UMLS:C0027627 - FACTA Search

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

A patient with liver metastases of human lymphocyte antigen (HLA) class II-negative malignant melanoma was treated with several cycles of adoptive immunotherapy with interleukin-2 and lymphokine-activated killer (LAK) cells. The authors evaluated the efficacy of regional transfer of LAK cells versus systemic intravenous administration. Initially, the patient was treated according to a regional treatment protocol, consisting of perfusion of the spleen with interleukin-2 and transfer of LAK cells into the portal vein; a partial remission was observed. Because of technical problems, interleukin-2 and LAK cells were administered intravenously in a second treatment cycle. This systemic treatment course resulted only in a minor mixed response of the hepatic metastases. A third treatment course was administered with the use of intravenous interleukin-2 infusion and arterial perfusion of the liver with LAK cells. The patient had separate hepatic arteries to both lobes of the liver as an anatomic variation. Because most of the tumor mass was present in the right lobe of the liver, a third of the LAK cells were injected into the right hepatic artery and the remaining cells were administered intravenously. The lesions in the right lobe of the liver regressed, but disease progression occurred in the left lobe. A fourth treatment cycle, consisting of intravenous infusion of interleukin-2 and arterial perfusion of both lobes of the liver with LAK cells, resulted in a complete response of all hepatic lesions, which has lasted 18 months to date. Because, in this patient, tumor regression was observed only in anatomic areas of the liver, which were perfused with LAK cells, it is suggested that the regional administration of LAK cells was essential for successful treatment.
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PMID:Regional administration of lymphokine-activated killer cells can be superior to intravenous application. 154 23

One hundred twenty-seven white European patients with differentiated thyroid cancer were typed for human lymphocyte antigen (HLA) DR specificities. There was no significant deviation from the HLA-DR distribution observed in 160 normal patient controls, neither in the entire group nor in the patient groups with nonmedullary types of thyroid cancer (61 with papillary and 44 with follicular, all nonradiation associated). Also, subdivision of patients with nonmedullary thyroid cancer according to age at diagnosis, presence of metastases, and presence of thyroglobulin antibodies in serum showed no significant deviation from the HLA-DR distribution. For the patients with medullary thyroid cancer (only sporadic [n = 20] or inherited isolated [n = 2] forms, no multiple endocrine neoplasias), there was a significant increase of HLA-DR2 (11 of 22 cases [50%]) in comparison with control patients (22%; P corrected to 0.02; relative risk, 3.6). These data suggest, in contrast to previous reports, that there is no genetic influence on the development of nonmedullary types of differentiated thyroid cancer. Medullary thyroid cancer without multiple endocrine neoplasia, however, may be associated with HLA-DR2.
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PMID:HLA-DR and differentiated thyroid cancer. Lack of association with the nonmedullary types and possible association with the medullary type. 319 50

Identification of antigens by monoclonal antibodies (MAbs) on sections of human melanoma by immunoperoxidase techniques was used to determine whether certain adhesion molecules and "selectin-like" molecules may be related to the metastatic potential of primary melanoma. The adhesion molecules examined were the leukocyte function antigen (LFA-1) and its ligand--intercellular adhesion molecule-1 (ICAM-1), the receptor alpha V beta 3 for vitronectin, its subunits alpha V and beta 3, and the CD36 receptor for thrombospondin (TSP). The criteria used to establish metastatic potential were relation of the molecules to tumor thickness and differences in expression: (i) between radial and vertical growth phases of the primary tumors and (ii) between 34 primary and 21 unrelated metastases. By these criteria ICAM-1, alpha V beta 3 and its subunit were associated with the malignant potential of primary melanoma. These molecules were not expressed on nevi or other skin cancers with low metastatic potential such as squamous (SCC) and basal cell carcinomas (BCC). In contrast, expression of TSP and the CD36 receptor for TSP were not related to metastatic potential. CD36 was expressed widely not only on melanoma but also on BCC, SCC and nevi. Similarly, the selectin-like molecule, CD44, was widely expressed on melanoma and non-melanoma carcinomas. The lymph node homing receptor, Leu 8, and the cutaneous lymphocyte antigen (CLA) were not detected on melanoma. Leu 8 was present on normal epithelium and SCCs, and common leucocyte antigen (CLA) was detected on lymphocytes in the epithelium and near melanoma. These results support previous suggestions that expression of ICAM-1 and V beta 3 integrin or its subunit beta 3 on melanoma may be a useful prognostic marker in primary melanoma. They do not support a role for CD44, Leu 8, CLA and TSP or its receptor CD36 in the metastatic process in melanoma.
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PMID:Immunohistological examination of the relationship between metastatic potential and expression of adhesion molecules and 'selectins' on melanoma cells. 751 76

Systemic effects on T-cell-mediated antitumor immunity, on expression of T-cell adhesion/homing receptors, and on the promotion of T-cell infiltration of neoplastic tissue may represent key steps for the efficacy of immunological therapies of cancer. In this study, we investigated whether these processes can be promoted by s.c. administration of low-dose (0.5 microg/kg) recombinant human interleukin-12 (rHuIL-12) to metastatic melanoma patients. A striking burst of HLA-restricted CTL precursors (CTLp) directed to autologous tumor was documented in peripheral blood by a high-efficiency limiting dilution analysis technique within a few days after rHuIL-12 injection. A similar burst in peripheral CTLp frequency was observed even when looking at response to a single tumor-derived peptide, as documented by an increase in Melan-A/Mart-1(27-35)-specific CTLp in two HLA-A*0201+ patients by limiting dilution analysis and by staining peripheral blood lymphocytes (PBLs) with HLA-A*0201-melanoma antigen-A/melanoma antigen recognized by T cells (Melan-A/Mart)-1 tetrameric complexes. The CTLp burst was associated, in PBLs, with enhanced expression of T-cell adhesion/homing receptors CD11a/CD18, CD49d, CD44, and with increased proportion of cutaneous lymphocyte antigen (CLA)-positive T cells. This was matched by a marked increase, in serum, of soluble forms of the endothelial cell adhesion molecules E-selectin, vascular cell adhesion molecules (VCAM)-1 and intercellular adhesion molecules (ICAM)-1. Infiltration of neoplastic tissue by CDS+ T cells with a memory and cytolytic phenotype was found by immunohistochemistry in eight of eight posttreatment metastatic lesions but not in five of five pretreatment metastatic lesions from three patients. Increased tumor necrosis and/or fibrosis were also found in several posttherapy lesions of two of three patients in comparison with pretherapy metastases. These results provide the first evidence that rHuIL-12 can boost the frequency of circulating antitumor CTLp in tumor patients, enhances expression of ligand receptor pairs contributing to the lymphocyte function-associated antigen-1/ICAM-1, very late antigen-4/VCAM-1, and CLA/E-selectin adhesion pathways, and promotes infiltration of neoplastic lesions by CD8+ memory T cells in a clinical setting.
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PMID:Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of metastatic lesions by memory CD8+ T cells in melanoma patients receiving interleukin 12. 1091 69

T cells resident in normal skin likely conduct immunosurveillance and are implicated in the development of inflammatory disorders such as psoriasis. This population of cells is difficult to study because existing techniques allow isolation of only few cells. We report here a novel method of isolating T cells from both normal and diseased human skin. Explants of skin cultured on three-dimensional matrices led to the outgrowth of dermal fibroblasts that elaborated T cell chemoattractant factors. These factors led to the migration of skin resident T cells out of skin explants where they could be collected and studied. Skin resident T cells isolated from explant cultures were CD45RO(+) memory T cells and expressed high levels of cutaneous lymphocyte antigen (CLA) and chemokine receptor (CCR)4. Inclusion of IL-2 and IL-15 in explant cultures produced up to a 10-fold expansion of skin-resident T cells, while maintaining the CLA(+)CCR4(+) skin-homing phenotype as well as a diverse T cell repertoire. This method also allowed efficient isolation of malignant T cells from the skin lesions of cutaneous T cell lymphoma and the isolation of tumor-infiltrating lymphocytes from primary squamous cell carcinomas and melanoma metastases.
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PMID:A novel method for the isolation of skin resident T cells from normal and diseased human skin. 1648 86

Various immunotherapeutic approaches for the treatment of renal cell carcinoma (RCC) have been developed for > 90 years. Existing immunotherapeutic strategies against RCC include: systemic administration of cytokines; therapeutic vaccines based on tumor cells or dendritic cells; monoclonal antibodies; and adoptive immunotherapy (T cell transfer or allogeneic hematopoietic cell transplantation). However, the overall efficacy of immunotherapy for advanced RCC remains moderate. With the advent of molecularly targeted biological therapies that turned out to be significantly effective in the treatment of metastatic RCC, to many oncologists immunotherapy may seem to be moving into the periphery of RCC treatment strategies. However, for the last 2 years there has been significant progress made in immunotherapeutic approaches for the treatment of RCC. Immunotherapy still remains the only systemic therapeutic strategy that is believed to potentially cure RCC patients. The development of active and passive specific immunotherapeutic approaches, along with the possibility to 'switch off' particular immunosuppressive mechanisms (e.g., elimination of regulatory T cells, blockage of cytotoxic T lymphocyte antigen-4 signaling), have paved the way for future trials of new immunotherapies of RCC. However, the new studies will have to enroll optimally selected patients (nephrectomized, with non-massive metastases and good performance status) and will use tumor response criteria that are specifically optimized for clinical trials of immunotherapy.
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PMID:Recent developments in renal cell cancer immunotherapy. 1747 9

Recent developments in the epidemiology, diagnosis and therapy of malignant melanoma are reviewed, with particular attention paid to established standards of care. When melanoma metastases are inoperable, they respond poorly to the various chemotherapy strategies, so that additional improvements are critically needed. Cytotoxic T-lymphocyte antigen-4 antibodies, multikinase inhibitors, anti-apoptotic strategies and several other approaches are in progress in Phase III trials both as monotherapy as well as in combination with standard chemotherapy.
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PMID:Recent aspects of medical care of malignant melanoma. 1899 25

Targeted biologic therapies such as anti-cytotoxic T lymphocyte antigen (CTLA-4) monoclonal antibodies, either as monotherapy or in combination with chemotherapy or vaccines, have shown great promise in late-stage melanoma, which has a very poor prognosis. Melanoma is relatively resistant to both chemotherapy and radiotherapy. Blockade of CTLA-4, which inhibits T-cell proliferation, promotes stimulation of adaptive immunity and T-cell activation, resulting in eradication of tumor cells. Two human monoclonal antibodies are under investigation in melanoma. Phase II and III clinical trials are currently evaluating the efficacy and safety of ipilimumab (MDX-010, Medarex, Inc., Princeton, NJ, and Bristol-Myers Squibb, Princeton, NJ) and tremelimumab (CP-675,206; Pfizer Pharmaceuticals, New York) in melanoma. Data are available on ipilimumab, which has been explored as monotherapy and in combination with vaccines, other immunotherapies such as interleukin-2, and chemotherapies such as dacarbazine. Overall response rates range from 13% with ipilimumab plus vaccine in patients with stage IV disease to 17% and 22% with ipilimumab plus dacarbazine or interleukin-2, respectively, in patients with metastatic disease. Responses have been durable, and among those experiencing grade 3 or 4 autoimmune toxicities, even higher response rates have been seen--up to 36%. While the optimal dose of ipilimumab has yet to be established, studies also indicate that higher doses may be more effective. Importantly, the lack of an initial clinical response may not predict ultimate treatment failure, because the onset of a response may follow progressive disease or stable disease. Pending results from registration studies with ipilimumab and lessons learned from registration studies conducted with tremelimumab will help to define the role of anti-CTLA-4 blockade in the treatment of metastatic melanoma.
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PMID:Overcoming immunologic tolerance to melanoma: targeting CTLA-4 with ipilimumab (MDX-010). 1900 Nov 47

Thus far the development of adjuvant therapies in melanoma has suffered greatly from the lack of effective drugs in stage IV melanoma. Chemotherapy, cytokines, vaccines, and combinations of drugs have been used with minimal success. This has led to adjuvant therapies that are not used uniformly or widely because of the rather marginal benefits, as no consistent and clinically significant impact on survival has been demonstrated. A new development for interferon-based adjuvant therapy seems to be the observation that better effects are observed in patients with lower tumor load and in patients with an ulcerated primary melanoma. A benefit for patients with more advanced lymphnodal involvement is quite unsure, clearly requiring new drugs to be explored. A new era in the treatment of melanoma treatment has arrived with the anti-cytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibodies. The randomized trial in advanced metastatic melanoma demonstrated a clear benefit with prolongation of survival. The anti-CTLA-4 monoclonal antibody ipilimumab has finally changed the landscape. It is therefore only logical that a worldwide adjuvant trial with ipilimumab versus placebo, the European Organization for Research and Treatment of Cancer (EORTC) 18071, is ongoing in patients with lymph node metastases, and that another adjuvant trial with ipilimumab compared to high-dose interferon (HDI) is planned in the United States. The EORTC 18071 trial will reach full accrual in 2011 and thus results are expected in 2013 or 2014.
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PMID:Anti-CTLA-4 antibody adjuvant therapy in melanoma. 2107 60

The tumor microenvironment is now recognized as a major factor in determining the survival and growth of disseminated tumor cells at potential metastatic sites. Tumor cells send signals to stroma cells and stimulate them to produce factors that in turn create favorable conditions for tumor cell metastasis. Activated fibroblasts constitute an important component of the tumor-associated stroma. We have previously shown that S100A4 protein produced by stromal fibroblasts in the primary tumor stimulates metastasis formation. Here we show that activated fibroblasts also stimulate the formation of metastases independently of S100A4 expression during organ colonization. To identify genes that could potentially interfere with fibroblast-driven metastasis, we used gene expression profiling of S100A4-deficient fibroblasts treated with and without tumor cell-conditioned media. Five differentially expressed genes encoding cell surface and secreted proteins with potential metastasis-modulating activity were selected. Expression of lymphocyte antigen 6 complex (Ly6c) and matrix metalloproteinase 3 (Mmp3) was upregulated in fibroblasts in response to tumor-conditioned medium, whereas expression of cadherin-16 (Cdh16), Ccn2, and fibulin-5 (Fbln5) was downregulated. Further analysis showed that Fibulin-5 is able to suppress the metastatic colonization of lungs and liver. Additional studies suggest a mechanism in which Fibulin-5 suppresses metastasis formation by inhibiting production of matrix metalloproteinase 9 (MMP9) and reducing the invasive behavior of fibroblasts. Together our data are consistent with the notion that tumors secrete factors that downregulate expression of Fbln5 in fibroblasts at sites of metastatic colonization, in turn upregulating Mmp9 expression and stimulating metastatic organ colonization.
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PMID:Role of fibulin-5 in metastatic organ colonization. 2145 78

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