Prognostic significance of bcl-2, c-myc, survivin and tumor grade in synovial sarcoma

Demır, Derya; Yaman, Banu; Anacak, Yavuz; Keçeci, Burçin; Kandİloğlu, Gülşen

doi:10.5146/tjpath.2013.01221

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…Indeed, c-Myc is upregulated in a number of sarcomas including leiomyosarcoma, osteosarcoma, chondrosarcoma, synovial sarcoma, ARMS and EwS. [32][33][34][35][36][37][38][39] Myc is a basic helix-loop-helix zipper transcription factor that regulates its target genes by binding to a conserved E-box DNA sequence CACGTG. 40 It mainly exerts its effect on the cell cycle by transcriptionally activating cyclins and CDKs or by repressing p15 INK4b , p21 CIP1 , and p27 KIP1 .…”

Section: Alterations In Cell Cycle Regulatorsmentioning

confidence: 99%

Molecular mechanisms underpinning sarcomas and implications for current and future therapy

Damerell

Pepper

Prince

2021

Sig Transduct Target Ther

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Sarcomas are complex mesenchymal neoplasms with a poor prognosis. Their clinical management is highly challenging due to their heterogeneity and insensitivity to current treatments. Although there have been advances in understanding specific genomic alterations and genetic mutations driving sarcomagenesis, the underlying molecular mechanisms, which are likely to be unique for each sarcoma subtype, are not fully understood. This is in part due to a lack of consensus on the cells of origin, but there is now mounting evidence that they originate from mesenchymal stromal/stem cells (MSCs). To identify novel treatment strategies for sarcomas, research in recent years has adopted a mechanism-based search for molecular markers for targeted therapy which has included recapitulating sarcomagenesis using in vitro and in vivo MSC models. This review provides a comprehensive up to date overview of the molecular mechanisms that underpin sarcomagenesis, the contribution of MSCs to modelling sarcomagenesis in vivo, as well as novel topics such as the role of epithelial-to-mesenchymal-transition (EMT)/mesenchymal-to-epithelial-transition (MET) plasticity, exosomes, and microRNAs in sarcomagenesis. It also reviews current therapeutic options including ongoing pre-clinical and clinical studies for targeted sarcoma therapy and discusses new therapeutic avenues such as targeting recently identified molecular pathways and key transcription factors.

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Section: Alterations In Cell Cycle Regulatorsmentioning

confidence: 99%

Molecular mechanisms underpinning sarcomas and implications for current and future therapy

Damerell

Pepper

Prince

2021

Sig Transduct Target Ther

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“…erefore, the apoptosis of hepatocellular carcinoma cells was substantially enhanced in the DEN + IVIG group in contrast to the DEN + NS group. In addition, the Bcl-2 family indirectly controls cell-autonomous death by interacting with the proto-oncogene c-myc [24].…”

Section: Discussionmentioning

confidence: 99%

Intravenous Immunoglobulin Inhibits Liver Cancer Progression by Promoting p38MAPK-Associated Apoptosis

Lin

Liu

et al. 2022

Journal of Oncology

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Objective. The aim of this study is to explore the effect of intravenous immunoglobulin (IVIG) on the development of rat hepatocellular carcinoma and its possible molecular mechanism. Methods. Sixty adult male Sprague-Dawley (SD) rats were randomly divided into three groups: control, diethylnitrosamine(DEN) + normal saline(NS), and DEN + IVIG groups, with 20 rats in each group. The rats in the DEN + NS group and DEN + IVIG group were given DEN 0.2 g/kg intraperitoneal injection once on day 1 and then 0.05% DEN aqueous solution in drinking water to establish a rat liver cancer model. Immunoglobulin (IgG) was injected intraperitoneally into the DEN + IVIG group twice a week at the dose of 100 mg/kg, and saline was administered intraperitoneally into the control group at a 50 mg/kg dosage. The body weight of each group of rats was recorded twice a week. All treatments were maintained continuously for 12 weeks. After the intervention, the liver function indexes of rats were measured by a fully automated biochemical analysis instrument. The liver histopathology was observed by hematoxylin-eosin(HE) staining. Immunohistochemistry was used to detect c-myc protein expression, and Western blotting was used to determine p38MAPK and p-p38MAPK protein expressions, as well as apoptosis-related proteins such as Bcl-2, Bax, and cleaved caspase-3. Results. Compared with the rats in the DEN + NS group, rats in the DEN + IVIG group showed substantially higher body mass ( P < 0.05 ), higher survival rate ( P < 0.05 ), and lower liver function indexes ( P < 0.05 ). Few focal necrosis of cancer cells and few nuclear division were observed in the rats in the DEN + IVIG group. The rats in the DEN + NS group showed lamellar necrosis of cancer foci, destruction of normal liver lobular structure, and hepatocellular carcinoma cells. Immunohistochemical analysis results revealed that the expression of c-myc was reduced in the DEN + IVIG group ( P < 0.05 ), and Western blotting confirmed that the Bcl-2 expression was decreased ( P < 0.05 ), while Bax, p38 MAPK, p-p38 MAPK, and cleaved caspase-3 protein expressions were increased ( P < 0.05 ). Conclusion. IVIG prophylactic injection can delay tumor development and induce apoptosis in primary hepatocellular carcinoma in rats. The mechanism is connected to the activation of the p38MAPK signaling pathway by upregulating the level of cleaved caspase-3 and Bax proteins while downregulating the level of Bcl-2 and c-myc proteins.

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“…MYC expression in synovial sarcoma was previously reported to be inversely related to disease-free survival. Demir et al 45 showed that cases with MYC nuclear positivity of more than 5% of cells had a decreased survival time compared to negative cases, while Shen et al 46 demonstrated that MYC protein expression in more than 5% of cells correlated with a higher relapse rate. In the latter paper, MYC positivity was not statistically significantly correlated with Ki67 (MIB1) proliferation index.…”

Section: Discussionmentioning

confidence: 99%

“…Demir et al. 45 showed that cases with MYC nuclear positivity of more than 5% of cells had a decreased survival time compared to negative cases, while Shen et al. 46 demonstrated that MYC protein expression in more than 5% of cells correlated with a higher relapse rate.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Profile of MYC Protein in Pediatric Small Round Blue Cell Tumors

et al. 2017

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Deregulation of MYC oncoprotein in cancers can result from multiple oncogenic mechanisms. Although MYC translocations define Burkitt lymphoma and MYC protein expression is a poor prognostic factor in undifferentiated neuroblastomas, the distribution of MYC protein (c-MYC) across other pediatric small round blue cell tumors (SRBCT) has not been well characterized. We undertook this study to assess MYC protein expression in a large cohort of pediatric lymphomas, sarcomas, and other SRBCT. Tissue microarrays containing 302 SRBCT were successfully evaluated by immunohistochemistry using anti-MYC clone Y69, with nuclear positivity scored as 0%, 1%-25%, 26%-50%, 51%-75%, or 76%-100%. MYC protein staining of >50% of lesional cells was identified in 60% of Burkitt lymphomas, 50% of B lymphoblastic lymphomas, 33% of T lymphoblastic lymphomas, 31% of rhabdomyosarcomas, 33% of Ewing sarcomas, and 25% of soft tissue sarcomas, not otherwise specified. Only 14% of neuroblastomas showed >50% staining, and of these, if known, MYCN was not amplified. No cases of Wilms tumor, synovial sarcoma, or desmoplastic small round cell tumor had >50% staining. Recurrences and metastases often had the same percentage of MYC staining (15/30). In conclusion, MYC protein exhibited variable expression across and within pediatric SRBCT subtypes. Overall, these findings provide a baseline for MYC expression in pediatric SRBCT and suggest that there may be multiple mechanisms of MYC upregulation in these different neoplasms.

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Prognostic significance of bcl-2, c-myc, survivin and tumor grade in synovial sarcoma

Cited by 7 publications

References 29 publications

Molecular mechanisms underpinning sarcomas and implications for current and future therapy

Molecular mechanisms underpinning sarcomas and implications for current and future therapy

Intravenous Immunoglobulin Inhibits Liver Cancer Progression by Promoting p38MAPK-Associated Apoptosis

Immunohistochemical Profile of MYC Protein in Pediatric Small Round Blue Cell Tumors

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