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)

A series of 30 myxofibrosarcomas is described. These malignant soft tissue tumours are characterized by a mucoid and nodular appearance, a coarse plexiform capillary pattern, and they are mostly seen subcutaneously (26 out of 30) in the extremities (24 out of 30) and trunk (4 out of 30) elderly people. Histochemical studies, comprising staining with Alcian blue and toluidine blue at different pH's with and without preceding digestion with testicular hyaluronidase and with the Scott technique, indicated the presence of hyaluronic acid but not sulphated glycosaminoglycans as chondroitinsulphates. Myxofibrosarcoma is believed to belong to the general category of fibroblastic and histiocytic malignant soft tissue tumours. The median diameter of the tumours was 7 cm. They were divided into 4 grades according to cellularity, cell atypia and mitotic activity. The grade III and IV tumours showed pronounced atypia, often with the bi- and multinucleated giant tumour cells and occasionally with giant cells of Touton's type, suggesting a relationship to malignant fibroxanthoma. All of the patients were treated surgically and one received also pre- and post-operative irradiation. None of the 2 grade I myxofibrosarcomas recurred, while 2 out of 7 grade II tumours, 6 out of 10 grade III tumours, and 7 out of 11 grade IV tumours recurred once and up to 9 times. Metastasis appeared in 7 out of 30 patients; grade I tumours were not seen in any of these cases. By the time of follow-up after intervals ranging from 1 month up to 27 years, 14 patients had died; 6 of these had died post-operatively or of intercurrent disease. The differential diagnosis between myxofibrosarcoma and other myxoid soft tissue tumours is discussed.
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PMID:Myxofibrosarcoma. A study of 30 cases. 1 96

The present investigation endeavors to characterize the mucosubstance content of 170 myxoid and chondromatous tumors and chordomas by histochemical methods. The results obtained using the critical electrolyte concentration (CEC) method as introduced by Scott and co-workers23,24 were compared with those obtained by staining with alcian blue and toluidine blue at different pH's with and without pretreatment with bovine testicular hyaluronidase. Tissues known biochemically to contain different heteroglycans were used as controls: synovial fluid and cock's comb (hyaluronic acid) stained with alcian blue up to a MgCl2 concentration of 0.1 M; fetal cartilage (chondroitin 4- and 6-sulphate) pulposus with notochordal remnants (keratan sulphate) up 10 1.0 M. The staining reaction of intramuscular myxoma and myxoid liposarcoma corresponded to that of synovial fluid and cock's comb (containing hyaluronic acid). Benign chondromatous tumors (osteochondroma, enchondroma, extraskeletal chondroma, chondromatosis in bursae, synovia, and tendon) as well as well-differentiated chondrosarcomas had a similar staining reaction to that of adult cartilage (containing keratan sulphate). However, the intensity of the reaction was lower in these tumors than in the adult cartilage, indicating that the keratan sulphate content of the tumors is lower. Most of the moderately well-differentiated chondrosarcomas, the poorly differentiated chondrosarcomas, and pulmonary metastases of chondrosarcoma, as well as mesenchymal chondrosarcoma and extra-skeletal chondrosarcoma possessed the same staining properties as fetal cartilage, known to contain chondroitin 4- and 6-sulphate but not keratan sulphate. A few of the moderately well-differentiated chondrosarcomas stained up to a MgCl2 concentration of 1.0 M. Three cases of poorly differentiated chondrosarcomas stained with alcian blue up to 0.35-0.45 M in the lowest differentiated areas, indicating the presence of sulphated heteroglycans, as chondroitin 4- and 6-sulphate. Most chordomas possessed the same staining properties as fetal cartilage; however, a few chordomas stained in the same way as notochordal remnants of nucleus pulposus (containing keratan sulphate), which are thought to be the origin of these tumors. The results of staining of the tumors in the present series with the Scott technique corresponds well with toluidine blue and alcian blue at different pH's with and without pretreatment of the sections with testicular hyaluronidase. Since bone and soft tissue tumors may contain varying mucosubstances depending on the tissue of origin and on differentiation, histochemical investigation of the heteroglycan content of these tumors may be a valuable diagnostic aid.
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PMID:Histochemical characterization of mucosubstances in bone and soft tissue-tumors. 24 81

Several years of clinical chemotherapy have shown that, despite modern refinements, cytotoxic agents are not able to eradicate metastases of most adult solid tumors but only to prolong survival by achieving a cell kill that is not 100 per cent. Among the possible causes of this phenomenon, two are discussed in detail. The first one is cell autonomy. It is shown that the numbers of generations reached by a metastatic clone until clinical detection is largely in excess of 100, which allows for a considerable number of mutations, and that in addition genetic destabilization leading to autonomy proceeds much more rapidly than anticipated by a random mutation process. Adaptative changes by genetic amplification in response to toxic injury add to this acceleration effect, accounting for the fact that most metastatic cells are totally resistant very early in the natural history of a human tumor. On the other hand, it is shown that dormant metastatic cells do exist, due either to lack of autocrine growth factors or to inhibiting agents secreted by other metastases. These cells can survive chemotherapy and then re-enter a proliferative state due to some mechanisms that are analyzed, accounting for semi-late and late failures. These obstacles call for other strategies of metastases management, such as arresting or differentiating agents, some of which have been successfully tested by the author's group, such as antiprostaglandins, antithrombin, somatostatin, hyaluronidase, and retinoic acid. It remains to study their optimal combinations, and the appropriate timing, in order to achieve, if not eradication, growth suppression for very long periods without toxicity.
Clin Exp Metastasis
PMID:Accelerated genetic destabilization and dormancy: two distinct causes of resistance in metastatic cells; clinical magnitude, therapeutic approaches. 240 88

Twenty-three cases of intramuscular myxoma were analyzed clinically and histologically. The mean age of the patients was 54 years, and two-thirds were women. Clinical follow-up of 2 to 17 years' duration revealed no recurrences or metastases. Intramuscular myxoma thus appears to be a completely benign tumor. One patient simultaneously had a myxoma in the muscle of the thigh and a lesion of fibrous dysplasia in the femur. In addition, 14 of 16 patients studied with x-ray had a significantly higher incidence of minor abnormalities in bones as compared with the normal population. The myxomas were characterized histologically by sparse cellularity, abundant intercellular material digestible with hyaluronidase, and lack of mitotic figures. At the ultrastructural level, the tumor cells showed characteristics of fibroblasts and myofibroblasts. Immunohistochemical analysis of intermediate filament proteins revealed vimentin- but no desmin-positivity in the tumor cells, and endothelial cell markers as well as S-100 protein were absent. This is compatible with fibroblastic-myofibroblastic nature of the myxoma cells.
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PMID:Intramuscular myxoma--a clinicopathological study of twenty-three cases. 403 56

Hyaluronan-binding sites were demonstrated on the cell surface of three malignant mesothelioma cell lines derived from human tumors using either [3H]hyaluronan or fluorescein-tagged hyaluronan. No hyaluronan-binding activity was observed on normal human mesothelial cells. The absence of hyaluronan receptors on normal human mesothelial cells was not due to a down-regulation by endogenously synthesized hyaluronan, since no binding sites appeared when the cells were cultured under conditions known to suppress hyaluronan synthesis (in starvation medium containing either hydrocortisone or n-butyrate) or to degrade endogenously synthesized hyaluronan (in the presence of Streptomyces or testicular hyaluronidase). The binding of [3H]hyaluronan on mesothelioma cells could be partially inhibited by prior incubation of the cells with trypsin, indicating that the hyaluronan-binding site is a protein. The binding sites on human malignant mesothelioma cells were shown to be saturable with about 54,000 hyaluronan molecules (M(r) 1.4 x 10(6)) bound per cell with a Kd of 0.3 x 10(-9) M. The binding was specific for hyaluronan inasmuch as a number of other macromolecules gave negligible inhibition of the binding. High molecular weight preparations of hyaluronan inhibited the binding more effectively than low molecular weight preparations; hyaluronan oligosaccharides down to a length of six monosaccharide units showed competing activity. The hyaluronan receptor appeared to be related to CD44 (a cell surface glycoprotein previously suggested to function as a hyaluronan receptor) since Hermes-1 monoclonal antibodies which inhibit the binding of hyaluronan to CD44 blocked a major part of the binding of hyaluronan to the mesothelioma cells. However, there was no strict correlation between the hyaluronan-binding activity on the mesothelioma cell lines tested and the levels of CD44 molecules on their cell surface, suggesting that only a subfraction of the CD44 molecules bound hyaluronan or that other hyaluronan-binding proteins also exist on those cells. The presence of hyaluronan receptors on mesothelioma cells, but not on their normal counterparts, may be of importance for the migration of the transformed cells in hyaluronan-enriched matrices and for their ability to form metastases.
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PMID:Hyaluronan receptors are expressed on human malignant mesothelioma cells but not on normal mesothelial cells. 751 23

Four cases are described of a distinctive morphologic variant of thymic carcinoid that was characterized by abundant stromal mucin admixed with the neuroendocrine elements resulting in a histologic picture reminiscent of metastatic mucin-secreting carcinoma. The patients were three men and a woman, aged 22 to 43 years. The tumors presented with symptoms of chest discomfort, cough, and dyspnea and were described as large anterior mediastinal masses on chest radiographs and computerized scans. Histologically, all cases showed nests and strands of tumor cells embedded in an abundant lightly eosinophilic, mucinous stroma with small cellular clusters as well as scattered single tumor cells seen floating in the mucin. The mucinous matrix was negative for periodic acid Schiff's and mucicarmine stains; alcian blue stains at pH 2.5 showed strong positivity of the mucinous material; this reaction was abolished by treatment with hyaluronidase, indicating the presence of nonepithelial stromal mucosubstances. Immunohistochemical stains showed strong positivity of the tumor cells with CAM 5.2, chromogranin, synaptophysin, and neuron-specific enolase, and negative staining with carcinoembyronic antigen and epithelial membrane antigen. Electron microscopy done in one case showed abundant dense-core cytoplasmic neurosecretory granules; there was no evidence of glandular secretory activity by the tumor cells. The tumors in two patients behaved in a highly aggressive fashion, with invasion of the chest wall, recurrence, and metastases to the lungs, pleura, and axillary, retroperitoneal, and mesenteric lymph nodes. Thymic carcinoid should be considered in the differential diagnosis of mediastinal neoplasms displaying prominent mucinous features. Application of immunostains and electron microscopy will be of value for establishing the correct diagnosis in this setting.
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PMID:Thymic carcinoid with prominent mucinous stroma. Report of a distinctive morphologic variant of thymic neuroendocrine neoplasm. 757 90

The adhesion to mesothelial monolayers of eight cultured ovarian tumour cell lines was studied in multiwell plates as a model for some of the interactions of ovarian cancer in the peritoneal cavity. When only the upper half of the conditioned medium (CM) from a confluent mesothelial cell culture was aspirated, the adhesion of the tumour cells was low (3.5%-36%). When the medium was removed completely the adhesion increased. The tumour cell lines showing the greatest enhancement of adhesion were those which had previously been shown to express the highest amounts of CD44. By adding erythrocyte suspensions to mesothelial cells it was shown that there was a pericellular coat around the mesothelial cells that could be destroyed by aspirating the medium, or by treating the medium with hyaluronidase (Hase). Treatment of the CM with Hase also considerably increased tumour cell adhesion. Furthermore, CM was shown to contain high amounts of hyaluronic acid (HA). HA blocked adhesion in the absence of CM, but the effect was not as large as that produced by the pericellular coat. It is proposed that pericellular HA produced by mesothelial cells has an important role in the invasion of ovarian tumour cells in the peritoneal cavity.
Clin Exp Metastasis 1995 Sep
PMID:Hyaluronic acid secreted by mesothelial cells: a natural barrier to ovarian cancer cell adhesion. 764 21

The regional chemotherapy of the human malignant melanomas (SK-MEL-2, -3, -5, -24) implanted in NMRI nu/nu mice with a combination of the hyaluronic-acid-cleaving enzyme hyaluronidase (HYase) and vinblastine is a very effective therapeutic procedure. In three out of four melanoma models (SK-MEL-2, -3, -5) the weekly peritumoral administration of high-dose HYase (100,000 IU/kg) 4 h prior to the injection of 0.3 mg/kg vinblastine in the vicinity of the tumor (seven weekly therapeutic cycles) caused marked antitumor effects, while HYase and vinblastine were inactive when given alone. The pretreatment with HYase, which is well tolerated by the test animals, prevented local inflammation reactions commonly seen after subcutaneous vinblastine administration. Tumor growth and metastatic behavior of the melanomas used were neither increased nor reduced by HYase after peritumoral administration without subsequent vinblastine injection. The curative activity of the regional chemotherapy with HYase/vinblastine could be demonstrated on the SK-Mel-3 melanoma. After an observation time of 18 weeks, tumor cells could no longer be detected in the subcutaneous region of the former lesion. Only macrophages, which had abundantly incorporated melanin, gave evidence of previously growing tumors. In contrast to the controls, no metastases could be observed in the axillary lymph nodes of the test animals.
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PMID:Hyaluronidase significantly enhances the efficacy of regional vinblastine chemotherapy of malignant melanoma. 775 17

We report 20 cases of a peculiar fatty tumor that occurred in 16 female and four male patients who were 14-70 years old (median, 36 years). Most lesions were situated in the subcutis, superficial muscular fascia, or skeletal muscle of the limbs and limb girdles (15), trunk (3), and the head and neck (2). They were 1.5-11 cm in size (median, 4 cm) and usually described as yellow (13 of 15) and encapsulated (13 of 15). Microscopically they were well circumscribed and consisted of nests, strands, and sheets of eosinophilic and vacuolated cells, which contained glycogen and fat droplets, resembling brown fat cells, lipoblasts and chondroblasts. In all cases there was a variable background of mature adipose tissue associated with a prominent, partially fibrinous to hyalinized myxoid matrix that contained acid mucopolysaccharides usually resistant to hyaluronidase digestion. Several cases had foci of serous atrophy, perivascular fibrosis, and small thrombi; two were focally calcified. The lesions stained for S100 protein (11 of 12), vimentin (10 of 11), and CD68 antigen with KP1 (9 of 11); focal staining for keratin was also seen (4 of 11), but none stained for epithelial membrane antigen or actin or with HMB45. Follow-up in 12 cases (median, 9.5 years) revealed no local recurrences or metastases. Despite its deep location and atypical cellular features, the lesion's nonaggressive behavior suggests it is benign and neither a myxoid liposarcoma nor a myxoid chondrosarcoma, with which it is most frequently confused. The presence of glycogen in vacuolated fat cells is similar to brown fat, and the presence of sulfated stromal mucins supports focal chondroid differentiation. Although the pathogenesis remains uncertain, a lipoma with hibernomatous features, myxoid change, chondroid metaplasia, and secondary degenerative features is favored over a lipogranulomatous process.
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PMID:Chondroid lipoma. A unique tumor simulating liposarcoma and myxoid chondrosarcoma. 821 55

We have previously shown that a protein-independent growing fibrosarcoma, Gc-4 PF has a high motile response to its cultured medium, which is associated with an increase in expression of gp78, a cell surface receptor for autocrine motility factor (AMF). Here we show that the cultured medium contains two motile activities, acidic and basic AMFs with regard to binding features on ion exchange chromatography. These two AMFs were purified by sequential DEAE anion exchange, CM cation exchange, and gel filtration chromatographies. However, both acidic and basic AMFs have a similar size of 55 kDa and 65 kDa under non-reducing and reducing conditions, respectively, with the same pI of 6.5. The stimulated motility of both AMFs was inhibited by the pertussis toxin (PT), but not by Streptomyces hyaluronidase. These two AMFs significantly stimulated the lung colonizing properties of the self-producing cells by 1.5-fold. These results suggest that both acidic and basic AMFs may correspond to the previously reported AMF and confirm directly that the AMF-gp78 signaling pathway is involved in cell motility associated with metastatic property.
Clin Exp Metastasis 1994 Mar
PMID:Differential purification of autocrine motility factor derived from a murine protein-free fibrosarcoma. 830 29


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