- [Identification of key pathways and drug repurposing for anaplastic thyroid carcinoma by integrated bioinformatics analysis]. [Journal Article]
- ZDZhejiang Da Xue Xue Bao Yi Xue Ban 2018 May 25; 47(2):187-193
- CONCLUSIONS: Using integrated bioinformatics analysis, we have identified hub genes and key pathways in ATC, and provide novel strategy for the treatment of ATC.
- [A Case of Carcinoma Showing Thymus-Like Differentiation (CASTLE) of the Thyroid]. [Journal Article]
- JUJ UOEH 2018; 40(3):259-266
- The case presented herein was a 70-year-old woman who had no compliant, but had a mass in the lower part of the right lobe of the thyroid detected by ultrasound (US). The US image of the tumor, measu...
The case presented herein was a 70-year-old woman who had no compliant, but had a mass in the lower part of the right lobe of the thyroid detected by ultrasound (US). The US image of the tumor, measuring 13 mm in diameter, showed a low and heterogeneous internal echo level with calcification and an irregular margin. The tumor appeared to extend to the adjacent sternothyroid muscle, and cervical lymph node swelling was detected in a computer tomography (CT) image, but no metastatic lesion was found by positron emission tomography (PET)-CT. In a fine needle aspiration cytology of the tumor, papillary thyroid carcinoma was suggested because of the atypical epithelial cells having some changes other than intranuclear inclusion bodies. A subtotal thyroidectomy and central neck lymph node dissection were performed. The excised tumor was histologically composed of irregular nests or sheets of atypical squamoid epithelial cells with some ductal structures that leached to the sternothyroid muscle and involved the right lower parathyroid gland. Carcinoma showing thymus-like differentiation (CASTLE) was diagnosed histopathologically and immunohistochemically with the following immunohistochemical results: Cluster of differentiation 5 (CD5) (+), tumor protein p63 (p63) (+), KIT proto-oncogene receptor tyrosine kinase (c-KIT(CD117)) (+), thyroglobulin (-), and thyroid transcription factor-1 (TTF-1) (-). CASTLE is a rare carcinoma of the thyroid that architecturally resembles thymic epithelial tumors. Many CASTLE patients have been misdiagnosed as other carcinomas, such as anaplastic carcinoma, poorly differentiated carcinoma or squamous cell carcinoma of the thyroid. Immunohistochemical examination, including CD5 played an important role in the final diagnosis of CASTLE, although the distinction from diagnosis as squamous cell carcinoma or mucoepidermoid carcinoma in Hematoxylin-Eosin staining was challenging in our case. Nodal metastasis and perithyroidal tumor extension of CASTLE can predict its worse prognosis. Thus, at least careful follow-up studies are mandatory in cases of CASTLE.
- Identification of Key Pathways and Genes in Anaplastic Thyroid Carcinoma via Integrated Bioinformatics Analysis. [Journal Article]
- MSMed Sci Monit 2018 Sep 14; 24:6438-6448
- CONCLUSIONS: We identified a series of key genes along with the pathways that were most closely related with ATC initiation and progression. Our results provide a more detailed molecular mechanism for the development of ATC, shedding light on the potential biomarkers and therapeutic targets.
- Utility of monoclonal PAX8 antibody for distinguishing intrathyroid thymic carcinoma from follicular cell-derived thyroid carcinoma. [Journal Article]
- EJEndocr J 2018 Sep 12
- Follicular cell-derived thyroid carcinomas, including thyroid squamous cell carcinomas (SCCs) and anaplastic carcinomas, are immunoreactive for paired-box gene 8 (PAX8), while non-follicular cell-der...
Follicular cell-derived thyroid carcinomas, including thyroid squamous cell carcinomas (SCCs) and anaplastic carcinomas, are immunoreactive for paired-box gene 8 (PAX8), while non-follicular cell-derived thyroid carcinomas stain negative for the PAX8 antibody. Intrathyroid thymic carcinoma (ITTC) arising from the intrathyroidal ectopic thymus exhibits moderate-to-strong nuclear reactivity for polyclonal PAX8. This is difficult to understand given that PAX8 is not associated with embryonic thymic development. We aimed to determine the diagnostic significance of monoclonal PAX8 antibody in distinguishing ITTCs from follicular cell-derived thyroid carcinomas. Ten ITTCs, 14 poorly differentiated thyroid carcinomas (PDTCs), 14 thyroid SCCs, 7 thymic tissue specimens, 7 thymomas, and 1 thymic carcinoma were analyzed using antibodies against polyclonal and monoclonal PAX8, thyroid transcription factor-1, p63, and CD5. Four ITTCs (40.0%) stained positive for polyclonal PAX8; none stained positive for monoclonal PAX8. All PDTCs and 92.9% of SCCs were immunoreactive for both polyclonal and monoclonal PAX8. All PDTCs, 46.2% of SCCs, and none of the ITTCs were immunoreactive for thyroid transcription factor-1. Eight ITTCs (80.0%), but none of the PDTCs and SCCs, were immunoreactive for CD5. We are the first to show that ITTCs stain negative for monoclonal PAX8. Monoclonal PAX8 is a more reliable marker than polyclonal PAX8 for determining follicular cell origin. We conclude that monoclonal PAX8 is a useful marker for distinguishing ITTCs from PDTCs and SCCs. Monoclonal PAX8 negativity is additional evidence in support of ITTCs not being follicular cell-derived thyroid carcinomas, but having a thymic origin.
- Molecular Genetic Alterations in Thyroid Transcription Factor 1-Negative Lung Adenocarcinoma in Cytology Specimens: A Subset With Aggressive Behavior and a Poor Prognosis. [Journal Article]
- CCCancer Cytopathol 2018 Sep 10
- CONCLUSIONS: Patients with TTF1-negative lung ADC have worse overall survival, a lower frequency of known mutations, and a higher frequency of ALK alterations.
- Poorly differentiated carcinoma of thyroid: Case report of an uncommon entity. [Letter]
- JCJ Cancer Res Ther 2018 Jul-Sep; 14(5):1142-1144
- Malignant thyroid tumors of follicular origin comprise a spectrum, with the indolent well-differentiated thyroid carcinoma (WDTC) at one end and lethal anaplastic thyroid carcinoma (ATC) at the other...
Malignant thyroid tumors of follicular origin comprise a spectrum, with the indolent well-differentiated thyroid carcinoma (WDTC) at one end and lethal anaplastic thyroid carcinoma (ATC) at the other. Poorly differentiated thyroid carcinoma (PDTC) lies intermediately between WDTC and ATC in terms of morphology and prognostic standpoint. This thyroglobulin producing neoplasm accounts for 4-7% of all thyroid malignancies. PDTC has been controversial due to lack of defined diagnostic criteria. We hereby report a case of PDTC in a 42-year-old female presenting with neck swelling, pain, and dysphagia for 10 months. She was diagnosed as colloid goiter on fine-needle aspiration cytology. On imaging, a large complex thyroid with central neck nodes was seen. Total thyroidectomy and central neck node dissection were done. Based on the morphology, immunostaining, and the diagnostic criteria, a diagnosis of PDTC was made. PDTC is a diagnostic challenge due to its rarity and previous equivocal diagnostic criteria.
- S100A4 Knockout Sensitizes Anaplastic Thyroid Carcinoma Cells Harboring BRAFV600E/Mt to Vemurafenib. [Journal Article]
- CPCell Physiol Biochem 2018 Sep 07; 49(3):1143-1162
- CONCLUSIONS: Our results show S100A4 knockout alone inhibits ATC cells (rich endogenous S100A4) survival and invasion, regardless of the BRAFV600E status, and potentiates the effect of vemurafenib on tumor regression in vitro and in vivo. In addition, S100A4 knockout potently inhibits the recovery from ERK1/2 activation inhibition and the AKT activation following vemurafenib treatment and reversed the vemurafenib resistance. This therapeutic combination may be of benefit in patients with ATC.
- The efficacy of HRAS and CDK4/6 inhibitors in anaplastic thyroid cancer cell lines. [Journal Article]
- JEJ Endocrinol Invest 2018 Sep 06
- CONCLUSIONS: This study suggests that TIP and PD, which are currently in clinical trials for other types of cancer, may play a relevant role in ATC treatment, depending on the specific tumour molecular profile.
- Interaction among susceptibility genotypes of PARP1 SNPs in thyroid carcinoma. [Journal Article]
- PlosPLoS One 2018; 13(9):e0199007
- Polymorphisms in DNA repair genes may alter the repair mechanism which makes the person susceptible to DNA damage. Polymorphic variants in these DNA repair pathway genes such as Poly (ADP-ribose) pol...
Polymorphisms in DNA repair genes may alter the repair mechanism which makes the person susceptible to DNA damage. Polymorphic variants in these DNA repair pathway genes such as Poly (ADP-ribose) polymerase- 1 (PARP1) have been associated with susceptibility of several types of cancer including thyroid. Many studies have been published on PARP1 gene polymorphisms and carcinogenesis with inconsistent results. The present study was designed to explore the link between the PARP1 polymorphisms and thyroid cancer risk. This case-control study was comprised of 456 thyroid cancer patients and 400 healthy controls. Three SNPs of PARP1 gene; rs1136410, rs1805414 and rs1805404 were analyzed using ARMS-PCR. The combined genotype and haplotype analysis were performed using haploview software 4.2. Major allele homozygote (CC) of rs1136410 and combined genotype (TT+TC) of rs180414 showed a significant association with thyroid cancer risk (OR = 1.30; 95% CI 0.99-1.77; P = 0.05) and (OR = 0.43; 95% CI = 0.27-0.67; P = 0.03). Histological subtype analysis showed the significant association of selected PARP1 SNPs with papillary, follicular and anaplastic subtypes in thyroid cancer patients. Haplotype analysis showed that TCT (p = 0.01), CTT (p = 0.02) and CTC (p = 0.03) were significantly higher in controls when compared to cases. However, TTC (p = 0.05) and TCC (p = 0.01) haplotype frequency was significantly higher in cases compared to controls. Global haplotype analysis showed that there was an overall significant difference between cases and controls (p = 0.001). Identification of these genetic risk markers may provide evidence for exploring insight into mechanisms of pathogenesis and subsequently aid in developing novel therapeutic strategies for thyroid cancer.
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- SPC24 Regulates breast cancer progression by PI3K/AKT signaling. [Journal Article]
- GENEGene 2018 Oct 30; 675:272-277
- Breast cancer is a heterogeneous disease, presenting as several diverse clinical and histologic varieties and it is now the most frequently diagnosed cancer and is the sixth leading cause of cancer-r...
Breast cancer is a heterogeneous disease, presenting as several diverse clinical and histologic varieties and it is now the most frequently diagnosed cancer and is the sixth leading cause of cancer-related death in Chinese women. SPC24 is an important component of the mitotic checkpoint machinery and its carcinogenic roles have been shown in several cancers, including anaplastic thyroid cancer, hepatocellular carcinoma, and osteosarcoma. However, the role of SPC24 in breast cancer is still unclear. Here, we show SPC24 is highly expressed in breast cancer compared with the normal tissues. In addition, we observe that SPC24 knockdown can lead to attenuated cell growth, increased cell apoptosis and cell cycle progression. Consistent with the breast cancer cell results, the in vivo growth of the SPC24-knocking down cells was significantly inhibited. Interestingly, molecular analysis indicates that SPC24 regulates PI3K/AKT kinase pathway, indicating the important of SPC24 for clinical treatment. In aggregate, our results provide an oncogenic functionality of SPC24 in breast cancer progression.