Matricellular proteins: Potential biomarkers in head and neck cancer.

The extracellular matrix (ECM) is a complex network of diverse multidomain macromolecules, including collagen, proteoglycans, and fibronectin, that significantly contribute to the mechanical properties of tissues. Matricellular proteins (MCPs), as a family of non-structural proteins, play a crucial role in regulating various ECM functions. They exert their biological effects by interacting with matrix proteins, cell surface receptors, cytokines, and proteases. These interactions govern essential cellular processes such as differentiation, proliferation, adhesion, migration as well as multiple signal transduction pathways. Consequently, MCPs are pivotal in maintaining tissue homeostasis while orchestrating intricate molecular mechanisms within the ECM framework. The expression level of MCPs in adult steady-state tissues is significantly low; however, under pathological conditions such as inflammation and cancer, there is a substantial increase in their expression. In recent years, an increasing number of studies have focused on elucidating the role and significance of MCPs in the development and progression of head and neck cancer (HNC). During HNC progression, there is a remarkable upregulation in MCP expression. Through their distinctive structure and function, they actively promote tumor growth, invasion, epithelial-mesenchymal transition, and lymphatic metastasis of HNC cells. Moreover, by binding to integrins and modulating various signaling pathways, they effectively execute their biological functions. Furthermore, MCPs also hold potential as prognostic indicators. Although the star proteins of various MCPs have been extensively investigated, there remains a plethora of MCP family members that necessitate further scrutiny. This article comprehensively examines the functionalities of each MCP and highlights the research advancements in the context of HNC, with an aim to identify novel biomarkers for HNC and propose promising avenues for future investigations.

Efficacy and safety of pralsetinib in Chinese advanced RET-mutant medullary thyroid cancer patients.

Pralsetinib has demonstrated efficacious activity in various solid tumors, including medullary thyroid cancer (MTC), as observed in the phase 1/2 global ARROW study (BLU-667-1101; NCT03037385). We evaluated the safety and efficacy of pralsetinib in Chinese patients with advanced RET-mutant MTC. In the extension cohort of ARROW, adult patients with advanced MTC, who had not received systemic therapy (except for cytotoxic chemotherapy), were treated with pralsetinib (400 mg once daily, orally). The primary endpoints were blinded independent central-reviewed (BICR) objective response rate (ORR) and safety. Between October 9, 2019, and April 29, 2020, 34 patients were enrolled at 12 centers across China. Among them, 28 patients tested positive for RET mutations in the central laboratory, and 26 of these, with measurable disease at baseline per BICR, were included in the analysis set for tumor response. As of April 12, 2021 (data cutoff), the ORR was 73.1% (95% CI: 52.2-88.4), and the median duration of response was not reached. The most common (≥15%) grade ≥3 treatment-related adverse events (TRAEs) in the 28 patients with RET-mutant MTC were neutrophil count decreased (8/28, 28.6%), blood creatine phosphokinase increased (6/28, 21.4%), and lymphocyte count decreased (5/28, 17.9%). Serious TRAEs were reported by six patients (21.4%), with the most common event being pneumonia (3/28, 10.7%). No patient discontinued treatment or died from pralsetinib-related adverse events. Pralsetinib demonstrated broad, deep, and durable efficacy, as well as a manageable and acceptable safety profile in Chinese patients with advanced RET-mutant MTC.

Research on forming method of additive manufacturing of frozen sand mold.

In order to promote the green and sustainable development of the foundry industry, it is necessary to further explore new methods and technologies for green foundry. This paper innovatively proposes a method of additive manufacturing of frozen sand mold, using water as the binder instead of resin binders for additive manufacturing in low-temperature environments, which effectively solves the problems of harmful gas emissions during the pouring process and the difficulty of direct recycling of molding sand, and realizes high-performance green casting of complex castings. In this paper, the liquid-solid phase transition mechanism of the binder for additive manufacturing of frozen sand mold and the change law of the normal temperature field and phase transition field of the pre-cooled powder bed porous medium at different temperatures are studied, and the process window of additive manufacturing of frozen sand mold is obtained, which provides a new green casting method for the foundry field.

Clinical features of multifocal papillary thyroid carcinoma and risk factors of cervical metastatic lymph nodes.

OBJECTIVE: To analyze the clinical features of multifocal papillary thyroid carcinoma (PTC) and the risk factors of cervical metastatic lymph nodes. METHODS: A total of 1524 patients with papillary thyroid carcinoma admitted in Gansu Provincial Cancer Hospital from January 2020 to August 2021 were enrolled, including 492 cases of multifocal PTC and 1032 cases of unifocal PTC. The clinicopathologic features of multifocal PTC and unifocal PTC were analyzed by comparing their differences in gender, ethnicity, age, body mass index, accompanying diabetes mellitus, accompanying hypertension, preoperative thyroid stimulating hormone and thyroglobulin levels, location of lesions, maximum diameter of lesions, sum of lesion diameters, central metastatic lymph nodes, lateral cervical metastatic lymph nodes, presence of Hashimoto's thyroiditis, and thyroid capsule invasion. Patients were also assessed according to the presence or absence of central metastatic lymph nodes and lateral cervical metastatic lymph nodes to understand clinicopathological parameter differences, and multivariate logistic regression analysis was used to explore the risk factors. RESULTS: Compared with unifocal PTC group, multifocal PTC group had significantly higher proportion of patients aged over 55 years, accompanying hypertension, central metastatic lymph nodes or cervical metastatic lymph nodes, Hashimoto's thyroiditis and capsule invasion (all P<0.05); 55.1% of patients with multifocal PTC had lesions distributed bilaterally, and the maximum diameter and diameter sum of the lesions were greater than those in unifocal PTC group (all P<0.01). Multivariate logistic regression analysis showed that male, maximum diameter of lesion more than 7 mm, capsular invasion were independent risk factors for central metastatic lymph nodes (all P<0.05); while male, maximum diameter of lesion more than 7 mm, preoperative thyroglobulin more than 55 ng/mL, and central metastatic lymph nodes were risk factors for lateral cervical metastatic lymph nodes in patients with multifocal PTC (all P<0.05). CONCLUSION: Patients with multifocal PTC have significantly higher central and lateral cervical metastatic lymph nodes, particularly for male patients with a maximum diameter of lesion more than 7 mm, invasion of capsule, and preoperative thyroglobulin more than 55 ng/mL.

[Predictors for central lymph node metastases in papillary thyroid microcarcinoma].

In recent years, with the wide application of ultrasound in health examination, the incidence of papillary thyroid microcarcinoma（PTMC） is increasing rapidly. There is more controversy about whether prophylactic central lymph node dissection（PCND） should be performed in PTMC patients with clinical lymph node negative（cN0）. Some clinical and pathological factors were associated with central lymph node metastasis in patients with PTMC. This paper review the risk factors for predicting central lymph node metastasis so as to screen high-risk PTMC patients who need to receive PCND, and guide clinicians to choose reasonable individualized surgery.

Anatomic extent of lymph node metastases as an independent prognosticator in node-positive major salivary gland carcinoma: A study of the US SEER database and a Chinese multicenter cohort.

BACKGROUND: We aimed to explore whether the anatomic extent of lymph node metastases (AE-LNM) could independently predict prognosis of node-positive major salivary gland carcinoma (MaSGC). METHODS: A total of 376 pathologically node-positive MaSGC patients were identified from the Surveillance, Epidemiology and End Results database and constituted the training cohort. Using the X-Tile program, these patients were divided into three groups based on AE-LNM degrees. Discrimination of overall survival (OS) and disease-specific survival (DSS) was evaluated and compared with the 8th American Joint Committee on Cancer (AJCC) pN classification. The results were externally validated by 220 patients in a Chinese multicenter cohort (Validation cohort). RESULTS: Using the training cohort, AE-LNM was divided into Extent 1 (spread to parotid LNs or level I), Extent 2 (spread to level II-IV) and Extent 3 (spread to level V or bilateral LNs or rare LNs). Regarding both OS and DSS, the AE-LNM model revealed clear separation of survival curves, while the pN classification failed to discriminate the prognosis of pN1 and pN2 patients. When we incorporated both the AE-LNM model and AJCC pN classification into the same multivariate Cox analyses, AE-LNM was still an independent prognostic factor, while the AJCC pN classification lost its significance. These results were externally validated by the validation cohort. CONCLUSION: AE-LNM is an independent nodal prognosticator for node-positive MaSGC and may have improved discriminative ability over the current AJCC pN classification. Integration of anatomic extent of LNM into the current AJCC N classification could be considered.

[Huikangling Tablet Intervened Peripheral Blood Micrometastasis of Differentiated Thyroid Carcinoma].

OBJECTIVE: To observe the clinical effect of Huikangling Tablet (HT, extracted from Scabrous Patrinia root) on peripheral blood micrometastasis of differentiated thyroid carcinoma (DTC) patients. METHODS: Totally 87 DTC patients with positive micrometastasis were randomly assigned to the treatment group (45 cases) and the control group (42 cases). DTC endocrine inhibition treatment standards were executed in all patients. They all took levothyroxine sodium (50 microg/tablet, from low dose, 25 microg each time, once per day, 0.5 h before breakfast), and its dosage was gradually added one week later. The dosage was adjusted according to tested results of TSH combined recurrence risk stratification and endocrine suppression induced adverse reactions risk stratification. Patients in the treatment group took HT (0.4 g per tablet, 3 tablets each time, three times per day for a total of 12 weeks) combined TSH suppression therapy, while those in the control group only received TSH suppression therapy. Peripheral micrometastatic cytokeratin 19 (CK19) and polymorphic epithelial mucin1 (MUC1) were detected by FCM at week 4 and 12. Meanwhile, distant metastasis and adverse reactions were observed. RESULTS: After 4-week treatment positive micrometastasis was shown in 18 cases (40%) of the treatment group and 29 cases (69%) in the control group with statistical difference (chi2 = 5.68, P < 0.05). After 12-week treatment positive micrometastasis was shown in 7 cases (15.6%) of the treatment group and 17 cases (44.7%) in the control group with statistical difference (chi2 = 8.49, P < 0.01). Pulmonary metastasis occurred in 2 cases and bone metastasis in 1 case of the control group at follow-ups. Cervical lymph node metastasis without accompanied recurrence of thyroid cancer occurred in one case of the treatment group. No obvious liver or renal abnormalities occurred. CONCLUSION: HT inhibited peripheral blood micrometastasis of DTC patients and its mechanism needed to be further studied.

Mutations of C-reactive protein (CRP) -286 SNP, APC and p53 in colorectal cancer: implication for a CRP-Wnt crosstalk.

C-reactive protein (CRP) is an established marker of inflammation with pattern-recognition receptor-like activities. Despite the close association of the serum level of CRP with the risk and prognosis of several types of cancer, it remains elusive whether CRP contributes directly to tumorigenesis or just represents a bystander marker. We have recently identified recurrent mutations at the SNP position -286 (rs3091244) in the promoter of CRP gene in several tumor types, instead suggesting that locally produced CRP is a potential driver of tumorigenesis. However, it is unknown whether the -286 site is the sole SNP position of CRP gene targeted for mutation and whether there is any association between CRP SNP mutations and other frequently mutated genes in tumors. Herein, we have examined the genotypes of three common CRP non-coding SNPs (rs7553007, rs1205, rs3093077) in tumor/normal sample pairs of 5 cancer types (n = 141). No recurrent somatic mutations are found at these SNP positions, indicating that the -286 SNP mutations are preferentially selected during the development of cancer. Further analysis reveals that the -286 SNP mutations of CRP tend to co-occur with mutated APC particularly in rectal cancer (p = 0.04; n = 67). By contrast, mutations of CRP and p53 or K-ras appear to be unrelated. There results thus underscore the functional importance of the -286 mutation of CRP in tumorigenesis and imply an interaction between CRP and Wnt signaling pathway.

Expression and correlation of sodium/iodide symporter and thyroid stimulating hormone receptor in human thyroid carcinoma.

AIMS: To investigate the expression of sodium/iodide symporter (NIS) and thyroid stimulating hormone receptor (TSHR) in human thyroid cancer. PATIENTS AND METHODS: NIS and TSHR mRNA levels quantified by real-time PCR as well as NIS and TSHR proteins evaluated by immunohistochemistry were examined in surgical specimens including 38 benign nodules, 32 thyroid carcinomas and 36 normal thyroid samples. RESULTS: NIS and TSHR mRNA levels in thyroid carcinomas were significantly lower than in benign nodules and normal thyroid samples (P <0.001). Interestingly, we found that NIS and TSHR mRNA expression in benign nodules had similar levels to those in normal thyroid tissues. However, NIS and TSHR protein expression in benign nodules and thyroid carcinomas was stronger than in normal thyroid samples (P <0.05) but mainly located in cytoplasm. In addition, there was a significant positive correlation between NIS and TSHR in benign nodules and normal thyroid samples (r = 0.551 and 0.667, respectively, P = 0.001 and 0.000, respectively) but there was no such correlation in thyroid carcinomas (r = 0.222, P = 0.376). CONCLUSIONS: In thyroid carcinomas, NIS and TSHR mRNA levels were lower but the proteins were overexpressed. The NIS protein mainly locates in the cytoplasm, which therefore lacks the ability of transporting and absorbing iodine in patients with thyroid carcinoma. In addition, there was no correlation between NIS and TSHR in thyroid cancer, which may explain why, even after TSH stimulation, 10-20% of these malignant tumors are unable to concentrate enough radioiodine for effective therapy.

[Diagnosis and surgical treatment of Castleman's disease].

OBJECTIVE: To explore the clinical features and surgical treatment of tumors associated with Castleman's disease (CD). METHODS: The clinical profiles of 19 patients with neck giant lymph node hyperplasia were analyzed retrospectively. There were 8 males and 11 females with a median age of 40 years old (range: 7 - 74). The tumor locations were neck (n = 12), neck & mediastinal cavity (n = 2), axillary fossa (n = 2), retroperitoneal area (n = 2) and abdominal cavity (n = 1). RESULTS: Eighteen of them underwent surgical resection of tumor or lymph nodes. All were diagnosed as CD by pathological examinations. There were 16 localized CD (LCD) including hyaline vascular type (HV type, n = 11), mixed type (mix type, n = 4) and plasma cell type-Hodgkin's disease (n = 1). Among 3 multicentric CD (MCD), there were 2 case of plasma cell type (PC type) and 1 case of mixed type (mix type). Long-term survival was achieved in 19 cases among which 1 case of plasma cell type MCD survived for 5 years and underwent a second operation and postoperative chemotherapy of CVP (cyclophosphamide, vincristine & prednisone) regimen for 3 cycles due to recurrence in 2 years and 1 case of plasma cell type LCD-Hodgkin's disease survived for 15 months and underwent a second operation and postoperative chemotherapy of ABVD (adriamycin, bleomycin, vinblastine & dacarbazine)regimen for 6 cycles due to recurrence in 6 months. One case of plasma cell type MCD in abdominal cavity on chemotherapy of CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine & prednisone) regimen for 6 cycles was discharged after a successful management of intestinal obstruction. CONCLUSIONS: The major clinical symptom of CD is a gradually enlarging painless mass. Surgical resection of tumor remains the first-line treatment for localized CD and the prognosis is excellent. Multicentric and plasma cell type CDs are prone to recurrence and transformation to lymphoma. And their first-line therapeutic should encompass multi-modality regimens of surgery and adjuvant chemotherapy. However, the clinical prognosis is still poor.

[Clinical analysis on giant lymph node hyperplasia on neck].

OBJECTIVE: To improve the diagnosis and management level of giant lymph node hyperplasia (Castleman's disease). METHODS: To retrospective analyze 10 misdiagnosed cases with Castleman's disease in order to give some suggestions for clinical diagnosis and differential diagnosis. RESULTS: Ten patients with neck giant lymph node hyperplasia underwent surgical treatment after misdiagnosis. There were 8 localized Castleman's disease constituted of 6 cases with hyaline vascular type and 2 cases with mixture type and 2 multicentric Castleman's disease constituted of 1 cases with plasma cell type and 1 cases with mixture type were classified according to the criteria described by Frizzera. Ten cases were diagnosed by secondary operation after misdiagnosis and were clinically characterized by painless neck lymphadenectasis, 2 cases with multicentric Castleman's disease accompanied with aspecific systemic symptom and (or) multi-system damage. Ten cases survived for 4 - 17 years during follow-up periods in which 1 case with plasma cell type, multicentric Castleman's disease was recurrent 2 years later and underwent lymphadenectomy and chemotherapy and have no local recurrence so far. CONCLUSIONS: Castleman's disease on neck is seldom seen and liable to misdiagnose. The diagnosis of Castleman's disease is based on its histopathological characteristics by lymph node resection biopsy. It should be considered in the differential diagnosis with lymph node tuberculosis, lymphadenitis, sarcoidosis and granuloma. Operation is the first choice for patient with localized type and multicentric type without serious involvement of multiple system functions.