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)

Factor XIIIa-positive dendrocytes present at the periphery and inside epithelial neoplasms are an heterogeneous group of cells. They are subsets of mesenchymal cells, cancer-associated macrophages and antigen-presenting cells. Factor XIIIa, other tissue transglutaminases, alpha 2-macroglobulin and tumour necrosis factor-alpha represent a complex network of mediators influencing tumour progression in the skin. In the present study we searched for the presence of dendrocytes and alpha 2-macroglobulin deposits inside and in the vicinity of cutaneous carcinomas (90 basal cell carcinomas and 46 squamous cell carcinomas) and malignant melanomas (69 primary and 28 metastatic tumours). We also studied the proliferation of the same neoplasms by Ki-67 immunohistochemistry. Dendrocytes were numerous, abutting on and infiltrating most basal cell carcinomas and thin malignant melanomas. In contrast, they were present in only low numbers or even absent in thick primary malignant melanomas and in their metastases. They appeared unmodified around squamous cell carcinomas compared with the surrounding skin. Extracellular deposits of alpha 2-macroglobulin were often found in locations where dermal dendrocytes were numerous. No correlation was found between the Ki-67 indices of carcinomas and the density of peritumoral dendrocytes. In contrast, negative relationships were found between the Ki-67 indices and the number of dendrocytes present inside basal cell carcinomas and thin malignant melanomas. This study has yielded circumstantial evidence to link the density of factor XIIIa-positive dendritic cells and a low proliferative rate of neoplastic cells in basal cell carcinomas and malignant melanomas.
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PMID:Factor XIIIa-positive dendrocytes and proliferative activity of cutaneous cancers. 886 52

Modified vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus (VV) that is unable to replicate in most mammalian cells, was evaluated as an expression vector for a model tumor associated antigen (TAA) and as a potential anti-cancer vaccine. We employed an experimental murine model in which an adenocarcinoma tumor line, CT26.CL25, was stably transfected with a model TAA, beta-galactosidase (beta-gal). Mice injected intramuscularly with a recombinant MVA (rMVA) expressing beta-gal (MVA-LZ), were protected from a lethal intravenous (i.v.) challenge with CT26.CL25. In addition, splenocytes from mice primed with MVA-LZ were therapeutically effective upon adoptive transfer to mice bearing pulmonary metastases of the CT26.CL25 tumor established 3 days earlier. Most importantly, i.v. inoculation with MVA-LZ resulted in significantly prolonged survival of mice bearing three day old pulmonary metastases. This prolonged survival compared favorably to mice treated with a replication competent recombinant VV expressing beta-gal. These findings indicate that rMVA is an efficacious alternative to the more commonly used replication competent VV for the development of new recombinant anti-cancer vaccines.
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PMID:Highly attenuated modified vaccinia virus Ankara (MVA) as an effective recombinant vector: a murine tumor model. 914 Dec 9

The molecular mechanisms by which tumor cells induce osteolytic metastases are likely to involve tumor cell adhesion to bone as well as the release of soluble mediators from tumor cells that stimulate osteoclast-mediated bone resorption. Bisphosphonates (BPs) are powerful inhibitors of the osteoclast activity and are, therefore, used in the treatment of cancer-associated osteolytic metastases. Here, we investigated the effect of BPs on breast and prostate carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. BP pretreatment of tumor cells inhibited tumor cell adhesion to unmineralized and mineralized osteoblastic extracellular matrices in a dose-dependent manner. In contrast, BP did not affect adhesion of normal cells (fibroblasts) to extracellular matrices. The order of potency for four BPs in inhibiting tumor cell adhesion to extracellular matrices was found to be: ibandronate > NE-10244 (antiresorptive active pyridinium analogue of risedronate) > pamidronate > clodronate. BP did not affect [3H]thymidine incorporation by tumor cells, as assessed by a mitogenesis assay, indicating that BP did not exert any cytotoxic effect at concentrations used to inhibit tumor cell adhesion. NE-58051, the inactive pyridylpropylidene analogue of risedronate, had no inhibitory effect on tumor cell adhesion compared to that observed with its active counterpart NE-10244, suggesting that the mechanism of action of BP on tumor cells involved a stereospecific recognition step. Although integrins mediate cell-matrix interactions, BP recognition by tumor cells did not modulate cell surface integrin expression. In conclusion, our results provide evidence for a direct cellular effect of BP in preventing tumor cell adhesion to bone, suggesting that BPs may be useful agents for the prophylactic treatment of patients with cancer that is known to preferentially metastasize to bone.
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PMID:Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. 930 66

A recombinant humanized antibody-interleukin 2 fusion protein (huKS1/4-IL-2) was used to direct IL-2 to the tumor microenvironment and elicit a T cell-mediated eradication of established pulmonary and hepatic CT26-KSA colon carcinoma metastases in syngeneic BALB/c mice. This antitumor effect was specific because a fusion protein, which was nonreactive with these tumor cells, failed to exert any such effect. The efficacy of the huKS1/4-IL-2 fusion protein in eliminating metastases was documented because mixtures of monoclonal antibody huKS1/4 with recombinant human IL-2 were ineffective and, at best, only partially reduced tumor load. Two lines of evidence indicated the eradication of metastases and the absence of minimal residual disease in animals treated with the fusion protein: first, the lack of detection of CT26-KSA cells by reverse transcription-PCR, which can detect one tumor cell in 10(6) liver cells; and second, the tripling of life span. The effector mechanism involved in this tumor eradication is dependent on T cells because the IL-2-directed therapy is ineffective in T cell-deficient SCID mice. The essential effector cells were further characterized as CD8+ T cells by in vivo depletion studies. Such T cells, isolated from tumor-bearing mice after fusion protein therapy, elicited MHC class I-restricted cytotoxicity in vitro against colon carcinoma target cells. Taken together, these data indicate that fusion protein-directed IL-2 therapy induces a T cell-dependent host immune response capable of eradicating established colon cancer metastases in an animal tumor model.
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PMID:Elimination of established murine colon carcinoma metastases by antibody-interleukin 2 fusion protein therapy. 935 62

Vascular endothelial growth factor (VEGF), a potent angiogenic mediator, is overexpressed in most solid tumors. On the basis of the knowledge that solid tumor growth beyond a small volume is critically dependent on angiogenesis, and that adenovirus (Ad) vectors can mediate efficient in vivo gene transfer and expression, we hypothesized that Ad-mediated transfer of a secreted form of the extracellular domain of the flt-1 VEGF receptor (Adsflt) would suppress tumor growth on a regional basis. To evaluate this concept, three tumor models were examined using a murine colon carcinoma cell line and syngeneic BALB/c mice. First, mice with preestablished splenic CT26.CL25 tumors and liver metastases were given Adsflt on AdNull intravenously and, after 15 days, spleens and livers were harvested to quantify tumor burden. Adslft-treated animals had minimal residual splenic tumors and liver metastases; in contrast, control animals had bulky splenic tumors and extensive liver metastases (p < 0.003). Second, mice with preestablished lung metastases showed a significant reduction in pulmonary metastases with regionally administered Adslft (intratracheal, p < 0.02) but not when the vector was systemically administered (intravenous, p > 0.9). Finally, mice with primary subcutaneous tumors treated with intratumoral administration of Adslft showed significant tumor suppression (p < 0.05) not observed in AdNull-treated mice or mice given Adslft intravenously (p > 0.3). We conclude that Ad-mediated in vivo regional delivery of a secreted form of the extracellular domain of the flt-1 VEGF receptor can effectively inhibit regional tumor growth, a strategy that may provide a means to control tumor growth within the treated organ without the risk of systemic antiangiogenesis.
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PMID:Regional suppression of tumor growth by in vivo transfer of a cDNA encoding a secreted form of the extracellular domain of the flt-1 vascular endothelial growth factor receptor. 958 5

Dendritic cells (DC) are specialized antigen-presenting cells that can activate naive and mature T-cells, induce cellular immunity, and stimulate strong antitumor reactions in vivo. This study was undertaken to examine the function of DC vaccines in suppressing the growth of hepatic metastases in C57BL/6 mice. Experimental mice received two i.v. doses of 1 x 10(6) bone marrow-derived DC, either unpulsed or pulsed with MCA-106 fibrosarcoma cell lysates, on days -14 and -7. Controls were injected with HBSS. Hepatic metastases were established on day 0 through intrasplenic injections of 1 x 10(5) MCA-106 tumor cells. Animals were sacrificed on day 21 and their livers were excised to assess tumor burden. Splenocytes from DC-treated groups were cytotoxic against MCA-106 cells, but not against the L929 and CT26 (syngeneic fibroblast and colon tumor, respectively) cell lines. All control mice developed grossly evident hepatic metastases, while 62 and 44% of the mice receiving MCA-106 cell lysate-pulsed DC and unpulsed DC vaccines, respectively, were completely free of tumor. Mean hepatic mass for the controls, including tumor, was almost double that for treated animals. Antibody depletion of either CD4+ or CD8+ lymphocytes abrogated the protective effect of the vaccine. This study demonstrates that immunization with DC confers cellular immunity, with both CD4+ and CD8+ T-cells playing a significant role, and impedes the subsequent establishment and growth of hepatic metastases in mice. The antitumor capabilities of DC justify their use in immunotherapeutic vaccines against human cancers.
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PMID:Vaccination with dendritic cells inhibits the growth of hepatic metastases in B6 mice. 963 84

IL-12 is a complex cytokine in both its structure and its range of biologic activities. Fusions of this heterodimeric molecule with an intact antitumor Ab were made to test the feasibility and efficacy of targeting IL-12 to tumors to elicit a local immune response. Fusion proteins composed of the human p35 and p40 subunits had IL-12 bioactivities that were nearly as potent on human immune cells as the rIL-12 standard, but were inactive on mouse cells. Hybrid IL-12 fusion proteins composed of mouse p35 and human p40, fused to Ab, were capable of inducing IFN-gamma, but were much less active on mouse spleen cells than a mouse IL-12 standard. Despite this relatively low activity, the hybrid fusion protein was as effective in a SCID mouse model as a fully active Ab-IL-2 fusion protein in eliminating established pulmonary metastases of CT26 colon carcinoma. Specific targeting of a human IL-12 fusion protein to metastatic prostate carcinoma xenografts was also shown to be effective in SCID mice transplanted with human lymphocyte-activated killer cells. These results demonstrate the importance of directing this potent cytokine to the tumor microenvironment and suggest an important alternative to systemic IL-12 administration or gene therapy for increasing its therapeutic index.
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PMID:Antibody-IL-12 fusion proteins are effective in SCID mouse models of prostate and colon carcinoma metastases. 963 39

Penile metastases from prostate cancer are rare and are usually a manifestation of wide-spread cancer dissemination. Isolated urethral metastases form a small fraction of these cases, have a longer survival rate and may represent spread by implantation following instrumentation. We report a case of prostatic carcinoma presenting with an isolated metastasis to the penile urethra after catheterisation and transurethral prostatectomy. The primary tumor had a prominent intraductal component whose architectural features were mimicked in the metastasis. The possible mechanisms of spread and the diverse appearances of cancer associated with an intraductal component are discussed.
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PMID:Intraductal carcinoma of the prostate metastatic to the penile urethra: a rare demonstration of two morphologic patterns of tumor growth. 964 10

Bronchial cancer associated with a homolateral malignant pleurisy is classed as T4 whether the pleural disease is a direct extension or metastatic. Effusions without neoplastic cells do not enter into the TNM classification. Investigations of pleural disease consist initially of needle biopsies, completed sometimes by a thoracoscopy, which enable a precise staging and also the achievement of a pleurodesis. A review of the literature does not currently establish the value of a pleurectomy in cases of a homolateral effusion in bronchial carcinoma. Surgical excision may be carried out in a case of neoplastic pleurisy where no pleural invasion is found without knowing the benefits in terms of survival. The inverse exists, with local or diffuse pleural invasion without pleurisy, which are difficult to evaluate by imagery techniques. Thus certain authors recommend pleural lavage during surgical operations for bronchial cancer even without pleural disease: positive cytology seems to be a poor prognostic feature and would justify adjuvant treatment. Thoracoscopy should be carried out when the neoplastic nature of a pleurisy has not been established by needle biopsy in order to evaluate the resectability of the tumour in the absence of surgical contra-indication. In the case of a disabling neoplastic pleurisy a pleurodesis carried out at the time of pleuroscopy may avoid the recurrence of the effusion. Talc is most often employed for pleurodesis but Bleomycin or Tetracycline are also used. In the case of failure to re-expand a shrunken lung the failure of the pleurodesis may lead to a pleuroperitoneal shunt. The type of homolateral pleural disease in bronchial cancer with local invasion by contiguity as against pleural metastases should appear in the TNM classification because there are different treatments and also a different prognosis.
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PMID:[Pleural effusion]. 969 Mar 6

The induction of tumor-specific T-cell responses that are effective in eradicating disseminated tumors and in mounting a persistent tumor-protective immunity is one of the major goals of tumor immunotherapy. Here, we demonstrate that we achieved this goal by directing interleukin 2 (IL-2) to the tumor microenvironment of colon carcinoma metastases in syngeneic mice with a recombinant antibody-IL-2 fusion protein (huKS1/4-IL-2). Eradication of established pulmonary metastases is induced by a CD8+ T cell-mediated immune response, which can be transmitted to naive syngeneic severe combined immunodeficient mice by adoptive transfer of CD8+ T cells from immune animals. This immune response was followed by the induction of a long-lived immunity against challenge up to 5 months later with CT26-KSA or wild-type CT26 murine colon carcinoma cells in BALB/c mice. This memory immune response was confirmed by flow cytometric analyses of CD8+ T cells isolated from secondary lymphoid tissue that revealed a phenotypic profile typical of early memory T cells. This long-lived protective tumor immunity was successfully boosted to become optimally effective in all experimental animals by injections of noncurative doses of IL-2 fusion protein 4 days after challenge with tumor cells. Taken together, our results indicate that the huKS1/4-IL-2 fusion protein elicits a long-lived cellular memory immune response that can be amplified by additional applications of IL-2 fusion proteins. This approach could become useful for the treatment of colorectal carcinoma in an adjuvant setting, particularly in patients with minimal residual disease.
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PMID:Induction of persistent tumor-protective immunity in mice cured of established colon carcinoma metastases. 973 3


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