Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0027627 (metastases)
103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The growth and spread of neoplasms depends on the establishment of an adequate blood supply, that is, angiogenesis. The onset of angiogenesis involves a change in the local equilibrium between proangiogenic and antiangiogenic regulators that are produced by tumor cells, surrounding stromal cells, and infiltrating leukocytes. In most normal tissues, factors that inhibit angiogenesis predominate, whereas in rapidly dividing tissues, the balance of angiogenic molecules favors stimulation of the process. A potent inhibitor of angiogenesis is interferon-alpha or -beta, shown to down-regulate transcription and protein production of basic fibroblast growth factor, collagenase type IV, and interleukin-8. The daily systemic administration of low (but not high) dose of interferon-alpha can produce significant inhibition of angiogenesis and, hence, regression of human tumors implanted orthotopically in nude mice. The recent elucidation of the interaction among proangiogenic molecules during physiological processes and the apparent disruption of this balance in neoplasia should allow the design of potent antiangiogenic therapies against primary cancers and metastases.
...
PMID:Angiogenesis and cancer metastasis. 1080 28

The combination of interferon-alpha (IFN-alpha) plus interleukin (IL-2) has been accepted in the treatment of metastatic renal cell carcinoma (MRCC), whereas vaccines based on IL-12 or dendritic cells (DCs) are still being investigated. Here the authors analyzed 1) the feasibility to generate functional monocyte-derived DCs (MDDCs) from patients treated with biological response modifiers (BRMs) who have MRCC, 2) the phenotypic modulations of these MDDCs during BRM treatment. Eight and 13 MRCC patients received IL-2 plus IFN-alpha or IL-12 immunotherapy, respectively. The adherent fraction of mononuclear cells from patients' blood drawn before, during, and after immunotherapy was incubated in clinically approved culture medium supplemented with 5% autologous serum, rhu granulocyte macrophage colony-stimulating factor, and rhuIL-4 for a week. At day 7 or 8 of culture, floating cells were examined in flow cytometric and functional assays (alloreactivity, proliferation assays in the presence of tetanus toxoid or tumor peptides, IL-12 secretion). In all patients except two, MDDCs could be generated but at a lower rate compared with healthy volunteers. Morphologic and phenotypical analyses revealed immature DCs with low levels of CD1a or CD83 expression throughout therapy with BRMs. Capacities in mixed leukocyte reactions were similar to those of healthy volunteers and stable during immunotherapy, whereas presentation of major histocompatibility complex class II tetanus toxoid peptide complexes was slightly enhanced during and after IL-12 therapy. IL-12 expression levels under IFN-gamma and CD40L stimulation were significantly lower in MDDC cultures from patients with MRCC compared with healthy volunteers. Overall, peripheral blood mononuclear cells from a cohort of 21 patients with metastatic disease who were treated with BRMs maintained their ability to differentiate into functional MDDCs with no selective quantitative or qualitative advantage.
...
PMID:Generation of monocyte-derived dendritic cells from patients with renal cell cancer: modulation of their functional properties after therapy with biological response modifiers (IFN-alpha plus IL-2 and IL-12). 1083 66

An outpatient regimen of interferon-alpha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU) was previously reported to have significant activity (response rate 48.6%) in patients with advanced renal cell carcinoma (RCC). The patient group reported were generally of good performance status (PS), had undergone previous nephrectomy and would be considered of good prognosis with respect to response and survival after treatment with IL-2. The characteristics of patients with RCC referred to specialist units in the UK differ from that patient group in that many patients present with metastatic disease, are of poor PS and are considered unfit for nephrectomy. We tested the three drug regimen in a representative patient group of 55 patients who had: median PS of 1 (range 0-2); median time from diagnosis to treatment of 2.7 months (0.2-113); and median number of sites of disease 3 (1-5). 22/55 had not had prior nephrectomy and 31 were considered of poor risk, 15 moderate risk and only 9 of good risk. Treatment consisted of an 8 week cycle of IFN-alpha 6 MU/m2 day 1 weeks 1 and 4 and thrice weekly weeks 2-3 and 9 MU/m2 thrice weekly, weeks 5-8. IL-2 20 MU/m2 days 3-5, weeks 1 and 4 and 5 MU/m2 thrice weekly weeks 2-3. 5-FU 750 mg/m2 day 1 of weeks 5-8. There were no complete responses (CR), 9 (17%) partial responses (PR) and 13 patients (24%) had stable disease. Sixteen patients withdrew early from treatment and were not evaluable for response. Amongst 25 evaluable patients who had undergone nephrectomy the response rate was 32% (95% CI: 14-50%). Only 1 response was seen in patients who had not undergone nephrectomy. Survival was predicted by PS, nephrectomy, number of sites of metastasis and risk group. Most patients experienced significant toxicity of grade I/II but few grade III/IV toxicities were seen as compared to intravenous IL-2 regimens. These data are part of a large data set that has been submitted for publication in The British Journal of Urology. The regimen has been shown to have activity but this is seen predominantly in patients of good PS, with prior nephrectomy and limited sites of disease. Patients of poor risk are likely to experience significant toxicity without benefit and should be offered alternative palliative therapies.
...
PMID:Cytokines in combination with chemotherapy for advanced renal carcinoma--the importance of patient selection. 1085 10

Patients with locally advanced stages of renal cell carcinoma are at high risk of relapse or progress even after initial radical surgery. Based on the proven efficacy of adoptive and active immunotherapeutic approaches of metastatic renal cell carcinoma, a phase II trial was started in 1989 using autologous, Newcastle disease virus modified and lethally irradiated tumor cell vaccines in combination with low-dose recombinant interleukin-2 (1.8 million U) and recombinant interferon-alpha 2a (1.0 million U) for a surgical adjuvant treatment. Patients were vaccinated (subcutaneous injection) once a week for 8-10 weeks and the treatment was started about 4-10 weeks after surgery. Up to now more than 208 patients with locally advanced renal cell carcinoma (stages pT2-3a, N1-2, M0; pT3b-4, N0-2, M0) were vaccinated after initial radical surgery (tumor nephrectomy with lymph node dissection and ipsilateral adrenalectomy and if necessary in combination with en bloc removal of venous extensions). We overview a follow-up of 203 evaluable patients with a median disease-free survival of 21 months (range of 2-64 months). During this observation period 18 relapses (8.9%) were diagnosed with 3 local relapses (1.5%), 10 lymph node metastases (5%) and/or distant organ metastases in 9 cases (4.5%). These progressive patients' disease was treated by surgery and/or combined immunochemotherapy. Toxicity encountered on this tumor cell vaccination was mild (WHO grade 1) and was characterized by flu-like symptoms and fever up to 38.8 degree Celsius for some hours beginning at 4 hours after the vaccine/cytokine application. Occasionally a transient local inflammation at the site of injection was observed. The comparison of the risk-factor-adapted group of adjuvant treated renal cell carcinoma patients (locally advanced stages) with historical data gave evidence for an improvement in disease-free survival on vaccination treatment. Although this was not a prospective randomized trial, we can summarize that the surgical adjuvant treatment of autologous tumor vaccines in combination with low-dose cytokines may improve relapse-free and overall survival in patients with locally advanced renal cell cancer.
...
PMID:Cytokines and tumor vaccination. 1085 11

Malignant melanoma is one of the most frequent malignancies of the skin. This is particularly true of malignant melanoma in juveniles. Its incidence has more than doubled from the 1970s to the mid-1990s. Presently, 15 new cases are recorded per 100,000 inhabitants a year in Germany. At Fachklinik Hornheide, a tumor center specializing in skin neoplasm with patients being referred from all over Germany, the number of melanoma patients treated per year has been approximately 500-550 for the past 10 years. In the present study, the state-of-the-art therapy for primary melanoma and treatment of the regional lymph node system is discussed. The radical treatment formerly advocated with wide tumor resection plus radical neck dissection is no longer justified for this immunogenic malignant tumor caused by endogenic as well as exogenic factors. "Sentinel lymph node" imaging by means of radioactive substances for diagnosing possible melanoma metastases in adjacent lymph nodes has changed the therapeutical concept. Tumor staging by means of ultrasound, CT, MRT, or PET allows the differentiation of tumors without distant metastases and a favorable prognosis, from melanomas which have to be considered as generalized disease. In addition to surgical resection of the tumor and neck dissection for removal of lymph nodes, adjuvant immunotherapy with interferon-alpha is capable of prolonging survival without a recurrence. Palliative chemotherapy or immunotherapy are valuable options for cases with generalized melanoma. Vaccination with a melanoma-associated antigen or dendritic cells is at an experimental stage and may become part of future treatment strategies.
...
PMID:[Malignant melanoma in the area of the head and neck]. 1093 58

Major prognostic factors for melanoma include thickness of the primary lesion, ulceration and presence or absence of regional lymph node metastases. These parameters form the basis for the American Joint Committee on Cancer staging system and the determination of the appropriateness of post-surgical adjuvant therapy. Among the numerous agents tested for the adjuvant therapy of high-risk melanoma, interferon-alpha 2b (IFN-alpha2b) administered at maximally tolerated doses is the only one to demonstrate an improvement in relapse-free and overall survival for these patients. This high-dose IFN-alpha2b regimen comprising an intensive intravenous induction phase followed by a more prolonged subcutaneously administered phase has now been tested in three, large, randomised trials done through the United States Cooperative Groups, and has shown consistent benefit in preventing relapse and improving survival for patients with thick primary melanomas and those with regional lymph node metastases. The relative importance of the induction component of this treatment regimen is being addressed in an ongoing intergroup trial for intermediate-risk melanoma. Data from completed and ongoing studies using high-dose IFN-alpha for the adjuvant therapy of melanoma are presented.
...
PMID:Update on the role of adjuvant interferon for high risk melanoma. 1100 31

Despite extensive investigations with many different treatment modalities, metastatic renal cell carcinoma (RCC) remains a disease highly resistant to systemic therapy. The outlook for patients with metastatic RCC is poor, with a 5-year survival rate of less than 10%. Late relapses after nephrectomy, prolonged stable disease in the absence of systemic therapy, and rare spontaneous regression are clinical observations that suggest host immune mechanisms could be important in regulating tumor growth. Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) have been extensively studied in advanced RCC with responses in the 10 to 20% range. Two randomized trials suggest that treatment with IFN-alpha compared with vinblastine or medroxyprogesterone results in a small improvement in survival. Prolonged responses with high-dose IL-2 is significant but is accompanied by formidable toxicity. Although the combination of IFN-alpha and IL-2 compared with monotherapy with IFN-alpha or IL-2 increases the response proportion, no improvement in survival could be demonstrated in a recent randomized trial. In addition, three randomized trials showed no survival benefit associated with IFN-alpha therapy given as adjuvant therapy following complete resection of locally advanced RCC. Small numbers of patients exhibit complete or partial responses to IFN-alpha and/or IL-2, but most patients do not respond and there are few long-term survivors. Clinical investigation of new agents and treatment programs to identify improved antitumor activity against metastases remain the highest priorities in this refractory disease.
...
PMID:Cytokine therapy in renal cell cancer. 1100 93

Cytokine therapy for patients with metastatic renal cancer is based on observations suggesting this neoplasm may be responsive to immunotherapy. Two cytokines, interferon-alpha (IFN-alpha) and interleukin 2 (IL-2) produce tumor regressions in 10% to 15% of patients with metastatic disease. Randomized trials demonstrate a modest survival advantage for patients treated with IFN-alpha. Combinations of IL-2 and IFN-alpha appear to be associated with improved response rates, but no demonstrable effect on survival. Additions of other cytokines (eg, GM-CSF) or chemotherapy to this combination has been investigated, but results do not suggest they enhance the outcome. Patient selection remains an important issue in this patient population. Individuals who are asymptomatic and have limited pulmonary or soft-tissue disease are most likely to benefit. The roles of immune dysregulation and the addition of novel cytostatic agents to these regimens are under investigation.
...
PMID:Cytokine therapy for metastatic renal cell carcinoma. 1135 35

Although the prognosis for patients with metastatic kidney cancer remains poor, a number of promising immunotherapeutic approaches for the treatment of metastatic disease have been developed over the past decade. The response of some patients to cytokines such as interleukin-2 and interferon-alpha, and more recently, vaccination with dendritic cell/tumor fusions has laid the ground work for ongoing immune-based investigational approaches. Allogeneic stem cell transplantation is a potent form of immunotherapy capable of delivering potentially curative immune-mediated anti-tumor effects against a number of different hematological malignancies. Knowledge of renal cell carcinoma's unusual susceptibility to immune attack has led to the hypothesis that tumor rejection, mediated through immunocompetent donor T-cells, might be generated against this solid tumor following the transplantation of an allogeneic immune system. Although clinical trials are early and ongoing, the recent observation of metastatic disease regression following non-myeloablative stem cell transplantation has identified renal cell carcinoma as being susceptible to a graft-versus-tumor effect. Disease responses following such therapy have ranged from partial to complete and have been observed even in patients who have failed conventional cytokine based strategies. This article reviews the design, methodology and early clinical results of studies investigating the use of allogeneic stem cell transplantation in metastatic renal cell carcinoma.
...
PMID:Allogeneic stem cell transplantation for renal cell carcinoma. 1149 71

The therapy of metastatic melanoma has not given satisfactory results. Single chemo- or immunotherapeutic agents in the adjuvant setting or combined chemoimmunotherapy for metastatic disease have generally been evaluated only in terms of clinical benefit. Considering that dacarbazine (DTIC) and interferon-alpha (IFN-alpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFN-alpha monotherapy, as well as by their combination in metastatic disease. The evaluated immunological parameters showed significant early increase in the activity of NK (natural killer) cells, CD4/CD8 ratio, CD4+ T cell number in patients treated with combined chemoimmunotherapy and an increase in expression of the early activation antigen CD38 on CD8+ cytotoxic T cells, both, in patients treated with combined chemoimmunotherapy and with IFN-alpha alone, while, no significant change in any one parameter was detected in the group of patients receiving DTIC. The kinetics of the observed immunological changes, restricted to combined chemoimmunotherapy, indicate that the engagement of antitumor immune response appears early but is short-lived and that this favorable effect should be augmented and prolonged by the timely introduction of additional immunomodulating agents.
...
PMID:Therapeutic implications of the kinetics of immunomodulation during single or combined treatment of melanoma patients with dacarbazine and interferon-alpha. 1158 85


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---