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)

Single, large doses of adriamycin, cyclophosphamide and 5-fluorouracil (5-FU) have been compared to the same amount of drug given in divided doses daily over a 3 or 5 day period in a solid tumor model which metastasizes to the regional lymph nodes and lungs. No significant increase in life expectancy occurred following adriamycin or cyclophosphamide. However, a significant reduction in life expectancy occurred after 5 fractionated doses of 5-FU but not after the large single dose. The increase in mortality following fractionated doses of 5-FU is attributed to the prolongation of the onset of recovery of bone marrow. Tumor volume reduction following a single dose of each agent was equal to or greater than the fractionated doses. The results of these studies on this chemotherapeutically resistant solid tumor indicate that small daily fractionated doses of adriamycin, cyclophosphamide or 5-FU result in increased morbidity and mortality without therapeutic benefit in tumor control. The time sequence of recovery of the limiting organ of the host (i.e., bone marrow) is similar to the time sequence of recovery of the tumor. Large intermittent single doses of chemotherapeutic agents given following recovery of the host from a previous treatment would be expected to be less toxic to the host and equally effective in control of tumor growth. None of the 3 chemotherapeutic agents was successful in tumor eradication. Previous studies of this series have shown that the utilization of sequential chemotherapy combined with radiotherapy can be successfully used for eradication of another solid tumor which did not metastasize. A similar therapeutic strategy using sequential combined modality therapy should also be effective in the control of the primary H-4-II-E tumor as well as its metastatic dissemination. Information gained from these experimental studies should eventually provide information which should be helpful in the clinical management of chemotherapeutically resistant solid tumors in man.
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PMID:Solid tumor models for the assessment of different treatment modalities: VIII. The scheduling of treatment for a chemotherapeutically resistant experimental solid tumor. 44 23

Vascular perfusion of 16 renal adenocarcinomas with radioactive DNA precursors provides a possibility of characterize proliferative compartments of this tumor type. Immediately after resection of the tumor-bearing kidney, the organ is perfused via renal artery with dextran-diluted, heparinized oxygenated blood at physiological temperature, pH, flow, and pressure in a recirculation system. DNA synthetizing cells are labeled by addition of 3H- or 14C-thymidine or both isotopes at different intervals. Beta camera scans and whole-tumor autoradiograms disclose a striking proliferative heterogeneity of the tumor. Cell proliferation depends on intratumoral localization, cellular differentiation, histological structure and vascular supply. Subpopulations of high proliferative activity are found at the invasive borderline near normal kidney, focally in subcapsular areas and in intrarenal metastases, but also immediately adjacent to necrotic areas in the tumor center. Quantitative evaluation of autoradiograms yields, at the cellular level, a significantly higher labeling index in granular cells (3.21%) than in clear cells (0.65%), with a large variability dependent on the histological structure. The highest number of DNA synthetizing cells is seen in papillary and mixed solid-tubular zones and at peripheral parts of solid areas, whereas in central parts of solid tumor cords and in highly differentiated tubular areas lower labeling indices are observed. The labeling index decreases exponentially as a function of the distance from the supporting blood vessel. In solid cords, no labeled cells are seen at a distance of more than 200 micron from the capillary. The ts determined by 3H/14C-thymidine double labeling is between 9.9 and 16.8 hr for granular cells and about 9.2 hr for clear cells. Potential population doubling time calculated for various subpopulations yields values between 4 and 50 days. It is concluded that cell loss is high, for granular cells in particular. Besides cell loss, a large nonproliferating compartment contributes to a delay of the tumor volume doubling time. Proliferative heterogeneity of advanced human tumors, as exemplified by the renal adenocarcinoma, bears important implications for therapy and prognosis.
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PMID:Analysis of proliferative compartments in human tumors. I. Renal adenocarcinoma. 47 95

Internal drainage of cerebrospinal fluid utilizing a mechanical tube has been an increasingly common and effective procedure for the relief of non-communicating hydrocephalus with intracranial tumor. However, several cases have recently been reported in which extraneural metastases of the tumor were initiated through the shunt tube implanted. The purpose of this paper is to present two cases with malignant brain tumor metastasizing extraneurally through ventriculoperitoneal shunt, and to review the reported cases in the literature. Case 1 The patient, a 9-year-old boy, had been suffering from headache and vomiting for 3 months prior to admission to the Neurosurgical Clinic, Gumma University Hospital. On admission, he had choked discs and cerebellar dysfunction with a staggering gait. The clinical diagnosis was a 4th ventricle tumor. On November 29, 1971, a suboccipital craniectomy was performed. A medullary tumor in the 4th ventricle was partially removed, and ventriculoperitoneal shunt was also performed. Subsequently postoperative irradiation was given, and the symptoms were abated. Histological diagnosis was ependymoblastoma. Thirteen months later, he was again admitted because of visual disturbance, psychic change and pituitary hypofunction. Bilateral frontal craniotomy revealed a large mass over the midline of the anterior skull base, accompanied by numerous meningeal neoplastic deposits. The tumor was partially removed and histologically proven to be meningeal metastases of ependymoblastoma. Irradiation was again given and the symptoms improved. But the 4th ventricle tumor recurred 5 months after the 2nd operation, and then a massive intraperitoneal effusion appeared. Cytological examination revealed clusters of tumor cells in the ascites. The patient died on September 8, 1974, namely 22 months after the ventriculoperitoneal shunt was implanted. Postmortem examination showed a solid tumor in the 4th ventricle which was accompanied by diffuse meningeal dissemination, and metastases were present throughout the peritoneal surface...
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PMID:[Extraneural metastases of malignant brain tumors through ventriculoperitoneal shunt--report of two autopsy cases and a review of the literature (author's transl)]. 55 82

Based upon the hypothesis that a factor most pertinent to the absence of an effective immune response in cancer is the inadequacy of the antigenic stimulus provided by the neoplasm, either in terms of weak immunogenicity of the tumor antigen or of the necessary antigen mass available to the reticuloendothelial tissues at any one time for effective sensitization, the host immune response capabilities were stimulated within a time frame synchronous with a greater release of tumor antigens. In the treatment of a metastasizing, solid tumor model syngeneic with F344 rats, immunotherapy was most effectively applied in combinations with chemotherapy and/or localized radiotherapy, therapeutic modalities that induced a degree of oncolysis and tumor resorption. Surgery combined with chemotherapy permitted evaluation of therapeutic effects against metastases. The methanol-soluble fraction of Mycobacterium butyricum was used as the nonspecific immunologic adjuvant.
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PMID:Influence of surgery, irradiation, chemotherapy, and immunotherapy on growth of a metastasizing rat mammary adenocarcinoma. 74 2

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

Peripheral plasma prostaglandin E (PGE) determinations were performed on a series of 79 patients with solid tumor neoplasms and correlated with their serum calcium levels. Fourteen patients were hypercalcemic and 11 of these had significant elevations in circulating plasma PGE. Ten of the hypercalcemic group had extensive metastases to bone. These findings support the recently developed hypothesis that prostaglandins are causally related to the genesis of hypercalcemia in malignancy.
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PMID:Plasma prostaglandins in hypercalcemic patients with neoplastic disease. 85 45

A mathematical model of the process of metastases is formulated in which the hematogenous metastatic process from a solid tumor is considered to consist of a series of stages. A mathematical expression is obtained for the probability that no metastases will have been established by a characteristic time interval after tumor initiation. The murine T241 fibrosarcoma that rapidly and reproduceably produces pulmonary metastases was studied. Estimates of parameters required for the expression of probability of metastases formation were derived experimentally. The probability remains close to one for a characteristic time at which point it drops to zero. This indicates that at least in this experimental system there is a predictable critical time period beyond which micrometastases are virtually certain to have been formed.
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PMID:Micrometastases formation: a probabilistic model. 90 56

A mathematical model is developed to describe the dynamics of the hematogenous metastatic process to the lung from a solid tumor growing in a peripheral body site. The accumulation of tumor cell clumps of various sizes in the pulmonary circulation and the formation of metastatic foci are described by a non-homogeneous, two-dimensional Markov process. An analytical solution is found for the special case of metastases produced by the intravenous injection of tumor cell clumps. The system is decoupled experimentally to determine the time-varying entrance rate of tumor cell clumps into the circulation from a growing fibrosarcoma and the number of metastatic foci produced by the intravenous injection of tumor clumps. Model validation is based on comparisons of model simulations with data for the development of metastatic foci and the probability of cure following tumor excision. The model is used to simulate hypothetical therapy to prevent tumor metastases.
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PMID:Stochastic model of metastases formation. 96 69

The cell-mediated immune response against a transplantable syngeneic metastatic solid tumor in mice was studied. The immune reactivity of spleen cells from tumor-bearing mice was found to vary during development of the tumor. For about a week after tumor transplantation, the spleen cells were able to protect recipient mice against challenge with tumor cells. Subsequently, the protective activity was replaced by an enhancing activity. Recipient mice that received tumor cells together with spleen cells from mice bearing tumors for about two or three weeks had a higher incidence of tumor takes and larger tumors than controls. This enhancement of tumor development was correlated with the size of the local tumor or metastases in the donors. The enhancing activity was found to be mediated by T lymphocytes and appeared to suppress the protective immune response of the recipients. We devised a system to strengthen the immune response of the host against the development of tumor metastases. In the tumor model used, removal of the local tumor after s.c. transplantation failed to prevent the development of lung metastases and death in most of the mice. However, syngeneic spleen cells which had been sensitized in vitro against tumor cells were found to serve as immunotherapeutic agents. Injection of such spleen cells into mice from which primary tumor implants had been removed surgically led to a markedly increased survival. Spleen cells from both normal and tumor-sensitized donors were effective, but splenocytes from mice bearing large tumors did not reduce metastatic development after sensitization in vitro. Thus, protection against the development of lethal metastases can be achieved with certain types of lymphocytes sensitized in vitro.
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PMID:A syngeneic metastatic tumor model in mice: the natural immune response of the host and its manipulation. 108 80

Subcutaneously transplanted 3-methylcholanthrene-induced KMT-17 tumor in WKA rats yielded not only a local solid tumor but also frequent metastases in regional lymph nodes. Neither active immunization with xenogenized identical tumor cells nor surgical excision of the solid tumor prohibited the metastases when each treatment was given 4 days after tumor transplantation. However, immunization combined with surgery significantly decreased the metastases and prolonged survival.
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PMID:Inhibition of metastasis in rats immunized with xenogenized autologous tumor cells after excision of the primary tumor. 112 31


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