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  • 1
    Online Resource
    Online Resource
    PPARγ Targets-Derived Diagnostic and Prognostic Index for Papillary Thyroid Cancer
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 20 ( 2021-10-12), p. 5110-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 20 ( 2021-10-12), p. 5110-
    Abstract: In most cases, papillary thyroid cancer (PTC) is highly curable and associated with an excellent prognosis. Yet, there are several clinicopathological features that lead to a poor prognosis, underscoring the need for a better genomic strategy to refine prognostication and patient management. We hypothesized that PPARγ targets could be potential markers for better diagnosis and prognosis due to the variants found in PPARG in three pairs of monozygotic twins with PTC. Here, we developed a 10-gene personalized prognostic index, designated PPARGi, based on gene expression of 10 PPARγ targets. Through scRNA-seq data analysis of PTC tissues derived from patients, we found that PPARGi genes were predominantly expressed in macrophages and epithelial cells. Machine learning algorithms showed a near-perfect performance of PPARGi in deciding the presence of the disease and in selecting a small subset of patients with poor disease-specific survival in TCGA-THCA and newly developed merged microarray data (MMD) consisting exclusively of thyroid cancers and normal tissues.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13205110
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Impact of Age-Related Genetic Differences on the Therapeutic Outcome of Papillary Thyroid Cancer
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 2 ( 2020-02-14), p. 448-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 2 ( 2020-02-14), p. 448-
    Abstract: The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide. PTC is the most common type of differentiated thyroid cancer and usually shows good prognosis. However, some PTC is driven to advanced stage by epithelial-mesenchymal transition (EMT)-mediated drug resistance, which is particularly noticeable in pediatric patients. There are limited options for systemic treatment, necessitating development of new clinical approaches. Here, we aimed to clarify genetic differences due to age of patients with PTC, and thereby aid in developing novel therapeutics. Patients with biochemically and histologically confirmed PTC were included in this study. PTC cells were acquired from young and older patients showing drug resistance, and were compared via microarray analysis. Cellular proliferation and other properties were determined after treatments with lenvatinib and sorafenib. In vivo, tumor volume and other properties were examined using a mouse xenograft model. Lenvatinib-treated group showed obvious suppression of markers of anti-apoptosis, EMT, and the FGFR signaling pathway, compared with control and Sorafenib-treated group. In the xenograft models, lenvatinib treatment induced significant tumor shrinkage and blocked the proto-oncogene Bcl-2 (B cell lymphoma/leukemia gene-2) and FGFR signaling pathway, along with reduced levels of EMT markers, compared with control and Sorafenib-treated group. Our findings clarify the age-dependent characteristics of pediatric PTC, giving insights into the relationship between young age and poor prognosis. Furthermore, it provides a basis for developing novel therapeutics tailored to the age at diagnosis.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12020448
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 3
    Online Resource
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    Clinicopathological and Genetic Characteristics of Patients of Different Ages with Diffuse Sclerosing Variant Papillary Thyroid Carcinoma
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 12 ( 2023-06-07), p. 3101-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 12 ( 2023-06-07), p. 3101-
    Abstract: Diffuse sclerosing variant papillary thyroid carcinoma (DSVPTC) is commonly observed in young patients, with a median age at diagnosis in the third decade of life. Further, the risk of recurrence is higher for DSVPTC than for classical PTC. Therefore, this study aimed to describe the clinicopathological and genetic characteristics of patients of different ages with DSVPTC. We retrospectively reviewed 397 patients who underwent thyroidectomy for DSVPTC at Gangnam Severance Hospital, Yonsei University, from January 2005 to December 2017. The mean age at diagnosis was 36.7 ± 11.6 years, with most patients (163, 41.1%) aged 31–40 years. DSVPTC was predominant in women (276, 69.5%). We observed recurrence in 46 (11.6%) patients, with regional nodal recurrence being the most common type of recurrence (32 patients, 69.6%). The mean tumour size was larger in younger patients than in older patients. DSVPTC was more aggressive in paediatric patients with a larger-sized tumour, more common multiplicity, and lateral neck metastasis. Through random sampling, we selected 41 patients by age group and examined the mutations in 119 genes using next-generation sequencing. BRAF, KRAS, and TERT displayed relatively higher mutation rates than other genes. DSVPTC displays different clinical, pathological, and molecular profiles than classical PTC. The BRAF, KRAS, and TERT mutations are the most important, with age-specific differences.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15123101
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 4
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    Prognosis of Anaplastic Thyroid Cancer with Distant Metastasis
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 23 ( 2022-11-24), p. 5784-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 23 ( 2022-11-24), p. 5784-
    Abstract: Anaplastic thyroid cancer (ATC) is derived from follicular thyroid cells and is associated with high mortality risk. Obtaining information to characterize ATC is difficult because ATC with distant metastasis is extremely rare. This study determined the clinical characteristics of ATC with distant metastasis. The medical records of 152 patients with ATC at Gangnam Severance Hospital were reviewed between January 2004 and March 2022. The primary endpoint was the overall survival of the total patient sample, patients with ATC and distant metastasis, and those with ATC and brain metastasis. Of the 152 patients with ATC, 88 had distant metastasis at diagnosis. The 5-year disease-specific survival was 24% for total ATC and 10% for ATC with distant metastasis. Survival for 〉 1 year was 32% for total ATC and 15% for ATC with distant metastasis. The median survival rate differed significantly between the total ATC and ATC with distant metastasis groups (228.5 vs. 171 days). Among the ATC cases, 11% had brain metastasis; thus, brain MRI or CT is worth considering at diagnosis and follow-up, even if there were no statistical difference in overall survival between patients with ATC with and without brain metastasis.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14235784
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 5
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    Online Resource
    Effect of Contents on the Electrical and Piezoelectric Properties of (1 − x)(Bi, Na)TiO3–x(Ba, Sr)TiO3 Lead-Free Piezoelectric Ceramics
    MDPI AG ; 2023
    In:  Materials Vol. 16, No. 4 ( 2023-02-09), p. 1469-
    Details
    In: Materials, MDPI AG, Vol. 16, No. 4 ( 2023-02-09), p. 1469-
    Abstract: In this study, the composition of lead-free piezoelectric ceramics (1 − x)(Bi0.5Na0.5)TiO3–x(Ba0.5Sr0.5)TiO3 with excellent piezoelectric properties was investigated. Crystal analysis and electrical and piezoelectric properties were analyzed according to the content of the BST composition. A phase change from rhombohedral to tetragonal structure was observed in 0.12 BST, and the densest and most uniform microstructure was confirmed in this composition. The dielectric constant increased from 905 to 1692 as the composition of BST increased to 0.12 BST. Afterward, as the composition of BST increased, the permittivity tended to decrease. Additionally, at 0.12 BST, Pr was the highest at 23.34 μC/cm2. The piezoelectric charge constant (d33) and the electromechanical coupling coefficient (kp) were 152 pC/N and 0.37, respectively, and showed the highest values at 0.12 BST. Curie temperature (Tm) was analyzed 242 °C at 0.12 BST, the optimal composition. It was confirmed that the characteristics of 0.12 BST were excellent in all conditions. Therefore, it was confirmed that 0.12 BST is the optimal composition for (1 − x)BNT–xBST piezoelectric ceramics.
    Type of Medium: Online Resource
    ISSN: 1996-1944
    URL: Article
    DOI: 10.3390/ma16041469
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2487261-1
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  • 6
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    Online Resource
    Using Type I Collagen Gel to Prevent Postoperative Intrauterine Adhesion: A Multicenter Retrospective Study
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 11 ( 2023-05-30), p. 3764-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 11 ( 2023-05-30), p. 3764-
    Abstract: We evaluated the clinical outcomes of using type 1 collagen gel after therapeutic resectoscopy; overall, 150 women aged 〉 20 who planned to undergo therapeutic resectoscopy were enrolled. The patients were randomly assigned to either of the anti-adhesive treatment groups: the type 1 collagen gel (Collabarrier®) (study group; N = 75) or the sodium hyaluronate and sodium carboxymethylcellulose gel group (control group; N = 75) after resectoscopy. One month after applying anti-adhesive materials, postoperative intrauterine adhesions were evaluated using second-look hysteroscopy; the incidence rate of postoperative intrauterine adhesions examined through second-look hysteroscopy showed no significant differences between the groups. There were no statistical differences between the frequency and mean scores of the type and intensity of adhesions in both groups. Finally, no significant differences in adverse events, serious adverse events, adverse device effects, and serious adverse device effects were noted between the two groups; type 1 collagen gel can be effectively and safely used in intrauterine surgery to minimize postoperative adhesions, thereby eventually decreasing the prevalence of infertility, secondary amenorrhea, and recurrent pregnancy loss in reproductive women.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12113764
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 7
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    Potential Therapeutic Agents against Paclitaxel—And Sorafenib-Resistant Papillary Thyroid Carcinoma
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 18 ( 2022-09-08), p. 10378-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 18 ( 2022-09-08), p. 10378-
    Abstract: Thyroid carcinoma, a disease in which malignant cells form in the thyroid tissue, is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for nearly 80% of total thyroid carcinoma cases. However, the management of metastatic or recurrent therapy-refractory PTC is challenging and requires complex carcinoma therapy. In this study, we proposed a new clinical approach for the treatment of therapy-refractory PTC. We identified sarco/endoplasmic reticulum calcium ATPase (SERCA) as an essential factor for the survival of PTC cells refractory to the treatment with paclitaxel or sorafenib. We validated its use as a potential target for developing drugs against resistant PTC, by using patient-derived paclitaxel- or sorafenib-resistant PTC cells. We further discovered novel SERCA inhibitors, candidates 7 and 13, using the evolutionary chemical binding similarity method. These novel SERCA inhibitors determined a substantial reduction of tumors in a patient-derived xenograft tumor model developed using paclitaxel- or sorafenib-resistant PTC cells. These results could provide a basis for clinically meaningful progress in the treatment of refractory PTC by identifying a novel therapeutic strategy: using a combination therapy between sorafenib or paclitaxel and specific SERCA inhibitors for effectively and selectively targeting extremely malignant cells such as antineoplastic-resistant and carcinoma stem-like cells.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231810378
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
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    Drug Discovery Using Evolutionary Similarities in Chemical Binding to Inhibit Patient-Derived Hepatocellular Carcinoma
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 14 ( 2022-07-19), p. 7971-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 14 ( 2022-07-19), p. 7971-
    Abstract: Drug resistance causes therapeutic failure in refractory cancer. Cancer drug resistance stems from various factors, such as patient heterogeneity and genetic alterations in somatic cancer cells, including those from identical tissues. Generally, resistance is intrinsic for cancers; however, cancer resistance becomes common owing to an increased drug treatment. Unfortunately, overcoming this issue is not yet possible. The present study aimed to evaluate a clinical approach using candidate compounds 19 and 23, which are sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) inhibitors, discovered using the evolutionary chemical binding similarity method. mRNA sequencing indicated SERCA as the dominant marker of patient-derived anti-cancer drug-resistant hepatocellular carcinoma (HCC), but not of patient-derived anti-cancer drug-sensitive HCC. Candidate compounds 19 and 23 led to significant tumor shrinkage in a tumor xenograft model of anti-cancer drug-resistant patient-derived HCC cells. Our results might be clinically significant for the development of novel combinatorial strategies that selectively and efficiently target highly malignant cells such as drug-resistant and cancer stem-like cells.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23147971
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
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    Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 20 ( 2020-10-10), p. 7469-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 20 ( 2020-10-10), p. 7469-
    Abstract: Cancer cells can exhibit resistance to different anticancer drugs by acquiring enhanced anti-apoptotic potential, improved DNA injury resistance, diminished enzymatic inactivation, and enhanced permeability, allowing for cell survival. However, the genetic mechanisms for these effects are unknown. Therefore, in this study, we obtained drug-sensitive HT-29 cells (commercially) and drug-resistant cancer cells (derived from biochemically and histologically confirmed colon cancer patients) and performed microarray analysis to identify genetic differences. Cellular proliferation and other properties were determined after treatment with oxaliplatin, lenvatinib, or their combination. In vivo, tumor volume and other properties were examined using a mouse xenograft model. The oxaliplatin and lenvatinib cotreatment group showed more significant cell cycle arrest than the control group and groups treated with either agent alone. Oxaliplatin and lenvatinib cotreatment induced the most significant tumor shrinkage in the xenograft model. Drug-resistant and metastatic colon cancer cells evaded the anticancer drug effects via angiogenesis. These findings present a breakthrough strategy for treating drug-resistant cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21207469
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
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    Discovery of Pharmaceutical Composition for Prevention and Treatment in Patient-Derived Metastatic Medullary Thyroid Carcinoma Model
    MDPI AG ; 2022
    In:  Biomedicines Vol. 10, No. 8 ( 2022-08-05), p. 1901-
    Details
    In: Biomedicines, MDPI AG, Vol. 10, No. 8 ( 2022-08-05), p. 1901-
    Abstract: Medullary thyroid carcinoma (MTC) is a well-known neuroendocrine carcinoma, derived from C cells of the thyroid gland. Additionally, MTC is an uncommon aggressive carcinoma that metastasizes to lymph nodes, bones, lungs and liver. For MTC, the 10-year general survival ratio of patients with localized disease is about 95%, whereas that of patients with local phase disorder is around 75%. Only 20% of patients with distant metastasis to lung at diagnosis survive 10 years, which is notably lower than survival for well-differentiated thyroid carcinoma (WDTC). The management of MTC with distant metastasis to lung could be re-surgery or chemotherapy. In this research, we planned to assess the in vitro and in vivo combinational anticancer effect of a novel combination of low-dose cisplatin and sorafenib in patient-derived MTC. The patient-derived MTC cell lines YUMC-M1, M2, and M3 were isolated and treated with a combination of cisplatin and sorafenib or either agent alone. Cisplatin and sorafenib acted in combination to forward tumor restraint compared with each agent administered alone at a low dose. Therefore, a combination of cisplatin and sorafenib could be a new therapeutic approach for MTC.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines10081901
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2720867-9
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