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

We investigated the efficacy of human melanoma-specific cytotoxic T-cells (CTLs) in treating experimental human melanoma metastases in a nude mouse model of adoptive immunotherapy. Hepatic metastases were generated by the intrasplenic injection of 1.5 x 10(6) human melanoma cells. Animals were then randomized to receive saline, interleukin-2 only, or CTLs and interleukin-2. CTLs were effective when administered 3 or 7 days after generation of hepatic metastases, with 96 and 88% of animals disease-free, respectively, when examined at one month. Interleukin-2 alone was not effective. In addition, CTLs were effective when as few as 2.5 x 10(6) T-cells were adoptively transferred. Only 33% of the animals were tumor-free when CTLs were administered on day 10, and CTLs were not effective when given at day 14. Human CTLs that were not cytotoxic for the tumor line used in vivo, when tested in a 51Cr assay, were also not effective in the model of immunotherapy. This suggests that the tumor-specific CTLs maintain their specificity in vivo, and eliminates a nonspecific inflammation directed against the human CTLs as a possible cause of the antitumor effect. These studies lay the foundation for clinical trials of CTLs in the adoptive immunotherapy of patients with metastatic melanoma.
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PMID:Human xenograft-nude mouse model of adoptive immunotherapy with human melanoma-specific cytotoxic T-cells. 172 11

The role of cell adhesion molecules (CAM) LFA1, ICAM-1, LFA3, VLA1, VLA4, CD29, CD44, and CD56 in tumor-infiltrating lymphocyte (TIL) and natural killer cell (NK)-mediated killing of target cells was studied. Melanoma cell lines and autologous TIL were derived from seven patients with metastatic melanoma, and cytotoxicity assays were done in the presence and absence of monoclonal antibodies (MoAb) to CAM expressed on melanoma cells or TIL. The melanoma cell lines analyzed were all positive for CD29 and LFA3 expression, negative for LFA1 expression, but showed variable expression of ICAM-1, VLA1, VLA4, CD44, and CD56. The effects of anti-CAM antibodies on TIL-mediated melanoma killing fell into three categories: (1) consistent inhibition of TIL-mediated killing was observed when melanoma cells were pretreated with anti-ICAM1 and anti-LFA-3 MoAb or when TIL were pretreated with anti-LFA1; (2) no effect was observed when melanoma cells were pretreated with anti-CD56; or (3) a discreet, but significant, inhibition was observed when target cells were pretreated with anti-CD29, anti-VLA1, anti-VLA4, and anti-CD44. Cytotoxicity was significantly enhanced by pretreatment of target cells with gamma-interferon (gamma-IFN), although gamma-IFN did not augment surface expression of the CAM studied. The NK-mediated killing of K562 cells was blocked by anti-LFA1, anti-CD18, and anti-ICAM, and partially inhibited by anti-CD44 MoAb. Together, these results suggest that several accessory CAM may play a role in regulating cellular cytotoxicity. Because cytotoxicity generally correlated with the level of expression of CAM in melanoma cells, weak CAM surface expression may provide a means for melanomas to escape immune surveillance.
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PMID:Expression of cell adhesion molecules in human melanoma cell lines and their role in cytotoxicity mediated by tumor-infiltrating lymphocytes. 173 16

Antigen expression was studied by immunohistochemistry in 133 human melanocytic skin lesions to gain insight into the initial steps of tumor development, i.e. in particular the change from melanocytes to benign nevi. We refer to the proposed progression model of Clark and co-workers. The following types of antigens were investigated: (i) intermediate filament antigens (vimentin), (ii) melanoma-associated antigens (HMB-45, NKI/C3, MA-930, LS59), (iii) proliferation-associated antigens (S-100, Ki67, Ro/SSA, calmodulin), (iv) progression-associated antigens (HLA-DR, ICAM-1), and (v) basal membrane antigens (bullous pemphigoid antigen, laminin, fibronectin, collagen type IV). The intensity of expression and the topography of immunoreactive pigment cells were compared with the stage of tumor progression. Special attention was paid to the early steps of this process, i.e. the disturbance of the epidermal melanin unit and the development of melanocytic ("nevocellular")nevi. A dramatic shift of antigen expression (antigen types [i] to [v]) was noted in benign nevi compared with melanocytes. Nevi with cellular atypia disclosed a tendency towards an increased percentage of tumor cells reactive for melanoma- and progression-related antigens (types [ii] and [iv]). However, there was no clear cut level of distinction of antigen expression (types [i] to [v]) between benign and primary malignant melanocytic tumors. So-called dysplastic nevi resembled benign tumors or melanocytes rather than malignant melanoma. Metastatic melanoma of skin showed a relatively high number of Ki67-positive, cycling melanoma cells. The results have a bearing on the concepts of melanocytic nevus ontogenesis and "maturation". It appears that melanocytes lose maturity on their way down to the dermis in contrast to traditional concepts (Abtropfung); this might be of importance for our understanding of melanoma development in association with melanocytic nevi. Our findings are discussed with regard to Clark's model of tumor progression.
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PMID:The initial steps of tumor progression in melanocytic lineage: a histochemical approach. 174 97

Murine, antihuman melanoma cell monoclonal antibody (mAb) 16.C8 was generated by fusing the murine myeloma cell line P3X63/Ag8.653 with splenocytes from a nude mouse bearing a human melanoma xenograft, after reconstitution with splenocytes from syngeneic immunocompetent BALB/c mice. The antibody reacted strongly with fresh human melanoma cells and exhibited preferential reactivity with established human melanoma and neuroectodermal tumor cell lines. Electrophoresis and Western blotting experiments indicated that 16.C8 is directed against a sialoglycoprotein antigen with a molecular weight of 110-120 kDa. mAb 16.C8 mediated lysis of melanoma cells in vitro in antibody-dependent cellular cytotoxicity assays using human mononuclear effector cells isolated from normal volunteers or malignant melanoma patients. In addition, the administration of mAb 16.C8 to nude mice bearing established human melanoma lung and liver metastases resulted in significant inhibition of tumor growth as shown by gross and histologic examination. In contrast, animals treated with Hanks' balanced salt solution or nonspecific immunoglobulin exhibited a large tumor burden. These results suggest that mAb 16.C8 may be of value in treatment of metastatic melanoma in humans.
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PMID:Cell binding and tumor inhibiting functions of a new antihuman melanoma murine monoclonal antibody. 176 67

We investigated the immunological properties of interleukin-2 (IL-2)-activated tumor-infiltrating lymphocytes (TIL), which were used for adoptive therapy of renal cell carcinoma (RCC) (seven patients) by focusing on natural killer (NK) cells, and metastatic melanoma (six patients) by focusing on cytotoxic T lymphocytes. TIL from five of seven cases proliferated well in culture with AIM-V serum-free medium and 1000 U/ml rIL-2 in 3-L gas permeable bags, whereas TIL from two RCCs exhibited delayed proliferation. Proliferation of CD3-CD56+ NK cells with major histocompatibility complex-nonrestricted cytotoxicity in RCC-TIL (n = 6, mean = 651-fold, ranging from 39- to 3450-fold) for the first 2-4 weeks was 63 times higher than that of noncytotoxic CD3+ T cells (n = 6, 10.3-fold ranging from 0.8 to 35-fold). Thereafter, CD3+ T cells predominantly proliferated, and proliferation of CD3+ T cells (n = 5, 743-fold) for 5-6 weeks were 24 times higher than that of CD3-CD56+ NK cells (n = 5, 31-fold). Significant numbers of RCC-TIL became adherent to the surfaces of the bags several weeks after initiation of culture. These adherent TIL consisted of more CD3-CD56+ NK cells and exhibited higher cytotoxicity than did nonadherent TIL. Adherent RCC-TIL produced interferon (IFN)-gamma, while nonadherent TIL did not. These results suggest that initially cytotoxic CD3-CD56+ NK cells and, later, noncytotoxic CD3+ T cells proliferated in culture of RCC-TIL for adoptive therapy. These noncytotoxic TIL were primarily transferred to RCC patients, who also received cyclophosphamide, IL-2, and IFN-alpha. In contrast to RCC-TIL, IL-2-activated melanoma TIL consisting of all CD3+ T cells displayed modest levels of cytotoxicity, primarily restricted to autologous melanoma cells in all cases tested. The cytotoxic melanoma TIL were adoptively transferred to melanoma patients. Three of seven RCC patients responded to the adoptive therapy.
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PMID:Study of tumor-infiltrating lymphocytes for adoptive therapy of renal cell carcinoma (RCC) and metastatic melanoma: sequential proliferation of cytotoxic natural killer and noncytotoxic T cells in RCC. 179 Jan 39

Tumour cell proliferation and particularly tumour cell motility are considered to be essential pre-requisites for invasive tumour growth. Despite abundant in vitro data on tumour cell motility, the behaviour of tumour cells in complex human tumour tissues is yet unknown. In this study, estimates of proliferation and motility are statistically derived from morphological tumour patterns in human melanocytic skin tumours. Two-dimensional, discrete, random computer simulations of tumour growth were carried out in order to determine the influence of tumour cell proliferation and motility on morphological patterns. A set of binary morphological criteria turned out to facilitate a significant estimate of the relative probabilities of motility and proliferation (CART analysis). When the same morphological criteria were applied to H & E stained slides of 45 melanocytic skin tumours, benign common nevi showed a predominance of motility, whereas primary and metastatic malignant melanoma revealed a predominance of proliferation. The direct assessment of the number of proliferating cells by Ki-67 staining shows a steep increase from benign nevi to primary and metastatic melanoma. These data provide first evidence that in benign common nevi the overall motility exceeds the very low degree of proliferation, whereas in malignant melanocytic tumours proliferation considerably exceeds tumour cell motility.
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PMID:Computer simulation analysis of morphological patterns in human melanocytic skin tumours. 179 95

Immunohistochemical deposition and distribution of fetal antigen 2 (FA2) was examined in normal brain tissue and in primary and metastatic tumors of the brain. In normal brain tissue FA2 was exclusively found linearly around the vessels, along pia and in arachnoidea. A similar localization was seen in primary brain tumors except in gliosarcoma where FA2 was distributed diffusely in the sarcoma region and was absent in the glioma region. In metastatic carcinoma with tumor stroma a diffuse staining reaction was seen in the stroma and with a basement membrane (BM) like staining at the tumor cell/stroma interface. Intracytoplasmic FA2 staining of the tumor cells was seen in areas without tumor stroma. In metastatic melanoma a BM like FA2 staining was seen around and between individual tumor cells. The staining patterns seen in the metastatic tumors were in accordance with that of the corresponding primary tumors.
Tumour Biol 1991
PMID:Fetal antigen 2 in primary and secondary brain tumors. 179 8

The examination of 623 melanoma patients in North Germany yielded the depigmentation disorder vitiligo in 23 cases (i.e. 3.7%). In 11 patients, the disease preceded their tumor, whereas in 11 patients, vitiligo developed after diagnosis of primary and/or metastatic melanoma into the regional lymph nodes. In 1 case, the onset of melanoma in relation to the tumor remained undefined. The prevalence of vitiligo increased with tumor risk factors based on tumor thickness and anatomical site of tumor location (i.e. for low risk 1.75%, intermediate risk 5.2% and high risk 5.8%). A comparison of the prevalence of vitiligo to the normal population of Northwestern Europe (i.e. 0.38-0.57%) showed a 7- to 10-fold increase for the patients with melanoma. A reverse analysis of the data yielded a 180-fold higher prevalence of melanoma in the group of patients with vitiligo. These results strongly support a more thorough examination of patients with vitiligo for primary melanoma.
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PMID:Vitiligo and cutaneous melanoma. A case study. 180 84

Immunotherapy with tumor-infiltrating lymphocytes (TIL) activated in the presence of recombinant interleukin 2 (IL2) in vitro and adoptively transferred to patients with metastatic melanoma or renal cell carcinoma has resulted in complete or partial responses in some cases. These results have generated a wave of optimism and expectations, which may be premature. Much has been learned about TIL biology and their functional characteristics recently, but only few clinical trials have been completed to date. In this review, therapeutic potential of human TIL is evaluated based on limited knowledge of the antitumor mechanisms involved and imperfect understanding of events which occur during systemic administration of TIL. Limitations and advantages of TIL therapy are discussed and approaches to optimizing this form of therapy which are likely to be implemented in the future are summarized.
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PMID:Cancer therapy with tumor-infiltrating lymphocytes: evaluation of potential and limitations. 181 Apr 38

Multiple metastatic melanoma lesions from three patients were cytogenetically characterized in order to assess the degree of intra-patient karyotypic heterogeneity. A total of 20 specimens were analysed: 12 samples from patient No. 1, five samples from patient No. 2, and three samples from patient No. 3. Sufficient mitoses were obtained to perform detailed analysis in 19/20 specimens following short-term culture. The modal chromosome number of all three cases was near-diploid, with all samples demonstrating multiple structural abnormalities. Abnormalities shared by all three patients were alterations of chromosomes 1 and 8. Other structural abnormalities common to two of the three patients involved chromosomes 6, 7, 9 and 10. Minor intra-tumour karyotypic variation was detected in all three cases. However, the majority of clonal alterations were retained in all metastatic lesions, clearly indicating the karyotypically stable and clonal nature of this neoplasm.
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PMID:Examination of clonal variants from human malignant melanoma studied by chromosome banding analysis. 182 35


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