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.

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 Defective Autophagy in MPN Were Predominantly Detected in Megakaryocytes in Philadelphia Negative (Ph -) Myeloproliferative Neoplasm

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5386-5386
Author(s):  
Jen-Chin Wang ◽  
Guanfang Shi ◽  
Karan Josan ◽  
Preethi Ramachandran ◽  
Vladimir Gotlieb ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Western Blot ◽  
Cell Signaling ◽  
Mononuclear Cells ◽  
Myeloproliferative Neoplasm ◽  
Beclin 1 ◽  
Positive Staining ◽  
Rt Pcr ◽  
Peripheral Blood Mononuclear ◽  
Cytoplasmic Staining

We previously reported that autophagy was defective in classical Philadelphia negative (Ph -) Myeloproliferative Neoplasm (MPN) by demonstrating increased p62, decreased Beclin-1 by RT-PCR and Western Blot (WB) methods and decreased LC3-II by WB (ASH annual meeting poster 2018) in peripheral blood mononuclear cells. Now, we further performed immunohistochemical staining of these autophagy markers on the bone marrow biopsy specimens. Methods: Formalin-fixed and paraffin-embedded bone marrow samples were stained with primary antibodies against Beclin-1 (mouse monoclonal, Millipore), LC3B (rabbit monoclonal, Cell Signaling Technology), and p62 (mouse monoclonal, Cell Signaling Technology). The tissue sections were analyzed using VENTANA BenchMark Ultra System (Ventana Medical Systems, Inc.) according to the manufacturer's protocol. Patients who were studied included 12 essential thrombocythemia (ET), 10 polycythemia (PV), and 5 myelofibrosis (MF) (including 1 post-ET MF and 1 post-PV MF). Scoring was given based on the degree of cytoplasmic staining. Score 1 included weak cytoplasmic stain, score 2 included moderate cytoplasmic stain and score 3 was given for strong cytoplasmic staining . Results: 1) As shown in Fig1, the predominant cells which stained positive including p62, Beclin-1 , or LC3 B were mostly found on the megakaryoctes, although very few of other cell types were found to have positive staining as well 2) As shown in Table 1, the immunostaining results were in general correlated to the RT-PCR , or western blot findings that a defective autophagy was demonstrated in MPN patients with combined finding of a stronger staining in p62,and weak staining in Beclin-1 and LC3B. Conclusion: We have demonstrated defective autophagy in these Ph (-) MPN, by immunostaining of the bone marrow specimens, and demonstrating positivity for defective autophagy predominantly in megakaryocytes. Since megakaryocytes are the most important cells involved in the pathogenesis of MPN, we propose that defective autophagy in megakaryocytes play an important role in the pathogenesis of these diseases. Disclosures Wang: Incyt: Research Funding.

Knockdown of BAG3 synergizes with olaparib to kill ovarian cancer cells via repressing autophagy

2020 ◽  
pp. jim-2020-001602
Author(s):  
Kexin Wang ◽  
Jianhua Zheng
Keyword(s):  
Ovarian Cancer ◽  
Western Blot ◽  
Transfection Efficiency ◽  
Parp Inhibitor ◽  
Beclin 1 ◽  
Cell Counting ◽  
Ovarian Cancer Cells ◽  
Western Blot Assay ◽  
Related Proteins

This study aimed at expounding the synergistic effect of Bcl-2-associated athanogene 3 (BAG3) knockdown and poly ADP-ribose polymerase (PARP) inhibitor on ovarian cancer (OC) cells and the potential mechanism. Short hairpin RNA (shRNA) targeting BAG3 (sh-BAG3) was transfected into SK-OV-3 (SKOV-3 ;SKOV3) and A2780 cells, and western blot assay was used to detect transfection efficiency. Cell proliferation and apoptosis were detected by the cell counting kit-8 method, 5-Bromodeoxyuridine (BrdU) experiment and flow cytometry analysis, respectively. The expressions of apoptosis-related proteins Bax and Bcl-2, as well as the expressions of autophagy-related proteins LC3-I, LC3-II and Beclin-1, were examined by western blot assay. Additionally, the cells were treated with autophagy activator rapamycin to investigate whether the tumor-suppressive function of BAG3 knockdown+PARP inhibitor was dependent on autophagy. In this work, we demonstrated that BAG3 knockdown further sensitized OC cells to olaparib treatment, reducing cellular viability and promoting apoptosis. Both sh-BAG3 and olaparib decreased the expression of Beclin-1 and the LC3-Ⅱ:LC3-I ratio, and their synergism further inhibited the process of autophagy. However, the aforementionede effects were reversed after the cells were treated with rapamycin. Based on these results, we concluded that BAG3 knockdown synergizes with olaparib to kill OC cells in vitro by repressing autophagy.

scholarly journals Recurrence rate in regional lymph nodes in 737 patients with follicular or Hürthle cell neoplasms

2016 ◽  
Vol 50 (3) ◽  
pp. 269-273 ◽  
Author(s):  
Andrej Vogrin ◽  
Hana Besic ◽  
Nikola Besic ◽  
Maja Marolt Music
Keyword(s):  
Lymph Nodes ◽  
Preoperative Diagnosis ◽  
Ultrasound Examination ◽  
Follicular Neoplasm ◽  
Lateral Neck ◽  
Regional Lymph Nodes ◽  
Neck Ultrasound ◽  
Hürthle Cell ◽  
Cell Neoplasm

Abstract Background Preoperative ultrasound (US) evaluation of central and lateral neck compartments is recommended for all patients undergoing a thyroidectomy for malignant or suspicious for malignancy cytologic or molecular findings. Our aim was to find out how frequent was recurrence in regional lymph nodes in patients with follicular or Hürthle cell neoplasm and usefulness of preoperative neck US investigation in patients with neoplasm. Patients and methods Altogether 737 patients were surgically treated because of follicular or Hürthle cell neoplasms from 1995 to 2014 at our cancer comprehensive center, among them 207 patients (163 females, 44 males; mean age 52 years) had thyroid carcinoma. Results Carcinoma was diagnosed in follicular and Hürthle cell neoplasm in 143/428 and 64/309 of cases, respectively. A recurrence in regional lymph nodes occurred in 12/207 patients (6%) during a median follow-up of 55 months. Among patients with carcinoma a recurrence in regional lymph nodes was diagnosed in follicular and Hürthle cell neoplasms in 2% and 14%, respectively (p = 0.002). Recurrence in regional lymph nodes was diagnosed in 3/428 of all patients with follicular neoplasm and 9/309 of all patients with Hürthle cell neoplasm. Conclusions Recurrence in lymph nodes was diagnosed in 0.7% of patients with a preoperative diagnosis of follicular neoplasm and 3% of patients with a Hürthle cell neoplasm. A recurrence in regional lymph nodes is rare in patients with carcinoma and preoperative diagnosis of follicular neoplasm. Preoperative neck ultrasound examination in patients with a follicular neoplasm is probably not useful, but in patients with Hurtle cell neoplasm it may be useful.

Predictive Factors of Malignancy in Thyroid Nodules Diagnosed as Follicular Neoplasm or Hürthle Cell Neoplasm on FNA

2012 ◽  
Vol 12 (4) ◽  
pp. 231
Author(s):  
Sun Hyong You ◽  
Chan Kwon Jung ◽  
Byung Joo Chae ◽  
Byung Joo Song ◽  
Sang Seol Jung ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Thyroid Nodules ◽  
Follicular Neoplasm ◽  
Hürthle Cell ◽  
Cell Neoplasm

scholarly journals Propofol Ameliorates ox-LDL-Induced Endothelial Damage Through Enhancing Autophagy via PI3K/Akt/m-TOR Pathway: A Novel Therapeutic Strategy in Atherosclerosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Hongyi Zhou ◽  
Fan Jiang ◽  
Yufang Leng
Keyword(s):  
Western Blot ◽  
Therapeutic Strategy ◽  
Endothelial Damage ◽  
Beclin 1 ◽  
Cell Counting ◽  
Bafilomycin A1 ◽  
Inhibitory Effects ◽  
Tor Pathway ◽  
Related Proteins ◽  
Novel Therapeutic

Objective: Atherosclerosis (AS) represents a common age-associated disease, which may be accelerated by oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury. This study aimed to investigate the effects of Propofol on ox-LDL-induced endothelial damage and the underlying molecular mechanisms.Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to ox-LDL to induce endothelial damage. HUVECs were pretreated with 0, 5, 25 and 100°μM Propofol, followed by exposure to 100°μg/ml ox-LDL for 24°h. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. The expression of autophagy- and apoptosis-related proteins was detected via western blot. Autophagosome was investigated under a transmission electron microscope. After co-treatment with autophagy inhibitor Bafilomycin A1 or si-Beclin-1, cell apoptosis was detected by flow cytometry. Furthermore, under cotreatment with PI3K activator 740Y-P, PI3K/Akt/m-TOR pathway- and autophagy-related proteins were examined by western blot.Results: With a concentration-dependent manner, Propofol promoted the viability of HUVECs exposed to ox-LDL, and increased LC3-II/I ratio and Beclin-1 expression, and decreased P62 expression. The formation of autophagosome was enhanced by Propofol. Furthermore, Propofol treatment elevated Bcl-2/Bax ratio and lowered Caspase-3 expression. Bafilomycin A1 or si-Beclin-1 distinctly ameliorated the inhibitory effects of Propofol on apoptosis in ox-LDL-exposed HUVECs. Moreover, Propofol lowered the activation of PI3K/Akt/m-TOR pathway in HUVECs under exposure to ox-LDL. However, its inhibitory effects were weakened by 740Y-P.Conclusion: Collectively, this study revealed that Propofol could ameliorate ox-LDL-induced endothelial damage through enhancing autophagy via PI3K/Akt/m-TOR pathway, which might offer a novel therapeutic strategy in AS.

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