Treatment Of Papillary Thyroid Carcinoma Research Articles

Network Pharmacological Analysis and Experimental Validation of the Effects of Silybin on Proliferation, Migration, and Immunotherapy of Papillary Thyroid Cancer.

The study aimed to use network pharmacology research and in vitro experiments to investigate the material basis and molecular mechanisms of silybin in the treatment of papillary thyroid carcinoma. Papillary thyroid cancer (PTC) has a decent prognosis; however, recurrence and metastasis are the leading causes of death in patients with PTC. A key research focus in thyroid cancer treatment is the inhibition of PTC proliferation, invasion, and migration. Silybin, the major active element in the traditional Chinese herb silymarin, has been used to treat a range of diseases, including cancer, but no study has been undertaken to determine whether it can help prevent PTC. In this study, we attempted to determine through network pharmacology and in vitro experiments if silybin inhibits the development of papillary thyroid cancer by inhibiting cell cycle and invasive migration. To predict the probable targets and underlying mechanisms of silybin against PTC, a network pharmacology research was performed. In vitro experiments were conducted to further evaluate silybin's anti-cancer properties and priority targets against PTC. The datasets revealed a total of 489 silybin targets acting on PTC, and functional enrichment analysis suggested that the target genes were enriched in functions and pathways related to PTC development, invasion, migration, and immunotherapy. By constructing these target PPI networks, the seven hub genes, fibronectin 1 (FN1), tissue inhibitor of metalloproteinases 1 (TIMP1), N-cadherin (CDH2), collagen type III alpha 1 chain (COL3A1), cyclin D1 (CCND1), AP-1 transcription factor subunit (JUN), and hepatocyte growth factor receptor (MET) were found. These hub genes were determined to be highly linked to a worse clinicopathological form, a higher risk of metastatic recurrence, and a worse prognosis of PTC. The common immunological checkpoint gene expression levels were positively correlated with the expression levels of the hub genes. Silybin decreased the proliferative and metastatic capacity of PTC cells, according to in vitro investigations. When PTC was treated with silybin, the FN1/AKT signaling pathway was blocked, CCND1 expression was reduced, and CDH2, Vimentin, Snail, Slug and PD-L1 expressions were dramatically reduced, while E-cadherin expression was significantly elevated. These findings provide preliminary evidence that silybin inhibits PTC cell proliferation, metastasis, and invasion by altering the FN1/AKT signaling pathway and inhibiting the EMT process. Silybin can reverse immunosuppression in papillary thyroid cancer by affecting immunological checkpoint gene expression levels. These studies provide a theoretical and experimental scientific basis for the potential anticancer effects of silybin on PTC.

Comparison of endoscopic thyroidectomy via the oral vestibule approach and the areola approach for papillary thyroid carcinoma

BackgroundThe endoscopic thyroidectomy areola approach (ETAA) has been widely applied for papillary thyroid carcinoma (PTC), but leaves scars and is not truly minimally invasive. The oral vestibular approach (ETOVA) leaves no scars and is even more minimally invasive. However, there have been few comparative studies of ETAA and ETOVA for PTC. The purpose of our research was to compare two PTC treatment methods in terms of feasibility, safety, efficacy, and cosmetic results.MethodsA total of 129 patients with PTC underwent thyroidectomy combined with central lymph node dissection by the same surgeon. Among them, 79 patients underwent the ETOVA, and the others underwent the ETAA. We compared the two groups in terms of operative outcomes, postoperative complications, and cosmetic results.ResultsNo significant differences were found in the clinical characteristics between the ETOVA and ETAA groups. There were no significant differences in the number of removed lymph nodes (P = 0.279) or the number of positive lymph nodes (P = 0.569), but the ETOVA group had a higher number of removed lymph nodes. There was also no significant difference in blood loss volume(P = 0.180), postoperative drainage volume (P = 0.063), length of hospital stay (P = 0.182), transient RLN injury rate (P = 1.000), permanent RLN injury rate (P = 1.000), or recurrence rate (P = 1.000). The ETOVA was a longer operation than the ETAA was (P < 0.01). The ETOVA group had less pain (VAS 1: P < 0.01, VAS 3: P = 0.001), less neck discomfort (1 month after surgery: P = 0.009, 3 months after surgery: P = 0.033), and better cosmetic results (P = 0.001).ConclusionsThe ETOVA is not inferior to the ETAA in terms of safety and curability of PTC and is advantageous in terms of central lymph node dissection, minimal invasiveness, and cosmetic results.Trial registrationThis study was approved by the Ethics Committee of Zhongshan Hospital of Xiamen University (2017 V1.0). No funding was received.

Tumor‑suppressive effects of Smad‑ubiquitination regulator 2 in papillary thyroid carcinoma.

Smad-ubiquitination regulator 2 (SMURF2) functions as a homolog of E6AP carboxyl terminus-type E3 ubiquitin ligase to regulate cell cycle progression and tumor growth factor expression. SMURF2 has been revealed to function as a tumor suppressor in a number of cancers; however, its function in papillary thyroid carcinoma (PTC) remains largely unknown. Therefore, the aim of the present study was to investigate the function of SMURF2 in PTC. Reverse transcription-quantitative PCR and western blotting were used to detect cellular expression of SMURF2 in vitro. After increasing or inhibiting the expression of SMURF2, MTT was used to detect the effect on tumor cell proliferation and Transwell assays were used to detect the effect on tumor cell migration and invasion. Finally, ELISA was used to detect the effects on glucose and glutamine metabolism in tumor cells and the findings revealed that SMURF2 was downregulated in PTC tissues. Moreover, SMURF2 inhibited the proliferation, invasion and migration of PTC cells, and promoted their apoptosis. Finally, SMURF2 inhibited cell glycolysis and glutaminolysis and affected metabolism in the PTC cell line, TPC-1. Thus, the findings of the present study suggest that SMURF2 may be a potential target in the treatment of PTC.

Association between different regional lymph node metastases of papillary thyroid carcinoma in adolescents and young adults.

Adolescents and young adults (AYA) describe the demographic aged between 15-39 years diagnosed with cancer. This group is particularly at risk of papillary thyroid carcinoma (PTC) with a greater severity compared with other ages. Through comparative design, the present study aimed to quantify central lymph node metastasis (CLNM) risk in AYAs. A total of 463 AYA patients with PTC and 489 patients >39 years old with PTC from Ningbo Medical Center Lihuili Hospital (Ningbo, China) were enrolled. Details such as demographic data, serum indices and fine-needle aspiration from the Electronic Medical Records System were extracted and analyzed. AYA patients had significantly higher rates of ipsilateral Hashimoto thyroiditis, thyroid capsular invasion (TCI), CLNM, larger tumors and more positive central lymph nodes (CLN). Independent risk factors of CLNM in AYA patients were as follows: Male sex, presence of TCI, multifocality, bilateral disease and maximum tumor diameter (MTD) ≥1.0 cm. Independent risk factors of lateral lymph node metastasis in AYAs with CLNM were as follows: MTD ≥1.0 cm, maximum diameter of positive CLN ≥1.0 cm, and presence of ipsilateral nodular goiter. Furthermore, AYA patients with PTC displayed significantly greater aggression in primary tumor invasion and neck lymph node metastasis. Based on these findings, a treatment stratification chart was created to guide the PTC treatment approach for AYAs. The present study is registered at the Chinese Clinical Trials Registry (trial registration no. ChiCTR2200064921) in November 2022.

BRAF V600E Mutation Lacks Association with Poorer Clinical Prognosis in Papillary Thyroid Carcinoma.

Previous literatures showed wide range of prevalence of BRAF V600E in papillary thyroid carcinoma (PTC). The correlation of BRAF V600E mutation with aggressive tumor characteristics and poor prognosis is controversial. The present study was designed to evaluate the association between BRAF V600E mutation with clinicopathological factors and tumor recurrence. We performed a retrospective chart review of 672 patients who underwent thyroid surgery for PTC during 2013 and 2018. The prevalence of the BRAF V600E mutation was studied. Its correlation with clinicopathologic characteristics and aggressive features, including macroscopic extrathyroidal extension, lymph node metastasis, and distant metastasis, were analyzed with Fisher's exact test. A total of 672 patients who underwent surgical treatment for PTC were included in this study with a mean age of 49.7 (± 13.2) years; 76.8% of the patients were detected with BRAF V600E mutation. Mean tumor size was 1.30 (± 1.07)cm. A significant association was demonstrated between negative BRAF V600E and larger primary tumor size, distant metastasis, and advanced staging (p < 0.05), whereas there was no significant association with age, sex, lymph node metastasis, extrathyroidal extension, and multicentricity. Kaplan-Meier curve showed similar disease-free survival rate between the two groups. Negative BRAF V600E tumors show more aggressive behavior with a higher risk of developing distant metastasis in patients with PTC. The usefulness of BRAF in predicting the prognosis of PTC remains questionable. Further molecular analysis should be conducted for contribution to aggressive tumor phenotype.

Thyroid Hemiagenesis: An Incidental Discovery during Treatment for Papillary Thyroid Carcinoma

Abstract Thyroid hemiagenesis (THA) is a rare congenital abnormality in which one of the thyroid lobes fails to develop normally. The prevalence rates range from 0.02% to 0.25%, with no gender preponderance and most commonly involve the left lobe. We report a case of left THA in a 37-year-old female that was found incidentally during total thyroidectomy for right papillary thyroid carcinoma. Most patients with THA are asymptomatic, however, may have subclinically raised thyroid-stimulating hormone levels or be predisposed to developing thyroid disorders such as nodular goiter, hyperthyroidism, Grave’s disease, Hashimoto’s thyroiditis, hyperparathyroidism, or malignancy. Usual imaging techniques such as ultrasonography, computed tomography, and magnetic resonance imaging allow the confirmation of diagnosis and provide clearer glandular and regional visualization. Additional modalities such as thyroid scintigraphy enable the functional assessment and identification of any suspicious nodules and aid in decision-making. THA is a very uncommon condition and the diagnosis is primarily made through imaging. Clinicians should be aware that this condition exists along with documented associations of concomitant thyroid disorders and malignancy.

Preoperative Prediction of Metastatic Lymph Nodes Posterior to the Right Recurrent Laryngeal Nerve in cN0 Papillary Thyroid Carcinoma.

The advantages of the dissecting the metastatic lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) remain a great deal of controversies in papillary thyroid carcinoma (PTC) patients without clinical evidence. The purpose of our retrospective research was to investigate the predictive factors of the LN-prRLN in cN0 PTC patients. Altogether 251 consecutive cN0 PTC participants accepted unilateral or bilateral thyroidectomy accompanied with LN-prRLN dissection between June 2020 and May 2023 were included in the research. Then, univariate and multivariate logical regression analysis were conducted to analyze the relationship between the LN-prRLN and these predictive factors, and a predictive model was also developed. Surgical complications of LN-prRLN dissection were also presented. The rate of LN-prRLN was 17.9% (45/251) in cN0 PTC patients after the analysis of postoperative histology. The age <55 years, multifocality, microcalcification, and BRAFV600E mutation were identified to be predictive factors of LN-prRLN in cN0 PTC patients. The risk score for LN-prRLN was calculated: risk score = 1.192 × (if age <55 years) + 0.808 × (if multifocality) + 1.196 × (if microcalcification in nodule) + 0.918 × (if BRAFV600E mutation in nodule). The rates of the transient hypoparathyroidism and hoarseness were 1.2% (3/251) and 2.0% (5/251), respectively. The age <55 years, multifocality, microcalcification, and BRAFV600E mutation are independent predictors of the LN-prRLN in cN0 PTC patients. An effective predictive model was established for predicting the LN-prRLN in cN0 PTC patients, with the aim to better guide the surgical treatment of PTC. A thorough inspection of the lateral compartment is recommended in PTC patients with risk factors. The multicenter research with long-term follow-up should be carried out to ascertain the optimal surgical approach for patients with PTC.

Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma

Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.

Ultrasound-guided radiofrequency ablation for the treatment of papillary thyroid carcinoma: a review of the current state and future perspectives.

Papillary thyroid carcinoma (PTC) is a highly prevalent cancer that typically exhibits indolent behavior and is associated with a favorable prognosis. The treatment of choice is surgical intervention; however, this approach carries the risk of complications, including scarring and loss of thyroid function. Although active surveillance can mitigate the risk of PTC overtreatment, the possibility of tumor growth and metastasis can elicit anxiety among patients. Ultrasoundguided thermal ablation has emerged as a safe and effective alternative for individuals who are ineligible for or decline surgery. This article provides a review of the clinical research on radiofrequency ablation as a treatment for PTC, offering a thorough examination of its efficacy, safety, and future perspectives.

Systemic pharmacology and bioinformatics: Exploring the modern biological mechanisms of rhubarb in the treatment of papillary thyroid carcinoma

AbstractTraditional Chinese medicine (TCM) has the potential to contribute to the treatment of tumor patients. The integration of TCM with fields such as bioinformatics is crucial to gaining insights into the active compounds, target genes, and therapeutic mechanisms of TCM. In this study, our objective was to investigate the active compounds, target genes, and therapeutic mechanisms of rhubarb in the treatment of papillary thyroid carcinoma (PTC) using network pharmacology and bioinformatics approaches. By integrating multiple omics data sources and analysis methods, we identified 37 highly confident rhubarb target genes for the treatment of PTC. Subsequently, six genes (TP53, JUN, ESR1, CDKN1A, TNF, and MYC) were identified as core targets in the protein‐protein interaction (PPI) network. The herb‐component‐target network suggested that β‐sitosterol played a key role in the antitumor effect of rhubarb, while docking analysis revealed that TP53, JUN, and ESR1 were core target genes binding with β‐sitosterol. Additionally, functional annotation implicated that Hepatitis B and P53 signaling were key pathways in the rhubarb therapy for PTC. This study provides insights into the pharmacology of rhubarb and facilitates research on its potential in the treatment of PTC.

Sonographic Evolution and Pathologic Findings of Papillary Thyroid Cancer After Radiofrequency Ablation: A Five-Year Retrospective Cohort Study.

Background: The criteria for determining technical efficacy of thermal ablation for papillary thyroid carcinoma (PTC) are not clearly defined. We analyzed the involution process of the ablation zone with clear pathologic results on core-needle biopsy (CNB) to clarify the relationship between sonographic changes and pathologic findings. Methods: This retrospective cohort study included 382 patients with unifocal T1N0M0 PTC who underwent radiofrequency ablation (RFA) between May 2014 and August 2021. Patients with a single ablation zone biopsy (recommended at 3 or 6 months for T1a and 6 or 12 months for T1b) and regular neck ultrasound (US)/contrast-enhanced ultrasound imaging follow-up at 1, 3, 6, and 12 months and every 6-12 months thereafter after RFA were included. Patients also underwent yearly chest computed tomography. CNB was performed in the target lesion ablation zone's central, peripheral, and surrounding thyroid parenchyma to detect the presence of tumor cells. If the thyrotropin (TSH) was >2 mU/L, levothyroxine was prescribed with the intention of keeping the TSH 0.5-2 mU/L. Technical efficacy was defined as tumor disappearance by imaging follow-up together with the pathologically confirmed absence of tumor cells in the ablation zone. Results: During the mean follow-up period of 67.8 ± 18.2 months (22-110 months), the overall incidence of persistent disease and the technical efficacy rate were 3.9% (15/382; 2.9% of T1a, and 12.2% of T1b) and 96.1%, respectively. Tumor size (p = 0.03) and subcapsular location (p = 0.04) were risk factors associated with persistent disease. The technical success rate was 100%. Of the 367 ablation zones with benign CNB results, 336 (91.6%) showed tumor disappearance on US and no re-emergence of imaging-visible tumors during follow-up. Male sex (p = 0.006), age <40 years (p = 0.003), T1a tumor (p < 0.01), and energy per milliliter (p < 0.03) were significantly associated with tumor disappearance. Conclusions: US-guided RFA is an effective treatment for small low-risk PTC. Tumor disappearance on US after RFA may suggest an excellent prognosis and confirm complete ablation of the macroscopic tumor, but this sonographic finding is generally late and requires histological confirmation.

Construction of a nomogram for central lymph node metastasis in papillary thyroid cancer based on gender grouping.

The status of central lymph nodes is crucial for determining the surgical approach to papillary thyroid carcinoma (PTC). Because of the differences between genders in central lymph node metastasis (CLNM), we aimed to construct separate predictive models for CLNM according to gender. In our study, a total of 1258 PTC patients who underwent thyroid cancer surgery from September 2021 to March 2023 were analyzed retrospectively. The data were analysed univariately and multivariately using SPSS software grouped according to gender and nomograms of CLNM were plotted using R software. The variables included in this study were sex, Age, body mass index, Diabetes, chronic lymphocytic thyroiditis (CLT), Suspicious central lymph node (SCLN), A/T, Margin, Microcalcification (MC), BRAF, Number, Location, CLNM. The preoperative nomogram in male patients included four clinical variables: CLT, Margin, Number, Size. The preoperative nomogram of female patients included six clinical variables: Age, SCLN, Margin, MC, Number, Size. The calibration curves showed great agreement in both the training group and the validation group. The decision curve analysis showed the feasibility of nomogram in predicting CLNM in both man and woman. Based on the successful establishment of nomogram, we can analyze the variability of CLNM between male and female, which may provide clinicians with personalized clinical schemes in the treatment of PTC.

Let-7a-5p abrogates progression of papillary thyroid carcinoma cells by decreasing nuclear receptor subfamily 6 group a member 1-mediated lipogenesis.

Increasing evidence shows that microRNAs (miRNAs) contribute vital roles in papillary thyroid carcinoma (PTC) carcinogenesis, proliferation, invasion,and so on. As the most common endocrine malignancy, there still have largely unknown molecular events. First, our analysis and open access database information indicates that the downregulation of let-7a-5p accelerates PTC progression. Next, lentivirus mediates the overexpression of let-7a-5p PTC cells, and found let-7a-5p suppressed cancer cells proliferation and invasion. Interestingly, bioinformatics analysis hints NR6A1 is the potential target gene of let-7a-5p. The regulation was validated by luciferase and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in PTC tissue and the clinic tumors. Moreover, let-7a-5p regulated NR6A1 involved in PTC cells lipogensis in vitro and in vivo. Finally, let-7a-5p abrogates PCT xenograft tumors growth, NR6A1 expression and lipogenesis. Taken together, our data indicates that let-7a-5p suppresses PCT progression through decreased lipogenesis, the related let-7a-5p/NR6A1axis might be promising candidate targets for PTC treatment.

Systematic pharmacology-based strategy to explore the mechanism of Semen Strychni for treatment of papillary thyroid carcinoma

The aim of the study was to investigated the mechanism of Strychnos nux-vomica L. (Semen Strychni, SS) against papillary carcinoma thyroid (PTC) by combined of network pharmacology and experimental verification. By searching the TCMSP, SEA and SwissTarget Prediction database, the main active ingredients and related targets were obtained. Utilizing Venny 2.1.0 String database and Cytoscape 3.7.2 to screened the intersection target and constructed protein–protein interaction (PPI) network diagram. Using R 4.0.4 software carried out the enrichment analysis of GO and KEGG. HPLC was carried out using LC-20A modular HPLC system to identify the bioactive compound brucine present in SS. Molecular docking was performed using Discovery 2019 software. The inhibition rate was detected by CCK8 method. Western blot was used to detect the expression levels of brucine anti-PTC related pathway proteins. 14 active components were screened out, of which 4 main components showed tight relationship with PTC. SS may play the anti-PTC role by acting on two main pathways (TNF signaling pathway and MAPK signaling pathway) and mediating various biological functions. HPLC analysis revealed that brucine was a suitable marker for standardization of the SS. 4 active components exhibit strong binding energy with core protein. Brucine could significantly reduce the activity of BCPAP cells compared with isobrucine, stigmasterol, (+)-catechin. Brucine may reduce the protein expression levels of IL-6, VEGFA, JUN, TP53, 1L1B, PTGS2, BCL2, CASP3, CASP8, and CASP9 while increase the protein expression levels of BAD, cleaved-CASP3, cleaved-CASP8, and cleaved-CASP9 in BCPAP cells, respectively. The active components of SS against PTC mainly include isobrucine, stigmasterol, (+)-catechin, brucine. Among them, brucine exhibits the strongest anti-PTC activity in BCPAP cells, which may reduce the PTC-related protein expression levels. Therefore, SS may exhibits the anti-PTC activities through multiple targets and pathways.

Significant dysregulation of lipid metabolism in patients with papillary thyroid carcinoma after thyroidectomy.

Thyroidectomy and thyrotropin suppressive therapy is the widely used surgical treatment for papillary thyroid carcinoma (PTC) patients. However, systematic metabolic changes of post-operative PTC patients were rarely reported. Here, untargeted metabolomic detection of cohorts from PTC before (t0) and 1-month-after (t1) thyroidectomy, were performed to characterize circulating metabolic signatures after surgical treatment. Our results showed PTC patients exhibited lower thyroid stimulating hormone degree, higher total thyroxine, and significant lipid-related metabolic alternations after thyroidectomy, which included 97 upregulations (including 93 lipids) and 5 downregulations (including 2 lipids and 3 nucleotides). Enrichment of metabolic pathways mainly included biosynthesis of fatty acids, purine metabolism, and linoleic acid metabolism. We also demonstrated that differential surgical approaches (hemi- and total thyroidectomy) and post-operative complication phenotypes (insomnia, fatigue), might lead to characteristic metabolic signatures. This study revealed dynamic changes of metabolite characteristics of PTC patients after surgical treatment, which were associated with clinical thyroid function parameters, surgical approaches, and complication occurrence. It enlightened us to pay more attention on the post-operative metabolic dysregulation of PTC patients and their long-term qualities of life, so as to provide cautious clinical decisions on surgical choices, treatments, and follow-up details.

Clinical effect of Lymph Node Dissection in the Lateral Neck for the treatment of Papillary Thyroid Carcinoma: Endoscopic Thyroidectomy versus Open Surgery.

To compare the clinical effect, safety, and cosmetic effect of lymph node dissection via endoscopic thyroidectomy and open surgery in the treatment of papillary thyroid carcinoma (PTC). A retrospective analysis was performed on 86 patients with PTC admitted to Baoding No.1 Central Hospital from January 2020 to December 2021. The enrolled patients were divided into the endoscopic thyroidectomy (n = 34) and open surgery (n = 52) groups based on different surgical methods. Further comparison was conducted on the surgical indexes, postoperative complications, changes of oxidative stress indexes, numerical score system (NSS) score of postoperative cosmetic satisfaction, scar length, and recurrence rate between the two groups. The operation time was longer, and the intraoperative blood loss was lower for the endoscopic thyroidectomy group than those for the open surgery group (P < 0.05). The oxidative stress indexes of the endoscopic thyroidectomy group were significantly better than those of the open surgery group (P< 0.05). The postoperative complication rate of the endoscopic thyroidectomy group was lower than that of the open surgery group (P < 0.05). At six months after surgery, the scar length was shorter, and the NSS score was higher in the endoscopic thyroidectomy group than those in the open surgery group (P < 0.05). Endoscopic thyroidectomy for PTC is safe and effective, with mild stress response, fewer postoperative complications, and good cosmetic effect.

Visible Light–Near-Infrared Photodetection on Cys-MoO3−x Nanoparticles for Photothermal Therapy against Papillary Thyroid Carcinoma

The excellent performance of semiconductor nanocrystals as sensitizers for photothermal therapy (PTT) has attracted the attention of many researchers; however, they are hindered by limited bandwidth and complex synthesis. To overcome these limitations, starting with an initial determination of photothermal conductivity, we synthesized and designed molybdenum and Cys-MoO3−x nanoparticles (NPs) for use in the minimally invasive treatment of papillary thyroid carcinoma (PTC), as the NPs are coated only with cysteine molecules. The obtained Cys-MoO2 NPs were used as a PTT reaction drug for topical application to PTC cells. The use of near-infrared photoconductive PTT in combination with low-toxicity biological chemotherapy reached a 90% efficacy for cancer treatment in vitro. The conducted experiments intuitively demonstrate that non-toxic Cys-MoO2 NPs are lethal to the cancer cells under visual (VL, 405 nm) and near-infrared (NIR, 808 nm) laser irradiation and can be precisely controlled. Therefore, this study provides a powerful, safe, and easily modified NP platform for photo-triggered PTC elimination with broad application prospects. Assessment of the ideal damage range indicates a high degree of controllability, allowing the tumor to be precisely targeted while minimizing damage to the surrounding healthy tissue. In conclusion, this study provides a convenient, safe, and powerful NP platform for the near-infrared photo-controlled PTT of PTC cells, which has broad application prospects for the elimination of PTC and other types of cancer.

PIWI interacting RNA-13643 contributes to papillary thyroid cancer development through acting as a novel oncogene by facilitating PRMT1 mediated GLI1 methylation

Recently, aberrant expression of PIWI-interacting RNAs (piRNAs) has been discovered in a variety of cancer cells. However, the roles of PIWI proteins and piRNAs in papillary thyroid carcinoma (PTC) are still elusive. RT-qPCR and Northern blotting were used to evaluate piR-13643 levels in PTC and para-carcinoma tissues, as well as in PTC cell lines. piR-13643 mimic and piR-13643 inhibitor were transfected into K-1 and B-CPAP cells. CCK-8, Transwell, annexin V-FITC/PI, flow cytometry and Western blot assays were performed to measure cell proliferation, invasion, apoptosis, cell cycle and E-cadherin and Vimentin proteins, respectively. Total RNA from B-CPAP cells was pulled down with PIWIL1, PIWIL2, or PIWIL3 specific antibodies or IgG as a control, respectively, followed by detection of piR-13643 expression with RT-qPCR. Immunoblotting of PRMT1 was detected in piR-13643 / PIWIL1 complex immune-precipitates by Co-IP assay. Subsequently, PRMT1 protein expression was detected by stably transfection of Flag tagged GLI1 (Flag-GLI1) into B-CPAP cells. Methylation assay with PRMT1 and wild-type or R597 lysine (R597K)-mutant GLI1. Then rescue experiments were applied to explore effects of piR-13643 and GLI1 on the malignant behavior of PTC cells. B-CPAP cells transfected with piR-13643 inhibitor were subcutaneously injected into nude mice to evaluate the effect of piR-13643 knockdown on the xenograft tumor growth of PTC. piR-13643 was elevated in PTC patient specimens and cell lines. piR-13643 overexpression facilitated cell proliferation, invasion and Vimentin level, and restrained apoptosis and E-cadherin expression, whereas piR-13643 knockdown showed the opposite results. Mechanically, piR-13643 could bind to PIWIL1 to form the PIWIL1/piR-13643 complex, and PRMT1 enhanced GLI1 transcription by methylating GLI1 at R597. Further, PIWIL1/piR-13643 promoted PRMT1-mediated GLI1 methylation. GLI1 knockdown countered the effects of piR-13643 mimic on cell malignant behaviors. piR-13643 knockdown preeminently prevented the xenograft tumor growth of PTC in vivo. This study confirmed that piR-13643 facilitates PTC malignant behaviors in vitro and in vivo by promoting PRMT1-mediated GLI1 methylation via forming a complex with PIWIL1, which may provide a novel insight for PTC treatment.

Modified gasless trans-subclavian approach endoscopic lateral neck dissection for treatment of papillary thyroid carcinoma: a series of 31 cases

Objective: To examine the feasibility of the modified gasless trans-subclavian approach endoscopic thyroidectomy for lateral neck dissection (LND) in papillary thyroid carcinoma (PTC). Methods: The clinical data of 31 patients with PTC who underwent modified gasless trans-subclavian approach endoscopic LND in the Department of Head and Neck Surgery, Run Run Shaw Hospital, from January to October 2022 were retrospectively analyzed. There were 2 males and 29 females, aged (32.6±8.3) years (range: 17 to 55 years). The maximum diameter of the primary thyroid lesion (M(IQR)) was 1.06 (1.16) cm (range: 0.53 to 2.44 cm), and the maximum diameter of the metastatic lymph node was (1.04±0.37) cm (range: 0.44 to 1.88 cm). Operation time, postoperative hospital stay, number of lymph nodes dissected, and postoperative complications were recorded. Outpatient follow-up was conducted until November 30, 2022. Results: All operations were successfully completed with the endoscopy approach without conversion to open surgery. The operation time was 160 (20) minutes (range: 100 to 215 minutes), and the postoperative hospital stay was 4 (2) days (range: 2 to 14 days). The number of lymph nodes obtained by dissection in the central and lateral compartment of the neck was 11 (12) (range: 0 to 37) and 34.7±14.8 (range: 15 to 69), respectively. Temporary hypoparathyroidism occurred in 4 cases and all recovered within 1 month after the operation. One case suffered from recurrent laryngeal nerve injury (continuing followed up to assess whether it is a temporary injury). The complication of LND included 1 case of chylous leakage that was recovered with conservative treatment, 1 case of Horner syndrome returned to normal 3 months after surgery. During follow-up, there was no residual tumor or recurrence. Conclusion: The modified gasless trans-subclavian approach endoscopic LND for PTC is feasible, with a thorough dissection and concealed incision.

Regulatory role of Chitinase 3-like 1 gene in papillary thyroid carcinoma proved by integration analyses of single-cell sequencing with cohort and experimental validations

Papillary thyroid carcinoma (PTC) is one of the most common thyroid carcinomas. The gross extrathyroidal extension and extensive metastases of PTC lead to high rates of recurrence and poor clinical outcomes. However, the mechanisms underlying PTC development are poorly understood. In this study, using single-cell RNA sequencing, the transcriptome profiles of two PTC patients were addressed, including PTC1 with low malignancy and good prognosis and PTC2 with high malignancy and poor prognosis. We found that epithelial subcluster Epi02 was the most associated with the malignant development of PTC cells, with which the fold change of Chitinase 3-like 1 (CHI3L1) is on the top of the differentially expressed genes between PTC1 and PTC2 (P < 0.001). However CHI3L1 is rarely investigated in PTC as far. We then studied its role in PTC with a series of experiments. Firstly, qRT-PCR analysis of 14 PTC patients showed that the expression of CHI3L1 was positively correlated with malignancy. In addition, overexpression or silencing of CHI3L1 in TPC-1 cells, a PTC cell line, cultured in vitro showed that the proliferation, invasion, and metastasis of the cells were promoted or alleviated by CHI3L1. Further, immunohistochemistry analysis of 110 PTC cases revealed a significant relationship between CHI3L1 protein expression and PTC progression, especially the T (P < 0.001), N (P < 0.001), M stages (P = 0.007) and gross ETE (P < 0.001). Together, our results prove that CHI3L1 is a positive regulator of malignant development of PTC, and it promotes proliferation, invasion, and metastasis of PTC cells. Our study improves understanding of the molecular mechanisms underlying the progression of PTC and provides new insights for the clinical diagnosis and treatment of PTC.