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)

The aims of this study were: (1) to characterize the biologic properties of the WGA-resistant (WR) Friend leukemia cells (FLC) as compared to the original nonmetastatic or highly metastatic FLC; (2) to investigate the possible correlations between the expression of some oncogenes (i.e., c-myc, H-ras and K-ras) and the in vitro and in vivo behavior of FLC. The tumorigenic behavior of the different FLC types strongly depended on the site of tumor injection. Both WR FLC and in vitro passaged FLC did not grow as ascites (when injected intraperitoneally) and developed large solid tumors (when injected subcutaneously), without forming any spleen or liver metastasis. In contrast, in vivo passaged FLC rapidly formed hemorrhagic ascites when injected intraperitoneally; the subcutaneous injection of these cells resulted in the development of solid tumors, which were smaller than the other FLC tumors, but capable of metastasizing to the liver and to the spleen. No significant differences were observed in the in vitro growth characteristics and cell cycle parameters among the different FLC types under various experimental conditions (i.e., FCS concentration or cell seeding densities). Similarly to the metastatic in vivo passaged parental cells, WR FLC exhibited a much lower erythroid differentiation after in vitro addition of either dimethyl sulfoxide or hexamethylene bisacetamide than the in vitro passaged FLC. High levels of c-myc oncogene mRNA were expressed in all FLC variants; no major variations in the c-myc expression were observed in FLC cultivated in medium supplemented with different FCS concentrations and/or seeded at various cell densities. In addition, no changes in the expression of H-ras or K-ras were observed between the different FLC types.
Invasion Metastasis 1991
PMID:Growth properties, differentiation capacity and oncogene expression in metastatic and nonmetastatic Friend leukemia cell variants. 176 32

Twenty percent (n = 6) of Stage III or IV breast cancer patients (n = 30) had bone marrow metastases detected in bilateral bone marrow biopsy/aspiration preparations using standard histologic preparations. Each metastasis was also detected by four separate monoclonal antibodies (MAbs) which recognize breast carcinoma associated antigens (DF3, anti-EMA, HMFG-2, and CAM5.2). These MAbs were then utilized to stain other bone marrow preparations (n = 81) to determine their utility for the detection of micrometastatic breast carcinoma. MAbs HMFG-2, anti-EMA, and DF3 were each strongly reactive with bone marrows containing histologically-evident metastatic breast carcinoma (18/18). These anti-epithelial membrane antigen MAbs, however, were also reactive with rare plasma cells and immature cells (as well as cell clusters) in some of the control bone marrow samples tested, including those from normal patients and patients with hematologic disorders. They also reacted with some of the preparations from patients with leukemia and lymphoma, and with uninvolved marrows from patients with non-epithelial malignancies. The anti-keratin MAb CAM5.2, in contrast, reacted with 83% (15/18) breast cancer metastases and failed to stain any cells in the various categories of control marrow preparations. These data suggested that MAb CAM5.2 might be utilized to immunohistochemically differentiate micrometastatic breast carcinoma from immature myeloid or erythroid elements. Each MAb was then reacted with histologically uninvolved marrow preparations from the remaining 24 of 30 breast cancer patients in an attempt to identify occult breast carcinoma metastases. While MAbs HMFG-2, DF3, and anti-EMA demonstrated reactive cells in some of these marrows, this reactivity was similar to that seen with control preparations. MAb CAM5.2, in contrast, was negative with all specimens. These data suggest that MAb CAM5.2 may be a useful immunologic probe for the detection and confirmation of metastatic breast carcinoma in bone marrow, while more caution must be employed in the interpretation of results obtained using MAbs anti-EMA, DF3, and HMFG-2.
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PMID:Comparison of monoclonal antibodies for the detection of occult breast carcinoma metastases in bone marrow. 245 2

Bone marrow aspiration and biopsy are excellent techniques for evaluating bone marrow, but this evaluation is limited to a small part of the total blood-forming organ. With the introduction of radionuclide bone marrow imaging, a simple technique became available that overcomes marrow sampling errors by giving a total body view of functioning marrow. Furthermore, the procedure is noninvasive and provides an atraumatic method for evaluating a number of clinical problems including a discrepancy between bone marrow histology and clinical status (possible marrow sampling error), the determination of amount of active marrow after radiation and chemotherapy when further therapy is being considered, detection of sites of extramedullary hematopoiesis, location of the optimal sites for bone marrow biopsy, the diagnosis and staging of diffuse hematologic disorders, detection of metastases, the diagnosis of bone marrow infarcts in hemolytic anemias, and detecting avascular necrosis of the femoral heads. There are two major classes of bone marrow agents: (1) those that are incorporated into the erythroid precursors such as radioiron and (2) colloids that are taken up by the reticuloendothelial system (RES). Indium-111 chloride was originally considered to be an erythropoietic agent but appears to share some properties of RES labels. The best label to use is dependent on the disease being evaluated.
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PMID:The clinical use of radionuclide bone marrow imaging. 299 33

Monoclonal antibodies which bind to breast cancer have been used to evaluate the detection of metastatic disease in axillary lymph nodes. Three monoclonal antibodies (H59, H71, and H72) were reacted with tissue sections of primary tumors and axillary nodes from 24 mastectomy specimens and four specimens from glandular mastectomies for benign disease. All three antibodies had been shown to react with subsets of normal and malignant breast tissue; did not bind erythroid, myeloid, or lymphoid tissue; and recognized antigens in paraffin-embedded tissue. The antibodies recognized cell surface antigens, and H59 and H72 bound to glycoproteins which are either sloughed or secreted. Primary tumors and tumors in lymph nodes from the same specimen were always bound by the same antibodies. Antibodies detected unrecognized microscopic tumor in nodes from one previously node-negative specimen and two specimens with positive nodes. This suggests that monoclonal antibodies may be useful for detecting metastatic breast cancer in nodes which by light microscopy are negative. Moderate binding of H59 and H72 antibodies to sinus histiocytes and perivascular cells was observed in all uninvolved nodes with sinus hyperplasia obtained from benign and malignant specimens. Thus, breast antigens can be identified in hyperplastic nodes in patients with no evidence of breast cancer. The antigens are detected predominately in the lymphoid sinuses and are bound to nonneoplastic cells. Therefore, breast antigens are regularly being processed and presented by normal lymphoid cells within the sinus. The binding of these monoclonal antibodies to axillary lymph nodes does not necessarily indicate the presence of metastatic disease. Dense binding to paracortical single cells was observed in tumor-containing lymph nodes and in uninvolved nodes obtained from mastectomy specimens with breast cancer. These cells are infrequent, and their number in an uninvolved node correlates with the pathological stage. They represent either binding to isolated lymphoid cells or metastatic tumor. Studies are under way to determine the origin of these cells.
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PMID:Presence of breast cancer antigens in uninvolved axillary lymph nodes. 400 59

Hematopoietic chimeras were produced at four different stages of ontogeny between two allogeneic strains of chickens. All chimeras produced by parabiosis at day 12 of embryogenesis and the majority (83%) of the ones produced at day 15 by intravenous injection of allogeneic stem cells remained healthy, chimeric, and specifically tolerant at both the humoral and cell-mediated level throughout a long examination period. Chimeras generated at day 17 of embryogenesis demonstrated specific unresponsiveness at the cell-mediated level but produced specific anti-donor alloantibodies directed against erythrocyte-associated major histocompatibility complex (MHC) (B-G) antigens. These chimeras and a minority (17%) of the chimeras generated at day 15 of embryogenesis developed severe antibody-mediated autoimmune hemolytic anemia after the 5th mo of age and succumbed to massive bursal lymphomas and metastases by the 10th mo of age. The immunological and pathological characteristics of these birds appear to reflect an autoimmune state rather than one of tolerance. Erythroid chimeras generated at day 21 of ontogenic development displayed normal levels of GVH reactivity. These birds were eventually able to eliminate the chimeric state and remained healthy until deliberately killed. These results show that there is a critical period in embryogenesis during which the induction of allogeneic erythrocytic chimerism leads to the development, in adult life, of severe autoimmune anemia, B cell lymphomas, and death. B-G MHC antigens are erythroid differentiation antigens of the chicken. Polymorphic determinants on B-G antigens appear to be important cross-reactive determinants (with environmental bacteria), against which a high background immunity exists. Evidence is presented that the immune response to B-G antigens is responsible for the development of autoimmunity and other pathological events that follow and that tolerance to class I MHC antigens (B-F antigens) shared by lymphocytes erythrocytes is maintained at the same time that B-G tolerance is broken.
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PMID:Tolerance and autoimmunity to erythroid differentiation (B-G) major histocompatibility complex alloantigens of the chicken. 612 77

This report documents the results of therapy in 23 patients treated for malignant thymoma between 1944 and 1979. Of the group, 22 patients had neoplasms which invaded mediastinal structures; six had distant metastases. Four patients had myasthenia gravis and one had erythroid hypoplasia associated with collagen vascular disease. No deaths were associated with primary therapy, which included an operative procedure in all cases. Follow-up ranged from 4 months to 18 years (mean 5.63 +/- 1.03 years, SEM). Fifteen patients died, with postoperative survival times ranging from 4 months to 18 years (mean 3.8 +/- 1.27 years). Five patients were alive without recurrence from 3 to 11 years postoperatively (mean 6.8 +/- 1.36 years), and three patients were alive with recurrence or distant metastases from 4 to 17 years postoperatively (mean 10.75 +/- 2.66 years). Differences in survival on the basis of tumor cell type were not statistically significant. Therapeutic groups were analyzed for 5 year survivors, tumor deaths within 5 years of therapy, deaths due to other causes, deaths due to tumor after 5 years, those presently alive, and longest known survivor. The data suggest that complete surgical excision offers the best chance of long-term survival when compared to partial resection plus irradiation (p less than 0.05). No statistical significance could be demonstrated between the groups who had complete resection with versus without postoperative irradiation. There also was no statistically significant difference between the group of patients receiving irradiation following partial excision of most of their tumor and the group receiving irradiation following only biopsy of the lesion. This observation suggests there is no value in so-called "debulking procedures" and suggests that irradiation may be of value in local control of thymoma. Perpetual surveillance is necessary since late recurrence is common.
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PMID:Management of patients with malignant thymoma. 669 21

In this study we have used tissue culture techniques to explore the mechanism by which metastatic cancer cells in the bone marrow interfere with erythropoiesis. The effect of transplantable Walker-256 (W256) cancer cells on Ep-stimulated erythroid colony formation (CFU-E) in methylcellulose cultures and 59Fe-heme synthesis by rat marrow cells in suspension cultures was studied. The number of CFU-Es per 4 X 10(5) marrow cells decreased by 55% in the presence of 4 X 10(2) cancer cells. Likewise, the stimulatory effect of Ep on normal marrow heme synthesis decreased by 89% when cancer cells were added to marrow cell cultures. By the immobilization of the cancer cells in an agar underlayer, the inhibitory effect of cancer cells on marrow erythropoiesis in an upper methylcellulose layer was demonstrated to be independent of cell contact. The CFU-E growth-inhibitory effect of cancer cells could be attenuated by drugs which interfere with cancer cell protein and DNA synthesis. Although these experiments suggest that cancer cells produce an inhibitor of erythropoiesis, a stable inhibitory factor was not isolated. In similar experiments, rat peritoneal macrophages were also able to inhibit in vitro erythropoiesis. We conclude that cancer cells have the capacity to inhibit erythropoiesis by a mechanism which is independent of cell contact.
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PMID:Cancer cell inhibition of erythropoiesis. 741 61

A 63-year-old woman was in hospital for persistent backache. Four months prior to admission she had been pointed out as having hypertension for the first time. On admission, she had anemia (hemoglobin 7.0 g/dl) with reticulocytosis, and a blood smear showed fragmented erythrocytes. A bone marrow aspirate disclosed erythroid hyperplasia and invasion of cancer cells. The chest roentgenogram showed a coin-lesion of the right lung and left pleural effusion. A diagnosis of microangiopathic hemolytic anemia (MAHA) associated with carcinomatosis was made, but the primary site of the cancer was unknown. Respiratory failure developed and the patient died a month later. Surprisingly, the autopsy revealed a malignant pheochromocytoma arising from the right adrenal gland with massive metastases to the lungs, liver, lymph nodes and systemic bones, and also disseminated intravascular coagulation (DIC). The DIC would probably account for the MAHA in this case. To our knowledge, this is the first reported case of malignant pheochromocytoma accompanied by MAHA.
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PMID:Malignant pheochromocytoma accompanied by microangiopathic hemolytic anemia: a case report. 800 27

The present study describes a new low molecular weight factor released by muscle cells, which inhibits proliferation of tumor cells in vitro and in vivo, is highly specific towards tumor cells, and has no observable effect on normal cells' proliferation. What first prompted us to investigate this factor was the observation that tumor metastases are extremely rare in striated muscles. Co-culturing of striated muscle cells with malignant cells led to marked morphological alterations in the latter, in contrast to the same cells when incubated without muscle cells. A conditioned medium of striated muscle cells was prepared and its effect tested on a variety of cells. This conditioned medium (CM) inhibited proliferation of tumor cell lines of murine (B16 melanoma, Madison 109 lung carcinoma, MCA-105 sarcoma, ESB lymphoma), or of human origin (HTB-38 adenocarcinoma, T47D breast carcinoma, CX1 colon carcinoma). The proliferation of normal cells (bone marrow cells, fetal liver erythroid cells) was not affected by the CM. Flow cytometric analysis of B16 melanoma cells following incubation with the CM revealed that 63% +/- 12 of the cells were in the G0/G1 phase of the cell cycle, compared to 47.8% +/- 8 of cells incubated with a medium (not conditioned) only. The activity of the CM and of certain fractions thereof was also demonstrated in vivo: they prevented tumor growth in mice inoculated intraperitoneally with MCA-105 sarcoma cells. Partial purification of the CM revealed that the active component was a non-proteinaceous compound with a molecular weight of about 500 D. The results clearly suggest that muscle cells produce a low molecular weight factor which can selectively inhibit the proliferation of tumor cells in vitro and in vivo. This factor is neither species nor tumor specific.
Clin Exp Metastasis 1996 May
PMID:Muscle cells produce a low molecular weight factor with anti-cancer activity. 867 72

Erythropoietin is well known for its role in the control of erythropoiesis, where it acts by binding to its cognate receptor (EpoR) on the surface of erythroid progenitor cells. Here we present the novel finding that the EpoR is also expressed in cells of the melanocytic lineage. It is expressed in transformed cell lines established from normal melanocytes and also in established human melanoma cell lines derived from melanoma metastases, but not in normal primary human melanocytes. The analysis of individual subclones isolated from spontaneously transformed melanocytes revealed that approximately 50% of all the clones examined expressed the EpoR. Further analysis of the individual growth characteristics of EpoR-positive and EpoR-negative clones indicated that, under standard cell culture conditions, expression of the receptor did not affect cell growth. Expression of this receptor is consequently most likely driven by an event that is associated with, but not absolutely required for, the transformed phenotype. While the definite function of this receptor in melanoma cells is still unknown and additional studies are required, our findings support the hypothesis that the EpoR may serve as a progression marker for human melanoma. This observation might be useful in the early diagnosis of melanoma.
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PMID:Erythropoietin receptor expression in human melanoma cells. 1109 2


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