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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rapid method for determining labeling indices in solid tumor specimens, tumor-induced effusions, and tumor-bearing bone marrows was utilized in 116 patients. Of these, 48 patients were studied pre- and postchemotherapy. The magnitude of a significant change in labeling index (LI percent) was determined statistically. Of the 48 patients studied serially, 42 were studied 17 days or less following completion of their chemotherapy. In 26 patients without a significant change in tumor LI percent, there was no subsequent clinical response to chemotherapy. Three additional patients in this group are inevaluable at present. In 11 patients, there was a significant fall in tumor LI percent following chemotherapy. Seven of these had a 50 percent or greater regression of demonstrable disease, one patient had definite tumor effect but the effect was not a partial response and three patients were not evaluable for clinical response. In two patients there was a significant increase in tumor LI percent and the patients had rapid tumor progression and death. Predictions derived from serial study of the LI percent by this method correlate significantly with subsequent behavior of the tumors tested following chemotherapy and may prove clinically useful in making decisions about when or whether to change therapy.
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PMID:Serial labeling index determination as a predictor of response in human solid tumors. 109 72

Neoplastic cells require an appropriate pericellular environment and new formation of stroma and blood vessels in order to constitute a solid tumor. Tumor progression also involves degradation of various extracellular matrix (ECM) constituents. In this review we have focused on the possible involvement of ECM-resident growth factors and enzymes in neovascularization and cell invasion. We demonstrate that the pluripotent angiogenic factor, basic fibroblast growth factor (bFGF) is an ECM component required for supporting cell proliferation and differentiation. Basic FGF has been identified in the subendothelial ECM produced in vitro and in basement membranes of the cornea and blood vessels in vivo. Despite the ubiquitous presence of bFGF in normal tissues, endothelial cell (EC) proliferation in these tissues is usually very low, suggesting that bFGF is somehow sequestered from its site of action. Our results indicate that bFGF is bound to heparan sulfate (HS) in the ECM and is released in an active form when the ECM-HS is degraded by cellular heparanase. We propose that restriction of bFGF bioavailability by binding to ECM and local regulation of its release, provides a novel mechanism for regulation of capillary blood vessel growth in normal and pathological situations. Heparanase activity correlates with the metastatic potential of various tumor cells and heparanase inhibiting molecules markedly reduce the incidence of lung metastasis in experimental animals. Heparanase may therefore participate in both tumor cell invasion and angiogenesis through degradation of the ECM-HS and mobilization of ECM-resident EC growth factors. The subendothelial ECM contains also tissue type- and urokinase type- plasminogen activators (PA), as well as PA inhibitor which may regulate cell invasion and tissue remodeling. Heparanase and the ECM-resident PA participate synergistically in sequential degradation of HS-proteoglycans in the ECM. These results together with similar observations on the properties of other ECM-immobilized enzymes and growth factors, suggest that the ECM provides a storage depot for biologically active molecules which are thereby stabilized and protected. This may allow a more localized, regulated and persistent mode of action, as compared to the same molecules in a fluid phase.
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PMID:Extracellular matrix-resident growth factors and enzymes: possible involvement in tumor metastasis and angiogenesis. 170 86

Basic fibroblast growth factor (bFGF) is a potent mitogen and angiogenic factor. bFGF is expressed by a variety of solid human tumors and has been implicated as an autocrine regulator of tumor growth. Different solid tumor lines including glioma, colon carcinoma and melanoma were examined for intracellular immunoreactive bFGF, high- and low-affinity bFGF receptors and mitogenic response to bFGF when grown in chemically defined medium. All tumor lines contained significant levels of bFGF. In addition, all tumor lines contained subsets of five forms of immunoreactive bFGF, as well as 0.68-20 x 10(6) low affinity bFGF binding sites (Kd = 15-300 nM). Most, but not all lines exhibited high affinity bFGF receptors (Kd = 25-40 pM). Glioma cell lines were distinguished by expressing the highest levels of bFGF protein as well as the most high-affinity receptors for bFGF. Furthermore, glioma cell lines were the only tumor type mitogenically responsive to bFGF. These results indicate that glioma cells express high levels of this potent mitogen and angiogenic factor relative to human colon carcinoma and melanoma cells. The expression of bFGF and bFGF receptors by glioma cells may be related to abnormal growth and neoplastic progression in these tumors.
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PMID:Basic fibroblast growth factor: a potential autocrine regulator of human glioma cell growth. 196 81

Interleukin-6 is a pleiotropic cytokine with a wide range of effects, including induction of B-cell and cytotoxic T-cell differentiation, and induction of acute phase reactant production by hepatocytes. Interleukin-6 also can act as an autocrine growth factor in malignancy. Various cell types produce interleukin-6, including T and B cells, monocytes, fibroblasts, and some solid tumor cells. In previous work we detected the production of substantial amounts of interleukin-6 by human ovarian cancer cells, including the ovarian cancer cell lines CAOV-3, OVCAR-3, and SKOV-3, and several primary ovarian tumor cultures. In this study we retrospectively examined 90 separate serum specimens for interleukin-6 in 36 patients with epithelial ovarian cancer. The mean serum interleukin-6 concentration of those ovarian cancer patients with macroscopic disease (n = 57) was 0.26 +/- 0.04 U/ml (mean +/- SEM). Healthy adult donors have interleukin-6 serum levels of 0.12 +/- 0.03 U/ml. Sixteen of 21 ovarian cancer patients with macroscopic disease (76%) had elevated (greater than 0.20 U/ml) levels of serum interleukin-6, with levels approaching 1 U/ml in some patients (p less than 0.01). Of those nine patients with bulky tumor (residual greater than 2 cm), eight (89%) had an elevated interleukin-6 level (mean, 0.31 +/- 0.05), while eight of 12 (66%) with minimal residual disease (less than 2 cm) had elevated levels. Only two of 15 (13%) patients who were in clinical remission and who had microscopic disease had elevated values. Of the 36 patients, 22 were CA 125 negative (less than 35 U/ml), and of these, four had elevated interleukin-6 levels. Of the 14 patients with an elevated CA 125 level, 12 (86%) had elevated interleukin-6 levels. In those 16 patients in whom serial levels of interleukin-6 were measured, rising levels were found over a 3 to 4 month interval in nine (56%); this correlated with tumor progression. Furthermore, the subsequent survival of patients was shown to correlate with the level of interleukin-6, such that patients whose levels were elevated greater than 0.20 U/ml interleukin-6 survived a mean of 12.5 months, compared with 27.2 months for patients with normal levels (p less than 0.001). These data support the concept that interleukin-6 may be a useful tumor marker in some patients with epithelial ovarian cancer, as it correlates with the tumor burden, clinical disease status, and survival.
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PMID:Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. 201 24

Treatment of neuroblastoma is an unsolved problem of pediatric oncology. In spite of highly intensified chemotherapy, the long-term survival rate of children with a metastatic neuroblastoma is below 10%. We therefore used 131I-metaiodobenzylguanidine (MIBG) for the first time to treat children with a neuroblastoma in relapse or primary unresponsiveness to chemotherapy. We had previously demonstrated that MIBG is useful for the scintigraphic imaging of neuroblastoma lesions and had investigated the cytotoxicity and uptake of MIBG in various neuroblastoma cell lines. We treated 6 children with neuroblastoma in a total of 19 courses. Three of the children suffered from a relapse of neuroblastoma; 3 had never gained a remission. Four of the 6 children lost their bone pain and fever during the first 3 days. In 5 of the 6 children the solid tumor as well as the bone marrow infiltration responded to MIBG treatment, with responses ranging from transitory decrease of the tumor mass to complete disappearance of abdominal tumors. We also witnessed a stabilization of osteolytic lesions, a decrease in elevated serum catecholamines, and a decrease in bone marrow infiltration. Five of the 6 children died of tumor progression 55-249 days after the first MIBG treatment.
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PMID:Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine. 248 76

At the cellular level, cancer is a genetic disease; genetic changes in somatic cells are essential events in neoplasia. In a majority of cases these changes involve large enough blocks of genetic material to be visible in the microscope. The chromosome aberrations in neoplastic disorders are probably of three kinds: (1) primary abnormalities, which are essential steps in establishing the tumor; (2) secondary abnormalities, which develop only after the tumor has developed, but which nevertheless may be important in tumor progression; and (3) cytogenetic noise, which is the background level of nonconsequential aberrations. These latter changes are, in contrast to the primary and secondary changes, randomly distributed throughout the genome. The primary abnormalities, of which several dozens have now been identified, are mostly strictly correlated with particular diseases and even with histopathological subtypes within a given disease. This has been evident in the leukemias for some years already, and information now accumulating on solid tumor karyology indicates a similar situation. Clonal chromosome abnormalities are a feature of both benign and malignant neoplasms, although the changes are often less massive in the former. Apart from being clinically useful as a diagnostic technique and an aid in prognostication, tumor cytogenetics also plays a role in identifying those genomic sites which harbor genes essential in the pathogenesis of neoplastic lesions. So far, two functionally different classes of directly cancer-relevant genes have been detected, the oncogenes and antioncogenes. There is every reason to believe that future investigations with cytogenetic and recombinant DNA methods will add to our knowledge of the biology of human neoplasia, in those tumor types where the characteristic genetic change is already partially known, and by identifying hitherto unknown karyotypic abnormalities.
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PMID:Primary chromosome abnormalities in human neoplasia. 266 10

Implantation of normal bladder mucosa beneath the kidney capsule of a syngeneic animal, results in a heterotopic bladder lined by a one to three cell layer of urothelium. This cystic structure can be maintained for greater than 90 days and displays many of the differentiation characteristics of a normal bladder, both at the light and electron microscopy level. Preneoplastic urothelial cells behave in a similar manner recreating a heterotopic bladder lined by urothelium displaying aberrant differentiation and surface morphology. All tumorigenic cell lines tested in this model produced solid tumor growth within a few weeks. The subrenal capsule represents an alternative site for the reconstitution of urothelial material at different stages of neoplastic progression.
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PMID:The subrenal capsule: an alternative site for the maintenance of normal and preneoplastic urothelium. 317 61

At four involved hospitals 16 children were treated with Metaiodobenzylguanidine (131J-MIBG). These children had a relapse of neuroblastoma stage III or IV or did not respond sufficiently to chemotherapy. In 10 children extreme bone pain disappeared and they became free of fever during the MIBG-treatment. 10 children responded to the therapy demonstrated either by decrease of the solid tumor part or by decrease of catecholamines in urine or plasma or by decrease of bone-marrow involvement. One patient reached a complete remission continuing up to present time (longer than 180 days). 9 patients died meanwhile of tumor progression. 131J-MIBG is an effective instrument, to get a decrease of the tumor up to a complete remission in extensively pretreated patients with tumor relapse, which are refractory to chemotherapy.
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PMID:[Initial experiences in the treatment of children with metastatic and recurrent neuroblastoma using meta-iodobenzylguanidine]. 372 87

Intrafootpad inoculation of syngeneic mice with Lewis lung carcinoma (3LL) cells led to the growth of a solid tumor at the site of transplantation, followed by development of metastases in the lungs. Surgical excision of the primary tumor resulted in an accelerated growth and increased incidence of pulmonary metastases. Inasmuch as 3LL tumor cells isolated from the local tumor differed antigenically from the cells isolated from the metastases, the genetic control of the local 3LL tumor growth and that of its lung metastases were tested. The local tumor grew in allogeneic mice, yet its growth rate was higher in syngeneic and semiallogeneic F1 hybrids than in allogeneic recipients. However, lung metastases did not appear in allogeneic animals. By analysis of the rate of growth of the local tumor in congenic mouse strains, the tumor progression appeared to be linked to the host's genetic background rather than to the H-2 region. The generation of lung metastases required compatibility at both background and H-2 haplotype. Tests of the development of metastases in mice of congenic resistant recombinant strains revealed that metastases developed only in animals that shared with the tumor the gene products of the D-end of the major histocompatibility complex. Thus metastasis formation was controlled by both a non-H-2 gene(s) and a gene(s) linked to the H-2D region or another nearby region to the right of H-2D.
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PMID:Control of progression of local tumor and pulmonary metastasis of the 3LL Lewis lung carcinoma by different histocompatibility requirements in mice. 693 34

The effect of aminohexyl-2-hydroxyethylmethacrylate polymer (HEMA-Hex) with sorbed methotrexate (MTX) or 3',5'-dibromoaminopterin (BrAP) on the survival of C3H mice with Gardner lymphosarcoma was studied. The measured bits of HEMA-Hex-MTX or HEMA-Hex-BrAP were implanted into the solid tumor growing 4 to 8 8 days. The doses of sorbed antimetabolites amounting in MTX 4.3 to 13.5 mg.kg-1 and in BrAP 5.1 and 12.6 mg.kg-1 were calculated from the area of the carrier and mean weight of animals. Following implantation i. p. injections of leucovorin or anhydroleucovorin were applied. The treatment of early tumors showed better results than that of advanced ones if evaluated either as prolonged survival or as a number of mice surviving the observation period. The 18-hr. interval between implantation of HEMA-Hex-MTX and anhydroleucovorin injection was optimum if considered both the protection of mice from lethal MTX toxicity and therapeutic effect measured as prolonged survival. Doses of leucovorin or anhydroleucovorin close to MTX doses in term mg.kg-1 resulted in best results. In case leucovorin was applied to tumor-bearing mice pretreated with HEMA-Hex with nonlethal dose of MTX, the survival of mice was shortened. Folic acid did not show this effect. Intra-tumorous implantation of HEMA-Hex-BrAP toxicity even if applied into an advanced tumor. The therapeutic effect of the sorbed BrAP seemed to decrease with tumor progression at a lower rate than of that the sorbed MTX. The application of anhydroleucovorin after implantation of HEMA-Hex-BrAP shortened the survival of tumor-bearing mice.
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PMID:Localized chemotherapy of Gardner's lymphosarcoma of C3H mice using combinations of carrier-sorbed antifolics and detoxicating tetrahydrofolates. 697 53


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