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)

We determined the optimal conditions for conducting experiments with the solid and ascites sublines of the 13762 rat mammary adenocarcinoma and examined the response of the tumor growth rate to BCG administered in admixture with tumor cells or separately at a remote site. Versene dissociation of the 13762 solid tumor produced better growth rates than did pronase-DNase, but the former decreased cell viability and yields. A dose of 10(6) or 10(5) tumor cells produced 100% growth by the sc and iv routes. Both sublines grew slower but produced metastases slightly sooner in the intradermal than in the sc site. The frequency of axillary lymph node metastases from the sc site increased as a function of the duration of the time interval between tumor implantation and surgical excision. Both solid and ascites tumors were weakly immunogenic. Administration of BCG in a split adjuvant protocol did not improve tumor immunity. Admixture of tumor cells with BCG suppressed tumor growth but when given at a remote site, BCG was ineffective. We concluded that the 13762 rat mammary adenocarcinoma is a useful system for BCG immunotherapy.
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PMID:Suitability of rat mammary adenocarcinoma 13762 as a model for BCG immunotherapy. 81 63

In the last decades several markers of pancreatic neoplasia have been proposed to obtain a diagnosis as earlier as possible. Prerequisites of a good tumor marker are high sensitivity and specificity. Among the various substances, serum determination of pancreatic enzymes has been found of no utility in early diagnosis of pancreatic cancer, due to its lack in sensitivity and specificity. Similar results with ribonuclease and deoxyribonuclease. Oncofetal antigens (CEA and POA) have been initially considered promising indices; however, further studies showed their limits. In particular CEA is greatly influenced by the presence of hepatic metastases; therefore, serum levels are detectable only in advanced stages. TPA is characterized by a high sensitivity, but lacks in specificity and its use is now avoided. A real progress in the field of tumor markers has been made in the last years with the monoclonal antibody technique: among them CA 19-9 showed a good sensitivity and a satisfactory specificity as regards the diagnosis of pancreatic cancer. However, it cannot be considered as absolute aid, since it is influenced by several factors, as tumor spread, jaundice and liver dysfunction.
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PMID:[Value and limitations of neoplasm markers in the diagnosis of pancreatic carcinoma]. 204 59

Serine proteases, such as alpha-chymotrypsin or elastase, caused an aggregation of rat ascites tumour cell lines, AH-130, AH-109A and YS, in a protein free medium which preserved the cell viability. This aggregation, which was monitored spectrophotometrically, was dependent upon the protease activities and was resistant to treatment with either a calcium chelating reagent (EDTA) or neuraminidase. However, the tumour cell aggregates were redispersed by treatment with deoxyribonuclease I (DNase I). This dispersal effect was dependent upon the DNase activity. A possible relationship between the tumour cell aggregation and development of blood-borne metastasis was studied. An intravenous inoculation in rats of tumour cell aggregates performed by the alpha-chymotrypsin treatment resulted in significantly higher numbers of lung metastatic foci than an injection of single cells. When the re-separated single cells, prepared in vitro by treatment with DNase I following alpha-chymotrypsin treatment, were injected instead of the aggregates, the enhancement of metastasis was reversed. These enhancement and reversal effects were mimicked in vivo by intravenous injections of protease and nuclease following inoculation of a single cell suspension. That is, the number of metastatic foci caused by single cell inoculation followed by an intravenous alpha-chymotrypsin injection, was higher than that in a control group receiving PBS instead of alpha-chymotrypsin. Again, this augmentation was reversed by an injection of DNase I following alpha-chymotrypsin injection. Furthermore, an injection of DNase I alone itself reduced the starting number of metastases resulting from injection of the single tumour cell suspension. These data suggest that the metastatic behaviour of tumour cells may be increased by protease inducible DNA dependent cell aggregation should it occur in the blood stream.
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PMID:Serine protease-induced enhancement of blood-borne metastasis of rat ascites tumour cells and its prevention with deoxyribonuclease. 212 Dec 20

To determine whether the production of experimental hepatic metastases in athymic nude mice by human colorectal carcinomas (HCC) correlated with the clinical outcome in patients, we harvested colorectal carcinomas from 82 patients, dissociated the tumors with collagenase and DNase, and injected them into groups of nude mice, either in the flank to assess experimental tumorigenicity or into the spleen to produce experimental metastasis in the liver. Growth in mice was then associated with clinicopathological factors and clinical outcome. Growth of HCC in either the flanks or the livers of nude mice was associated with the time to recurrence in a Wilcoxon analysis. Analysis of the outcome data in a Cox proportional hazards model suggested that there was an interaction between tumorigenicity and metastatic potential of HCC in nude mice and serum CEA concentration in the patient and stage of disease. A univariate analysis indicated that both tumorigenicity and metastatic potential of HCC in nude mice were significantly associated with the serum CEA concentration of the patient but not with the other variables of stage of disease, mucin production, local tissue invasion, state of differentiation, or sex. A subset of 57 patients was operated upon for cure and followed prospectively for up to 61 months. Tumorigenicity and, to a lesser extent, experimental metastatic potential were associated with disease recurrence in 23 of these patients. Seventy-eight % of the subset of patients who were operated upon for cure developed liver metastasis as one site of their progressive disease. Thus, the ability of HCC cells isolated from surgical specimens to grow in athymic nude mice correlates with the development of advanced disease in patients.
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PMID:Metastatic potential of human colorectal carcinomas implanted into nude mice: prediction of clinical outcome in patients operated upon for cure. 258 33

A preoperative serum carcinoembryonic antigen (CEA) concentration greater than 5 ng/ml portends a poor prognosis for patients with colorectal carcinoma. The purpose of this study was to determine if the tumorigenicity of colorectal carcinomas in nude mice was associated with the preoperative serum CEA concentration. Neoplasms from 53 patients were either implanted as fragments or dissociated with collagenase and DNase, and 3 x 10(6) viable cells were injected into the flanks of BALB/c nude mice. The growth potential of tumors resected from patients with CEA levels exceeding 5 ng/ml was greater than that of tumors from patients with normal serum CEA: 26 of 33 carcinomas from patients with CEA greater than or equal to 5 ng/ml were tumorigenic in nude mice, whereas only 8 of 22 neoplasms from patients with normal serum CEA were tumorigenic in nude mice (P less than 0.001). Primary colorectal cancers, not metastases, were the basis for the association between tumorigenicity and preoperative CEA. Tumorigenicity was also associated with stage of disease, since Dukes' D primary tumors and metastases were more tumorigenic than Dukes' A to C primary tumors. Growth in nude mice was not associated with other prognostic factors such as tumor site, mucin production, local invasion, or stage of histological differentiation. The tumorigenic capability of human colorectal carcinomas may be associated with the preoperative serum CEA concentration and may reflect an increased potential to develop clinical metastases.
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PMID:Growth potential of human colorectal carcinomas in nude mice: association with the preoperative serum concentration of carcinoembryonic antigen in patients. 334 36

Tumor pairs, selected on the basis of their different capacities to metastasize in vivo (SP73/AS and ASML from the rat, Eb/ESb from the mouse), have been assayed for their membrane associated actin through the DNase inhibition assay. It is found that, provided inhibitions per cell are corrected for the influence of gross heterogeneities in size distributions, the more metastatic tumor cells have significantly higher DNase I inhibitions than their less invasive counterparts. This observation, which extends our previous study of normal recirculating lymphocytes, is rationalized by postulating a participation of these actin pools to a property critical for both normal recirculation and metastatic spreading, arguments are presented which favor cell surface deformability as a possible candidate.
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PMID:DNase I inhibitions in tumors of different metastasizing capacities: a possible index of invasiveness. 623 Jan 49

Acid and alkaline DNAse levels were determined in the serum of 224 breast cancer patients and in the extracts of 121 breast tissue and 48 lymph node biopsies of the above patients. The DNase levels were compared to the histological diagnoses of the tumors. Serum and tissue DNase levels were found to be significantly increased in malignancies as compared to benign conditions. A close correlation was found between serum and tissue DNase levels. Measurement of DNase levels within tumors could become clinically important i.e. screening of patients for metastatic disease, or in vitro testing of tumor cells sensitivity to therapeutic regimes.
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PMID:Correlation between serum and tissue deoxyribonuclease levels in breast cancer patients. 714 51

Effects of alpha-chymotrypsin and deoxyribonuclease I (DNase I) on the early phase of blood-borne lung metastasis in rats were studied using confocal laser scanning microscopy and AH-109A cells labeled either with carboxyfluorescein diacetate succinimyl ester or with 51Cr. Intravenous administration of alpha-chymotrypsin or DNase I appeared to enhance or inhibit, respectively, the tumor cell arrest in lung microvasculature as a reflection of reduction or promotion of the tumor cell clearance in the microvasculature. These results suggest that the effects of alpha-chymotrypsin and DNase I are related to induction of tumor cell aggregation and disaggregation in the blood stream, respectively.
Invasion Metastasis 1995
PMID:Effects of serine protease and deoxyribonuclease on intravascular tumor cell arrest in rat blood-borne lung metastasis. 767 31

Murine L5178Y-ML cells, when transplanted subcutaneously into the flank of (BALB/c x DBA/2)F1 mice, grew locally and always formed spontaneous metastases in the liver. Even after surgical removal of the primary tumour mass 5 or 7 days after tumour cell inoculation, all mice died due to liver metastases within 18 days. Using this model of tumour metastasis, we examined whether serine protease or deoxyribonuclease I (DNase I) would affect metastasis. Spontaneous liver metastasis of L5178Y-ML cells was enhanced by systemic administration of alpha-chymotrypsin at 3, 4 and 5 days or at 5, 6 and 7 days after tumour cell inoculation. This result was consistent with a previous report on blood-borne lung metastasis. In contrast, systemic administration of DNase I at 3, 4 and 5 days or at 5, 6 and 7 days after tumour cell inoculation inhibited liver metastasis. Neither treatment affected primary tumour growth. An influence of DNase I on tumour cell arrest in the microvasculature of the liver was suggested by scanning electron microscopy. DNase I treatment resulted in a statistically significant prolongation of the survival period, however, the effect was not satisfactory. A more striking anti-metastatic treatment resulting in a greater prolongation of the survival period was achieved by combining surgical removal of the primary tumour mass with DNase I treatment. These results suggest that DNase I could be a potential therapeutic agent used in conjunction with surgery to prevent clinical blood-borne metastasis.
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PMID:Deoxyribonuclease treatment prevents blood-borne liver metastasis of cutaneously transplanted tumour cells in mice. 842 81

Immune responses to three Epstein-Barr virus (EBV) lytic proteins, DNase, thymidine kinase (TK), and BMRF-1 gene products (50/52 kDa diffused early antigen, EA-D complex) were determined in EBV-infected control individuals and patients with nasopharyngeal carcinoma (NPC). Immunofluorescence assays (IFA) were used to detect their humoral immune responses using recombinant EBV lytic proteins expressed in a baculovirus system as antigens. Cell proliferation assays were performed to evaluate their cellular immune responses by monitoring 3H-thymidine incorporation. Seventy patients with NPC and 32 non-cancer controls were analyzed. The results of IFA showed antibody titers to all three EBV lytic proteins to be higher in the patients with NPC especially for the IgA class. Positivity rates of the three IgA antibodies also were higher in the patients with NPC population. Furthermore, the profiles of the IgA antibodies correlated with those to total early antigens (EA) expressed in the early phase and viral capsid antigen (VCA) expressed in the late phase, of EBV replication. The most interesting finding was that antibody titers to the three EBV lytic proteins were associated significantly with metastases of cervical lymph nodes in patients with NPC. As for cellular immunity to the EA-D complex and DNase, weak responses were observed in the cell proliferation assays. Peripheral blood cells from most individuals could not be stimulated to proliferate, except for a few patients with NPC whose antibody titers against the EA-D complex and DNase also were very high.
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PMID:Immune responses to Epstein-Barr virus lytic proteins in patients with nasopharyngeal carcinoma. 1522 2


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