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)

A strategy for improved treatment of malignant gliomas grade III-IV is presented. The strategy can briefly be described as surgical removal of the bulky tumor, high precision external irradiation of small brain volumes over and near the primary tumor area with high doses from proton beams, and thereafter treatment of spread cells with toxic radionuclides. Proton beams suitable for this are under development. The clinical effects of high single doses on malignant gliomas grade III-IV are presently tested with conventional gamma radiation. Targeting of spread glioma cells with toxic radionuclides tagged to epidermal growth factor, EGF, or to EGF-dextran is presently tested in experimental systems and can, in the near future, be tested in combination with local high doses of external proton radiation. The possibilities to combine proton beams with EGF-guided neutron capture therapy will be considered in a longer perspective.
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PMID:Strategy for planned radiotherapy of malignant gliomas: postoperative treatment with combinations of high dose proton irradiation and tumor seeking radionuclides. 131 Sep 61

A monoclonal antibody (mAb) directed against the cytokeratin (CK) polypeptide no. 18 specifically expressed in cells derived from simple epithelia was used to detect epithelial tumor cells in bone marrow aspirates. Of 156 patients with colorectal carcinoma, 42 presented with cells at the time of primary surgery. The incidence of positive findings varied considerably with the size and the localization of the primary tumor, the involvement of regional lymph nodes, and the presence of clinically manifest metastases. Applying a sensitive double-staining procedure, we could demonstrate that epithelial cells in bone marrow showed a heterogeneic expression of receptors for epidermal growth factor (EGF-R) and transferrin (Tf-R) as well as of the proliferation-associated Ki67 antigen. Also human leukocyte antigen (HLA) class I antigens differed widely in their expression on the CK-positive cells. Clinical follow-up studies on 85 patients showed a significantly higher relapse rate in patients presenting with CK-positive cells in their bone marrow at the time of primary surgery. Twenty-three patients were monitored for the presence or absence of CK-positive cells in bone marrow over time. The majority of monitored patients (18 of 23) exhibited a constant pattern of immunocytochemical findings during the time of observation. Thus, the technique may be useful in identifying high-risk patients as well as in monitoring adjuvant therapeutic trials.
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PMID:Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance. 169 90

Prostate cancer, the most prevalent cancer affecting men, frequently metastasizes to the axial skeleton where it produces osteoblastic lesions with growth rates often exceeding that of the primary tumor. To evaluate the role of tumor cell-host stromal interaction and stromal specific growth factors (GFs) in prostate cancer growth and progression, we coinoculated athymic mice with human prostate cancer cells (LNCaP) and various nontumorigenic fibroblasts s.c. LNCaP tumor formation was most consistently induced by human bone (MS) fibroblasts (62%), followed by embryonic rat urogenital sinus mesenchymal (rUGM) cells (31%) and Noble rat prostatic fibroblasts (17%), but not by NIH-3T3, normal rat kidney, or human lung CCD16 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. The human prostate component of these tumors was confirmed with immunohistochemical staining for prostate-specific antigen (PSA), Northern analysis for PSA expression, and Southern analysis for human repetitive Alu sequences. Elevations in serum PSA paralleled the histomorphological and biochemical findings. LNCaP and fibroblast cell-conditioned media (CM) was used to determine whether autocrine and paracrine mitogenic pathways exist between LNCaP and fibroblast cells in vitro, and various defined GFs were tested to identify possible active factors. Mitogenic assays revealed a 200-300% bidirectional stimulation between LNCaP and bone or prostate fibroblast-derived CM. Lung, normal rat kidney, and 3T3 fibroblast CM were not mitogenic for LNCaP cells. Among the purified GFs tested basic fibroblast growth factor (bFGF) was the most potent mitogen, stimulating LNCaP growth 180% in a concentration-dependent manner. Transforming growth factor alpha and epidermal growth factor were both minimally mitogenic. Coinoculation of LNCaP cells with a slowly absorbed matrix (Gelfoam) absorbed with bFGF or dialyzed and concentrated rUGM or MS CM was also capable of inducing LNCaP tumor formation in vivo. These observations illustrate that fibroblasts differentially modulate prostate cancer growth through the release of paracrine-mediated GFs, possibly including bFGF, and that tumor-stromal cell interactions play an important role in prostate cancer growth and progression.
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PMID:Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. 171 49

The DNA ploidy pattern and amplification of ERBB and ERBB2 genes were examined in paraffin-embedded tissue from gastric carcinomas using flow cytometry and a slot-blot hybridization technique. The incidence of aneuploidy in well differentiated adenocarcinomas (56%) was significantly higher (p less than 0.05) than that in poorly differentiated adenocarcinomas (21%). The DNA ploidy pattern was not remarkably different between the primary tumors and metastatic deposits in lymph nodes. Of the nine specimens having an aneuploid stem cell line in the primary tumor and/or in metastases, three showed ERBB2 gene amplification and one showed ERBB gene amplification. The incidence of epidermal growth factor (EGF) immunoreactivity in tumor cells showed no difference between diploid and aneuploid tumors. These findings indicate that aneuploidy is frequently associated with amplification of ERBB and ERBB2 genes.
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PMID:DNA ploidy pattern and amplification of ERBB and ERBB2 genes in human gastric carcinomas. 197 Jun 90

In a serum-free medium we have established two new human breast carcinoma cell lines from a single primary tumor. Cultures were maintained on chemically defined medium CDM3 or on minor modifications of this medium, Dulbecco's modified Eagle medium-Ham's F12 supplemented with epidermal growth factor, insulin, transferrin, estradiol, hydrocortisone, triiodothyronine, cyclic AMP, phosphoethanolamine, ethanolamine, fibronectin, fetuin, ascorbic acid, bovine serum albumin, and trace element salts including selenite (Petersen and van Deurs, Cancer Res., 47: 856-866, 1987). Primary cultures comprised both NADPH-neotetrazolium reductase-positive carcinoma cells and NADPH-neotetrazolium reductase-negative cells of stromal appearance, as well as normal epithelial cells (Petersen and van Deurs, Cancer Res., 46: 2013-2020, 1986). In subsequent passages the cells were monitored exclusively using the tumorigenicity assay on nude mice. Two cell lines, one nontumorigenic, HMT-3909S1, and one tumorigenic, HMT-3909S8, were selected from the primary cultures. Selection of S8 through subline S4 required transient supplementation of CDM3 with fetal calf serum. Permanent lines S1 and S8 were maintained on serum-free medium. Further characterization of the two cell lines in terms of normal breast gland differentiation (Petersen and van Deurs, Differentiation, 39: 197-215, 1988) was carried out using immunocytochemistry, immunochemistry, electron microscopy, and cytogenetics. S8 appeared to be identical with the NADPH-neotetrazolium reductase-positive carcinoma cells of the primary cultures, with a particular subpopulation of carcinoma cells in the tumor of origin, and with the tumorigenic cells of the nude mice. This subline was aneuploid, typically epithelial in morphology, and expressed keratins K8 and K18 and the glycoprotein MAM-6, typical of luminal epithelial cells in the normal breast gland. Subline S1 appeared more like the elongated cells in the primary cultures and like a second subpopulation of cells in the carcinoma of origin. However, S1 cells were in fact epithelial, since they expressed keratins. Also, S1 cells seemed to be a triploidation of a cell with close resemblance to S4, while only few cytogenetic differences were found between S4 and S8, suggesting an origin of S1 and S8 via S4 from a single hypothetical stem cell.
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PMID:Differential tumorigenicity of two autologous human breast carcinoma cell lines, HMT-3909S1 and HMT-3909S8, established in serum-free medium. 215 55

A tumor-associated epidermal growth factor (EGF)-like activity was detected in the urine of breast cancer patients by means of an EGF radioreceptor assay and an anchorage-independent growth assay. The clonogenic growth factor activity of pooled void volume eluate fractions from a Bio-Gel P-30 column was completely neutralized by an anti-human epidermal growth factor antiserum but not by an anti-transforming growth factor alpha antiserum. This activity was determined in the urine of 71 breast cancer patients. A statistically significant correlation was found between EGF-like clonogenic activity and axillary lymph node status, tumor size, stage of disease, and grade of differentiation of the primary tumor. The Bio-Gel P-30 void volume fraction was used to purify the EGF-related polypeptide to apparent homogeneity by subsequent binding to and elution from A431 cells followed by isoelectric focusing. A polypeptide of a pI of approximately 3.4 was identified to be related to EGF by neutralization and immunoprecipitation experiments with anti-human epidermal growth factor antisera. This polypeptide migrated as a single band of Mr 43,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
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PMID:A Mr 43,000 epidermal growth factor-related protein purified from the urine of breast cancer patients. 229 5

We have analyzed the expression of the genes for the precursors of epidermal growth factor (pro-EGF) and transforming growth factor alpha (proTGF-alpha) as well as for the EGF receptor in tissue specimens of a large number of adult patients with renal cell carcinoma. Since normal kidney tissue was available from the same patients we could directly compare the expression of these genes in tumors with that in adjacent normal renal tissue. Our experiments reveal underexpression of the proEGF gene in all tumors analyzed (21 of 21) and overexpression of the genes for proTGF-alpha (33 of 33 analyzed) and EGF receptor (22 of 23 analyzed) in tumor samples, when compared with normal kidney tissue. The expression of the proTGF-alpha gene appeared to depend on grade and differentiation of the tumor, since well differentiated tumors (grade 1) expressed more proTGF-alpha mRNA than the adjacent normal tissue but significantly less than poorly differentiated tumors (grade 2 or 3), which are the most aggressive ones. In none of these tissue specimens did we find, by Southern analysis, amplification of the proTGF-alpha or EGF receptor gene. Therefore, overexpression of these genes must be due to another effect, perhaps an alteration of their mRNA turnover. Although the EGF receptor gene (c-erbB1) is overexpressed in nearly all carcinomas analyzed, there was no linear coexpression with the proTGF-alpha gene. In contrast, transcription of the proEGF gene was completely turned off in tumor tissue. Although we have found by restriction fragment length polymorphism analysis, in one of three tumor samples, evidence for a somatic mutation within the proEGF gene, we do not know yet, due to the limited number of Southern analyses, whether this somatic mutation is causally involved in the decrease of proEGF mRNA expression and, hence, is representative of renal cell carcinoma. To our knowledge, this is the first observation on primary tumor tissue in humans that upon malignant transformation the gene for a polypeptide growth factor gene is underexpressed.
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PMID:Modulation of pro-epidermal growth factor, pro-transforming growth factor alpha and epidermal growth factor receptor gene expression in human renal carcinomas. 235 42

Associations between epidermal growth factor (EGF) and carcinoma of the prostate (CAP) have not been systematically investigated. We used indirect immunohistochemical techniques to demonstrate cytoplasmic EGF in paraffin-embedded sections of the following primary prostatic tissues: benign prostatic hyperplasia (BPH) (N = 10), BPH adjacent to CAP (N = 42), clinically localized CAP (N = 45), untreated metastatic CAP (N = 10), and metastatic CAP after varying periods of androgen deprivation (N = 10). In six of the latter 10 cases biopsies of the primary tumor obtained before androgen deprivation therapy were also available for study. Three of the BPH specimens (6%) and 44 of the CAP specimens (68%) stained. Forty per cent of the localized tumors stained but all untreated and treated metastatic tumors stained (p less than 0.01). There were direct but statistically insignificant correlations between the demonstration of EGF and both the Gleason score of localized and untreated metastatic tumors and the pathologic stage of localized tumors. The proportion of malignant cells stained in EGF positive tumors was similar regardless of Gleason score, pathologic stage or the presence or absence of metastases. However, the proportion of cells stained was greater in five of six specimens obtained during hormonal deprivation compared to specimens of the same tumor obtained before treatment. These data suggest that some prostatic cancers interact with EGF and that the interaction may be influenced by the androgenic milieu.
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PMID:Epidermal growth factor and prostatic carcinoma: an immunohistochemical study. 245 Oct 41

A high molecular weight form of epidermal growth factor (EGF) was detected by means of an EGF radio-receptor assay and an anchorage-independent growth assay in the urine of breast cancer patients. Preliminary data indicate that the activity of this growth factor is associated with lymph node status and tumor size and that the activity becomes reduced after removal of the primary tumor. The EGF-related polypeptide was purified to homogeneity by a combination of Sephadex G-25 and Bio Gel P-30 chromatography followed by binding to, and elution from, EGF receptor rich A431 cells. Final purification was achieved after isoelectric focusing by following the biological activity of eluted polypeptides. A polypeptide of a pI of 3.4 was identified to carry EGF-like activity. This polypeptide migrated as a single band of 43 kDa in SDS-PAGE. Its biological activity was neutralized by a specific anti-hEGF-antibody indicating an immunological relationship with hEGF.
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PMID:Purification of a high molecular weight form of epidermal growth factor from urine of breast cancer patients. 278 43

A new human ovarian cancer cell line has been initiated which clones without agar in vitro. The cell line has been characterized by growth of a tumor resembling the primary tumor in a nude mouse, by human lactic dehydrogenase isozyme pattern, by human karyotype, and by lack of contamination by other cell lines. Initial studies have demonstrated the presence of epidermal growth factor receptors in this cell line. The utility of this line for clonogenic studies is demonstrated by dose-response studies with doxorubicin, cisplatinum, and 13-cis-retinoic acid.
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PMID:Development and characterization of a human ovarian cancer cell line which clones without agar in vitro. 298 Nov 93


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