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)

This unit has in the past evaluated the Nb rat prostatic adenocarcinoma model with respect to chemotherapies. Recently, this unit has been evaluating agents that may have a role in decreasing metastatic rate. The three androgen-insensitive tumors, Nb Pr A.I. I, II, III, have been evaluated herein. Agents that have been used include indomethacin, heparin, heparin plus cortisone, and heparan sulfate (SP54). It has been shown that these agents do play a role in reducing the metastasis. In evaluation of Nb Pr A.I, I, control animals had a metastatic rate of 57%. In treatment with indocin, only 21% of the animals, three of 14 animals treated, had a metastasis, and treatment with heparin and cortisone resulted in one of 14 animals having metastasis. Similar observations were seen when treatment with SP54 and heparin was evaluated in the Nb Pr A.I. III; 18 and 27% of treatment group animals had metastasis, whereas 55% of control groups had metastasis. Similarly, in the Nb Pr A.I. II evaluation, control animals having a metastatic rate of 43% had heparin plus cortisone and heparin alone, and this particular tumor model revealed complete resolution with no animals having metastatic disease. The majority of these agents have not effected tumor volume in terms of reduction as much as the best chemotherapeutic agents in this model system include cyclophosphamide and cis-platinum.
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PMID:Metastasis in the androgen-insensitive Nb rat prostatic carcinoma system. 403 15

In this review, evidence that proteoglycans are involved in cell adhesion and related behavior is considered, together with their putative role(s) during tumorigenesis. Proteoglycans are large, carboxylated and/or sulfated structures that interact with specific binding sites on cell surfaces. Their distribution and synthesis in tissues alter with the onset of tumorigenesis so that hyaluronic acid is generally increased and heparan sulfate decreased in the developing tumor and surrounding tissue. However, the precise role of proteoglycans during the tumorigenic process is far from clarified. Data suggest any putative roles will be related to the adhesive properties that these molecules confer to cells. Hyaluronic acid and chondroitin sulfate appear to be weakly adhesive molecules that may promote 'transformed' characteristics when they occur on cells in large amounts. These characteristics include reduced cell spreading, increased cell motility, as well as reduced contact inhibition. Consistent with such properties, neither hyaluronic acid nor chondroitin sulfate are localized in specialized adhesion sites such as focal or close contacts. In contrast, heparan sulfate is associated with increased cell-substratum adhesion and is involved in the spreading of cells onto fibronectin and other substrata. Its presence is generally associated with reduced motility and with a well-spread morphology. Unlike hyaluronate and chondroitin sulfate, heparan sulfate is found in specialized contacts. These adhesive properties of proteoglycans predict an instructive role in tumor development, and recent experiments have defined an involvement of these molecules in metastatic arrest. Additional studies utilizing invasive and metastatic tumor variants including tumor cells that employ different mechanisms to invade are required to clarify the role of proteoglycans in tumor progression.
Cancer Metastasis Rev 1984
PMID:Proteoglycans and cell adhesion. Their putative role during tumorigenesis. 608 29

Radioimmunoassay determinations of the biochemical tumor markers, alpha-fetoprotein or human chorionic gonadotropin, revealed elevated serum levels in 94 per cent of the patients with advanced disease. No falsely positive values have been observed. The markers are useful in monitoring the response to therapy and, when persistently elevated after therapy, indicate the presence of residual malignant tumor, usually embryonal carcinoma. However, they have a more limited role in the management and followup of the great majority of new patients with non-seminomatous germ cell tumors of the testis (stages A and B) owing to a falsely negative incidence of 38 per cent in patients found to have retroperitoneal metastases at lymphadenectomy. Furthermore, marker levels obtained during chemotherapy, even in the presence of residual tumor, frequently are normal. Thus, they have a limited role in the early detection of residual disease in patients treated systematically with prophylactic chemotherapy. A meticulous retroperitoneal lymphadenectomy remains the single most important factor in dictating the use of adjuvant chemotherapy, the specific agent and the combination and duration of therapy. The prophylactic use of actinomycin D in stage A and the early aggressive use of vinblastine sulfate and bleomycin in stage B2 have reduced the incidence of recurrence substantially. A prospective plan of management used in 95 consecutive patients since 1974 has resulted in survival free of tumor of 100 per cent for patients with stage A disease, 91 per cent for stage B and 61 per cent for stage C.
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PMID:Relevance of biochemical tumor markers and lymphadenectomy in management of non-seminomatous testis tumors: current perspective. 615 25

The authors report the autopsy case of a 73-year-old man with widespread, metastatic, malignant chondroid syringoma, with a long clinical history. Three years after resection of the primary tumor on the back, the tumor recurred at the same site, metastasized to the cervical lymph nodes 7 years later, and finally, after 13 years exhibited widespread metastases. Histologically, the tumor showed cords and nests of cuboidal or polygonal tumor cells with little cellular pleomorphism and few mitoses surrounded by a mucoid matrix. Histochemically, the matrix contained hyaluronic acid and sulfated acid mucopolysaccharides, such as chondroitin sulfate A and/or C. To the knowledge of the authors there have been nine reported cases of malignant chondroid syringoma in the English literature, four of which had distant metastasis. A review of the literature reveals that malignant chondroid syringoma is more common in women and occurs most often in trunk and extremities, which is in contrast to its benign counterpart, its histologic appearances vary greatly, and it may even have benign appearances.
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PMID:Malignant chondroid syringoma. Report of a case with widespread metastasis and review of pertinent literature. 619 72

This study was designed as a Phase II clinical trial in advanced recurrent or metastatic squamous cell carcinoma of the cervix with a combination of bleomycin (B: 10 u/m2/d) and cisplatin (P: 20 mg/m2/d) administered for five consecutive days in intravenous infusion for 7 hours and vincristine (V: 1 mg/m2) and methotrexate (M: 40 mg/m2) administered only on day one of each cycle which was repeated every 28 days up to a maximum of 6 times. Over a period of 2 years, 15 evaluable patients with measurable disease received at least 3 courses of therapy. Six had recurrent disease and nine had distant metastases. All had previous radiation therapy. There were two dropouts after the first course due to nausea and vomiting which was practically universal. Other side effects included: mild paresthesias of the extremities (89%), stomatitis (41%), diarrhea (17%), moderate pancytopenia and hypomagnesemia which was reduced from 65% to 17% when magnesium sulfate 10% was administered with cisplatin. Sixty-six percent of the evaluable patients achieved remission (7 partial and 3 complete) usually before the fourth course of therapy. The disease-free interval was of 29.7 +/- 15 weeks in all responders (40.6 +/- 15.5 weeks in complete responders). The mean survival from the start of BPVM therapy was of 55.8 +/- 33.3 weeks in responders and of only 14 +/- 2.9 weeks in nonresponders (P less than 0.01). It is concluded that BPVM is an effective combination chemotherapy in advanced squamous cell carcinoma of the cervix. These results should be confirmed in a Phase III trial.
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PMID:Effective chemotherapy for advanced carcinoma of the cervix with bleomycin, cisplatin, vincristine, and methotrexate. 619 75

It has previously been shown that protamine sulfate is an angiogenesis inhibitor. Regional infusion of protamine into the peritoneal cavity is now reported to prevent the growth of intraperitoneal vascularized tumor masses in rats. Walker 256 carcinoma was implanted directly into the liver or into the peritoneal cavity of rats. Hepatic implants grew in the liver with metastases to the wound and mesentery. Injected tumor cells grew as solid tumor masses in the mesentery. Bloody ascites developed after 7 days. Animals received an intraperitoneal infusion of protamine or saline. Protamine significantly inhibited growth of solid tumors in the mesentery (P less than 0.001). Histology showed tumor cells growing only in monolayer but without vascularization. Ascites was not bloody. In saline-treated animals large vascularized tumors grew in the peritoneal cavity and ascites became bloody.
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PMID:Prevention of carcinomatosis and bloody malignant ascites in the rat by an inhibitor of angiogenesis. 619 88

Reactivity of B16 melanoma cell surface proteins with antisera to the major envelope glycoprotein, gp70, of murine leukemia viruses was assessed by radioimmunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Surface proteins from cultured monolayers of the B16 melanoma and variant lines B16-F1, B16-F1(1r6), B16-F10, and B16-F10(1r6), and from purified B16 melanoma tumor cells, contained three glycosylated components specifically reactive with gp70 antisera, with apparent molecular weights of 70,000, 80,000, and 85,000 (B16-gp70, B16-gp80, and B16-gp85). Antisera raised in syngeneic C57BL/6 mice by immunizing with X-irradiated B16, B16-F10, or B16-F10(1r6) cells immunoprecipitated only solubilized B16-gp70, B16-gp80, and B16-gp85. Absorption of mouse antiserum to B16-gp70/80/85 antigens with purified viruses from various sources indicated that antigens on all three molecules were related to endogenous AKR-type murine leukemia virus antigens. Mice hyperimmunized against melanoma cells were challenged subcutaneously with 4 X 10(4), 10(5), or 2.5 X 10(5) viable B16 or B16-F10 cells, inocula that were lethal and nonmetastatic in unimmunized mice. The lowest cell dose was rejected by 90% of immunized mice. Tumors grew in an average of 58% of immunized mice challenged with 10(5) cells, pulmonary metastases occurring in 61% of those mice. Inocula of 2.5 X 10(5) cells grew in all immunized mice, with a 60% incidence of metastasis. These studies indicate that host immunity to B16-gp70/80/85 antigens can either inhibit or stimulate B16 melanoma tumor progression.
Invasion Metastasis 1984
PMID:Multiple antigens related to the major envelope glycoprotein of murine leukemia virus expressed on B16 melanoma cells as targets of host immune response. 632 88

In this review some of the major mechanistic pathways by which tumor cells are thought to invade host tissues are discussed. Tumor invasion has been conceived to be the result of pathological, close-range interactions between malignant cells and host stroma. The sequence of events that characterize invasion can be summarized as follows: (a) Tumor cell clusters break from the confinement of the primary tumor. Loss of intercellular junctions (desmosomes), alterations in the chemical composition and physical properties of the cell surface coat (loss of fibronectin and heparan sulfate; excessive amounts of hyaluronate), and loosening of cell-substrate interactions (loss of hemidesmosomes, fibronectin, and heparan sulfate), are among the most frequently listed causes of tumor cell shedding. (b) Increased proteolytic activities at the invasion front cause focal alterations in the surrounding extracellular matrix, thereby changing its physical properties. Collagenases and cathepsins, as well as elastase and other neutral proteinases are the enzymes most frequently associated with matrix destruction and invasion. In some tissues this process is effectively regulated by inhibitors of matrix-degrading, proteolytic enzymes. (c) Tumor cells migrate into the altered matrix, possibly moving as aggregates along guidance tracks provided by host structures (blood vessels, lymphatics, nerves) or matrix macromolecules (collagen and fibronectin tracks). Migration seems to be preceded by increased swelling of glycosaminoglycan (i.e., hyaluronate) in the matrix, ahead of the migrating cell population. Various host cell types (mast cells, fibroblasts, endothelial cells, macrophages, etc.) may participate in these events.
Cancer Metastasis Rev 1983
PMID:Tumor invasion and host extracellular matrix. 635 11

Fifty-five patients with newly diagnosed, estrogen receptor negative, metastatic breast cancer were entered in a trial of mitoxantrone, 10 mg/m2 intravenous (IV), cyclophosphamide, 500 mg/m2 IV, and 5-fluorouracil, 1000 mg/m2 IV, which were given on day 1 of a 21-day treatment interval. This trial was designed to test the efficacy of substituting mitoxantrone for doxorubicin as part of a combination that has proved to be effective in inducing remission. The trial was also intended to evaluate the response of resistant disease and of stable metastatic disease to a combination of doxorubicin and vinblastine sulfate. The cardiotoxic potential of mitoxantrone was evaluated in all the patients by serial measurements of ejection fraction and by endocardial biopsy of the right ventricle. Patients who achieved a complete response or a partial response (with bone as the only site of disease) on the three-drug combination were continued on this treatment for 2 years, or for 1 year following a complete response, whichever was shorter or as cardiac monitoring permitted. Therapy with doxorubicin, 25 mg/m2/d for two days, followed by continuous infusion vinblastine sulfate, 1.4 mg/m2/d for four days, was given to all patients who progressed after two courses or were stable after six courses of three-drug therapy. The preliminary results from 50 patients show that 4 attained a complete response and 30 a partial response, giving a total response rate of 68%. The median duration of response was more than 7 months (range greater than 5 to greater than 15 months). One patient in complete remission relapsed after 8 months and failed reinduction therapy with doxorubicin-vinblastine sulfate. Myelosuppression, principally granulocytopenia, was the major side effect of cyclophosphamide-mitoxantrone-5-fluorouracil. Mild to moderate vomiting occurred in 76% of patients and alopecia in 88%. This therapy was discontinued in four patients because of a decreased cardiac ejection fraction and/or symptoms of heart failure. No cardiac biopsy score, however, has been greater than 1.0. These results suggest that a combination of cyclophosphamide-mitoxantrone-5-fluorouracil is effective in untreated, estrogen receptor negative, metastatic breast cancer and is comparable to the doxorubicin combination. Myocardial injury occurs with mitoxantrone, and a safe cumulative dose has yet to be established.
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PMID:Mitoxantrone, cyclophosphamide, and 5-fluorouracil in the treatment of hormonally unresponsive metastatic breast cancer. 638 62

Anchorage-independent growth of tumor cells constitutes a phenotype highly associated with malignant transformation and appears to be important in the ultimate event of tumor metastasis, i.e., secondary tumor colonization. The role of a specific, melanoma-associated chondroitin sulfate proteoglycan population in anchorage-independent growth was assessed. Melanoma cells cultured in soft agar containing monoclonal antibody (mAb) 9.2.27, which recognizes such molecules on the surface of these cells, showed a 67-74% specific decrease in their colony formation. In contrast, neither mouse myeloma IgG nor monoclonal anti-HLA-A,B,C antibody (W6/32) had any effect on colony formation of the melanoma cells grown in soft agar. Human melanoma cells cultured in the presence of mAb 9.2.27 or W6/32 did not exhibit any changes in their DNA or protein synthetic metabolism. These findings suggest that 9.2.27-defined chondroitin sulfate proteoglycans on the surface of human melanoma cells may be involved in cell--cell interaction important in anchorage-independent growth.
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PMID:Inhibition of anchorage-independent growth of human melanoma cells by a monoclonal antibody to a chondroitin sulfate proteoglycan. 657 84


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