Ulcerative Colitis

PLoS Medicine — Tue, 25 Mar 2008 09:25:35 +0100

Paul Allen and colleagues describe the development of a mouse model of fulminant ulcerative colitis with multiple genetic hits in immune regulation which can be moderated by anti-cytokine therapy and broad-spectrum antibiotics. (Source: PLoS Medicine)

Papillary renal cell carcinoma: clinicopathological characteristics in 40 patients

Clinical and Experimental Nephrology — Fri, 07 Mar 2008 06:55:57 +0100

Conclusion PRCCs include two distinct morphological types of tumor and type-2 PRCCs tends to have unfavorable features in comparison with type-1 PRCCs. These results support the clinical basis for the need to perform morphological subtyping of PRCCs when clinically evaluating such patients. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10157-008-0041-xAuthors Takeo Kosaka, Keio University School of Medicine Department of Urology 35 Shinanomachi, Shinjyuku-ku Tokyo 160-8582 JapanShuji Mikami, Keio University School of Medicine Department of Pathology 35 Shinanomachi, Shinjyuku-ku Tokyo 160-8582 JapanAkira Miyajima, Keio University School of Medicine Department of Urology 35 Shinanomachi, Shinjyuku-ku Tokyo 160-8582 JapanEiji Kikuchi, Keio University...

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Establishing the role of cytokine therapy in advanced renal cell carcinoma

BJU International — Fri, 15 Feb 2008 11:39:12 +0100

BJU International, Volume 0, Issue 0, Page ???, OnlineEarly Articles. Tribute to Professor Pieter De Mulder, from Martin Gore Pieter and I were often pitted against each other in debates at international meetings on the role of cytokine therapy. The truth is that there was little disagreement between us, but we both ... (Source: BJU International)

Controlled Delivery of T-box21 Small Interfering RNA Ameliorates Autoimmune Alopecia (Alopecia Areata) in a C3H/HeJ Mouse Model.

Am J Pathol — Sat, 02 Feb 2008 05:00:00 +0100

Authors: Nakamura M, Jo JI, Tabata Y, Ishikawa O Autoimmune alopecia (alopecia areata) is considered to be triggered by a collapse of immune privilege in hair follicles. Here we confirmed that infiltrating CD4 T lymphocytes around hair follicles of patients with alopecia areata were primarily CCR5-positive with few CCR4-positive cells, suggesting a dominant role of Th1 cells in the alopecic lesion. Given this finding, we sought to elucidate the effect of cytokine therapy in C3H/HeJ mice, a mouse model of alopecia areata, by applying recombinant interleukin-4 and neutralizing anti-interferon-gamma antibody. We found that local injections of both interleukin-4 and neutralizing anti-interferon-gamma antibody effectively treated alopecia in C3H/HeJ mice. Results from immunohistochemistry a...

Economic evaluation of sunitinib malate in second-line treatment of metastatic renal cell carcinoma in Finland.

Clinical Therapeutics — Fri, 01 Feb 2008 05:00:00 +0100

Conclusions: Based on the results of this cost-effectiveness analysis, sunitinib is potentially cost-effective as a second-line treatment of mRCC compared with the treatment currently practiced in Finnish hospitals. The ICER (euro/QALY gained) obtained in the present study was less than the value considered suitable for novel oncology treatments. PMID: 18343276 [PubMed - in process] (Source: Clinical Therapeutics)

Impact of histology on the treatment outcome of metastatic or recurrent renal cell carcinoma

Cancer Immunology, Immunotherapy — Thu, 03 Jan 2008 19:44:19 +0100

This study suggests that survival with a diagnosis of RCC is predicted by tumor histology and disease free interval, and this impacts on the ability to respond to standard therapy. Patients with mixed and clear cell histology respond to cytokine therapy. Other therapies should be sought for patients with sarcomatoid RCC. Content Type Journal ArticleCategory PaperDOI 10.1007/BF02787344Authors Jingjing Wu, Montefiore Medical Center Department of Oncology 111 East 210th Street 10467 Bronx NY USAGeralyn Caliendo, Montefiore Medical Center Department of Oncology 111 East 210th Street 10467 Bronx NY USAXiao-Ping Hu, Montefiore Medical Center Department of Oncology 111 East 210th Street 10467 Bronx NY USAJanice P Dutcher, Montefiore Medical Center Department of Oncology 111 East 210th Stre...

Successful treatment of neonatal herpes simplex-type 1 infection complicated by hemophagocytic lymphohistiocytosis and acute liver failure.

The Tohoku Journal of Experimental Medicine — Tue, 01 Jan 2008 05:00:00 +0100

Authors: Yamada K, Yamamoto Y, Uchiyama A, Ito R, Aoki Y, Uchida Y, Nagasawa H, Kimura H, Ichiyama T, Fukao T, Kohno Y Neonatal disseminated herpes simplex virus (HSV) infection with acute liver failure (ALF) and neonatal hemophagocytic lymphohistiocytosis (HLH) are severe diseases. We recently experienced a male infant with HLH and ALF induced by HSV type 1 (HSV-1). The infant, born at 39 weeks of gestation by normal delivery, developed a fever on day 4. On day 9, laboratory investigations showed progressive liver dysfunction and coagulopathy, and the serum ferritin was excessively elevated. Furthermore, the blood levels of interleukin (IL)-6, IL-10, and interferon-gamma were also elevated. HSV-1 DNA was detected in the serum and cerebrospinal fluid by the real-time PCR method. A diag...

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Intervention for apoptosis in cardiomyopathy

Heart Failure Reviews — Fri, 14 Dec 2007 15:55:43 +0100

Abstract Apoptosis plays an important role in pathogenesis of primary and secondary cardiomyopathies. It is proposed that antiapoptotic interventions may constitute an effective strategy for these diseases. Some of the antiapoptotic interventions are “old wine in a new bottle” measures already included in the conventional pharmacotherapy. As specific antiapoptotic treatment, caspase inhibitors and anti-TNF-α antibody are in early phases of clinical trials in non-cardiac diseases or being contemplated for clinical studies. Non-pharmacotherapies such as cardiac resynchronization and left ventricular assist device also exert cardioprotection partly by antiapoptotic mechanisms. In the field of regenerative medicine, myocardial transplantation of bone marrow-derived stem c...

Controlled-release particulate cytokine adjuvants for cancer therapy.

Endocrine, Metabolic and Immune Disorders Drug Targets — Sat, 01 Dec 2007 05:00:00 +0100

Authors: Egilmez NK, Kilinc MO, Gu T, Conway TF Cytokine therapy can induce tumor regression in cancer patients but systemic administration of cytokines is accompanied with severe toxicity. Loco-regional delivery represents an effective and less toxic alternative to systemic injection. However; the requirement for frequent repeated injections of recombinant cytokine or the logistical difficulties associated with gene-modification have limited wide-spread use of loco-regional therapy. A simpler alternative local delivery strategy involves the use of controlled-release cytokine depot formulations. These formulations provide the advantage that physiological doses of cytokines are directly released to the tumor microenvironment in a sustained manner. Anti-tumor efficacy of IL-2; IL-12; GM-...

IL-17/Th17 targeting: On the road to prevent chronic destructive arthritis?

Cytokine — Sat, 24 Nov 2007 05:00:00 +0100

Authors: Lubberts E Interleukin-17A (IL-17A) contributes to the pathogenesis of arthritis. Data from experimental arthritis indicate IL-17 receptor signaling as a critical pathway in turning an acute synovitis into a chronic destructive arthritis. The identification of six IL-17 family members (IL-17A-F) may extend the role of this novel cytokine family in the pathogenesis of chronic destructive joint inflammation. Whether the successful anti-IL-17A cytokine therapy in murine arthritis can be effectively translated to human arthritis need to be tested in clinical trials in humans. Interestingly, IL-17A and IL-17F are secreted by the novel T helper subset named Th17. This novel pathogenic T cell population induces autoimmune inflammation in mice and is far more efficient at inducing Th1...

Therapeutic angiogenesis for peripheral artery disease: cytokine therapy.

VASA. Zeitschrift fur Gefasskrankheiten. Journal for Vascular Diseases — Thu, 01 Nov 2007 04:00:00 +0100

Authors: Kuhlmann MT, Klocke R, Nikol S In recent years the importance of circulating bone marrow-derived cells in angiogenesis and collateral growth has been demonstrated in peripheral artery disease (PAD) and other ischaemic diseases. Although the mechanisms by which these cells exert their angiogenetic/arteriogenetic effects are not completely understood, improving the accumulation of bone marrow-derived cells at the site of vascular growth using cytokines has become one aim in some of the regenerative therapies. Interestingly recent data indicate that in addition to effects attributed to such accumulated cells there are also direct effects of cytokines used via their receptors. Several investigations in animal hind limb models of ischaemia have demonstrated the beneficial effect of...

[Genitourinary Cancer] Tumor Necrosis Factor {alpha} As a New Target for Renal Cell Carcinoma: Two Sequential Phase II Trials of Infliximab at Standard and High Dose

Journal of Clinical Oncology — Tue, 09 Oct 2007 04:00:00 +0100

Conclusion This is the first direct clinical evidence suggesting that TNF- may be a therapeutic target in RCC. Plasma levels of TNF-, IL-6, and CCL2 may have predictive and prognostic significance. (Source: Journal of Clinical Oncology)

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Cytokine therapy for cancer.

Surgical Oncology Clinics of North America — Mon, 01 Oct 2007 04:00:00 +0100

Authors: Kim-Schulze S, Taback B, Kaufman HL This review provides a review of the basic biology of the major cytokines under consideration for use in tumor immunotherapy. The authors also describe the clinical role of cytokine therapy for human tumors, with a focus on melanoma and renal cell carcinoma. Finally, they present details of new cytokines and suggest possible direction for future clinical investigation using new cytokines or combinations of biologic agents. A better understanding of cytokine biology, coupled with new insights into the role of immunoregulation and the microenvironment in patients who have cancer, has provided new therapeutic targets for the treatment of human cancer. PMID: 18022545 [PubMed - in process] (Source: Surgical Oncology Clinics of North America)

[Physiotherapeutic and rehabilitation therapy for ankylosing spondylitis : Status quo and are they still necessary in the age of anti-cytokine therapy?]

Zeitschrift fur Rheumatologie — Wed, 26 Sep 2007 04:00:00 +0100

Authors: Lange U, Kürten B, Müller-Ladner U, Uhlemann C Ankylosing spondylitis (AS) is one of the most common chronic inflammatory rheumatic diseases characterized by erosions and bone proliferation with consecutive morphologic and functional deficits. Physiotherapeutic and rehabilitation measures are often necessary for AS patients for their whole life. In recent years, biologicals have substantially improved the outcome in AS patients, but their positive influence on vertebral and joint functions still requires differential indicative physiotherapeutic strategies and rehabilitation, in most cases in combination with effective analgesic and anti-inflammatory medication. Although physical therapy and rehabilitation have not been investigated in large controlled trials, they a...

[Is there an indication for neoadjuvant or adjuvant systemic therapy in renal cell cancer?]

Der Urologe. Ausg. A — Thu, 06 Sep 2007 04:00:00 +0100

Authors: Doehn C, Merseburger AS, Jocham D, Kuczyk MA Looking at the most frequent urological tumors kidney cancer has the worst prognosis. Primary therapy consists of operative tumor removal in most cases. A tumor cutoff between 4 and 5 cm represents the turn towards a significant risk for postoperative tumor relapse. In those patients neoadjuvant or adjuvant therapy would be indicated. However, no phase III trials on neoadjuvant therapy of kidney cancer have been published in the literature.In contrast, five phase III trials on adjuvant therapy of kidney cancer have been published. In four trials interferon-alpha and/or interleukin-2 were applied. None of these trials had a positive outcome. Moreover, adjuvant cytokine therapy was associated with significant side effects in 30% of pa...

Therapeutic angiogenesis for peripheral artery disease: gene therapy.

VASA. Zeitschrift fur Gefasskrankheiten. Journal for Vascular Diseases — Wed, 01 Aug 2007 04:00:00 +0100

This article reviews both regulation of angiogenesis and the development of therapeutic strategies based on this knowledge using gene therapy. This includes knowledge from animal experiments as well as from phase I and phase II clinical trials. This information may be particularly important at a time when angiogenesis gene therapy enters the stage of phase III clinical testing hopefully leading to the first time approval of this completely new class of drug in the near future. Following articles of this series will review therapeutic angiogenesis approaches based on cytokine therapy and stem cell therapy. PMID: 18019272 [PubMed - in process] (Source: VASA. Zeitschrift fur Gefasskrankheiten. Journal for Vascular Diseases)

Anti-cytokine autoantibodies: Epiphenomenon or critical modulators of cytokine action

Biotherapy — Thu, 19 Jul 2007 07:21:39 +0100

Abstract Low amounts of high-affinity autoantibodies to various cytokines have been detected in sera from healthy donors. Their levels, although highly variable, are increased in the circulation of patients subjected to cytokine therapy or suffering from a variety of immunoinflammatory diseases. It has been suggested that these autoantibodies play a regulatory role in the intensity and duration of an immune response. The antibodies may prevent the binding of a cytokine to its specific cell surface receptor thereby neutralizing its biological activityin vivo. They may also act as carrier proteins preventing the rapid elimination of a cytokine from the circulation and thus increase its bioactivity. Additionally or alternatively, autoantibodies may modulate cytokine-induced in...

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Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins

Journal of Translational Medicine — Mon, 02 Jul 2007 04:00:00 +0100

Background: Sunitinib malate (SUTENT) is an oral, multitargeted tyrosine kinase inhibitor, approved multinationally for the treatment of advanced RCC and of imatinib-resistant or -intolerant GIST. The purpose of this study was to explore potential biomarkers of sunitinib pharmacological activity via serial assessment of plasma levels of four soluble proteins from patients in a phase II study of advanced RCC: VEGF, soluble VEGFR-2 (sVEGFR-2), placenta growth factor (PlGF), and a novel soluble variant of VEGFR-3 (sVEGFR-3). Methods: Sunitinib was administered at 50 mg/day on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment) to 63 patients with metastatic RCC after failure of first-line cytokine therapy. Predose plasma samples were collected on days 1 and 28 of each cycle and analy...

Antiapoptotic cytokines in combination with pegfilgrastim soon after irradiation mitigates myelosuppression in nonhuman primates exposed to high irradiation dose.

Experimental Hematology — Sun, 17 Jun 2007 13:34:55 +0100

CONCLUSION: These results suggest the safety and efficacy of EACK in managing severe radiation exposure. PMID: 17560010 [PubMed - as supplied by publisher] (Source: Experimental Hematology)

Systemic therapy for patients with advanced, unresectable ormetastatic renal cell carcinoma: moving to guidelines.

Canadian Urological Association Journal — Fri, 01 Jun 2007 04:00:00 +0100

This article reviews these agents in the context of their use in clinical practice and provides suggestions about the appropriateness of various agents in specific clinical situations. PMID: 18542783 [PubMed - in process] (Source: Canadian Urological Association Journal)

Current status of cytokine therapy in management of patients with metastatic renal cell carcinoma.

Canadian Urological Association Journal — Fri, 01 Jun 2007 04:00:00 +0100

Authors: Kapoor AK, Hotte SJ Cytokine therapy with interferon-alpha and interleukin-2 has arguably been the standard treatment for patients with metastatic renal cell carcinoma for more than 20 years. In this paper, the current evidence for the use of cytokine therapy in this patient population is discussed, including the significant toxicity associated with these agents. A low overall response rate and a marginal survival advantage are observed with interferon-alpha and interleukin-2; however, these therapies have significant toxicity and impair quality of life. Unlike the current tyrosine-kinase inhibitors, complete tumour responses may be seen with interleukin-2, but again this therapy has significant morbidity and mortality. Newer anti-angiogenesis agents may be combined with curre...

[Institutional report - Experimental] ICVTS on-line discussion A Equivocal results for cytokine therapy

Interactive CardioVascular and Thoracic Surgery — Tue, 22 May 2007 04:00:00 +0100

(Source: Interactive CardioVascular and Thoracic Surgery)

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Report On Kidney Cancer Symposium - Algorithm For Systemic Therapies In Metastatic Disease

Urology / Nephrology News From Medical News Today — Sun, 20 May 2007 07:00:00 +0100

Is there still a role for cytokine therapy in the treatment of metastatic RCC? A qualified maybe was the response of the group to this question. Improvements in our ability to select patients that are more likely to respond to high dose IL-2 based on clinicopathologic parameters may permit continued selective utilization of cytokine therapy in the treatment of metastatic RCC. [click link for full article] (Source: Urology / Nephrology News From Medical News Today)

Do the results of the new trials change the standard treatment of metastatic renal cell cancer?

Onkologie — Tue, 01 May 2007 04:00:00 +0100

Authors: Mulder SF, van Spronsen DJ, De Mulder PH With the emergence of novel angiogenesis inhibitors, we are moving to a new era for patients with metastasized renal cell carcinoma. Since the results achieved reflect more a modification of the natural course of the disease than a cure, past achievements should not be neglected. Low-risk patients with clear cell histology, especially those with pulmonary metastasis only, should still be offered cytokine therapy. For intermediate-risk patients sunitinib is the treatment of choice. For high-risk patients, temsirolimus has to date provided the most convincing data, its availability is however limited. Data with sorafenib and sunitinib in the high-risk group are still anecdotal. The toxicity profiles of these 2 drugs are different and migh...

ASCO 2006 highlights: Targeted therapy for renal cell carcinoma.

Cancer Treatment Reviews — Wed, 14 Mar 2007 04:00:00 +0100

Authors: Michaelson MD In the past few years, advances in the understanding of the pathogenesis of renal cell carcinoma (RCC) have resulted in the identification of new therapeutic targets, and ultimately, the development of new targeted agents for the treatment of the disease. This paper reviews latest data in RCC for the recently approved agents sunitinib and sorafenib, as well as other molecularly targeted drugs, presented at the annual meeting of the American Society for Clinical Oncology, held in Atlanta, Georgia, in June 2006. Clinical findings to date show that these new agents are challenging the role of cytokines in this setting, and for some (e.g. sunitinib) a substantially improved efficacy profile (progression-free survival and response) over conventional cytokine therapy h...

[Molecular pathology and targeted therapy of clear cell renal cancer.]

Magyar Onkologia — Sat, 13 Jan 2007 18:38:02 +0100

Authors: Tímár J, Kopper L, Bodrogi I The golden standard of care for advanced renal cell cancer (RCC) was until now the cytokine therapy with relatively low response rates. Advances of molecular genetics in RCC revealed several molecular targets such as VHL and angiogenic genotype or EGFR in the clear cell variant. Among the novel targeted agents, multiple tyrosine kinase inhibitors were proved to be clinically effective against advanced clear cell renal cancer, changing the standard of care. It is a further question how molecular diagnostics can improve these results by the detection of these targets or gene defects in individual tumors. PMID: 17216004 [PubMed - in process] (Source: Magyar Onkologia)

[Cytokine-based and targeted therapy of metastatic renal cell carcinoma--a current analysis]

Aktuelle Urologie — Mon, 01 Jan 2007 05:00:00 +0100

Authors: Johannsen M, Ringsdorf M, Römer A, Loening SA, Roigas J The systemic treatment of renal cell cancer represents a challenge for uro-oncologists. Although no internationally recognised treatment regime has been defined, cytokine therapy has been the standard of care for metastatic disease. The growing understanding of the relevant mechanisms in the molecular biology of renal cell carcinoma has led to the development of targeted therapies. Novel tyrosine kinase and angiogenesis inhibitors have had a beneficial effect on progression-free and overall survival in patients with advanced renal cell cancer and represented a significant progress. Even though several important aspects regarding treatments and combinations of these drugs with each other as well as with cytokines stil...

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Cytokine therapy for Crohn's disease: advances in translational research.

Annual Review of Medicine — Mon, 01 Jan 2007 05:00:00 +0100

Authors: Pizarro TT, Cominelli F Crohn's disease (CD) and ulcerative colitis (UC), the two idiopathic inflammatory bowel diseases (IBDs), affect almost two million individuals in North America and several million worldwide. Cytokines are important in the pathogenesis of CD, and their manipulation has successfully reduced disease severity and maintained remission. Following the discovery of novel cytokines and the role they may play in gut mucosal immunity, as well as the emergence of new concepts and changing paradigms in CD pathogenesis, the roles of several cytokines have been elucidated and tested in both preclinical animal models and clinical trials of patients with IBD. Complementary to this, proof of concept for new cytokine targets is rapidly developing, with the possibility of ...

[Review Articles] Role of Cytokine Therapy in 2006 and Beyond for Metastatic Renal Cell Cancer

Journal of Clinical Oncology — Fri, 08 Dec 2006 07:00:00 +0100

Metastatic renal cell cancer (mRCC) has a long history as a disease with poor prognosis and limited therapeutic options. Immunotherapy has been the mainstay of treatment since the 1980s, and there have been a number of largely phase II studies examining various schedules of interferon-alpha and interleukin-2 based treatments. With the development of molecular targeted drugs the armentarium against mRCC has significantly expanded and cytokine treatments should be only directed at those most likely to benefit with durable remissions and prolonged survival. (Source: Journal of Clinical Oncology)

Novel targets and therapies for metastatic renal cell carcinoma.

Oncology (Williston Park, N.Y.) — Fri, 01 Dec 2006 05:00:00 +0100

Authors: Feldman DR, Motzer RJ For the past 20 years, the systemic treatment of metastatic renal cell carcinoma (RCC) has been limited primarily to cytokines, with few patients showing benefit. However, recent advances in understanding the pathobiology of RCC have led to the identification of novel therapeutic targets for this disease. Drugs specifically designed to inhibit these targets have been developed, with several showing superior efficacy over traditional cytokine therapy. Moreover, these agents are well tolerated and have improved the span of progression-free, and in some cases, overall survival. As a result, between December 2005 and January 2006, two of these targeted therapies--sunitinib (Sutent) and sorafenib (Nexavar)--were approved by the U.S. Food and Drug Administratio...

Immunomodulatory drugs (IMiDs): a new treatment option for myelodysplastic syndromes.

Current Pharmaceutical Biotechnology — Sun, 01 Oct 2006 04:00:00 +0100

Authors: Kale V, List AF The IMiDs represent a new proprietary class of thalidomide analogues that possess greater potency and less toxicity than the parent compound. As a group, these agents share the pharmacologic property of modulating cellular response to ligand activation, the precise biologic effect of which is cell lineage and stimulant-dependent. Lenalidomide (CC-5013; Revlimid), a second generation IMiD, has shown significant erythropoietic activity in patients with lower risk MDS that have failed or are not candidates for recombinant erythropoietin treatment. Unlike cytokine therapy, lenalidomide suppresses select MDS clones and enhances erythropoietin receptor signaling to restore erythropoiesis. Activity is greatest in patients with interstitial deletions involving chromoso...

Suppression of proinflammatory cytokine production in macrophages by lansoprazole

Pediatric Surgery International — Fri, 25 Aug 2006 07:09:18 +0100

In this study, we examined the effect of two types of ATPase inhibitors on the expression patterns of typical proinflammatory cytokines. Peritoneal MPs from 6- to 8-week-old mice were cultured for 48 h in the presence of lansoprazole (P-ATPase inhibitor), bafilomycin A1 (V-ATPase inhibitor), or the control solvent dimethylsulfoxide. The MPs were then examined for cytokine expression by quantitative real-time polymerase chain reaction (PCR), and culture supernatants were examined for cytokine production with a multiplex assay in a suspension array system. The possible existence of P-ATPase mRNA in MPs was explored using reverse-transcriptase PCR. P-ATPase mRNA was not detected in MP cells. However, all examined proinflammatory cytokines decreased significantly in their mRNA and protein exp...

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Combined IL-21 and Low-Dose IL-2 therapy induces anti-tumor immunity and long-term curative effects in a murine melanoma tumor model

Journal of Translational Medicine — Tue, 13 Jun 2006 06:00:00 +0100

Conclusion: These observations support the potential use of IL-21 and low-dose IL-2 therapy in combination with a tumor-antigen vaccine and lymphopenic conditioning in future cancer clinical trials to maintain high numbers of anti-tumor memory CD8+ T cells with the potential to sustain long term tumor regression and survival. (Source: Journal of Translational Medicine)

ASCO 2006 - Plenary Session: Renal Cell Cancer

Cancer / Oncology News From Medical News Today — Mon, 12 Jun 2006 00:00:00 +0100

UroToday.com - The treatment of patients with metastatic renal cell carcinoma has relied upon the use of cytokine therapy such as interferon-alfa or interleukin-2. These treatments resulted in a minority of patients benefiting. While a small proportion of highly selected patients have derived long-term benefit from cytokine therapy, most do not. The median survival of patients with metastatic renal cell cancer treated with IFN-alfa is 4 - 6 months. [click link for full article] (Source: Cancer / Oncology News From Medical News Today)

Phase II data for sunitinib in second-line treatment of metastatic renal cell carcinoma

NeLM Headline News — Wed, 07 Jun 2006 00:00:00 +0100

Preliminary results from an open-label Phase II trial of sunitinib in the second-line treatment of metastatic renal cell carcinoma (mRCC) have been reported in the Journal of the American Medical Association (JAMA). Sunitinib is an oral small molecule multi-kinase inhibitor, which targets several receptor tyrosine kinases, including platelet-derived growth factor receptors (PDGFR), vascular endothelial growth factor receptors (VEGFR), and stem cell factor receptor (KIT). Metastatic RCC has an estimated 5 year survival rate of below 10%. Historically, RCC is one of the most uniformly resistant solid tumours in oncology and the usefulness of chemotherapy is severely limited. Immunotherapy with the cytokines interferon alpha (IFNa) and/or interleukin-2 (IL2) is currently employed in the tre...

PRELIMINARY COMMUNICATION: Sunitinib in Patients With Metastatic Renal Cell Carcinoma

JAMA — Tue, 06 Jun 2006 06:00:00 +0100

Conclusion The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.Trial Registration clinicaltrials.gov Identifier: NCT00077974 (Source: JAMA)

ASCO: Targeted Agents Herald New Age for Renal Cell Carcinoma

MedPage Today Nephrology — Mon, 05 Jun 2006 01:17:44 +0100

ATLANTA -- A targeted therapy that the FDA approved for renal cell carcinoma in January lengthened survival by six months when used as first-line therapy and more than doubled treatment response compared with standard cytokine therapy, researchers reported today. (Source: MedPage Today Nephrology)

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[Molecular pathology and targeted therapy of clear cell renal cancer]

Magyar Onkologia — Sun, 01 Jan 2006 05:00:00 +0100