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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A continuously growing cultured cell line has been obtained in vitro, starting from a specimen of ascites fluid obtained from a patient with ovarian cancer, in whom a poorly-differentiated adenocarcinoma was diagnosed. This cell line, named OC-A1, is routinely grown in standard, serum-supplemented culture medium and has been fully stabilized to long-term growth and characterized for both cultural and genetic parameters. OC-A1 cells express a set of characteristics, as determined in vitro which, when compared with the in vivo primary tumor, confirm the high malignity of this cancer. In addition, karyotype analysis showed a translocation of chromosome 8 which is correlated with the amplification of c-myc oncogene. However, the expression of this oncogene was found to be significantly inhibited by a new regulatory activity, recently found to be present in a liposarcoma cell line. Conditioned medium from these cells was indeed able to inhibit the growth of OC-A1 cells, arresting their cell cycle in the G1 phase and inducing them to apoptosis. Finally, the cell programmed death appeared to be related to the expression of antioncogene p53.
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PMID:Establishment and growth regulation of a novel ovarian cancer cell line from a poorly-differentiated adenocarcinoma: proposal for a new treatment. 1042 82

In this study, we evaluated the role of the c-myc oncogene in response to cisplatin (DDP) treatment using two melanoma lines derived from the primary tumor (LP) and metastatic lymph node (LM) of the same patient. These cell lines, which retain the phenotypic profile of the original tumors, were studied for growth behavior, expression of c-Myc oncoprotein, and HLA-I antigen. The LM line shows a higher tumorigenic ability, an increased expression of c-Myc protein, and a lack of HLA-I antigen, compared with the LP line. In addition, LP tumor was relatively sensitive to DDP administration, whereas LM tumor was resistant to DDP treatment. To verify whether the increased c-Myc expression observed in the LM line might be responsible for DDP resistance, a c-myc antisense phosphorothioate oligodeoxynucleotide ([S]ODN) was used to down-regulate c-Myc expression. The administration of DDP plus c-myc antisense [S]ODNs produced a decrease in c-Myc protein levels of approximately 50%, accompanied by a tumor weight inhibition of 65%, similar to that obtained when the sensitive line was treated with DDP alone (tumor weight inhibition = 70%). Analysis of apoptosis demonstrated that the sensitivity to DDP of the LP line was related to the ability of tumor cells to undergo apoptosis. Conversely, DDP treatment was not able to induce apoptosis in the LM line, whereas apoptosis was evident both after treatment with c-myc antisense [S]ODNs alone and, more extensively, in combination with DDP. Taken together, these results clearly indicate an important role of c-myc oncogene in the resistance of melanoma to DDP and demonstrate that treatment with c-myc antisense [S]ODN sensitizes a human melanoma line to DDP treatment.
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PMID:Increase of cisplatin sensitivity by c-myc antisense oligodeoxynucleotides in a human metastatic melanoma inherently resistant to cisplatin. 1049 37

We examined genomic DNA from each of three human-derived gastric cancer cell lines, using the technique of restriction landmark genomic scanning (RLGS) which allows monitoring of approximately 2, 000 NotI landmarks. The resulting DNA spots from cancer cell DNA were compared with those in normal mucosa or gastric primary tumor. In all, 9 intense spots were detected from two of the three cancer cell lines. Two highly intensified spots were common in the two cancer cell lines and proven to be originated from DNA region containing the human c-myc proto-oncogene on chromosome 8. The degree of amplification of c-myc DNA was similar to each other and was estimated to be 60-fold as compared to those from normal mucosa DNA. On the basis of chromosome-assigned RLGS (CA-RLGS), other spots were assigned to each chromosome, such as one on chromosome 8, two each from chromosome 20, and three on one of chromosome 9-12. The remaining spot seems to be due to demethylation of a repetitive element. Twenty-four spot that were lost due to either homozygous deletion or methylation on corresponding NotI cleavage sites were commonly observed in all cancer cells. These spots were also assigned to each chromosome: one each from chromosome 2, 6, 7, 13, 14, 16, and 20, two each from chromosome 3 and 5, and nine from chromosome 9-12 by CA-RLGS. Many of the multi-copy spots corresponding to ribosomal RNA genes were greatly decreased due mainly to methylation on CpG islands along with minor rDNA variants, indicating that only minor rRNA genes may be silenced in these cancer cells. These results show that the present alterations detected by RLGS might be useful for identification of candidate genes inactivated or expressed unexpectedly in tumor development and tumor progression in the stomach.
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PMID:Detection of genetic alterations in the human gastric cancer cell lines by two-dimensional analysis of genomic DNA. 1089 39

Transgenic mice expressing c-myc and v-Ha-ras specifically in the mammary gland under the control of the mammary specific promoter MMTV develop unifocal mammary tumors with a half time of about 46 days, and these tumors express high levels of osteopontin mRNA and protein. In order to evaluate the requirement for osteopontin expression by these tumors, we have crossed transgenic mice expressing these two oncogenes with mice with a targeted disruption of the osteopontin gene. Littermates expressing both myc and ras, and with either wild-type or disrupted OPN alleles were evaluated for tumor incidence and growth rate. Both of these parameters were found to be unaffected by a lack of osteopontin in the whole animal. Ras and myc expression level, measured at the level of mRNA, was not different in tumors of the two genotypes. Macrophage accumulation, while extremely variable among different tumors, did not correlate with the OPN status of the animals. Expression of the related gene BSP was not detected in any of the tumors, and was similar in bones of wildtype and OPN -/- mice. Similarly, the vitronectin gene was expressed at very low levels in tumors of either genotype. These results indicate that despite its high level of expression, OPN is either not required for mammary primary tumor formation and growth in this system, or can be replaced by molecules other than BSP and vitronectin in mice that totally lack osteopontin.
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PMID:Mammary tumor development in MMTV-c-myc/MMTV-v-Ha-ras transgenic mice is unaffected by osteopontin deficiency. 1107 61

A significant number of patients with liver metastases from colorectal cancer (CRC) achieve 5-year survival after liver resection. Increased expression of genetic markers in the primary tumor are known to predict outcome after colonic resection, but the predictive value of such markers after resection of hepatic metastases is unknown. The objective of this study was to evaluate whether DNA content and multiple genetic markers, separately or expressed together, can predict patient outcome (liver recurrence and survival) after resection of hepatic metastases. We studied the paraffin-embedded liver tissue of 71 consecutive patients who had undergone a potentially curative resection of hepatic metastases from CRC. Using DNA flow cytometry and immunohistochemical staining techniques we determined the DNA content and the level of co-expression of seven tumor-associated proteins: proliferating cellular nuclear antigen (PCNA), epidermal growth factor receptor (EGFr), p53, c-erbB-2, H-ras, c-myc, and nm23. Three endpoints (liver recurrence, cancer specific, overall survival) were correlated with these tumor markers. The 5-year overall survival of the group was 31.2%. There was no correlation detected between the DNA aneuploidy and overall or cancer-specific survival. Similarly, expression of the individual tumor-associated proteins did not predict survival. Patients whose tumors co-expressed multiple markers had survivals similar to those whose tumors expressed fewer markers. However, a significant difference in hepatic recurrence was found between the p53-positive and p53-negative patients (p = 0.007), with marker-negative tumors having decreased recurrence. In conclusion, this study demonstrates that the DNA content and genetic markers c-myc, c-erbB-2, EGFr, H-ras, p53, PCNA, and nm23 do not predict survival after potentially curative resection of hepatic metastases from CRC. However, the immunoreactivity of p53 may be an important marker of local recurrence in the liver, which may be useful if re-resection of metastatic liver tumors is considered a viable management option in this disease.
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PMID:Genetic markers of survival and liver recurrence after resection of liver metastases from colorectal cancer. 1157 82

To determine whether genetic changes are markers of cancer progression and patient survival in Stage T(2-3)N(1-3)M(0) prostatic carcinoma, we compared 26 patients who died of tumor relapse after prostatectomy and lymphadenectomy (case group) with 26 matched patients who were alive at the time of the matched case's death (control group). Nine unmatched cases were also included in this study. In 37 cases, paired primary tumors (119 foci) and lymph node metastases (114 foci) were available for study. Fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, and 17 and region-specific probes for D7S486 (7q31), c-myc (8q24), LPL (8p22), and p53 (17p13) was performed on available primary carcinomas and lymph node metastases. In primary tumor foci, +7q31, -8p22, +c-myc, substantial additional increases of myc (AI-c-myc), and -p53 were observed in 65%, 74%, 43%, 29%, and 31% of foci, respectively. AI-c-myc was strongly associated with higher cancer Gleason score (P =.003). Heterogeneity of genetic changes was frequently observed among multiple cancer foci. Lymph node metastases of prostate cancer usually shared genetic changes with paired primary tumors. In addition, the genetic change pattern with -8p, +c-myc or AI-c-myc, +7q, and +p53 was slightly higher in lymph node metastases (22%) than in primary tumors (6%) (P =.08). In matched case and control patients, simultaneous gain of 7q31 (+7q31) and CEP7 (+CEP7) was identified in 59% and 68% of specimens for case and control groups, respectively (P =.48). Loss of 8p22 (-8p22) was identified in 77% and 69% of specimens for case and control groups, respectively (P = 1.0). Simultaneous gain of c-myc (+c-myc) and CEP8 (+CEP8) without overt additional increase of c-myc copy number relative to CEP8 copy number, was identified in 38% and 54% of specimens for case and control groups, respectively (P =.27). AI-c-myc was identified in 54% and 23% of specimens for case and control groups, respectively (odds ratio = 3.0, P =.06). Loss of p53 (-p53) was identified in 46% and 15% of specimens for case and control groups, respectively (odds ratio = 4.0, P =.04). Our results indicate that FISH anomalies are very common in both primary tumors and lymph node metastases of Stage T(2-3)N(1-3)M(0) prostate cancer; that AI-c-myc is associated with higher cancer Gleason score; that AI-c-myc and -p53 are associated with prostate cancer progression and are potential markers of survival in Stage T(2-3)N(1-3)M(0) prostate cancer; and that lymph node metastases usually have similar or additional genetic changes compared with primary tumors, and multiple lymph node metastases usually have similar genetic changes.
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PMID:Loss of p53 and c-myc overrepresentation in stage T(2-3)N(1-3)M(0) prostate cancer are potential markers for cancer progression. 1179 39

This study examined the role of TGF-beta1 in human keratinocyte malignancy. Two carcinoma-derived human oral keratinocyte cell lines, BICR 31 and H314, were selected on the basis of their known resistance to TGF-beta1-induced G(1) arrest, the presence of wild type TGF-beta cell surface receptors and normal Ras. Smad 4 protein was undetectable in both cell lines, but Smad 2 and Smad 3 were expressed at levels comparable with a fully TGF-beta responsive cell line, and treatment of the cells with TGF-beta1 resulted in the phosphorylation of Smad 2. Treatment with exogenous TGF-beta1 resulted in a failure to induce transcription from an artificial Smad-dependent promoter and a failure to down-regulate c-myc, but resulted in an up-regulation of AP-1 associated genes (Fra-1, JunB and fibronectin). Transient transfection of Smad 4 into BICR 31 restored TGF-beta1-induced growth inhibition and Smad-dependent transcriptional activation. Protracted treatment of cells with exogenous TGF-beta1 resulted in the attenuation of cell growth in vitro. To over-express TGF-beta1, both cell lines were transfected with latent TGF-beta1 cDNA; neutralization studies of conditioned media demonstrated that whilst the majority of the peptide was in the latent form, a small proportion was present as the active peptide. Cells that over-expressed endogenous TGF-beta1 grew more slowly in vitro compared to both the vector-only controls and cells that did not over-express the peptide. Orthotopic transplantation of cells that over-expressed endogenous TGF-beta1 to the floor of the mouth in athymic mice resulted in marked inhibition of primary tumor formation compared to controls. Expression of a dominant-negative TGF-beta type II receptor in cells that over-expressed endogenous TGF-beta1 resulted in enhanced cell growth in vitro and diminished the tumor suppressor effect of the ligand in vivo, indicating that the endogenous TGF-beta1 was acting in an autocrine capacity. The results demonstrate that over-expression of endogenous TGF-beta1 in human malignant oral keratinocytes leads to growth inhibition in vivo and tumor suppression in vitro by mechanisms that are independent of Smad 4 expression and TGF-beta1-induced G(1) arrest.
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PMID:TGF-beta1 acts as a tumor suppressor of human malignant keratinocytes independently of Smad 4 expression and ligand-induced G(1) arrest. 1189 91

To form metastases, tumors must break from the primary tumor site, invade surrounding tissues, enter and survive within the circulation and ultimately colonize a distal tissue. Each of these steps requires the cooperative function of numerous proteins--proteins that facilitate angiogenesis (e.g., VEGF), cell survival (e.g., Bcl-2), invasion (e.g., MMPs), and autocrine growth stimulation (e.g., c-myc, cyclin D1). Although expression of these proteins is regulated at many levels by disparate stimuli, translation of these key malignancy-related proteins is regulated primarily by the activity of the mRNA cap-binding protein eIF-4E, the rate-limiting member of the eIF-4F translation initiation complex. By binding the cap structure at the 5' terminus of cellular mRNAs, eIF-4E recruits mRNAs to the eIF-4F complex, which then scans from the 5' cap through the untranslated region (5'UTR), unwinding secondary structure to reveal the translation initiation codon and to enable ribosome loading. Messenger RNAs with short unstructured 5' UTRs are more easily translated than mRNAs harboring lengthy, highly structured 5' UTRs, as these prohibit efficient scanning and start codon recognition. As such, the translation of these mRNAs, which typically encode proteins involved in angiogenesis (e.g., VEGF), tumor growth (cyclin D1) and survival (Bcl-2), is suppressed except when eIF-4E is engaged with the eIF-4F complex--a common event in many human and experimental cancers. This review focuses on the hypothesis that enhanced eIF-4E function contributes to metastatic progression by selectively upregulating the translation of key malignancy-related proteins that together conspire to drive the metastatic process.
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PMID:Translational control and metastatic progression: enhanced activity of the mRNA cap-binding protein eIF-4E selectively enhances translation of metastasis-related mRNAs. 1274 84

Although many reports suggest that aberrant regulation of cytokine signaling pathways via the interleukin-2 receptor (IL-2R) induces tumorigenic transformation, constitutively active IL-2R in tumors has not been reported. We searched for genomic alteration of the IL-2/15R beta-subunit gene (IL-2/15R beta) in cytokine-independent cell lines established from radiation-induced mouse thymic lymphomas. In the TL34 cell line and its primary tumor, one of the IL-2/15R beta alleles was rearranged by the insertion of an intracisternal A particle (IAP) retrotransposon. The IAP-IL2/15R beta chimeric gene expressed chimeric mRNA in which IAP-coding Gag-Pol mRNA was fused to IL-2/15R beta mRNA and coded for Gag-Pol-IL-2/15R beta chimeric protein. Forced expression of the Gag-Pol-IL-2/15R beta chimeric cDNA in a mouse cytotoxic T-cell line (CTLL-2) converted IL-2-dependent cell growth to IL-2-independent growth, suggesting that the chimeric protein activates some of the IL-2 signaling pathways necessary for cell proliferation. Downregulation of the expression of the Gag-Pol-IL-2/15R beta chimeric protein in TL34 by antisense RNA inhibited cell growth, and concomitantly reduced the level of c-myc protein. These results suggest that the Gag-Pol-IL-2/15R beta is a constitutively active form that transmits proliferative signals by expressing downstream target genes, including c-myc. Thus, we demonstrated that the chimeric receptor gene produced by the insertion of an IAP functions as an oncogene by providing IL-2-independent autonomous growth potential.
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PMID:Formation of an active form of the interleukin-2/15 receptor beta-chain by insertion of the intracisternal A particle in a radiation-induced mouse thymic lymphoma and its role in tumorigenesis. 1276 10

Transplantable tumor (KE) and clone cell (KE-F11) lines were established from a spontaneous malignant schwannoma found in an aged F344 rat. The primary tumor and KE tumors consisted of oval or spindle cells arranged in ill-defined bundles. Cultured KE-F11 cells exhibited polygonal or spindle configurations. Immunohistochemically, neoplastic cells in KE and KE-F11 reacted to vimentin, S-100 protein, neuron-specific enolase, myelin basic protein, and glial fibrillary acidic protein in varying degrees, indicating neurogenic features; occasional cells reacted to alpha-smooth muscle actin. Cells positive for lysosomal enzymes (acid phosphatase and non-specific esterase), and ED1 (rat macrophage specific) were observed in KE-F11, and electron microscopically, cells with many lysosomes were frequently present, indicating expression of macrophage-like phenotypes. Bioassay analysis revealed that KE-F11 cells produced high levels of nerve growth factor. DNA synthesis was inhibited by addition of transforming growth factor-beta1 (TGF-beta1), and Northern blot analysis revealed that expression of c-myc, a cell cycle-related immediate early gene, was depressed by TGF-beta1. Likely, TGF-beta1 is a factor capable of inhibiting cellular growth of Schwann cells. mRNA expression of the low-density lipoprotein receptor-related protein (LRP) was seen in KE-F11 cells by Northern blot analysis, and the level was decreased by lipopolysaccharide (LPS) treatment. LRP may be attributable to regulation of Schwann cell functions. KE-F11 cells seeded on laminin-coated dishes exhibited more extended cytoplasmic projections than on collagen type I-coated dishes. The present study provides evidence that biological properties of malignant schwannoma-derived cells might be affected by exogenous factors such as TGF-beta1, LPS and laminin. These tumor lines may be useful for studies on pathobiological characteristics of Schwann cells.
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PMID:Characterization of newly established tumor lines from a spontaneous malignant schwannoma in F344 rats: nerve growth factor production, growth inhibition by transforming growth factor-beta1, and macrophage-like phenotype expression. 1281 82


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