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)

128 tumors from three different human renal-cell carcinomas and from one human transitional bladder cancer were transplanted into NMRI mice treated with cyclosporin A at various dosages. Their acceptance rate, proliferation rate, and morphologic and growth characteristics were studied and compared with those of the same human tumors after transplantation into NMRI nu/nu mice. The acceptance rate was 80% in mice treated with cyclosporin A at 100 mg/kg-1 and 150 mg/kg-1/day. The highest acceptance rate was observed after transplantation into nu/nu (thymus-aplastic) mice (100%). Morphologically, the transplanted tumor was similar in the two animal groups and identical with the primary tumors. Metastases were not seen in either animal model. The NMRI mice treated with cyclosporin A had leukocyte infiltration into the transplanted tumor. The growth rate of the human tumors in normal mice depended on the cyclosporin A dosage, and was highest in the nu/nu mice. The proliferation rates of the transplanted human tumors, as judged by flow cytometry, were rather similar in all groups.
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PMID:Xenogenic transplantation of human bladder- and renal-cell carcinoma into NMRI mice treated with cyclosporin A and into NMRI nu/nu mice. Introduction of a new experimental cancer model. 359 Apr 1

Recent work in our laboratory has demonstrated that the repeated injections of high doses of recombinant interleukin 2 (IL 2) can dramatically reduce the number of established pulmonary and hepatic metastases and the growth of intradermal tumors in a variety of murine tumor models. We have thus undertaken studies to define the mechanisms underlying these in vivo effects of IL 2. Using an in vivo DNA-labeling technique in which we employed 5-[125I]iodo-2'-deoxyuridine (125IUdR), we examined the in vivo cell proliferation in the tissues of mice treated with IL 2. A proliferation index (PI) was calculated by dividing the raw counts per minute (cpm) of tissues in IL 2-treated mice by the cpm in corresponding tissues of control animals. At an IL 2 dose of 6000 U given i.p. three times a day, the highest 125IUdR incorporation was seen in the lungs, liver, spleen, kidneys, and mesenteric lymph nodes (PI = 6.9, 6.9, 5.1, 7.1, 24.6, respectively, at 5 days). The amount of lymphoid proliferation in these organs was a direct function of the dose of IL 2 administered. Other tissues including thymus, intestines, skin, and hind limb showed no significant increase in 125IUdR uptake even after host treatment with the highest doses of IL 2. Blood and brain demonstrated intermediate incorporation of the radiolabel. Preirradiation of the host largely eliminated the proliferative response to IL 2. Histologic studies of normal and irradiated mice receiving IL 2 corroborated the result of the 125IUdR findings. In normal IL 2-treated mice, large collections of activated lymphoid cells were seen, most prominently in the lungs, liver, and kidneys, whereas markedly decreased lymphoid proliferation was evident histologically in preirradiated mice. A fluorescein-labeled monoclonal antibody directed against the Thy-1.2 surface determinant was used to identify these dividing cells in frozen tissue sections as T lymphoid cells. Activated lymphocytes isolated from the lungs, liver, spleen, and mesenteric lymph nodes of IL 2-treated mice demonstrated significant lysis of a fresh murine sarcoma target in short-term 51Cr-release assays. These studies demonstrate that the systemic administration of recombinant IL 2 causes in vivo activation and proliferation of host lymphoid cells and has important implications for the adoptive immunotherapy of tumors.
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PMID:Systemic administration of recombinant interleukin 2 stimulates in vivo lymphoid cell proliferation in tissues. 389 54

Because more than 80% of all cancer deaths are caused by metastases, development and evaluation of methods for fighting tumor dissemination should be major tasks of present cancer research. Formation of metastases is favoured by both reduced numbers of immune cells in the bloodstream and impaired oxygen transport into tissues. These closely related signs often emerge concomitantly when the organism is endangered by circulating tumor cells released from the original tumor by therapeutic manipulations. From knowledge of these facts the O2-multistep immunostimulation technique has been developed as a way of diminishing the risk of tumor spread. The process combines temporary elevation of the number of circulating immune cells with continuous improvement of oxygen transport into tissues. The former is achieved by a peptide mixture isolated from thymus glands in combination with the chemical immunomodulator 2-cyano-ethyl urea; the latter is the outcome of several variants of the O2-multistep therapy discussed here. The efficiency ranges of the different variants are quantified on the basis of findings that allow assessment of the number of tumor cells which can be destroyed by this treatment. This number may be about 100 times the number of malignant cells that must be killed in terms of an effective metastasis prophylaxis (approximately 3 X 10(5)). The estimated efficiency range represents therefore a not yet fully exhausted preventive and possibly even therapeutic potential. To speed the introduction of the procedures described into practice, all clinical oncologists are encouraged to refer their patients to established facilities for O2-multistep immunostimulation after termination of any conventional therapy.
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PMID:Fundamentals of combating cancer metastasis by oxygen multistep immunostimulation processes. 389 51

The specific tissue distribution of melanoma-associated ganglioside II3-alpha-N-acetylneuraminosyl-alpha 2----8-N-acetylneuraminosyllactosylceramide (GD3) was studied on 175 cryopreserved, unfixed human tissue sections with R-24 mouse monoclonal antibody by indirect immunoperoxidase staining. A striking specificity of monoclonal antibody R-24 for malignant melanoma tissues was established. Ganglioside GD3 was detected in all 21 tissue sections of 21 patients with primary melanoma and in all 37 probes of 24 patients with metastatic malignant melanoma. The majority of tumor cells in the samples of primary malignant melanoma expressed GD3; however, GD3 expression was more heterogeneous in samples of metastatic lesions even in different metastases of the same patient. Of 11 nevi, 9 reacted with monoclonal antibody R-24, while melanocytes in the basal layer of normal skin stained only weakly and irregularly. None of the 32 normal and 12 fetal human tissue types were R-24 positive, but a strong cytoplasmic staining was observed with single cells in the dermis and in the interstitial tissue of the gastrointestinal tract, in the interlobular septa of the thymus, and in other distinct locations. Only two malignant carcinoid tumors of 38 nonmelanomatous tumors tested reacted with monoclonal antibody R-24.
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PMID:Immunohistochemical localization of ganglioside GD3 in human malignant melanoma, epithelial tumors, and normal tissues. 389 88

Based on the light microscopical features of normal thymic epithelial cells, human thymoma was divided in different types, namely cortical, medullary, and mixed ones, according to the epithelial cell (EC) type. Lymphoid cell populations with morphological features of either cortical or medullary thymocytes were found according to different types of EC in thymoma. The histological variation of the different types of thymoma are demonstrated. In a retrospective study of 58 thymomas and 13 thymic carcinomas, malignant invasive character as well as the occurrence of myasthenia gravis were both found to be related to the neoplastic proliferation of the cortical epithelial cells, whereas in the usual mixed type of thymoma and the medullary type no gross invasion or metastases were noticed. These results are discussed in view of recent concepts and immunological findings of thymus microarchitecture.
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PMID:Thymoma and thymic carcinoma. Relation of thymoma epithelial cells to the cortical and medullary differentiation of thymus. 392 79

Lymphocytes that bind in vitro to sheep erythrocytes in a rosette formation are thymus-derived. A modified technique that does not detect the total number of rosette-forming cells (RFC) was used to study normal subjects and various disease states. Of 100 healthy subjects, 95 had more than 15% RFC (mean 28.4+/-6.5%). We studied 104 patients with solid tumors, who were classified according to clinical status and stage of therapy. Of 19 newly diagnosed patients, 13 had less than 15% RFC. Of 44 untreated patients undergoing relapse, 32 had less than 15% RFC. In both categories, patients with metastases had fewer RFC than patients with localized disease. 11 patients were studied 2 wk after cessation of therapy; four of them showed less than 15% RFC. Only one of 30 patients in remission had less than 15% RFC. In seven patients followed for various periods of time, the numbers of RFC correlated generally with clinical status. 11 patients with chronic lymphatic leukemia had very low percentages of RFC. 21 of 21 patients with symptoms of viral upper respiratory diseases had less than 15% RFC. RFC returned to normal values between 5 days and 7 wk after disappearance of clinical symptoms. 20 patients with bacterial infections had normal numbers of RFC. Of 25 patients with miscellaneous nonimmunologically related diseases, two had low numbers of RFC. It appears that the percentage of RFC may be valuable in evaluating not only immunological defenses but also the status of patients with solid tumors, lymphomas, viral diseases and, perhaps, bacterial infections.
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PMID:Thymus-derived rosette-forming cells in various human disease states: cancer, lymphoma, bacterial and viral infections, and other diseases. 454 Jul 11

Single cell suspensions of two allogeneic tumours (W-256 and Y-P388) injected intravenously produced macrocolonies in the lungs of rats. Colony forming efficiency (CFE, the number of colonies produced by each viable cell injected) was low in 6-week or older rats but was markedly increased by 1000-1500 rad local thoracic irradiation (LTI) given 7-14 days before the tumour cell injection, or by antilymphocytic serum (ALS) but not by sublethal whole body irradiation (WBI). Similarly, LTI increased the incidence of pulmonary metastases produced by a solid tumour growing in the leg muscle. Stimulation of CFE by LTI was a strictly local phenomenon and not due to effects of irradiation on thymus, spleen or other tissues of the rat. LTI failed to increase CFE in immunized rats. It is concluded that (1) LTI stimulates clonogenic growth of tumour cells arrested in the lungs, by causing inflammatory reactions accompanied by regenerative cellular proliferation of lung tissue, which increases the "plating" efficiency of tumour cells, (2) the increase in CFE in lungs is not due to suppression of immunity to tumour growth by LTI.
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PMID:Stimulation of clonogenic growth of tumour cells and metastases in the lungs by local x-radiation. 470 2

Breast carcinoma frequently metastasizes to endocrine organs, a behavior which may have prognostic or therapeutic relevance. Whether endocrine organ involvement represents a trophic influence on some carcinomas or is simply a "mass effect" of tumor dissemination is uncertain. To investigate this question, the authors reviewed the clinical and pathologic features of 187 subjects with metastatic breast carcinoma, all of whom had been subjected to complete autopsy at The Johns Hopkins Hospital. Metastases to primary endocrine organs, ie, the anterior pituitary, thyroid, parathyroid, or adrenal cortex, occurred in 57%, and metastases to secondary endocrine organs, ie, the pineal, posterior pituitary, thymus, adrenal medulla, or pancreas, occurred in 62% of patients. In general, patients with endocrine organ metastases were significantly younger and had significantly greater numbers of metastases and greater overall tumor burden than those without endocrine organ metastases (all P less than 0.001). There was no correlation between endocrine organ metastases and survival, therapy, histologic type of tumor, or grade of anaplasia or desmoplasia. Metastases to primary endocrine organs were correlated with one another and with metastases in secondary endocrine organs. Metastases in secondary endocrine organs were intercorrelated and also correlated with several nonendocrine organs, chiefly the heart, liver, and gut (all P less than 0.005). These findings indicate that metastases of breast carcinoma to endocrine organs occur in a setting of widely disseminated tumor. However, the observed correlations among metastatic sites suggest that the distributions are nonrandom; these distributions may reflect fundamental properties of some breast carcinomas with respect to hormone receptors, biologic behavior, or environmental growth requirements.
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PMID:Endocrine organ metastases from breast carcinoma. 614 Aug 49

Changes in interferon and thymus factor as well as in cAMP levels and lymphocyte populations were recorded from patients with mammary carcinoma. They were equally recordable from those in whom no clinical tumour had been detectable at the time of postsurgical examinations as well as from patients with metastases distant from the primary tumour. The possibility for centralised disorder of immunological tumour cell defence in carcinoma patients is discussed.
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PMID:[Changes in interferon and thymus factor levels as well as in lymphocyte populations in patients with mammary carcinoma (author's transl)]. 616 32

The effects of silica and carrageenan on primary tumor growth and metastases were evaluated in c57bl/6 and BALB/c mice transplanted with the poorly immunogenic Lewis lung (3ll) carcinoma, mFS6 sarcoma and Madison 109 carcinoma spontaneously metastasizing to the lungs. Silica and carrageenan significantly enhanced lung metastases and decreased primary tumor weight in all three experimental models. A similar augmentation of lung secondaries was found after i.v. inoculation of 3LL tumor cells. The effects of carrageenan on primary 3LL tumor growth and metastases were observed also in thymus-deprived animals. The effect of macrophage toxins was studied also in C57BL/6 mice transplanted with the M5076/73A ovarian carcinoma. This tumor spontaneously metastasizes to various abdominal organs, but not to the lung. After treatment with carrageenan, lung metastases were observed, but no effect on secondaries at other anatomical sites or on the primary tumor was detectable. It is suggested that host defense mechanisms impaired by silica and carrageenan may have divergent effects in the regulation of growth of some primary tumors and spontaneous lung metastases.
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PMID:Divergent effects of macrophage toxins on growth of primary tumors and lung metastases in mice. 624 11


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