Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases have been implicated in the growth and spread of metastatic tumors. This role was investigated in an orthotopic transplant model of human colon cancer in nude mice using the matrix metalloproteinase inhibitor BB-94 (batimastat). Fragments of human colon carcinoma (1-1.5 mm) were surgically implanted orthotopically on the colon in 40 athymic nu/nu mice. Administration of BB-94 or vehicle (phosphate buffered saline, pH 7.4, containing 0.01% Tween 80) commenced 7 days after tumor implantation (20 animals/group). Animals received 30 mg/kg BB-94 i.p. once daily for the first 60 days and then 3 times weekly. Treatment with BB-94 caused a reduction in the median weight of the primary tumor from 293 mg in the control group to 144 mg in the BB-94 treated group (P < 0.001). BB-94 treatment also reduced the incidence of local and regional invasion, from 12 of 18 mice in the control group (67%) to 7 of 20 mice in the treated group (35%). Six mice in the control group were also found to have metastases in the liver, lung, peritoneum, abdominal wall, or local lymph nodes. Only two mice in the BB-94 group had evidence of metastatic disease, in both cases confined to the abdominal wall. The reduction in tumor progression observed in the BB-94-treated group translated into an improvement in the survival of this group, from a median survival time of 110 days in the control group to a median survival time of 140 days in the treated group (P < 0.01). Treatment with BB-94 was not associated with any obvious toxic effect, and these results suggest that such agents may be effective as adjunctive cancer therapies.
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PMID:Matrix metalloproteinase inhibitor BB-94 (batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. 806 71

Previous studies have shown that multilamellar vesicles (MLV) or other carriers containing purified human C-reactive protein (CRP) have therapeutic activity in preclinical tumor models. Here we evaluated the therapeutic effects of MLV containing novel synthetic peptides, derived from the structure of CRP, on the extent of (a) established lung metastases of fibrosarcoma T241 in C57Bl/6 mice, (b) survival of C57Bl/6 mice bearing established liver metastases of colon carcinoma MCA-38, and (c) primary tumor growth of Renca renal carcinoma in Balb/c mice. In all cases, a single synthetic CRP peptide, RS-83277, demonstrated significant antitumor effects comparable to that seen with intact CRP. Two other synthetic CRP peptides, RS-83287 and RS-83147, showed no therapeutic activity and were comparable to control MLV containing only buffer. None of the peptides contained sequences homologous with that of the phagocyte stimulant, tuftsin. Activity of MLV-encapsulated RS-83277 was dose-dependent, and a comparable dose of the soluble peptide, given either alone or following injection of buffer-MLV, was ineffective. These results demonstrate immunotherapeutic potential for a novel synthetic peptide derived from CRP, and endogenous acute-phase protein.
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PMID:Therapeutic effects of a synthetic peptide of C-reactive protein in pre-clinical tumor models. 843 77

Records of 487 patients in long-term follow-up after Ro resection of colorectal carcinomas between January 1, 1980 and December 31, 1989 were analyzed. Every patient underwent regular examinations according to a defined schedule after curative resection of colorectal carcinoma. The date of evaluation was June 31, 1991. During a median observation time of 48 months (range, 15-132 months), tumor recurrence was observed in 149 patients (30.6 percent), with 56.4 percent of these suffering from tumor-associated symptoms. As the primary manifestation of tumor recurrence, only distant metastases (DM) were found in 76 patients (51 percent), only local recurrence (LR) in 46 patients (30.9 percent), and both DM and LR in 27 patients (18.1 percent). Patients with rectal carcinoma developed LR more frequently (P < 0.05) (19.5 percent) than patients with colon carcinoma (11.8 percent). The probability of developing distant metastases was not different (P < 0.05) for colon or rectal carcinoma but depended on primary tumor stage (P < 0.05). Only 36 patients (24.2 percent) with recurrence could undergo further curative resection. Fifty patients (33.5 percent) were given palliative therapy, and 63 patients (42.3 percent) were given no oncologic treatment. Only 9 of the 36 patients (6 percent of all recurrence patients) undergoing Ro resection were free of tumor for more than two years. In no case was a third Ro resection possible. The survival time of these patients was increased significantly after Ro resection of tumor recurrence (P = 0.03). Our study suggests that only a very few patients may live longer as a result of regular follow-up programs after curative resection for colorectal carcinoma.
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PMID:Does methodic long-term follow-up affect survival after curative resection of colorectal carcinoma? 844 34

Solitary and early brain metastases from colon carcinoma are unusual. This possibility must be kept in mind, in patients with cerebral metastasis of unknown adenocarcinoma. These patients could benefit from colonoscopy and CEA studies with the aim of achieving more early diagnosis and surgical resection. The case of a 48-year-old woman with brain metastasis diagnosed 4 months before the primary tumor, a colon cancer, is reported.
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PMID:[Early cerebral metastasis of colonic adenocarcinoma]. 866 71

The effect of Tiazofurin (TR)-a C nucleoside with significant antineoplastic activity-have been studied on the liver metastasis formation of human colorectal carcinoma xenografts. TR treatment (especially at a dose of 300 mg/kg bwt) produced significant inhibition of metastasis formation in the liver and induced a significant and dose dependent decrease in the serum CEA level. There was not clear connection between the alteration of the weight of the primary tumor bearing spleen and the anti-metastatic activity of TR. In tumor cells derived from tumors obtained from TR treated animals a considerable decrease was observed in the expression of MMP2 metalloproteinase. Furthermore, TR induced a significant dose dependent inhibition of the microinvasiveness of colon carcinoma cells on EHS matrix. Based on the data presented here and published elsewhere, the authors suggest that in the remarkable liver metastasis inhibitory effects of TR modulation and the nonproliferative events of the multistep metastatic cascade plays an important role.
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PMID:Antiinvasive effects of Tiazofurin on liver-metastatic human colon carcinoma xenografts. 904 7

The immune system takes note of the presence of a malignant tumor but in most cases an effective defense reaction is hardly likely to come about. In patients with a solid tumor a tumor-directed immune response will usually be manifested as sensitization of T-lymphocytes to different tumor associated antigens (TAA). There is hope, however, that deeper insights into the mechanisms which ensure the selective clonal expansion and differentiation of antigen-sensitized lymphocytes and an appropriate stimulation of tumor specific effector cells will make it possible to inhibit or at least to impede the outgrowth of metastases following the surgical resection of the primary tumor. Active specific immunization (ASI) is one way to activate tumor specific T-or B-lymphocytes. In this paper, we give a short survey on the state of the art of ASI, outline newer approaches to improve its effectiveness and summarize results of clinical studies with ASI in patients with malignant melanoma or colorectal carcinoma. Among the epidemiologically important tumors, malignant melanoma is that one which seems to be most immunogenic and therefore has been studied intensively. The reason we refer to colorectal carcinoma is that we ourselves have some preliminary experiences with ASI in patients with colon carcinoma.
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PMID:Active specific immunotherapy in hepatic metastasis. 912 91

Vaccination with gene-transfected tumor cells has recently been proposed as a new strategy in the immunotherapy of cancer. Since autologous tumor cells provide an optimal antigen profile, the possibility of generating single cell suspensions from renal cell carcinoma (RCC), malignant melanoma (MM), colon carcinoma (CC), and non-small-cell lung cancer (NSCLC) biopsies was investigated. One hundred and seventy-four tumor biopsies were processed by mechanic and enzymatic dissociation, yielding 1-2 x 10(6) cells/g tumor (median), irrespective of tumor type. Primary tumor cell cultures (PTCC) of > or = 10(7) cells were established from 29 of 86 (34%) RCC, 14 of 38 (37%) MM, 11 of 23 (48%) NSCLC and 4 of 27 (15%) CC specimens. The amount of non-tumor cells, as assessed by morphology and immunocytology, was generally low (< 30%) in RCC (35 of 41) and MM (11 of 17), while it exceeded 60% in 8 of 11 PTCC from NSCLC and 3 of 11 CC. A high tumor cell yield was obtained in biopsies with a high degree of vascularization and in the virtual absence of necrosis. Thus, PTCC > or = 10(7) cells were obtained in 73% of MM with a high degree of vascularization and in 22% of MM with a low degree of vascularization (p < 0.007). Long-term tumor cell cultures exceeding 20 passages were established in 24 of 86 (18%) RCC, 7 of 38 (18%) MM and 3 of 27 (11%) CC, while successful implantation in nude mice was achieved in 8 of 20 RCC and 5 of 10 MM. Thus, under the conditions described, > or = 10(7) primary tumor cells of high purity could be generated from about one third of RCC and MM biopsies, while the success rate increased to > 50 and > 70%, respectively, in samples with a high degree of vascularization generated by an optimized biopsy technique excluding necrotic parts.
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PMID:Processing of tumor tissues for vaccination with autologous tumor cells. 925 2

A 75-year-old man with a history of resected colon carcinoma presented to his primary care physician because of a new onset of coughing. The patient had expectorated a small piece of solid tissue; pathologic examination of the tissue found it to be consistent with metastatic colon adenocarcinoma. After further work-up, a right upper lobectomy was performed. The surgical specimen removed during the lobectomy showed a tumor that was histologically identical to the patient's prior colonic primary tumor.
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PMID:An unusual presentation of metastatic colon cancer to the lung. 944 Jun

Previous studies have identified and characterized both murine in vivo and human in vitro T cell responses reflecting specific mutations in the ras proto-oncogenes at codon 12, 13, or 61. In an attempt to determine whether peptide epitopes reflecting point mutations in the ras oncogenes are immunogenic in humans for the production of CD4+ and/or CD8+ T cell responses, a phase I clinical trial was initiated in metastatic carcinoma patients whose primary tumors harbor mutations in the K-ras proto-oncogenes at codon 12. The peptides used here as immunogens, which were administered in Detox adjuvant, spanned the ras sequence 5-17 and reflected the amino acid substitution of glycine (Gly) at position 12 to aspartic acid (Asp), cysteine (Cys), or valine (Val). Three of eight evaluable patients have demonstrated peptide-specific cell-mediated immunity, as determined by the production of T cell lines resulting from the vaccination. First, an antigen (Ag)-specific, major histocompatibility complex (MHC) class II (DP)-restricted CD4+ T cell line was established in vitro from postvaccination lymphocytes of a non-small cell lung carcinoma patient whose primary tumor contained a Cys12 mutation when cultured on the immunizing peptide. Moreover, CD4+ proliferation was inducible against the corresponding mutant K-ras protein, suggesting productive T cell receptor recognition of exogenously processed Ag. Second, an Ag-specific, MHC class I (HLA-A2)-restricted CD8+ cytotoxic T lymphocyte (CTL) line was established in vitro from postvaccination lymphocytes of a colon carcinoma patient whose primary tumor contained an Asp12 mutation. To that end, a 10-mer peptide, nested within the 13-mer immunizing peptide, was identified [i.e., ras5-14(Asp12)], which was shown to bind to HLA-A2 and display specific functional capacity for expansion of the in vivo primed CD8+ CTL precursors. Third, both Ag-specific, MHC class II (DQ)-restricted CD4+ and MHC class I-restricted (HLA-A2) CD8+ T cell lines were generated from a single patient with duodenal carcinoma whose primary tumor contained a Val12 mutation when cultured on the immunizing 13-mer peptide or a nested 10-mer peptide [i.e., ras5-14(Val12)], respectively. Evidence is thus provided that vaccination with mutant ras oncogene peptides in adjuvant may induce specific anti-ras cellular immune responses, with no detectable cross-reactivity toward normal proto-ras sequences. Moreover, we have identified for the first time human HLA-A2-restricted, CD8+ CTL epitopes reflecting specific point mutations in the K-ras oncogenes at codon 12 which, in concert with the activation of the CD4+ T cell response, may have important implications for both active and passive immunotherapies in selected cancer patients.
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PMID:Generation of stable CD4+ and CD8+ T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations. 951 98

Two human cell lines, one established from a colon carcinoma (SW480) and the other from its lymph node metastasis (SW620), were compared with respect to their migration capacity employing a three-dimensional collagen matrix and time-lapse video recording. Non-motile cells were characterized by a round shape, whereas motile cells appeared in an elongated form with pseudopodia. The primary tumor cells showed a higher spontaneous locomoting activity than the cells from the metastasis. Using single cell analysis, the distance migrated within 15 h was slightly increased in the presence of hyaluronic acid (HA) in both cell lines. An investigation of the amount of CD44 on the cell surface using the anti-CD44 antibody Hermes-1 showed only minor concentrations of this glycoprotein on cells from the metastasis, whereas a much higher amount was found on cells derived from the primary tumor. The distribution of CD44 on the cell surfaces of HA-treated and untreated cells did not differ as shown by confocal laser scanning microscopy in SW480. The results indicate a restricted influence of HA on migration in the two cell lines.
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PMID:Differences in the migration capacity of primary human colon carcinoma cells (SW480) and their lymph node metastatic derivatives (SW620). 983 20


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