TY - JOUR AB - BACKGROUND: Skin Cutaneous Melanoma (SKCM) is a highly aggressive malignant tumor with a significant increase in mortality upon metastasis. The molecular mechanisms driving melanoma progression remain largely unclear. Recent studies have highlighted the importance of epigenetic alterations, especially DNA methylation, in melanoma development. This study aims to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) in genome-wide profiles between primary and metastatic melanoma. METHODS: Gene expression profiling datasets GSE8401 and gene methylation profiling datasets GSE86355 were collected from the GEO database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were systematically identified. Integration of DEGs and DMGs yielded a set of MeDEGs, which subsequently underwent functional enrichment analysis. The protein-protein interaction (PPI) network was constructed using STRING and visualized using Cytoscape software. Survival analysis was used to select prognostic hub genes. In addition, 37 SKCM and 37 normal skin tissues from the First Affiliated Hospital of Soochow University (FAHSU) were collected for immunohistochemical (IHC) staining and evaluation. Furthermore, DNA methylation patterns of CDC6 were analyzed. To validate these findings, SKCM cell cultures were utilized to elucidate the expression and behavioral characteristics of CDC6. Additionally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted for CDC6. RESULTS: In our study, we discovered 120 hypomethylated-upregulated genes and 212 hypermethylated-downregulated genes. The hypomethylated-upregulated genes were notably associated with biological processes such as spindle assembly checkpoint signaling, mitotic spindle assembly, and negative regulation of mitotic metaphase/anaphase transition. Our pathway analysis revealed significant enrichment in pathways related to dilated cardiomyopathy, amino sugar metabolism, progesterone-mediated oocyte maturation, and chemical carcinogenesis. Conversely, hypermethylated-downregulated genes were found to be enriched in processes like epidermis development, keratinocyte differentiation, and skin development. Additionally, pathway analysis highlighted associations with estrogen signaling, Staphylococcus aureus infection, axon guidance, and arachidonic acid metabolism. Following the establishment of PPI networks and survival analysis, we identified 11 prognostic hub genes: CCNA2, CDC6, CDCA3, CKS2, DTL, HJURP, KRT5, KRT14, KRT15, KRT16, and NEK2. Notably, among the 11 hub genes, our findings indicate that CDC6 plays a pivotal role in enhancing the proliferation, migration, and invasion capabilities of melanoma cells in vitro. CONCLUSIONS: Our comprehensive genomic analyses reveal that genes with aberrant methylation exhibit differential expression during the transition from primary to metastatic melanoma. The identified genes, especially CDC6, which plays a crucial role in enhancing melanoma cell proliferation, migration, and invasion, provide valuable insights into potential methylation-based biomarkers. These findings could contribute significantly to advancing precision medicine in SKCM. AU - Liao, L.* AU - Han, W. AU - Shen, Y.* AU - Shen, G.* C1 - 71298 C2 - 56031 CY - One New York Plaza, Suite 4600, New York, Ny, United States TI - Comprehensive analysis of aberrantly methylated differentially expressed genes and validation of CDC6 in melanoma. JO - J. Cancer Res. Clin. Oncol. VL - 150 IS - 7 PB - Springer PY - 2024 SN - 0171-5216 ER - TY - JOUR AB - PURPOSE: In 2016, the University of Munich Molecular Tumor Board (MTB) was implemented to initiate a precision oncology program. This review of cases was conducted to assess clinical implications and functionality of the program, to identify current limitations and to inform future directions of these efforts. METHODS: Charts, molecular profiles, and tumor board decisions of the first 1000 consecutive cases (01/2016-03/2020) were reviewed. Descriptive statistics were applied to describe relevant findings. RESULTS: Of the first 1000 patients presented to the MTB; 914 patients received comprehensive genomic profiling. Median age of patients was 56 years and 58% were female. The most prevalent diagnoses were breast (16%) and colorectal cancer (10%). Different types of targeted or genome-wide sequencing assays were used; most of them offered by the local department of pathology. Testing was technically successful in 88%. In 41% of cases, a genomic alteration triggered a therapeutic recommendation. The fraction of patients receiving a tumor board recommendation differed significantly between malignancies ranging from over 50% in breast or biliary tract to less than 30% in pancreatic cancers. Based on a retrospective chart review, 17% of patients with an MTB recommendation received appropriate treatment. CONCLUSION: Based on these retrospective analyses, patients with certain malignancies (breast and biliary tract cancer) tend to be more likely to have actionable variants. The low rate of therapeutic implementation (17% of patients receiving a tumor board recommendation) underscores the importance of meticulous follow-up for these patients and ensuring broad access to innovative therapies for patients receiving molecular tumor profiling. AU - Heinrich, K.* AU - Miller-Phillips, L.* AU - Ziemann, F.* AU - Hasselmann, K.* AU - Rühlmann, K.* AU - Flach, M.* AU - Biro, D.* AU - von Bergwelt-Baildon, M.* AU - Holch, J.* AU - Herold, T.* AU - von Baumgarten, L.* AU - Greif, P.A.* AU - Jeremias, I. AU - Wuerstlein, R.* AU - Casuscelli, J.* AU - Spitzweg, C.* AU - Seidensticker, M.* AU - Renz, B.* AU - Corradini, S.* AU - Baumeister, P.* AU - Goni, E.* AU - Tufman, A.* AU - Jung, A.* AU - Kumbrink, J.* AU - Kirchner, T.* AU - Klauschen, F.* AU - Metzeler, K.H.* AU - Heinemann, V.* AU - Westphalen, C.B.* C1 - 65656 C2 - 52871 TI - Lessons learned: The first consecutive 1000 patients of the CCCMunichLMU Molecular Tumor Board. JO - J. Cancer Res. Clin. Oncol. PY - 2022 SN - 0171-5216 ER - TY - JOUR AB - Background Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are the most common malignant liver tumors in childhood. Both tumor types exhibit genetic and epigenetic alterations in the WNT/beta-catenin signaling pathway, which is a key regulator of liver progenitor cells in embryonic development. The tumors demonstrate a high rate of beta-catenin mutations and gene expression changes of several WNT antagonists. However, the role of the WNT inhibitory factor secreted frizzled-related protein 1 (SFRP1) has not been addressed in pediatric liver cancer so far. Results In our study, we investigated the gene expression level, DNA methylation status and functional relevance of SFRP1 in HB cell lines and in pediatric liver tumor patient samples. SFRP1 was downregulated due to DNA promoter methylation in all tested HB cell lines. Overexpression of SFRP1 in HB cell lines diminished tumor cell proliferation, colony formation and migration potential. In addition, the SFRP1-expressing HB cell lines showed reduced WNT/beta-catenin signaling pathway activity and decreased expression of WNT target genes. To evaluate the utility of SFRP1 as a biomarker in pediatric liver cancer, we determined the gene expression level and DNA methylation status of SFRP1 in 45 pediatric liver tumor patient samples. The correlation analysis of different clinical parameters and tumor characteristics revealed a significant correlation of reduced SFRP1 expression with the presence of mutant beta-catenin. The methylation status of SFRP1 was furthermore associated to a pediatric liver tumor type with HCC-like characteristics, TERT mutations and an older age at diagnosis. Conclusion Altogether, our data demonstrate that the epigenetic suppression of the WNT/beta-catenin antagonist SFRP1 has an important impact on the malignant behavior of HB cells. Although SFRP1 methylation is a common event in HCC-like pediatric liver tumors, its potential as a prognostic or diagnostic biomarker needs to be further investigated. AU - Regel, I.* AU - Eichenmüller, M.* AU - Mahajan, U.M.* AU - Hagl, B. AU - Benitz, S.* AU - Häberle, B.* AU - Vokuhl, C.* AU - von Schweinitz, D.* AU - Kappler, R.* C1 - 58637 C2 - 48361 CY - One New York Plaza, Suite 4600, New York, Ny, United States SP - 1153-1167 TI - Downregulation of SFRP1 is a protumorigenic event in hepatoblastoma and correlates with beta-catenin mutations. JO - J. Cancer Res. Clin. Oncol. VL - 146 IS - 5 PB - Springer PY - 2020 SN - 0171-5216 ER - TY - JOUR AB - BackgroundFirst-line rituximab therapy together with chemotherapy is the standard care for patients with advanced follicular B-cell lymphoma, as rituximab together with chemotherapy prolongs progression-free and overall survival (Herold et al. 2007; Marcus et al. 2005). However, as not all patient subgroups benefit from combined immuno-chemotherapy, we asked whether the microenvironment may predict benefit from rituximab-based therapy.DesignTo address this question, we performed a retrospective immunohistochemical analysis on pathological specimens of 18 patients recruited into a randomized clinical trial, where patients with advanced follicular lymphoma were randomized into either chemotherapy or immuno-chemotherapy with rituximab (Herold et al. 2007).ResultsWe show here that rituximab exerts beneficial effects, especially in the subgroup of follicular lymphoma patients with low intrafollicular CD3, CD5, CD8, and ZAP70 and high CD56 and CD68 expression.ConclusionRituximab may overcome immune-dormancy in follicular lymphoma in cases with lower intrafollicular T-cell numbers and higher CD56 and CD68 cell counts. As this was a retrospective analysis on a small subgroup of patients, these data need to be corroborated in larger clinical trials. AU - Budau, L.* AU - Wilhelm, C.* AU - Moll, R.* AU - Jäkel, J.* AU - Hirt, C.* AU - Dölken, G.* AU - Maschmeyer, G.* AU - Neubauer, E.* AU - Strauch, K. AU - Burchert, A.* AU - Herold, M.* AU - Neubauer, A.* C1 - 56550 C2 - 47101 CY - 233 Spring St, New York, Ny 10013 Usa SP - 2149-2156 TI - Low number of intrafollicular T cells may predict favourable response to rituximab-based immuno-chemotherapy in advanced follicular lymphoma: A secondary analysis of a randomized clinical trial. JO - J. Cancer Res. Clin. Oncol. VL - 145 IS - 8 PB - Springer PY - 2019 SN - 0171-5216 ER - TY - JOUR AB - Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal. Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total). During therapy, UA levels declined from normal values to hypouricemic values (all p < 0.001). Alongside hematopoietic recovery, UA serum levels returned to baseline values. During aplasia, UA levels remained low and started steadily increasing (defined as > two consecutive days, median one 2-day increase) at a median of 1 day before rising leukocytes in allogeneic HCT (p = 0.01) and together with leukocytes in autologous HCT (median one 2-day increase). During induction chemotherapy, a UA increase was also observed alongside rising leukocytes/neutrophils but also several times during aplasia (median 3 increases). Most HCT patients had no detectable leukocytes during aplasia, while some leukocytes remained detectable after induction therapy. No increase in UA levels was observed without concomitant or subsequent rise of leukocytes. Changes in UA serum levels can indicate incipient or remaining immunological activity after HCT or induction therapy. They may, therefore, help to differentiate between PGF and GF. AU - Haen, S.P.* AU - Eyb, V.* AU - Mirza, N.* AU - Naumann, A.* AU - Peter, A. AU - Loeffler, M.W.* AU - Faul, C.* AU - Vogel, W.* AU - Bethge, W.A.* AU - Rammensee, H.-G.* AU - Kanz, L.* AU - Heni, M. C1 - 51027 C2 - 42908 CY - New York SP - 759-771 TI - Uric acid as a novel biomarker for bone-marrow function and incipient hematopoietic reconstitution after aplasia in patients with hematologic malignancies. JO - J. Cancer Res. Clin. Oncol. VL - 143 IS - 5 PB - Springer PY - 2017 SN - 0171-5216 ER - TY - JOUR AB - PURPOSE: The therapeutic activity of the epidermal growth factor receptor (EGFR)-directed monoclonal antibody cetuximab in gastric cancer is currently being investigated. Reliable biomarkers for the identification of patients who are likely to benefit from the treatment are not available. The aim of the study was to examine the drug sensitivity of five gastric cancer cell lines towards cetuximab as a single agent and to establish predictive markers for chemosensitivity in this cell culture model. The effect of a combination of cetuximab with chemotherapy was compared between a sensitive and a nonsensitive cell line. METHODS: EGFR expression, activation and localisation, the presence and subcellular localisation of the cell adhesion molecule E-cadherin as well as MET activation were examined by Western blot analysis, flow cytometry and immunofluorescence staining. Cells were treated with varying concentrations of cetuximab and cisplatin and 5-fluorouracil in tumour-relevant concentrations. The biological endpoint was cell viability, which was measured by XTT cell proliferation assay. Response to treatment was evaluated using statistical methods. RESULTS: We assessed the activity of cetuximab in five gastric cancer cell lines (AGS, KATOIII, MKN1, MKN28 and MKN45). The viability of two cell lines, MKN1 and MKN28, was significantly reduced by cetuximab treatment. High EGFR expression and low levels of receptor activation were associated with cetuximab responsiveness. MET activation as well as mutations of KRAS and CDH1 (gene encoding E-cadherin) was associated with cetuximab resistance. CONCLUSION: These data indicate that our examinations may be clinically relevant, and the candidate markers should therefore be tested in clinical studies. AU - Heindl, S.* AU - Eggenstein, E.* AU - Keller, S.* AU - Kneissl, J.* AU - Keller, G.* AU - Mutze, K.* AU - Rauser, S. AU - Gasteiger, G.* AU - Drexler, I.* AU - Hapfelmeier, A.* AU - Höfler, H. AU - Luber, B.* C1 - 7523 C2 - 29782 SP - 843-858 TI - Relevance of MET activation and genetic alterations of KRAS and E-cadherin for cetuximab sensitivity of gastric cancer cell lines. JO - J. Cancer Res. Clin. Oncol. VL - 138 IS - 5 PB - Springer PY - 2012 SN - 0171-5216 ER - TY - JOUR AU - Werner, M.* AU - Becker, K.F.* AU - Keller, G.* AU - Höfler, H. C1 - 21802 C2 - 19991 SP - 207-216 TI - Gastric adenocarcinoma : Pathomorphology and molecular pathology. JO - J. Cancer Res. Clin. Oncol. VL - 127 PY - 2001 SN - 0171-5216 ER - TY - JOUR AB - Cisplatin-resistant mouse fibrosarcoma cells, SSK-R, were isolated after short and low-dose drug treatment of the sensitive SSK cells in vitro. These SSK-R sublines exhibit up to sevenfold cisplatin resistance and are characterized mainly by an increased metallothionein content. Loss of drug resistance after about 140-180 cell divisions in drug-free medium coincides with loss of metallothionein content. The glutathione level is the same in the sensitive and resistant sublines; inhibition of glutathione synthesis by buthionine sulphoximine enhances the sensitivity in both cells lines by a factor of 2.7. The resistant sublines are not cross-resistant to radiation; a radiation exposure followed immediately by cisplatin treatment results in an additive effect. The cellular cisplatin content is slightly reduced in SSK-R2 cells and it remains at this level also upon loss of drug sensitivity. AU - Eichholtz-Wirth, H. AU - Born, R. AU - Reidel, G.* AU - Hietel, B. C1 - 40305 C2 - 40076 SP - 227-233 TI - Transient cisplatin-resistant murine fibrosarcoma cell characterized by increased metallothionein content. JO - J. Cancer Res. Clin. Oncol. VL - 119 IS - 4 PY - 1993 SN - 0171-5216 ER - TY - JOUR AU - Issels, R.D. AU - Mittermüller, J. AU - Gerl, A. AU - Simon, W. AU - Ortmaier, A. AU - Denzlinger, C. AU - Sauer, H. AU - Wilmanns, W. C1 - 18510 C2 - 11660 SP - 141-147 TI - Improvement of Local Control by Regional Hyperthermia Combined with Systemic Chemotherapy (ifosfamide plus etoposide) in advanced Sarcomas: Updated Report on 65 Patients. JO - J. Cancer Res. Clin. Oncol. VL - 117 (Suppl.IV) PY - 1991 SN - 0171-5216 ER - TY - JOUR AU - Mezger, J. C1 - 40803 C2 - 0 SP - 502 TI - Letter to the editors. JO - J. Cancer Res. Clin. Oncol. VL - 117 IS - 5 PY - 1991 SN - 0171-5216 ER - TY - JOUR AU - Hueltner, L. AU - Welle, M. AU - Strauss, P.G. AU - Moeller, J. AU - Doermer, P. C1 - 18395 C2 - 11597 TI - Consecutive Stages on Neoplastic Transformation in Mouse Bone Marro-derived Mast Cells. JO - J. Cancer Res. Clin. Oncol. PY - 1990 SN - 0171-5216 ER - TY - JOUR AU - Polack, A. AU - Hergenhan, M. AU - Kloz, U. AU - Hecker, E. AU - Bornkamm, G.W. C1 - 18352 C2 - 11543 TI - Description of an EBV Derived System Detecting Tumorpromoters of the Diterpene Ester Type with High Sensitivity. JO - J. Cancer Res. Clin. Oncol. PY - 1990 SN - 0171-5216 ER - TY - JOUR AU - Zimber-Strobl, U. AU - Suentzenich, K.-O. AU - Falk, M. AU - Laux, G. AU - Cordier, M. AU - Calender, A. AU - Billaud, M. AU - Lenoir, G.M. AU - Busson, P. AU - Tursz, T. AU - Bornkamm, G.W. C1 - 18346 C2 - 11537 TI - Analysis of EBV-terminal Protein Gene Expression Provides Evidence for Integration of Viral DNA Into the Host Genome in Burkitt Lymphoma and Nasapharyngeal Carcinoma Cells. JO - J. Cancer Res. Clin. Oncol. PY - 1990 SN - 0171-5216 ER - TY - JOUR AB - A total of 11 i.p. injections of 1 mg/kg 5-azacytidine given within 21 weeks induced a sudden outbreak of a leukemia-like disease in female CBA mice about 2 weeks after the last injection. The outbreak of disease was highly synchronous; 68% of animals who had survived the treatment period succumbed within a period of 5 days, 2/3 of them on a single day. The lesion had a characteristic form commonly presenting as a result of hemorrhagic effusion in the thoracic and/or abdominal cavities, associated with diffuse infiltration of lymphatic and fatty tissue by lymphoblasts. It appears that a critical combination of factors was responsible for the unexpected appearance of the lesion. Female BALB/c mice treated identically were not affected. The factors indicating that the lesion was induced by an epigenetic mechanism are discussed. AU - Luz, A. AU - Murray, A.B. C1 - 42616 C2 - 36446 SP - 525-527 TI - Sudden outbreak of a leukemia-like lesion in female CBA mice after repeated injections of 5-azacytidine. JO - J. Cancer Res. Clin. Oncol. VL - 114 IS - 5 PY - 1988 SN - 0171-5216 ER - TY - JOUR AB - During x-ray-induced development of malignant lymphomas in mice their urinary excretion of eight modified nucleosides was monitored and the values were compared to the results of the histological examination of the animals at time of their sacrifice. It was found that the pathologically augmented excretion of modified nucleosides begins as much as several weeks before the malignant lymphomas can be diagnosed clinically. Thus some mice had increased levels of modified nucleosides even 10 weeks before sacrifice, though at the time of sacrifice the histological investigation reveled only some small foci of reticulum cell neoplasm in their spleen. It is therefore stressed that the usefulness of the determination of urinary modified nucleosides as an early noninvasive screening test for cancer in man and as an in vivo carcinogenicity test should be evaluated. AU - Thomale, J.* AU - Luz, A. AU - Nass, G.S.* C1 - 41734 C2 - 40331 SP - 302-307 TI - Excretion of modified nucleosides during development of malignant lymphomas in mice after whode body irradiation. JO - J. Cancer Res. Clin. Oncol. VL - 108 IS - 3 PY - 1984 SN - 0171-5216 ER - TY - JOUR AB - Electron microscopic investigation of 16 cases of human bone tumor revealed the presence of intranuclear vermicellar bodies (IVB) in cells of two osteosarcomas and one ossifying fibroma. The spherical nuclear inclusions consisted of electron-dense, interwoven, threadlike structures measuring approximately 20-30 nm in diameter. The nature and significance of the IVB remain obscure at present. AU - Marquart, K.H. C1 - 41452 C2 - 38661 SP - 74-76 TI - Intranuclear vermicellar bodies in human osteosarcoma and ossifying fibroma cells. JO - J. Cancer Res. Clin. Oncol. VL - 106 IS - 1 PY - 1983 SN - 0171-5216 ER - TY - JOUR AB - The promoting activity of the commercial PCB mixture Clophen A 50 on preneoplastic, enzymealtered islands in rat liver was investigated. Female Sprague-Dawley rats, 3 and 6 weeks old, were pretreated with nitrosamines for island initiation. There-after Clophen A 50 was administered repeatedly. Island development was examined between 2 and 12 weeks. Clophen A 50 by itself initiated few enzyme-altered islands, indicating a weak carcinogenicity. In Clophen A 50-treated adult rats, the majority of nitrosamine-initiated islands persisted. Without Clophen A 50 more than 80% of the islands disappeared between 6 and 12 weeks. Moreover, PCBs caused a striking increase in island number and total area during the last 2 weeks. In weanlings, islands persisted with or without the promoting stimulus. However, treatment with Clophen A 50 caused an earlier appearance and a higher number and total area of islands. The increase in the yield of DEN-initiated islands in both age groups is suggested to be due to the promotion of initiated but dormant cells. By pretreatment with N-NM instead of DEN, a shift to larger islands was observed additionally. The data indicate that weanlings are highly susceptible to initiation and promotion and may thus provide a sensitive tool to screen for tumor initiating and promoting agents. AU - Oesterle, D. AU - Deml, E. C1 - 41892 C2 - 38483 SP - 141-147 TI - Promoting effect of polychlorinated biphenyls on development of enzyme-altered islands in livers of weanling and adult rats. JO - J. Cancer Res. Clin. Oncol. VL - 105 IS - 2 PY - 1983 SN - 0171-5216 ER - TY - JOUR AB - Fractionated X-irradiation of pregnant mice was performed either during late organogenesis (gestational days 11-13), during the early fetal period (g.d. 14-16), or during both periods (g.d. 11-16). The offspring were observed for 39 months. A significant increase of ovary tumor frequency was observed with 3x1.2 Gy, applied either in late organogenesis or in the early fetal period. Lower X-irradiation doses were ineffective in these periods with respect to ovary tumor development. A sharp increase in ovary tumor frequency resulted after irradiation with 6x0.8 Gy or 6x1.2 Gy. The highest incidence of ovary cysts was observed after 3x1.0 Gy or 3x1.2 Gy on g.d. 11-13, while the frequency of these cysts was lowest in the animals irradiated six times, which, however, showed a high ovary tumor frequency. Autoradiography of the fetal ovaries either 1 or 6 days after irradiation at the late organogenesis stage revealed a persistent depression of this organ's proliferation rate throughout pregnancy. This may be consistent with the low tumor inducibility after X-irradiation in this period. AU - Schmahl, W.G. AU - Kriegel, H. C1 - 41640 C2 - 38147 SP - 65-74 TI - Ovary tumors in NMRI mice subjected to fractionated X-irradiation during fetal development. JO - J. Cancer Res. Clin. Oncol. VL - 98 IS - 1 PY - 1980 SN - 0171-5216 ER - TY - JOUR AB - Long-term animal experiments with prenatally X-irradiated offspring have so far not unequivocally settled the question of elevated tumor susceptibility. We have pursued this problem further in a modified 2-stage carcinogenesis-Berenblum/Mottram experiment. Prenatal X-irradiation of mice has thus been regarded as a possible initiator stimulus, with a postnatal promotion stimulus being given by applying the phorbol ester TPA to the offsprings' skin. This treatment has, however, not produced a higher tumor yield, neither of the skin nor of the internal organs, than that produced by X-irradiation in utero alone. This failure seems partly due to the dysplastic nature of the epidermis of prenatally X-irradiated mice, which also fails to respond to TPA application by way of hyperplasia or by an increased inflammation tendency and ulcer formation. We suggest that a decrease in prostaglandin synthesis after prenatal X-irradiation is an important factor for the unchanged tumor susceptibility, especially of the skin. AU - Schmahl, W.G. AU - Kriegel, H. AU - Senft, E. C1 - 42509 C2 - 38144 SP - 109-117 TI - Can prenatal X-irradiation in mice act as an initiator stimulus in a modified 2-stage Berenblum/Mottram experiment with postnatal promotion with phorbol ester TPA?. JO - J. Cancer Res. Clin. Oncol. VL - 97 IS - 2 PY - 1980 SN - 0171-5216 ER - TY - JOUR AB - Eight cell lines were established from murine osteosarcomas induced in vivo with the radionuclides 224Ra and 227Th. They have been compared by light and electron microscopy, by karyology, and by their growth properties. The morphology, the growth pattern, and the ability to induce tumors in mice indicate that five of them are tumor cell lines. Chromosome studies demonstrated that the five cell lines have marker chromosomes. The other cell lines only showed some criteria generally used to score for transformation of fibroblasts and they may be derived from stromal cells. All cell lines release virus particles in the culture fluid which have the typical properties of RNA tumor viruses. They possess C-type morphology, a density of 1.16--1.18 g/cm3, a 60--70 S RNA, a RNA dependent DNA polymerase and they induce syncytia in rat XC cells. The possible significance of these virus particles in radiation osteosarcomagenesis is discussed. AU - Erfle, V. AU - Schulte-Overberg, S. AU - Marquart, K.H. AU - Adler, I.-D. AU - Luz, A. C1 - 27602 C2 - 32761 SP - 149-162 TI - Establishment and characterization of C-type RNA virus-producing cell lines from radiation-induced murine osteosarcomas. JO - J. Cancer Res. Clin. Oncol. VL - 94 IS - 2 PB - Springer PY - 1979 SN - 0171-5216 ER -