scholarly journals Differential Expression of Glycolysis-Related Proteins in Follicular Neoplasms versus Hürthle Cell Neoplasms: A Retrospective Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Hye Min Kim ◽  
Ja Seung Koo
Keyword(s):  
Immunohistochemical Staining ◽  
Tissue Microarrays ◽  
Extrathyroidal Extension ◽  
Clinical Implications ◽  
Hexokinase Ii ◽  
Large Tumor ◽  
Expression Levels ◽  
Glut 1 ◽  
Hürthle Cell ◽  
Related Proteins

Purpose. Although currently classified as variants of follicular neoplasms (FNs), Hürthle cell neoplasms (HCNs) exhibit distinct biological characteristics. Hence, the metabolism of both neoplasms may also be different. The aims of this study were to investigate and compare the expression of glycolysis-related proteins in HCNs and FNs and to determine the clinical implications of such expression. Methods. Tissue microarrays were constructed with 265 samples of FNs (112 follicular carcinomas (FCs) and 153 follicular adenomas (FAs)) as well as 108 samples of HCNs (27 Hürthle cell carcinomas (HCCs) and 81 Hürthle cell adenomas (HCAs)). Immunohistochemical staining for the glycolysis-related molecules Glut-1, hexokinase II, CAIX, and MCT4 was performed. Results. The expression levels of Glut-1, hexokinase II, CAIX, and MCT4 were significantly higher in HCNs than in FNs (p<0.001). Glut-1, hexokinase II, CAIX, and MCT4 expression levels were highest in HCC, followed by HCA, FC, and FA (all p<0.001). In HCC, hexokinase II positivity was associated with large tumor size (>4 cm) (p=0.046), CAIX positivity with vascular invasion (p=0.005), and MCT4 positivity with extrathyroidal extension (p=0.030). Conclusion. The expression levels of the glycolysis-related proteins Glut-1, hexokinase II, CAIX, and MCT4 were higher in HCNs than in FNs and in HCCs than in HCAs.

scholarly journals Expression of Autophagy-Related Proteins in Hürthle Cell Neoplasm Is Different from That in Follicular Neoplasm

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yoon Jin Cha ◽  
Hye Min Kim ◽  
Ja Seung Koo
Keyword(s):  
Western Blot ◽  
Immunohistochemical Staining ◽  
Beclin 1 ◽  
Follicular Neoplasm ◽  
Clinical Implications ◽  
Positive Staining ◽  
Hürthle Cell ◽  
Cell Neoplasm ◽  
Expression Rate ◽  
Related Proteins

Purpose. We aimed to evaluate expression of autophagy-related proteins in Hürthle cell neoplasm (HCN) and follicular neoplasm (FN) and assess the clinical implications. Methods. 265 FNs (112 follicular carcinomas and 153 follicular adenomas) and 108 HCNs (27 Hürthle cell carcinomas and 81 Hürthle cell adenomas) were made into a tissue microarray. Immunohistochemical staining and Western blot for autophagy-related proteins (beclin-1, light chain (LC) 3A, LC3B, p62, and BNIP3) were performed, and the results were statistically analyzed. Results. A higher expression rate of beclin-1, LC3B, p62, and BNIP3 was found in HCN than in FN (P<0.001). The expression rate of beclin-1, LC3B, p62, and BNIP3 was the highest in HCCs followed by HCAs, FCs, and FAs in that order (P<0.001). HCCs were positive for the largest number of autophagy-related proteins followed by HCAs, FCs, and FAs (P<0.001), and most of the positive markers identified in HCCs were the high autophagy type (P<0.001), defined by positive staining for three or more of the five autophagy-related proteins. Conclusion. The autophagy-related proteins, beclin-1, LC3A, LC3B, p62, and BNIP3, were more frequently expressed in HCNs than in FNs, and HCCs showed the highest expression rate.

Expression of Glucose Metabolism-Related Proteins in Adrenal Neoplasms

Pathobiology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Eun Kyung Kim ◽  
Hye Min Kim ◽  
Ja Seung Koo
Keyword(s):  
Prognostic Factors ◽  
Glucose Metabolism ◽  
Expression Patterns ◽  
Univariate Analysis ◽  
Hexokinase Ii ◽  
Expression Levels ◽  
Adrenal Cortical Adenoma ◽  
Adrenal Neoplasms ◽  
Cox Analysis ◽  
Related Proteins

<b><i>Purpose:</i></b> The aim of this study was to investigate the expression patterns of glucose metabolism-related proteins and their clinicopathologic implications in adrenal cortical neoplasms (ACN) and pheochromocytoma (PCC). <b><i>Methods:</i></b> Immunohistochemical staining was performed to evaluate glucose metabolism-related proteins (GLUT1, CAIX, hexokinase II, G6PDH, PHGDH, and SHMT1) in 132 ACN cases (115 adrenal cortical adenoma [ACA] and 17 adrenal cortical carcinoma [ACC]) and 189 PCC cases. <b><i>Results:</i></b> Expression levels of GLUT1 in tumor cells ([T]; <i>p</i> &#x3c; 0.001), GLUT1 in stromal cells ([S]; <i>p</i> &#x3c; 0.001), G6PDH (<i>p</i> &#x3c; 0.001), and SHMT1 (<i>p</i> = 0.002) were higher in ACN than in PCC. GLUT1 (T; <i>p</i> = 0.045) and PHGDH (<i>p</i> = 0.043) levels were higher in ACC than in ACA. In a univariate analysis of ACN, GLUT1 (T; <i>p</i> = 0.017), CAIX (S; <i>p</i> = 0.003), and PHGDH (<i>p</i> = 0.009) levels were correlated with a shorter overall survival (OS). GLUT1 (T; <i>p</i> = 0.001) and PHGDH (<i>p</i> &#x3c; 0.001) were related to a shorter OS in PCC. GLUT1 (T) positivity (<i>p</i> = 0.043) in ACN predicted a poor OS in a multivariate Cox analysis. In PCC, high GAPP score (<i>p</i> = 0.026), GLUT1 (T; <i>p</i> = 0.002), and PHGDH (<i>p</i> &#x3c; 0.001) were independent prognostic factors for poor OS. <b><i>Conclusions:</i></b> The adrenal gland tumors ACN and PCC had different expression patterns of glucose metabolism-related proteins (GLUT1, G6PDH, and SHMT1), with higher expression levels in ACN than in PCC. GLUT1 and PHGDH were significant prognostic factors in these adrenal neoplasms.

scholarly journals Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast Phyllodes Tumor

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hye Min Kim ◽  
Yu Kyung Lee ◽  
Ja Seung Koo
Keyword(s):  
Overall Survival ◽  
Immunohistochemical Staining ◽  
Univariate Analysis ◽  
Phyllodes Tumor ◽  
Tissue Microarrays ◽  
Histologic Grade ◽  
Cancer Associated Fibroblast ◽  
Stromal Component ◽  
Clinicopathologic Parameters ◽  
Related Proteins

Purpose. The purpose of this study was to investigate the expression of cancer-associated fibroblast- (CAF-) related proteins and the implications in breast phyllodes tumor (PT).Methods. Tissue microarrays of 194 PT cases (151 benign PT, 27 borderline PT, and 16 malignant PT) were constructed. We performed immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4-hydroxylase, FAPα, S100A4, PDGFRα/β, and NG2) and analyzed the results according to clinicopathologic parameters.Results. Expression of PDGFRαand PDGFRβin the stromal component increased with increasing histologic grade of PT (p=0.003andp=0.034, resp.). Among clinicopathologic parameters, only expression of FAPαin stroma was associated with distant metastasis (p=0.002). In univariate analysis, stromal expression of PDGFRαwas associated with shorter overall survival (p=0.002). In Cox multivariate analysis, stromal overgrowth and PDGFRαstromal positivity were associated with shorter overall survival (p=0.006andp=0.050, resp.). Furthermore, expression of PDGFRβin stroma was associated with shorter overall survival in patients with malignant PT (p=0.041).Conclusion. Stromal expression of PDGFRαand PDGFRβincreased with increasing histologic grade of PT. In addition, PDGFR stromal positivity was associated with shorter overall survival. These results suggest that CAFs are associated with breast PT progression.

scholarly journals A PCR-based expression signature of malignancy in follicular thyroid tumors

2007 ◽  
Vol 14 (2) ◽  
pp. 381-391 ◽  
Author(s):  
Theodoros Foukakis ◽  
Arief Gusnanto ◽  
Amy YM Au ◽  
Anders Höög ◽  
Weng-Onn Lui ◽  
...  
Keyword(s):  
High Risk ◽  
Gene Selection ◽  
Thyroid Neoplasms ◽  
Thyroid Tumors ◽  
Large Tumor ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Expression Levels ◽  
High Risk Disease ◽  
Follicular Thyroid Tumors

The diagnosis of follicular thyroid carcinoma (FTC) in the absence of metastasis can only be established postoperatively. Moreover, high-risk FTCs are often not identifiable at the time of diagnosis. In this study, we aimed to identify transcriptional markers of malignancy and high-risk disease in follicular thyroid tumors. The expression levels of 26 potential markers of malignancy were determined in a panel of 75 follicular thyroid tumors by a TaqMan quantitative RT-PCR approach. Logistic regression analysis (LRA) was used for gene selection and generation of diagnostic and prognostic algorithms. An algorithm based on the expression levels of five genes (TERT, TFF3, PPARγ, CITED1, and EGR2) could effectively predict high-risk disease with a specificity of 98.5%. The metastatic potential could be predicted in all four cases with apparently benign or minimally invasive (MI) disease at the time of diagnosis, but poor long-term outcome. In addition, a second model was produced by implementing two genes (TERT and TFF3), which was able to distinguish adenomas from de facto carcinomas. When this model was tested in an independent series of atypical adenomas (AFTA) and MI-FTCs, 16 out of 17 AFTAs were classified as ‘benign’, while MI-FTCs with vascular invasion (sometimes referred to as ‘moderately invasive’) and/or large tumor size tended to classify in the ‘malignant’ group. The reported models can be the foundation for the development of reliable preoperative diagnostic and prognostic tests that can guide the therapeutic approach of follicular thyroid neoplasms with indeterminate cytology.

scholarly journals Long Noncoding RNA CTBP1-AS Regulates Ovarian Granulosa Cells Proliferation and Autophagy and Participates in Polycystic Ovary Syndrome

2021 ◽  
Author(s):  
Kaixuan Sun ◽  
Yinling Xiu ◽  
Jianbo Song ◽  
Yuexin Yu
Keyword(s):  
Granulosa Cells ◽  
Peripheral Blood ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Polycystic Ovary ◽  
Blood Leukocytes ◽  
Expression Levels ◽  
Ovarian Granulosa Cells ◽  
Related Proteins ◽  
Ovarian Syndrome

Abstract ObjectiveThis study aims to investigate the expression of long noncoding RNA CTBP1-AS in patients with polycystic ovarian syndrome (PCOS) and its effects on the proliferation and autophagy of ovarian granulosa cells. MethodsReal-time polymerase chain reaction assay was used to analyze the expression levels of CTBP1-AS in peripheral blood leukocytes of 40 PCOS patients and 40 non-PCOS women and the CTBP1-AS expression in ovarian granulosa cells and transfect ovarian granulosa cells with pcDNA3.1-CTBP1-AS and si-CTBP1-AS, respectively. Consequently, the CCK-8 kit was used to analyze the effect of CTBP1-AS on the proliferation of ovarian granulosa cells. Moreover, Western blotting was used to detect the expression levels of autophagy-related proteins LC3II/I and P62. ResultThe CTBP1-AS expression in the peripheral blood of PCOS patients was higher compared with non-PCOS patients (P < 0.05). Furthermore, the CTBP1-AS expression of ovarian granulosa cells in PCOS patients was higher compared with non-PCOS patients (P < 0.05). Consequently, CTBP1-AS overexpression in ovarian granulosa cells promotes the proliferation of ovarian granulosa cells and autophagy levels (P < 0.05). The CTBP1-AS expression interference in ovarian granulosa cells can inhibit the proliferation of ovarian granulosa cells and autophagy levels (P < 0.05). ConclusionThe CTBP1-AS expression in peripheral blood and ovarian granulosa cells of PCOS patients significantly increased, and CTBP1-AS could promote the proliferation of ovarian granulosa cells and the level of autophagy.

scholarly journals Expression levels of caspase-3 and gasdermin E and their involvement in the occurrence and prognosis of lung cancer

2021 ◽  
Author(s):  
yuanli huang ◽  
GuangHui Zhang ◽  
Qing Zhu ◽  
Xia Wu ◽  
LIGao Wu
Keyword(s):  
Lung Cancer ◽  
Caspase 3 ◽  
Clinical Stage ◽  
The Body ◽  
Caspase 8 ◽  
Survival Prognosis ◽  
Expression Levels ◽  
Protein Levels ◽  
Normal Tissues ◽  
Related Proteins

Abstract Background Pyroptosis plays a dual role in the development of cancer and malignancy, and as such, may potentially be a new target for cancer treatment. However, the inflammatory response to pyroptosis may have adverse effects on the body. The roles of gasdermin E (GSDME), caspases, and related proteins associated with pyroptosis in cancer remain controversial. This study aimed to explore whether the expression levels of caspase-3 and GSDME affect the clinical stage, pathological grade, and survival prognosis of patients with lung cancer. Methods We examined the protein levels of GSDME, caspase-3, caspase-8, and caspase-9 in lung tissues from 100 patients with lung cancer by using immunohistochemistry. Results We found that GSDME, caspase-3, and caspase-8 were more highly expressed in the tumor tissues than in the adjacent normal tissues. Moreover, we found that GSDME could serve as a prognostic factor because there was a positive correlation between its expression level and the postoperative survival rate of patients with lung cancer. Conclusions GSDME may be an independent factor affecting the prognosis of patients with lung cancer. However, the role of GSDME and its related proteins in cancer requires further research.

scholarly journals SPOP Could Play a Potential Inhibitory Role in Human Renal Cell Carcinoma

2021 ◽  
Author(s):  
zhi chen ◽  
Zuan Li ◽  
Deyong Nong ◽  
Ximing Li ◽  
Guihai Huang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Immunohistochemical Staining ◽  
Human Renal Cell Carcinoma ◽  
Expression Levels ◽  
Normal Tissues ◽  
Proliferation And Apoptosis

Abstract Background: SPOP, a substrate adaptor of Cul3 ubiquitin ligase, plays crucial roles in solid neoplasms by promoting the ubiquitination and degradation of substrates. Limited studies have shown that SPOP is overexpressed in human renal cell carcinoma (RCC) tissue. However, the exact role of SPOP in RCC remains unclear and needs to be further elucidated. The present study showed that SPOP was expressed at different levels in different RCC cell lines. The purpose of this study was to explore the roles of SPOP in the biological features of RCC cells and determine the expression levels of SPOP in human tissue microarrays (TMAs) and kidney tissues.Methods: Here, SPOP was overexpressed by lentiviral vector transfection in ACHN and Caki-1 cells, and SPOP was knocked down in Caki-2 cells with similar transfection methods. The transfection efficiency was evaluated by quantitative PCR and western blotting analyses. The role of SPOP in the proliferation, migration, invasion and apoptosis of cell lines was determined by the MTT, wound-healing, Transwell and flow cytometry assays. Moreover, the cells were treated with different drug concentrations in proliferation and apoptosis assays to investigate the effect of sunitinib and IFN-α2b on the proliferation and apoptosis of SPOP-overexpressing cells and SPOP-knockdown RCC cells. Finally, immunohistochemical staining of SPOP was performed in kidney tissues and TMAs, which included RCC tissues and corresponding adjacent normal tissues.Results: Overexpression of SPOP inhibited cell proliferation, migration and invasion and increased cell apoptosis. Interestingly, sunitinib and IFN-α2b at several concentrations increased the proliferation inhibitory rate and total apoptosis rate of cells overexpressing SPOP. The findings of the present study showed that the SPOP protein was significantly expressed at low levels in most clear cell RCC (ccRCC) tissues and at relatively high levels in the majority of adjacent normal tissues and kidney tissues. Kaplan-Meier survival analysis showed that there was no statistically significant difference in cumulative survival based on the data of different SPOP expression levels in TMA and patients.Conclusions: In contrast to previous studies, our findings demonstrated that overexpression of SPOP might suppress the progression of RCC cells, which was supported by cell experiments and immunohistochemical staining. SPOP could be a potential tumour inhibitor in RCC.

Hürthle Cell Carcinoma: A Critical Histopathologic Appraisal

2001 ◽  
Vol 19 (10) ◽  
pp. 2616-2625 ◽  
Author(s):  
Alexander Stojadinovic ◽  
Ronald A. Ghossein ◽  
Axel Hoos ◽  
Marshall J. Urist ◽  
Ronald H. Spiro ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Growth Pattern ◽  
Extrathyroidal Extension ◽  
Nodal Metastases ◽  
Hürthle Cell ◽  
Hürthle Cell Carcinoma ◽  
Hurthle Cell Carcinoma ◽  
Widely Invasive ◽  
Invasive Carcinomas

PURPOSE: Controversy exists over the ability of morphology to predict the biologic behavior of Hürthle cell carcinoma. The aim of this study was to conduct a critical histopathologic review of Hürthle cell carcinoma and to correlate morphologic parameters with clinical outcome. PATIENTS AND METHODS: Patients with histologically confirmed Hürthle cell carcinoma treated between 1940 and 2000 form the basis of this study. Adenomas were excluded. Tumors of unknown malignant behavior ([UMB] n = 17) had solid growth pattern, incomplete capsular invasion (Ci), or both but no vascular invasion (Vi). Minimally invasive carcinomas ([MIC] n = 23) had one focus of intra- or extracapsular Vi, one focus of complete Ci, or both. Widely invasive carcinomas ([WIC] n = 33) demonstrated more than one focus of Vi, more than one focus of Ci, or both. The primary end points were relapse-free survival (RFS) and disease-specific survival (DSS). Rates of recurrence/death were estimated by Kaplan-Meier method. The univariate influence of prognostic factors on end points was analyzed by log-rank test, and multivariate analysis was performed by Cox regression. RESULTS: Median follow-up was 8 years. No patients with UMB or MIC relapsed or died of disease. Of WIC, 73% relapsed and 55% died of disease. Age, size, and extent of resection did not influence outcome. Adverse predictors of RFS and DSS among WIC were extrathyroidal extension, nodal metastasis, positive margin, and solid growth pattern (P < .05). Both Ci and Vi were associated with worse DSS (P < .05). On multivariate analysis, extrathyroidal extension and nodal metastases were independent predictors of outcome (P < .05). CONCLUSION: Patients with Hürthle cell carcinoma have a prognosis that is predicted by well-defined histomorphologic characteristics. Unlike differentiated thyroid cancer, nodal metastases predict a worse outcome in widely invasive Hürthle cell carcinoma, as does extrathyroidal extension.

scholarly journals Mechanism of Metformin on LPS-Induced Bacterial Myocarditis

Dose-Response ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 155932581984740 ◽  
Author(s):  
Minghua Li ◽  
Yawei Gou ◽  
Hongmei Yu ◽  
Tiefeng Ji ◽  
Yi Li ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Potential Role ◽  
Nuclear Factor ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Expression Levels ◽  
Opposite Trend ◽  
Mitogen Activated Protein ◽  
Related Proteins

Aims: Metformin is commonly used to treat type 2 diabetes mellitus; however, in recent years, it was found to play a potential role in the protection of myocardial injury. In this study, we intended to investigate whether metformin had protective effects on bacterial myocarditis. Methods and Results: We stimulated rat cardiac myoblast H9c2 cells with lipopolysaccharide (LPS) and administrated with metformin. The results showed that cell viability after LPS stimulation was greatly reduced. The expression levels of phosphorylated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinases (JNK), nuclear factor (NF)-κB (NF-κB), BAX, and cleaved Caspase3 were significantly increased, while the expression of antiapoptotic protein Bcl-2 showed a prominent decrease compared to control. Nevertheless, the cells activity increased remarkably after metformin administration, and the expression levels of intracellular related proteins showed the opposite trend to that of the LPS group. Conclusion: We demonstrate that LPS stimulation may activate intracellular MAPK/JNK and NF-κB signaling pathways and thus induce cell apoptosis. In contrast, metformin reduced apoptosis by inhibiting this signaling pathway and increasing the expression level of Bcl-2. Moreover, it was found that metformin could enhance the ability of cells to antagonize redox damage by regulating the activities of superoxide dismutase and lactate dehydrogenase and subsequently promote the recovery of cardiomyocyte function.

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