Synuclein-γ (SNCG) may be a novel prognostic biomarker in uterine papillary serous carcinoma

Morgan, Jacqueline; Hoekstra, Anna V.; Chapman‐Davis, Eloise; Hardt, Jennifer; Kim, Julie; Buttin, Barbara M.

doi:10.1016/j.ygyno.2009.04.036

Cited by 28 publications

(26 citation statements)

References 17 publications

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“…And multivariable analyses showed that γ-synuclein was correlated with OS of the patients, which is the same as previous observations of an association between γ-synuclein expression and OS in uterine papillary serous carcinoma15 and is the same with Mhawech-Fauceglia,16 who considered that γ-synuclein protein expression is associated with poor outcome in endometrial adenocarcinoma and γ-synuclein expression as an independent prognostic factor in endometrial adenocarcinoma. Probably, due to the small number of the patients who got a recurrence (only 6 of 60 patients formed disease recurrence), when analysed the impact of γ-synuclein expression and clinicopathological features to the prognosis of DFS, no significant difference was found (data not shown), in contrast to previous studies 9 14.…”

Section: Discussionsupporting

confidence: 88%

“…The clinical follow-up studies confirmed that patients with γ-synuclein expression predict poor clinical outcome in breast cancer9 and in colon cancer 14. Morgan et al 15 demonstrated that γ-synuclein could be a novel biomarker as a prognostic tool and a therapeutic target in uterine papillary serous carcinoma. And Mhawech-Fauceglia16 considered that SNCG protein expression is associated with poor outcome in endometrial adenocarcinoma.…”

Section: Introductionmentioning

confidence: 90%

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An exploratory analysis of γ-synuclein expression in endometrioid endometrial cancer

et al. 2012

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ObjectiveThis study aims to investigate the expression of γ-synuclein in endometrioid endometrial carcinoma and assess if the γ-synuclein expression correlates with the aggression of the tumour and its prognostic value in endometrioid endometrial carcinoma.DesignThis retrospective study evaluated (60) specimens of the primary untreated endometrioid endometrial carcinoma and (12) normal endometrium tissues, and the expression of γ-synuclein was checked by immunohistochemistry. The correlation between γ-synuclein expression and the clinicopathological features of patients with endometrioid endometrial carcinoma was analysed, and SPSS V.13.0 software was used for statistical analysis.ResultsThe expression of γ-synuclein was positive in 48.3% (29/60) endometrioid endometrial carcinomas compared with the control group, and the difference was significant (p=0.001). The expression level of γ-synuclein in endometrioid endometrial carcinoma was closely associated with FIGO (International Federation of Gynecology and Obstetrics) stages, the depth of myometrial invasion and lymph nodes metastases (p<0.05), but not correlated with the histopathological grades, the patient's age and the expression of ER (estrogen receptor) and PR (progesterone receptor) (p>0.05). In univariate and multivariate analyses, the γ-synuclein expression was significantly associated with a shorter overall survival (95% CI 1.429 to 101.892, p=0.020).ConclusionsThis study suggests that the expression of γ-synuclein is expected to be a useful marker for endometrioid endometrial carcinoma invasion, metastasis and prognosis in endometrioid endometrial carcinoma.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 90%

An exploratory analysis of γ-synuclein expression in endometrioid endometrial cancer

et al. 2012

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“…I. Fidler (MD Anderson, Houston, TX) and Dr. A. Santin (Yale University, New Haven, CT) and have been characterized in previous reports. (30, 31). Each cell line was derived from a patient with USC.…”

Section: Methodsmentioning

confidence: 99%

Dual HER2 Targeting Impedes Growth of HER2 Gene–Amplified Uterine Serous Carcinoma Xenografts

Groeneweg

Hernández

Byron

et al. 2014

Clinical Cancer Research

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Purpose Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that commonly harbors HER2 gene amplification. We investigated the effectiveness of HER2 inhibition using lapatinib and trastuzumab in vitro and in xenografts derived from USC cell lines and USC patient derived xenografts (PDXs). Experimental Design Immunohistochemistry and fluorescence in situ hybridization were performed to assess HER2 expression in 42 primary USC specimens. ARK1, ARK2 and SPEC2 cell lines were treated with trastuzumab or lapatinib. Cohorts of mice harboring xenografts derived from ARK2 and SPEC2 cell lines and EnCa1 and EnCa2 primary human USC samples were treated with either vehicle, trastuzumab, lapatinib or the combination of trastuzumab and lapatinib. Acute and chronic post treatment tumor samples were assessed for downstream signaling alterations and examined for apoptosis and proliferation. Results HER2 gene amplification (24%) correlated significantly with HER2 protein over-expression (55%). All models were impervious to single agent trastuzumab treatment. Lapatinib decreased in vitro proliferation of all cell lines and in vivo growth of HER2 amplified xenografts (ARK2, EnCa1). In addition, dual therapy with trastuzumab and lapatinib resulted in significant anti-tumor activity only in ARK2 and EnCa1 tumors. Dual HER2 therapy induced on target alteration of downstream MAPK and PI3K pathway mediators only in HER2 amplified models, and was associated with increased apoptosis and decreased proliferation. Conclusions While trastuzumab alone did not impact USC growth, dual anti-HER2 therapy with lapatinib led to improved inhibition of tumor growth in HER2 amplified USC and may be a promising avenue for future investigation.

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“…diversified cancer types, including gastric cancer, but rarely expressed in tumor-matched non-neoplastic adjacent tissues (0.6%) [Shi et al, 2011;Liu et al, 2016]. These findings suggest that knockdown of SNCG expression may be an effective therapy in several cancer types [Morgan et al, 2009;Han et al, 2012]. However, studies examining the correlation of SNCG expression with gastric cancer biological effects in vitro and in vivo are missing or are limited only to the meta-analysis of gene and tissue expression profiles in gastric cancer.…”

Section: Silencing Of Sncg Inhibited the Growth Of Sgc7901 Cells In Vivomentioning

confidence: 99%

siRNA Targeting of the SNCG Gene Inhibits the Growth of Gastric Carcinoma SGC7901 Cells in vitro and in vivo by Downregulating the Phosphorylation of AKT/ERK

Fan¹,

Liu²,

Tian³

et al. 2018

Cytogenet Genome Res

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The aim of the study was to evaluate the effects of synuclein-γ (SNCG) silencing on gastric cancer SGC7901 cells and to elucidate the associated mechanisms. pGCSIL-lentiviral siRNA targeting of the SNCG gene was employed to inhibit SNCG expression. Several experiments such as quantitative real-time PCR, Western blotting, MTT, colony formation, migration assay, and flow cytometry were performed to investigate the biological behavior of infected SGC7901 cells. BALB/c nude mice were used as tumor xenograft models to assess the effects of SNCG silencing on tumor growth. Western blot analysis was carried out to determine the relative levels of AKT, p-AKT, ERK, and p-ERK expression. Our results showed that SNCG was overexpressed in SGC7901 cells as compared to normal gastric mucosal epithelial cells. SGC7901 cells transfected with SNCG siRNA demonstrated significantly decreased gastric cancer growth (p < 0.01), reduced cell migration, cell cycle arrest in the G0/G1 phase, promoted tumor cell apoptosis (p < 0.01), and inhibited tumorigenesis in xenograft animal models. Western blot analysis indicated that the protein levels of p-AKT and p-ERK were much lower in the SNCG siRNA group than in the control groups. The results of the present study suggest that SNCG siRNA plays a significant role in the proliferation, migration, and tumorigenesis of gastric cancer by downregulating the phosphorylation of AKT and ERK. RNA interference-mediated silencing of SNCG may provide an opportunity to develop a novel treatment strategy for gastric cancer.

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Synuclein-γ (SNCG) may be a novel prognostic biomarker in uterine papillary serous carcinoma

Cited by 28 publications

References 17 publications

An exploratory analysis of γ-synuclein expression in endometrioid endometrial cancer

An exploratory analysis of γ-synuclein expression in endometrioid endometrial cancer

Dual HER2 Targeting Impedes Growth of HER2 Gene–Amplified Uterine Serous Carcinoma Xenografts

siRNA Targeting of the <b><i>SNCG</i></b> Gene Inhibits the Growth of Gastric Carcinoma SGC7901 Cells in vitro and in vivo<b> </b>by Downregulating the Phosphorylation of AKT/ERK

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