Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A randomized phase II trial was performed to compare the efficacy and toxicity of interleukin 2 (IL-2) with an IL-2 and interferon alpha (IFN-alpha) regimen for the treatment of metastatic renal carcinoma. Sixty patients with recurrent renal cell carcinoma (RCC) who had previously undergone a nephrectomy were randomized to receive three cycles of IL-2 or IL-2 with IFN-alpha2b. Eighteen MU of IL-2 were administered subcutaneously on Mondays-Fridays for 3 weeks out of 4. Those patients randomized to receive the combination received the same regimen of IL-2 with 9 MU of IFN-alpha2b subcutaneously on Mondays, Wednesdays and Fridays for 3 weeks out of 4. Thirty patients were randomized to receive each arm. Twenty-nine were evaluable in each arm. Twenty-two patients received three cycles of IL-2 but only 14 patients received three cycles of IL-2/IFN-alpha because of the greater toxicity of the combination. The principal toxicities included nausea, fatigue and fever. There were no complete responses in either arm and only two patients who were treated with IL-2 attained a partial response. Twelve patients in each arm had stable disease and 15 patients in the IL-2 arm and 16 patients in the IL-2/IFN-alpha arm progressed through treatment. There were no significant differences in survival. Ten patients who received IL-2 are alive with a median follow-up of 266 days, whereas six patients who received IL-2/IFN-alpha are alive after a median of 278 days. The median survival from the time of identification of metastatic disease is 444 days in the IL-2 arm and 381 days in the IL-2/IFN-alpha arm. The IL-2/IFN-alpha combination is more toxic than IL-2 alone and this resulted in a reduced number of cycles of treatment. However, the median survival of the two groups was the same, suggesting that further evaluation of the IL-2/IFN-alpha combination should be confined to large prospective randomized clinical trials.
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PMID:A randomized phase II trial of interleukin 2 and interleukin 2-interferon alpha in advanced renal cancer. 970 84

Malignant lymphomas, hematological malignancies, sarcomas, occult head and neck primaries, Merkel cell carcinomas and malignant melanomas are among the tumors that are rarely seen in the head and neck region. Almost 20% of patients with acute leukemia initially present with symptoms of the oral cavity (ulcerations, gingival hypertrophy, etc.). If a malignant lymphoma is suspected, the lymph node should be removed in toto to ascertain diagnosis. Furthermore, in order to make sure that the immunohistological work-up or electron microscopic analysis is adequate, the pathologist should be informed prior to extirpation of the suspicious lymph node. The same diagnostic procedure is indicated for metastases from undifferentiated or small cell cancer of an unknown primary. Metastatic squamous cell or undifferentiated carcinoma to a solitary cervical lymph node from an unknown primary can be cured by multimodal therapy (extirpation, radical neck dissection and adjuvant radiation) in 30% of the cases. Following polychemotherapy, long-term survival may also be achieved in disseminated stages of undifferentiated carcinoma or poorly differentiated adenocarcinoma in an occult primary. When osteosarcoma of the jaw is suspected, core biopsy has to be planned carefully: in order to prevent tumor seeding, the needle track has to be excised during definitive surgery. Most authors propose (neo-)adjuvant chemotherapy (or chemoradiation) for head and neck osteosarcoma, especially when additional risk factors, i.e. a large primary or poorly differentiated sarcoma, are present. Patients with positive margins should receive adjuvant radiotherapy in soft tissue sarcoma. Local control of angiosarcoma is possible exclusively by radiation. Adjuvant radiation is also indicated in Merkel cell carcinoma. Because this tumor spreads in a "cascade" fashion, elective node dissection may also provide a chance for cure. Excision with wide margins is the principal therapeutic step in malignant melanoma. Due to the anatomic localization, adequate resection may not be possible in mucosal melanoma of the head and neck. When regional lymph nodes are involved, radical lymph node dissection and adjuvant radiation have to be added to the therapeutic concept. There is an emerging role for adjuvant interferon alpha in intermediate and high-risk melanoma.
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PMID:[Management of hematologic systemic diseases and rare tumor entities with manifestations in the oromaxillofacial area]. 973 65

A cancer treatment is described in which i.m. injection of plasmid DNA (pDNA) encoding murine interferon alpha (mIFN-alpha) leads to potent antitumor effects on primary and metastatic tumors in mice. Mice bearing s.c. B16F10 melanoma, Cloudman melanoma, or glioma 261 tumors were injected i.m. with mIFN-alpha pDNA. In all three tumor models, a significant reduction in tumor volume and enhancement of survival was found after IFN pDNA therapy. The mIFN-alpha pDNA could be injected as infrequently as once every other week and still produce a significant antitumor effect, and, in a metastatic tumor model, the therapy markedly reduced the number of lung tumor metastases. Depletion of immune cell subsets indicated that CD8(+) T cells were required for the antitumor response. These studies demonstrate that primary and metastatic tumors can be treated systemically by i.m. injection of a plasmid encoding a cytokine gene.
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PMID:A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon alpha. 999 62

Metastatic renal cell carcinoma has a poor prognosis. The efficacy of immunotherapy with interferon alpha (IFN-alpha) or interleukin 2 (IL-2) or their combination has been investigated extensively. The best schedule and optimum dose and combination is not known. On the basis of three prognostic factors, viz. WHO performance score, time between initial diagnosis and treatment of metastases, and number of metastatic sites, patients can be divided in prognostic groups. Patients classified in the favourable or intermediate prognostic group may survive longer after immunotherapy and therefore are candidates for such therapy. Patients who are classified in the poor prognostic group will not profit from any known systemic therapy.
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PMID:[Immunology in clinical practice. XVII. Immunotherapy of metastatic renal cell carcinoma. Work Group Immunotherapy, Dutch Oncology]. 1002 61

Carcinoid tumours in the intestine are slowly growing neuroendocrine tumours. Patients as a rule report symptoms of the carcinoid syndrome: attacks of diarrhoea and of flushing. When the earliest symptoms manifest themselves, metastases are already present, virtually always localized in the liver. At a late stage, heart failure may occur, difficult to treat and caused by fibrosis of the tricuspid valve in the presence of protractedly raised blood serotonin levels. To diagnose carcinoid tumours, use is made of radioactive substances binding to hormone receptors such as 131I-MIBG and 111-In-octreotide. When multiple metastases exist, only palliative treatment is possible. The drugs used are the somatostatin analog octreotide, interferon alpha, radioactive MIBG and non-radioactive MIBG; these drugs may also be used in combination. The therapies mentioned have approximately the same effect: symptoms improve in 60-80%, while 30-50% show a biochemical response, i.e. decrease of the number of breakdown products in the urine of the hormones produced by the tumour; tumour size decreases in 0-12%.
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PMID:[Carcinoid tumors of the intestines: developments in the Netherlands for diagnosis and palliative treatment]. 1022 Nov 20

Adenocarcinomas of the breast behave clinically and epidemiologically in ways that show host resistance factors are important for outcome in addition to grade and stage of malignancy. Immune reactivity to autologous tumors is indicated by the general presence of lymphoid infiltration (LI) and regional lymph node changes; however, these changes predict favorable outcome only in non-metastatic disease. LI is characterized by CD4+ and CD8+ tumor infiltrating lymphocytes reflecting latent cell-mediated immunity (CMI). CMI and humoral immune reactivity have been demonstrated to autologous tumor and a variety of tumor-associated antigens (TAA) have been implicated including CEA, HER-2/neu, MAGE-1, p53, T/Tn and MUC-1. Immune incompetence involving CMI is progressive with the stage of breast cancer and is prognostically significant. Immunotherapy of several types has been designed to address this immunodeficiency and the TAAs involved. Animal models have employed drug therapy, cytokine transfection, vaccines with autologous tumor, cytokines like interferon alpha (IFN-alpha) and interleukin-2 (IL-2), TAA tumor vaccines, and immunotoxins with evidence of tumor regression by immunologic means. Immunotherapy of human breast cancer is a rapidly growing experimental area. Positive results have been obtained with natural IFN and interleukins, particularly in combination strategies (but not with high dose recombinant IFN or IL-2), with autologous tumor vaccine (but not yet with transfected autologous tumor); with a mucin carbohydrate vaccine (Theratope) in a combination strategy (but not with mucin core antigen) and with several immunotoxins. Combination strategies involving immunorestoration, contrasuppression, adjuvant, and immunotoxins are suggested for the future.
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PMID:The immunology and immunotherapy of breast cancer: an update. 1023 Aug 72

Bone marrow stroma produces positive and negative growth regulators which constitute the hematopoietic microenvironment. As many tumors metastasize to the bones, these regulators may also influence tumor growth. Hematopoietic cytokines may indeed exert both positive and negative effect on tumor growth. We report that, when mixed with tumor cells. adherent bone marrow cells inhibit primary tumor growth and metastases formation in mice transplanted with Lewis lung carcinoma or B16 melanoma. Peritoneal macrophages or lymph node cells did not exert any influence. The tumor inhibition was apparently due to soluble factor(s) released by marrow stromal cells. In cocultures with B16 melanoma cells, adherent bone marrow cells exerted a significant antiproliferative effect which was increased by previous culture of the bone marrow cells with granulocyte-macrophage colony-stimulating factor but not with macrophage colony-stimulating factor. Neither neutralizing antibodies against tumor necrosis factor-alpha, transforming growth factor-beta or interferon alpha/beta nor addition of Escherichia coli lipopolysaccharide to generate inflammatory cytokines could affect the antiproliferative effect of bone marrow stromal cells. The bone marrow stroma factor(s) which inhibit tumor growth might, therefore, be a novel growth regulator.
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PMID:Factor(s) from nonmacrophage bone marrow stromal cells inhibit Lewis lung carcinoma and B16 melanoma growth in mice. 1035 34

Sentinel node (SN) mapping and biopsy is a procedure that accurately stages the regional lymph node (LN) basin. Defined patterns of lymphatic drainage allow intraoperative determination of the first (sentinel) lymph node in the regional basin, and the absence of metastatic disease in the SN accurately reflects the absence of melanoma in the remaining regional nodes. The use of radiocolloid and a hand-held gamma detecting probe (GDP) together with a vital blue dye provides optimal results, and allows for the successful identification of the SN in over 99% of the procedures. Close collaboration between surgeons, nuclear radiologists and pathologists is required to ensure optimal results. Examination of serially sectioned SNs by hematoxylin-eosin staining (H&E), immunohistochemical staining and perhaps in the near future RT-PCR should reduce the number of patients with missed microscopic melanoma in the regional lymph nodes. Furthermore, the survival benefit recently reported in patients with melanoma metastatic to regional nodes using high dose of interferon alpha-2b signals that the surgeons should aggressively examine patients for the presence of occult regional melanoma metastases. Intraoperative SN mapping and SN biopsy are cost-effective procedures that allows accurate identification of regional lymph nodes that contain metastatic melanoma.
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PMID:Sentinel node localisation: A new prospective in the treatment of nodal melanoma metastases. 1037 90

Treatment of metastatic malignant melanoma with interferon alpha (IFNalpha) results in objective remission in approximately 15% of patients. In a previous investigation, we found that about 50% of the patients achieved at least minor or short-lived remissions. In some tumours extensive areas of regressive tumour change occurred. However, even in these areas remnants of tumour cells were generally found. The short duration of the immune response in some patients and the incomplete eradication of the tumour can be due either to selection of non-immunogenic tumour cells or to down-regulation of the immune reactivity to the tumour. In the present paper, the expression of the zeta chain of the T cell receptor in CD3+ lymphocytes and the expression of CD28 in CD3+, CD4+ and CD8+ lymphocytes was studied in resectable melanoma metastases from 20 treated (IFNalpha or IFNalpha in combination with cisplatinum and dacarbazine) and 16 untreated patients. A double-staining technique was used, and the occurrence and distribution of lymphocytes showing down-regulation of the zeta chain or CD28 were separately registered in different areas of the metastases: close to the tumour cells in areas of unaffected tumour growth, in areas with regressive tumour changes, in areas with marked fibrosis and in stromal areas with densely packed lymphocytes. CD3+ zeta lymphocytes were found in all metastases, but their number and distribution varied considerably. Down-regulation of the zeta chain was most often found in areas of regressive changes. In contrast, T lymphocytes infiltrating close to the tumour cells had a stronger expression of the zeta chain (P = 0.016). Down-regulation was also found in stromal areas of densely packed lymphocytes and in areas of fibrosis. The pattern of down-regulation of CD28 in various subsets of lymphocytes was similar to that of zeta chain. The same pattern of down-regulation of CD28 and the zeta chain was found in both untreated and treated patients, indicating that the down-regulation is not due to treatment but to the release of immunosuppressor factors from areas with high tumour cell density or extensive destruction of tumour cells. These results concur well with the view that IFNalpha treatment can result in immune-mediated tumour cell destruction early in the treatment period and that this immune response to the tumour can be followed by immunosuppression within a few weeks.
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PMID:On down-regulation of the immune response to metastatic malignant melanoma. 1047 42

A right renal tumor was found in a 74-year-old man with multiple metastases to the lungs and liver. Tumor thrombus extending into the inferior vena cava and a right spermatic varicocele were also noted at the first visit. Interferon alpha-2b and interferon gamma were administered for treatment. Partial remission of lung metastases, complete remission of hepatic metastases, and disappearance of the varicocele occurred after 4, 6 and 8 weeks, respectively. Then the primary right renal tumor was resected. Although only interferon alpha-2b was continued twice weekly by self-injection, complete remission of the lung metastases was obtained 13 weeks after the initiation of therapy. No evidence of recurrence or new metastasis has been found after 18 months. These results indicate that even advanced renal cell carcinoma may show a rapid response to interferon alpha. Interferon alpha is worth trying for metastatic renal cell carcinoma and should be continued for at least a few months.
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PMID:[Complete remission of lung and hepatic metastases from renal cell carcinoma by interferon alpha-2b therapy: a case report]. 1054 Jul 7


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