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)

Two molecular recombinants (EU-8 and K-3) constructed from ring-necked pheasant virus and UR2AV, the helper virus associated with avian sarcoma virus UR2, caused a high incidence of a hitherto unreported pathological condition in chick skeletal muscle. A disease spectrum was observed in which muscle was infiltrated by proliferating fibroblasts and caused white streaks, white diffuse areas, or well-defined elongated tumors. Fibroblast proliferation was progressive, and the gross presentation depended on the rapidity and extent of proliferation. There was evidence of anaplasia but not frankly malignant disease or metastases. The disease was produced at a high frequency when 10-day-old embryos were infected. Breast muscle (pectoralis major and minor) was affected with variable severity in all birds, thigh muscles were affected occasionally, while other thoracic, external abdominal, and wing muscles were affected very rarely. Progression of proliferative muscle lesions was demonstrated by sequential necropsies and microscopic examination of muscle samples. The disease appeared before 2 weeks of age, and thin white streaks with minimal cellular proliferation were the earliest lesions observed. Elongated, spindle-shaped tumors were the most advanced form of proliferation observed. The advanced lesions showed cellular anaplasia and signs of rapid growth, and appeared most commonly at 6 weeks of age or later. Histologically, mild proliferation correlated with normal appearing fibroblasts producing collagen. Severe proliferation correlated with anaplastic, rapidly dividing cells producing little collagen and a high mitotic index. A decrease in the virus dose resulted in less severe fibromatosis, but at least one chicken infected with a low virus dose showed severe disease. When 10- or 35-day-old hatched chicks were injected in the breast muscle with EU-8 or K-3, a low incidence of lymphoid leukosis was observed, but no fibromatosis resulted during an observation period of 27 weeks. Infectious virus was extracted from the fibromatosis in the breast muscle, and extracted virus caused the same disease when injected in 10-day-old embryos. No transforming activity was observed on normal chick embryo fibroblast monolayers. Cell cultures were established from areas in the breast muscle affected by fibromatosis, and from discrete tumors. These cells did not show any signs of transformation in culture. Supernatants obtained from these cell cultures caused fibromatosis when injected into 10-day-old embryos, but did not transform normal chick embryo fibroblasts.
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PMID:Proliferative fibromatosis in avian skeletal muscle caused by cloned recombinant avian leukosis viruses. 303 May 43

As discussed in the preceding sections, there are several indications that the lymphocyte homing receptors involved in the normal process of lymphocyte recirculation are also relevant to the behavior of metastatic cells. Cell fusion experiments indicate that previously nonmetastatic cells can acquire metastatic capacity from fusion with normal lymphocytes. Murine T lymphomas that bear high levels of functional homing receptors can metastasize to peripheral lymphoid organs, whereas those lymphomas lacking homing receptors cannot. Virtually all lymph node metastases of lymphomas contain a high proportion of MEL-14hi cells, even if the primary tumor has been selected to be relatively deficient in these cells. Further investigations of the biology of lymphocyte homing receptors will reveal whether or not there are additional lymphocyte homing receptors and will clarify the role of lymphocyte homing receptors in metastasis. Antibodies against three lymphocyte homing receptors could therefore be useful for diagnosis and treatment of metastatic disease.
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PMID:Homing receptors and metastasis. 306 47

The incidence of malignant lymphomas in Japan is relatively low compared to that in western European countries and the United States. However, in limited areas in Japan a specific type of lymphoid malignancy called adult T-cell leukemia/lymphoma (ATL), which is caused by human T-cell leukemia virus type I (HTLV-I), is highly prevalent, and there are also many healthy carriers of HTLV-I in the same areas. A cross-sectional seroepidemiological study of HTLV-I showed that the age-specific proportion of healthy HTLV-I carriers in these ATL-endemic areas increased with age, especially over 40, and was higher in females than in males. Three main routes of HTLV-I transmission are recognized: 1) vertical transmission from mother to child mainly through breast milk; 2) horizontal transmission from man to woman through semen, and; 3) parenteral transmission from carrier donor to non-carrier recipient. The annual incidence rate of ATL among HTLV-I carriers is estimated at 2.0 in males and 0.5 in females, and the cumulative risk for ATL in HTLV-I carriers during a 70-year life span is 1%-5%. Possible risk factors for ATL in addition to HTLV-I infection were considered, i.e. genetic factors, environmental factors, nutritional condition, thymus involution etc., but none of these were found to be clearly associated with ATL. To determine whether there exist particularly susceptible hosts for ATL in the ATL endemic areas, HLA types were examined, but no conclusive results on the positive relationships between HLA types and ATL manifestation or HTLV-I infection were obtained. From follow-up studies on the age-specific distribution of HTLV-I carriers in Japan, it is now speculated that the HTLV-I infection rate might have decreased naturally in the more recent generational cohort groups, even in the ATL-endemic areas. However, ATL in Japan is an important subject for study in the field of cancer epidemiology, and several trial intervention programs for the prevention of ATL, such as controls of vertical transmission from mother to child through breast milk, are now ongoing in the ATL-endemic areas of Japan.
Cancer Metastasis Rev 1988 Nov
PMID:Malignant lymphomas in Japan: epidemiological analysis of adult T-cell leukemia/lymphoma (ATL). 306 1

Increased sialylation and branching of asparagine-linked oligosaccharides have recently been associated with both neoplastic transformation and the metastatic phenotype. Swainsonine, an inhibitor of Golgi alpha-mannosidase II blocks the synthesis of sialylated tri- and tetraantennary asparagine-linked oligosaccharides and results in the expression of hybrid-type oligosaccharides at the cell surface. Both the lymphoid tumor line MDAY-D2 and B16F10 melanoma cells were less metastatic when grown in swainsonine (0.3 micrograms/ml) for 48 h prior to injection of the cells into the lateral tail veins of mice. The addition of swainsonine (2.5 micrograms/ml) to the drinking water of the mice further reduced the incidence of lung colonization by B16F10 melanoma cells. MDAY-D2 tumors removed from mice on swainsonine-supplemented drinking water showed a loss of leukoagglutinin-binding complex-type oligosaccharides similar to that of tumor cells cultured in medium containing swainsonine. The growth rate of s.c. MDAY-D2 tumors was not reduced by the addition of swainsonine to the drinking water of the host; however, when mice were given two i.p. injections of the interferon-inducing agent polyinosinic:polycytidylic acid in addition to swainsonine, the primary tumor grew at a reduced rate compared to either treatment alone. Swainsonine alone did not inhibit tumor cell growth in vitro; however, the drug enhanced the antiproliferative effect of interferon. The survival time of mice bearing established MDAY-D2 metastases was extended by treating the animals with swainsonine and polyinosinic:polycytidylic acid; however, the number of long-term survival was unchanged. Swainsonine-treated tumor cells appeared to be compromised in two ways: reduced organ colonization potential; and drug-treated MDAY-D2 cells were more sensitive to the antiproliferative effects of interferon in vitro and in vivo.
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PMID:Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis. 309 60

Previous studies have shown that successful adoptive immunotherapy of a newly induced, weakly immunogenic murine sarcoma, MCA 105, can be achieved either with fresh noncultured immune spleen cells or with immune cells after in vitro stimulation and expansion. In this study, we utilized in vivo and in vitro depletions with monoclonal antibodies (mAb) of T-cell subpopulations expressing the L3T4 or Lyt-2 antigens to investigate the phenotype of the T-cells that mediate in vivo tumor regression. The efficiency of depletion was assessed by flow microfluorometric analysis and by the ability of specifically treated spleen cell populations to generate allogeneic cytotoxic T-lymphocytes. The therapeutic efficacy of adoptively transferred fresh noncultured MCA 105 immune cells was abrogated by in vivo administration of either L3T4 or Lyt-2 mAb to mice bearing 3-day established pulmonary metastases. In vitro treatment of fresh noncultured MCA 105 immune cells with either L3T4 or Lyt-2 mAb and complement also abrogated their antitumor efficacy confirming the initial findings. However, mixing L3T4 and Lyt-2 mAb and complement-treated MCA 105 immune cells reconstituted the antitumor efficacy indicating that cellular cooperation between these two lymphoid subpopulations was essential for the regression of established tumors. Unlike fresh noncultured immune cells, the antitumor efficacy of in vitro sensitized and expanded immune cells was abrogated by in vivo treatment with Lyt-2 but not with L3T4 mAb indicating Lyt-2+ cells alone played a major role in mediating the regression of tumors. These findings provide evidence for an in vitro-induced differentiation of therapeutic T-lymphocytes. Our results thus suggest that the antitumor activities expressed by the two types of cells may represent T-cells at different stages of immunological differentiation.
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PMID:In vitro differentiation of T-cells capable of mediating the regression of established syngeneic tumors in mice. 310 46

Human B-cell tumors have been established in athymic, BALB/c mice using the EBV-positive Burkitt lymphoma cell line Namalwa. One-hundred-one of 104 animals (97%) developed tumors 10-14 days following s.c. injection of a mixture of 20 x 10(6) Namalwa and 5 X 10(6) irradiated human fibrosarcoma (HT-1080) cells. Tumors developed at the site of injection and reached approximately 300 mm2 (product of cross-sectional diameters) after 21 days; no metastases were found. Histological analysis showed that tumors consisted solely of lymphoid cells. Immunofluorescence assays demonstrated that while 85% of the tumor cells retained reactivity with the monoclonal B-cell antibody BA-1, 96% retained reactivity with antibody BA-2 and 43% with BA-3. A similar reactivity profile was observed with cultured Namalwa cells. Tumors were passaged serially 10 times without significant change in BA-1, BA-2, or BA-3 reactivity. Indirect immunofluorescence demonstrated that antibody BA-2 reached tumor cells within 2 h following i.p. injection; antigen modulation was not observed. These results demonstrate the suitability of this B-cell model for testing the in vivo efficacy and stability of anti-B-cell immunoconjugates.
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PMID:Establishment of a human B-cell tumor in athymic mice. 310 70

The melanoma-associated antigen P3.58 is rarely found on benign proliferating melanocytes but is consistently expressed on advanced malignant melanomas which have a high probability of metastasis. Previous studies have shown that its expression on normal tissues is limited to vascular endothelia and lymphoid follicle germinal centers and that it is also expressed by activated monocytes in vitro. In the studies reported here, anti-P3.58 monoclonal antibodies (mAb) were shown to partially inhibit antigen-specific and anti-CD3-induced T cell proliferation and to completely block a lymphocyte/monocyte clustering which occurs in the absence of added antigen. This inhibition is highly specific for P3.58 mAb and was not affected by mAb directed to major histocompatibility complex or T cell antigens. P3.58 therefore seems to be involved in an antigen-independent attraction or adhesion of lymphocytes. P3.58 is the second example (HLA-DR being the first) of an association between the expression of an immune function-associated molecule and the development of metastatic disease in melanoma.
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PMID:The tumor progression-associated human melanoma antigen P3.58 mediates monocyte-lymphocyte interactions in vitro. 322 Jan 5

Carcinomas histologically resembling nasopharyngeal lymphoepithelioma have been identified in the salivary gland, thymus, tonsil, and uterine cervix. Five patients with similar tumors primary in the skin are described. The patients ranged in age from 50 to 81 yr. Four neoplasms were situated on the head, and one was located on the shoulder. Microscopically, they were concentrated in the mid- and deep dermis and lacked connections with epidermis. The pattern was of multiple nodules, smaller irregular islands, and cords. The uniform tumor cells had moderate amounts of lightly eosinophilic cytoplasm and vesicular nuclei with one or two prominent nucleoli. A lymphoid infiltrate was intimately associated with each neoplasm and obscured the malignant epithelium in one. Neither squamous nor glandular differentiation was present, but all tumors exhibited intracytoplasmic mucin. Immunohistochemistry was positive for cytokeratin (5 of 5; diffuse) and epithelial membrane antigen (4 of 5; 3 diffuse, 1 focal). Focal reactivity was also noted for carcinoembryonic antigen (1 of 5), neuron-specific enolase (1 of 5), and vimentin (1 of 5). S100 protein, leukocyte common antigen, Factor VIII-related antigen, prostate-specific antigen (males), Leu M1, and salivary amylase reactivity were absent. One patient developed local recurrence and metastases after 39 mo and was dead of disease at 57 mo. The remaining four were free of disease after 46, 27, 25, and 6 mo of follow-up. The diagnosis of lymphoepithelioma-like carcinoma of the skin is based on microscopic findings and exclusion of occult malignancy. The tumor can be confused with a lymphoid infiltrate and is differentiated from Merkel cell carcinoma primarily on cytologic grounds. The neoplasm may be of adnexal origin.
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PMID:Lymphoepithelioma-like carcinoma of the skin. 323 11

The systemic administration of recombinant interleukin-2 (IL-2) either alone or in combination with lymphokine activated killer cells is a new approach to the immunotherapy of metastatic cancer in man. Renal toxicity is often a dose-limiting side effect of IL-2 administration. This prospective study of 17 consecutive patients receiving parenteral high dose IL-2 documents a reversible syndrome of hypotension, oliguria, fluid retention, azotemia and very low urinary excretion of sodium (median FeNa of 0.04%). The median nadir urinary uric acid to urinary creatinine ratio during IL-2 therapy was 0.2. This IL-2 regimen induces a reversible renal hypoperfusion syndrome (pre-renal azotemia) without evidence of acute uric acid nephropathy. Hypophosphatemia [median serum phosphorus of 1.9 mg/dl (0.61 mmol/l)] prompted further study of tubular function. Urinary excretions of phosphorus, calcium and magnesium were very low. Arterial blood gases revealed hyperventilation without alkalemia. The hypophosphatemia probably reflects increased utilization of inorganic phosphorus by rapidly proliferating lymphoid cells.
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PMID:Metabolic and renal effects of interleukin-2 immunotherapy for metastatic cancer. 326 37

The present study shows that the distribution of T lymphocytes in gastrointestinal carcinomas and their metastases mimic the distribution of T lymphocytes in normal intestine. The composition of the peritumoral reaction resembled that of normal lamina propria with a predominance of CD3 + CD4 + T cells. In contrast, lymphocytes located between carcinomatous cells showed phenotypical features similar to those of intraepithelial lymphocytes (IEL) in normal intestine; in particu(abstractlar they expressed the antigen defined by HML-1, a monoclonal antibody raised against normal human intestinal IEL which reveals 95% IEL but very few cells in lymphoid (abstractorgans and blood. As normal intestinal IEL, the majority of intratumoral lymphocytes had the CD3+ CD8+ phenotype. A panel of monoclonal antibodies and double immunostaining techniques permitted a better characterisation of minor subsets of IEL. Two subsets of HML1 + CD3 + CD4- CD8- and of HML1+ CD3- cells, representing 2% and 3% of normal intestinal IEL respectively, did not significantly increase in carcinomatous epithelium. In contrast, in carcinomatous epithelium, but not in normal intestinal epithelium, we observed the appearance of a few lymphocytes displaying the phenotype of activated T cells (CD25+) or of natural killer cells (NKHI+) or of suppressor cells (CD11+). Such cells may participate in antitumoral defence. Although a similar population of HML1+ lymphocytes is associated with normal and carcinomatous intestinal epithelium, some interactions between lymphocytes and epithelial cells may not be maintained in tumoral epithelium. It has previously been shown that HLA-DR expression by enterocytes is modulated by intraepithelial lymphocytes. In our study, no correlation could be shown between the degree of lymphocytic infiltration and the expression of HLA-DR antigens on carcinomatous cells.
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PMID:Same peculiar subset of HML1 + lymphocytes present within normal intestinal epithelium is associated with tumoral epithelium of gastrointestinal carcinomas. 326 3


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