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

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Query: UMLS:C0027651 (tumor)
685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

10B1-para-boronophenylalanine (10B1-BPA), one of our boronated dopa analogues developed for thermal neutron capture therapy, has been found to have a selective affinity for malignant melanoma. We have established a method of 'in situ' detection of subcutaneous melanoma lesions, using this melanoma-seeking 10B-labeled compound. In this study, we applied an 'in situ' 10B microanalysis system via detection of the prompt gamma-ray from the 10B(n, alpha)7Li reaction triggered by irradiating the 10B-containing target with pure thermal neutrons, called prompt gamma-ray spectrometry, to hamsters bearing Greene's melanoma in subcutis and to a human patient whose occipital subcutaneous tumor was suspected of being a metastatic melanoma. In the hamsters, the time-dependent 10B dynamics showed increased 10B accumulation in melanoma, after 10B1-BPA administration, in contrast to that in non-melanoma normal skin. In the human patient, after subcutaneous injection of 10B1-BPA into perilesional sites 4 cm distant from the tumor margin, the average 10B concentration in the tumor was determined to be 24 ppm (microgram/g), in contrast to 3 ppm in skin covering the tumor and 1.1 ppm in blood, indicative of selectively high 10B1-BPA uptake by the tumor.
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PMID:In situ detection of cutaneous melanoma by prompt gamma-ray spectrometry using melanoma-seeking 10B-dopa analogue. 207 38

The human natural killer (NK) cell has long been known to mediate spontaneous, non-major histocompatibility complex-restricted cytotoxicity and antibody-dependent cellular cytotoxicity. It is only fairly recently, however, that the role NK cells play in other functions of the immune system has been realized. The NK cell participates either directly or indirectly in multiple developmental, regulatory and communication networks of the immune system and thus is important in human health and disease. The NK cell has distinct morphologic, phenotypic and ultrastructural characteristics that distinguish it from T and B lymphocytes. Human NK cells are heterogeneous, and functionally different subpopulations of NK cells can be distinguished. NK activity may be regulated by soluble products of hematopoietic as well as non-hematopoietic cells and by a wide variety of exogenous biological response modifiers. Both lymphocytes and monocytes are capable of regulating of NK cell growth and activity. Populations enriched in human NK cells can be obtained utilizing the property of adherence to plastic and subsequent expansion in the presence of IL-2. The adherent lymphokine activated killer (A-LAK) cells represent populations of CD3-CD56+ (up to 98%) IL-2 activated NK cells. They are highly effective in eliminating tumor cells both in vitro and in vivo in animal models of tumor metastasis. A-LAK cells are being used for therapy in the phase I clinical trial in patients with metastatic melanoma and renal cell carcinoma. The studies described emphasize the biologic importance of the NK cell, its therapeutic potential, and a need for more extensive monitoring of NK activity in human disease.
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PMID:The biology of human natural killer cells. 209 2

Radiologic detection of bone lesions from malignant melanoma is reported to be uncommon or infrequent. To ascertain the characteristics and frequency of detection of melanoma metastases to the axial skeleton by CT, we retrospectively reviewed 464 body CT studies of 125 consecutive melanoma patients for presence, appearance, and site of skeletal metastases. Results were correlated with patient's age, sex, clinical course, and both the Clark and Breslow classifications of the primary lesion. Of 98 patients with metastatic disease evident on their CT studies, 17 (17%) had bony metastases; two (12%) of these 17 patients had skeletal lesions as the only CT evidence of metastatic disease. Metastatic bony lesions were predominantly osteolytic, slightly expansile, and commonly located in the spine. Associated soft-tissue masses were frequent, but periosteal reaction and identifiable tumor matrix were not seen. Skeletal metastases were found only in those patients with thick or intermediate primary melanoma (Breslow) classified as Clark level III or greater, and the CT demonstration of osseous metastases was a poor prognostic sign. The data suggest that CT detection of skeletal melanoma metastases is not uncommon. When CT is performed to evaluate for metastatic melanoma, the axial skeleton should be carefully examined, especially in those patients with more advanced primary lesions.
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PMID:Metastases from malignant melanoma to the axial skeleton: a CT study of frequency and appearance. 211 30

To investigate the specificity of human tumor-infiltrating lymphocytes (TIL) against autologous tumors, TIL from five metastatic melanoma patients were expanded with rIL-2 and assessed for cytotoxicity in chromium release assays. TIL from a patient showing preferential cytotoxicity against autologous melanoma cells were further analysed. TIL were cloned by limiting dilution. Four out of 27 clones showed substantial cytotoxicity against autologous melanoma and one clone, designated as No. 8a-5 (CD3+, CD4-, CD8+, CD56-), selectively killed autologous melanoma but did not kill six different allogeneic melanoma, K562, or autologous or allogeneic Con A lymphoblast targets. Cytotoxicity of No. 8a-5 cells was inhibited by anti-HLA class I MAb (w6/32), by anti-beta 2-microglobulin MAb, and by anti-CD3 (OKT3) MAb, suggesting that the specific cytotoxicity was HLA class I-restricted and that the clone utilized the T-cell receptor complex for recognition of targets. Pretreatment with rIFN-gamma increased the sensitivity of autologous melanoma targets to lysis by No. 8a-5 cells. Exogenous rIL-4 enhanced [3H]TdR incorporation by these TIL. In contrast, rIFN-gamma reduced the sensitivity of the autologous melanoma to lysis by uncloned TIL, and rIL-4 suppressed the cytotoxicity and cell proliferation of uncloned TIL. These results indicate that both specific and non-specific cytotoxic cells can be developed from the same TIL and that these can be differentially regulated.
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PMID:Differential regulation by interleukin-4 and interferon-gamma of an autologous melanoma-specific cytotoxic T-cell clone and the tumor-infiltrating lymphocytes from which it was established. 211 66

A Phase I clinical trial has been initiated at the University of Arizona Cancer Center which combines escalating oral doses of the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO), with systemic hyperthermia (approximately 41.5 degrees C) in the treatment of metastatic melanoma. The rationale for the combination of hyperthermia and polyamine biosynthesis inhibitors in the treatment of human cancers includes studies which show that depletion of endogenous polyamines, as a result of treatment with DFMO, sensitizes both rodent and human tumor cells to the cytotoxic effects of hyperthermia. Heat shock induces the first enzyme in polyamine catabolism, spermidine/spermine N1-acetyltransferase (N1-SAT). The consequently acetylated forms of spermidine and spermine are then constitutively oxidized by the enzyme polyamine oxidase (PAO). Both CHO and human A549 lung cancer cells exhibit heat-inducible polyamine acetylation, display potent heat sensitization after polyamine depletion, and ultimately reveal prolonged expression of thermotolerance. Conversely, HeLa cells do not demonstrate heat-inducible polyamine catabolism, are not sensitized to heat with DFMO, and display more rapid kinetics of thermotolerance decay. These laboratory studies suggest that enhancement of the cytotoxic action of hyperthermia by DFMO occurs as a consequence of the inhibition of polyamine catabolism, a heat-inducible process that affords some form of protection to cells undergoing heat stress. Human melanoma cultures demonstrate heat-inducible polyamine catabolism and are sensitized to hyperthermic cytotoxicity by DFMO. To date, 24 systemic hyperthermia treatments have been delivered to nine patients with metastatic melanoma in conjunction with oral DFMO under this Phase I clinical trial.
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PMID:Polyamine biosynthesis inhibitors combined with systemic hyperthermia in cancer therapy. 211 88

Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.
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PMID:Active-specific immunotherapy for melanoma. 213 1

Previous studies have suggested that class II major histocompatibility (MHC) antigen expression on melanoma cells may influence immune responses against melanoma and the nature of lymphocytic infiltrates against the tumor. This question was examined further by immunoperoxidase studies on sections from 29 primary and 30 metastatic melanoma with monoclonal antibodies (MAbs) against different lymphocyte subsets. The results indicated that expression of MHC class II DR* antigens on melanoma cells was associated with increased overall lymphocytic infiltration and that this applied particularly to the CD8+ subset of T cells. The CR3 receptor (CD 11b) was expressed predominantly on T cells and not macrophages but infiltration by CD11b+ cells did not correlate strongly with DR expression on melanoma cells. Dual staining with MAbs to CD8 and CD11b revealed that, whereas most of the CD8+ cells in DR- primary melanoma and DR+ metastatic melanoma were CD11b+, only approximately 50% of the CD8+ cells in DR+ primary melanoma were also CD11b+. Expression of CD11b on T cells was reported to define a suppressor subset of T cells. If the latter is correct the present results suggest that DR expression on primary melanoma is associated with infiltration by the cytotoxic T cell subset, whereas in the absence of DR antigens and in metastases this subset is absent and the predominant subset appears to be CD8+ CD11b+ T cells with suppressor activity. The biologic and prognostic significance of these findings remains to be determined.
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PMID:Immunohistological relation between DR antigen expression on melanoma cells and infiltration by CD8+ T cells. 214 56

We have developed a human melanoma metastasis model in nude mice. In this model, a human variant cell line (451-LU) was obtained that spontaneously metastasized in nude mice. This variant cell line was selected from the lung of a nude mouse after several in vivo passages of human melanoma WM164 cells previously isolated from a melanoma metastasis of a patient. The WM164 cells were not competent for metastasis in nude mice prior to this selection. We compared the phenotypes of the parental nonmetastatic cell line and the metastatic variant with respect to growth at clonal seeding densities in protein-free medium (growth factor independence), in vitro invasion through reconstructed basement membranes, secretion of proteolytic enzymes, expression of tumor-associated antigens, and chromosomal abnormalities. Metastatic 451-LU cells showed significantly increased growth factor independence when grown at clonal seeding densities as compared to the parental cells. In in vitro chemoinvasion assays, metastatic 451-LU cells were significantly more invasive than the parental cells. The metastatic variant secreted collagenase and tissue type plasminogen activator at levels 10- and 3-fold higher than the parental WM164 cells, respectively. Polyclonal antibodies to tissue type plasminogen activator significantly inhibited invasion through reconstructed basement membranes. In metastatic 451-LU cells, expression of nerve growth factor receptor was elevated, both at the protein and transcriptional level. Metastatic cells were aneuploid with a mode of 97 chromosomes, whereas the parental nonmetastatic cells had a mode of 52 chromosomes. Our studies suggest that metastatic melanoma cell variants selected in vivo show increased independence of exogenous growth factors when grown at clonal cell densities, enhanced invasiveness in vitro, greater secretion of proteolytic enzymes, and increased chromosome mode as compared to the nonmetastatic parental cells. The data further suggest that melanoma cells isolated from metastatic lesions and maintained in vitro have an unstable invasive phenotype but that metastatic variant cells can readily be selected.
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PMID:In vitro properties of human melanoma cells metastatic in nude mice. 215 14

Immunohistochemical localization of nerve growth factor (NGF) receptor in normal skin and melanocytic tumor was analysed using monoclonal antibody. In normal skin and fetal skin NGF receptor was good marker for cutaneous nerve sheath and schwann cells. In melanocytic lineage, the NGF receptor was not expressed in fetal, normal and dermal melanocyte and weakly positive in only small part of nevus cell nest. Positive staining was seen in primary and metastatic melanoma lesion and restricted to melanoma cell membrane. The distribution of the receptor suggests that the NGF-receptor may be involved in the control of proliferation and malignant transformation in melanocytic lineage.
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PMID:[Expression of nerve growth factor-receptor in normal skin and melanocytic tumor]. 216 92

The serum antibody response to human melanoma has prognostic and potential physiological consequences. The specificity of the host B cell antibody response may be an important determinant of disease outcome. We have utilized Epstein-Barr virus (EBV) transformation to analyze the repertory of the host B cell response to melanoma. Production of antibody that binds selectively to autologous (eight cases) or allogeneic (four cases) short-term-cultured melanoma cells was assessed from EBV-transformed B lymphoblastoid cells. Forty-two cultures of EBV-transformed B cells that secreted IgM and 23 that secreted IgG antibodies gave patterns of differential reactivity with autologous or allogeneic melanoma. Antibody-forming B cells persisted in producing melanoma-reactive IgG and IgM for 8-21 weeks. Preselection of B cells by adsorption to tumor cell antigens before transformation enhanced the frequency of antibody secretion. The specificity of the antibody produced by the longest-producing culture appears to be restricted to a subset of melanomas. The patient from whom this tumor-restricted IgG-producing B cell was retrieved was unusual, having had a transient serum IgG of similar specificity, and having manifest a syndrome of vitiligo at the time of her development of serum antimelanoma antibody, followed by disease-free survival of resected recurrent metastatic melanoma to the present (more than 6 years). This study has given support to findings of conventional serology, revealing the production of melanoma-reactive antibody from B cells of patients who have demonstrable serological response to tumor.
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PMID:Human IgG and IgM monoclonal antibodies against autologous melanoma produced by Epstein-Barr-virus-transformed B lymphocytes. 217 72


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