Tetraspanin 1 regulates papillary thyroid tumor growth and metastasis through c-Myc-mediated glycolysis.

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer and is characterized by its tendency for lymphatic metastasis, leading to a poor prognosis. Tetraspanin 1 (TSPAN1) is a member of the tetra-transmembrane protein superfamily and has been implicated in tumorigenesis and cancer metastasis in various studies. However, the role of TSPAN1 in PTC tumor development remains unclear. In this study, we aimed to investigate the impact of TSPAN1 on PTC cell behavior. Our results demonstrate that knockdown of TSPAN1 inhibits PTC cell proliferation, migration, and invasion, while overexpression of TSPAN1 has the opposite effect. These findings suggest that TSPAN1 might play a role in the tumorigenesis and invasiveness of PTC. Mechanistically, we found that TSPAN1 activates the ERK pathway by increasing its phosphorylation, subsequently leading to upregulated expression of c-Myc. Additionally, we observed that TSPAN1-ERK-c-Myc axis activation promotes glycolytic activity in PTC cells, as evidenced by the upregulation of glycolytic genes such as LDHA. Taken together, our findings indicate that TSPAN1 acts as an oncogene in PTC by regulating glycolytic metabolism. This discovery highlights the potential of TSPAN1 as a promising therapeutic target for PTC treatment. Further research in this area could provide valuable insights into the development of targeted therapies for PTC patients.

Application of secondary sentinel lymph node biopsy in cn1a papillary thyroid carcinoma surgery: a lesson from athletic players

Objective: This study aims to evaluate the efficacy of secondary sentinel lymph node (SLN) biopsy in cN1a papillary thyroid carcinoma (PTC) surgery, drawing parallels to strategic approaches akin to those employed by athletic players.Methods: We selected eleven patients diagnosed with suspected cN1a PTC from January 2020 to July 2020. Carbon nanoparticles were utilized to mark lymph nodes, analogous to strategic marking in athletic games, ensuring precise identification during surgery. The secondary SLN biopsy technique was implemented, reflecting the precision and planning seen in athletic strategies.Results: The average tumor size was 12.64±5.63 mm. Notably, 2 patients exhibited extrathyroidal spread, 3 had thyroiditis, and all had neck metastases. The SLN identification rate stood at 100%, mirroring the accuracy expected in athletic performance. Out of the group, 3 patients had sentinel lymph node metastasis, with additional metastasis in non-SLN areas in 1 patient. The detection rate, false-negative rate, and overall accuracy paralleled the high performance and reliability seen in athletic endeavors. A total of 42 lateral SLNs were identified, with the majority being grade IV. This strategic identification is akin to an athlete's ability to focus on key areas during play (AU)

Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial.

PURPOSE: Alhough antiangiogenic agents are the bedrock of treatment for radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), novel antiangiogenic agents with optimized features like greater target-binding affinities and more favorable pharmacokinetics profile are needed. This phase II randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of anlotinib, a multikinase inhibitor, for RAIR-DTC. PATIENTS AND METHODS: Patients (ages between 18 and 70 years) with pathologically confirmed locally advanced or metastatic RAIR-DTC were enrolled and randomly received 12 mg anlotinib once daily or placebo on day 1 to 14 every 3 weeks. Patients on placebo were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and safety. RESULTS: Between September 2015 and August 2018, 76 and 37 patients randomly received anlotinib and placebo, respectively. Patients receiving anlotinib had a significantly longer median PFS [40.5 months, 95% confidence interval (CI), 28.3-not estimable (NE) versus placebo 8.4 months, 95% CI, 5.6-13.8; HR = 0.21, 95% CI, 0.12-0.37, P < 0.001], meeting the primary endpoint. OS was still immature, with a trend of benefit with anlotinib (HR = 0.57, 95% CI, 0.29-1.12). All patients in the anlotinib group experienced adverse events (AE); 8 (10.5%) discontinued treatment due to AEs. CONCLUSIONS: Anlotinib demonstrated promising efficacy and favorable tolerance in the treatment of locally advanced or metastatic RAIR-DTC, supporting further research to establish its role in the treatment of this serious disease.

Utility of video-assisted method for identifying and preserving the external branch of the superior laryngeal nerve during thyroidectomy.

Background: The EBSLN is vulnerable to damage during thyroidectomy, results in voice related complications, negatively affect patient quality of life, routine identification of the EBSLN prior to surgical manipulation is necessary for a complication-free thyroidectomy. We aimed to validate a video-assisted procedure for identifying and preserving the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy and analyze the EBSLN Cernea classification and the localization of the nerve entry point (NEP) from the insertion of the sternothyroid muscle. Methods: A prospective descriptive study was performed; 134 patients, who scheduled for lobectomy with an intraglandular tumor max diameter ≤ 4 cm and without extrathyroidal extension, were randomly divided into the video-assisted surgery (VAS) and conventional open surgery (COS) groups. We used the video-assisted surgical procedure for visually identifying the EBSLN directly, and compared the differences in the visual identification rate and total identification rate of the two groups. We also measured the localization of the NEP using the insertion of the sternothyroid muscle as a reference. Results: There was no statistically significant difference in clinical characteristics between the two groups. The visual identification rate and total identification rate were significantly higher in the VAS group than the COS group (91.04% vs. 77.61%, 100% vs. 89.6%). The EBSLN injury rate was 0 in both groups. The mean vertical distance (VD) of the NEP from the sternal thyroid insertion was 1.18 mm (SD 1.12 mm, range, 0-5 mm), with approximately 88.97% of the results occurring within the 0-2 mm range. The mean horizontal distance (HD) was 9.33 mm (SD 5.03 mm, range, 0-30 mm), with over 92.13% of the results occurring within the 5-15 mm range. Conclusion: Both the visual and total identification rates of the EBSLN were significantly higher in the VAS group. This method provided a good visual exposure rate of the EBSLN, aiding in identifying and protecting the EBSLN during thyroidectomy.

Bioinformatics identify the role of chordin-like 1 in thyroid cancer.

The abnormal expression of chordin-like 1 (CHRDL1) is identified in many cancers, while the effect of CHRDL1 in thyroid cancer (THCA) remains unclear. The University of California Santa Cruz, Gene Expression Profiling Interactive Analysis, University of Alabama at Birmingham Cancer, and Gene Expression Omnibus database (GSE33570, GSE33630, and GSE60542) were used for determining the mRNA and methylation expression of CHRDL1 in tumor and normal tissues. Human Protein Atlas was used for exploring the protein expression level of CHRDL1. The genes correlated to CHRDL1 were assessed by cBioPortal database. The prognostic value of CHRDL1 was evaluated through Kaplan-Meier method, cox regression, and nomogram analysis. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and gene set enrichment analysis were used for predicting potential function of CHRDL1. The relationship between CHRDL1 and immune cell infiltration was determined by Pearson method. The downregulated mRNA and protein expressions of CHRDL1 were identified in THCA through the analysis of data from The Cancer Genome Atlas, Gene Expression Omnibus, and Human Protein Atlas database. The survival analysis showed that the CHRDL1 expression significantly affected disease-free interval (DFI) and progression-free interval, and CHRDL1 was an independent predictor of DFI. Besides, we found that C-C motif chemokine ligand 21 could significantly affect DFI time when it was co-expressed with CHRDL1. Additionally, the function of CHRDL1 was enriched in cell migration, apoptosis, and immune cell receptor. The downregulated expression of CHRDL1 was observed in THCA and caused poor prognosis. CHRDL1 may be involved in signal pathway related to cancer development and immune response, which suggested it could be a potential biomarker.

Anlotinib in patients with medullary thyroid carcinoma with negative prognostic factors: A sub-analysis based on the ALTER01031 study.

Background: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer; however, it accounted for 13.4% of the disease-specific mortalities. ALTER01031 (NCT02586350) was a randomised, placebo-controlled phase 2b trial that evaluated the efficacy and safety of anlotinib in locally advanced or metastatic MTC. This post hoc analysis aimed to evaluate the efficacy and safety of anlotinib in older patients and those with bone metastases using ALTER01031. Methods: In ALTER01031, anlotinib significantly prolonged the median progression-free survival (PFS) from 11.1 months to 20.7 months compared with placebo in the whole population. Patients who were older (≥ 50 years) or had bone metastases were selected. PFS and overall survival (OS) were estimated and compared between patients receiving anlotinib or placebo in each subgroup. A sub-analysis of tumour response and safety was also performed. Results: Patients with older age or bone metastases experienced rapid disease progression as the median PFS was 6.8 months and 7.0 months respectively in the placebo group. Anlotinib significantly improved the median PFS to 17.5 months (P = 0.002) and 20.7 months (P = 0.029) with hazard ratio (HR) of 0.31 (95% CI, 0.15-0.68) and 0.44 (95% CI, 0.20-0.94) compared with placebo. Significant benefit in OS was observed in patients with older age after a longer follow-up (HR = 0.47 [95% CI, 0.22-0.99], P = 0.041). The safety profile of these subgroups was similar to that of the entire population. Conclusion: This sub-analysis demonstrated significant survival benefits and favourable safety of anlotinib in patients with MTC who had old age or bone metastases, supporting the feasibility of anlotinib in these patients.

Circular RNA circ_0000644 promotes papillary thyroid cancer progression via sponging miR-1205 and regulating E2F3 expression.

The dysregulation of circular RNAs (circRNAs) facilitates the tumorigenesis of papillary thyroid carcinoma (PTC). This study was targeted at determining the functions and mechanism of circ_0000644 in regulating PTC development. Circ_0000644, microRNA-1205 (miR-1205) and E2F transcription factor 3 (E2F3) expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Actinomycin D (ActD) and Ribonuclease R (RNase R) assays were used to verify the circular characteristic of circ_0000644. After circ_0000644 was knocked down, PTC cell growth, migration, invasion and apoptosis were assessed by cell counting kit-8 (CCK-8) assay, Transwell assay and flow cytometry analysis, respectively. The regulating relationships among circ_0000644, E2F3 and miR-1205 were confirmed through RNA immunoprecipitation (RIP) assay and dual-luciferase reporter assay. Besides, the regulatory effects of circ_0000644 on the protein level of E2F3 was analyzed via Western blot. In PTC, circ_0000644 was highly expressed, and it was located mainly in the cytoplasm, and it had stable structure. The knockdown of circ_0000644 repressed PTC cell growth, migration, and invasion, and facilitated apoptosis. Circ_0000644 could directly interact with miR-1205 to repress the expression of miR-1205, and it served as a miR-1205 sponge to modulate E2F3 expression in PTC cells. Circ_0000644 up-regulates E2F3 expression via sponging miR-1205 to promote PTC progression.

TINCR inhibits the proliferation and invasion of laryngeal squamous cell carcinoma by regulating miR-210/BTG2.

BACKGROUND: Terminal differentiation-induced ncRNA (TINCR) plays an essential role in epidermal differentiation and is involved in the development of various cancers. METHODS: qPCR was used to detect the expression level of TINCR in tissues and cell lines of laryngeal squamous cell carcinoma (LSCC). The potential targets of TINCR were predicted by the bioinformation website. The expression of miR-210 and BTG2 genes were detected by qPCR, and the protein levels of BTG2 and Ki-67 were evaluated by western blot. CCK-8 assay, scratch test, and transwell chamber were used to evaluate the proliferation, invasion, and metastasis ability of LSCC cells. The relationships among TINCR, miR-210, and BTG2 were investigated by bioinformatics software and luciferase reporter assay. The in vivo function of TINCR was accessed on survival rate and tumor growth in nude mice. RESULTS: We used qRT-PCR to detect the expression of TINCR in laryngeal squamous cell carcinoma (LSCC) tissues and cells and found significantly lower levels in cancer tissues compared with adjacent tissues. Additionally, patients with high TINCR expression had a better prognosis. TINCR overexpression was observed to inhibit the proliferation and invasion of LSCC cells. TINCR was shown to exert its antiproliferation and invasion effects by adsorbing miR-210, which significantly promoted the proliferation and invasion of laryngeal squamous cells. Overexpression of miR-210 was determined to reverse the tumour-suppressive effects of TINCR. BTG2 (anti-proliferation factor 2) was identified as the target gene of miR-210, and BTG2 overexpression inhibited the proliferation and invasion of LSCC cells. BTG2 knockdown relieved the inhibitory effects of TINCR on the proliferation and invasion of LSCC. Finally, TINCR upregulation slowed xenograft tumour growth in nude mice and significantly increased survival compared with control mice. CONCLUSION: The results of this study suggest that TINCR inhibits the proliferation and invasion of LSCC by regulating the miR-210/BTG2 pathway, participates in cell cycle regulation, and may become a target for the treatment of LSCC.

Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma: A Randomized, Double-Blind Phase IIB Trial.

PURPOSE: Medullary thyroid cancer (MTC) accounts for about 2% of all thyroid cancer, but has a relatively poor prognosis compared with differentiated thyroid cancer. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This multicenter, randomized, double-blind, placebo-controlled phase IIB study (ALTER 01031 and NCT02586350) was conducted to investigate the efficacy and safety of anlotinib in MTC. PATIENTS AND METHODS: Patients with histopathologically confirmed, unresectable locally advanced or metastatic MTC were enrolled and randomly assigned in a 2:1 ratio to receive anlotinib (12 mg once daily from day 1 to 14 every 3 weeks) or placebo. Patients in placebo group were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: Ninety-one patients were enrolled. At data cutoff date, the median PFS was significantly prolonged in the anlotinib group than in the placebo group (20.7 months vs. 11.1 months, P = 0.029; HR, 0.53; 95% confidence interval, 0.30-0.95). The ORR of anlotinib treatment was 48.4%. The incidence of treatment-related adverse events (TRAE) was 100% and 89.7% in the anlotinib and placebo groups, respectively. The most common TRAEs of all grades in the anlotinib group were palmar-plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%), and hypertriglyceridemia (48.4%). CONCLUSIONS: Anlotinib demonstrates its efficacy and safety in this phase IIB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.

Thyroid hormone postconditioning protects hearts from ischemia/reperfusion through reinforcing mitophagy.

Triiodothyronine (T3), the biologically active form of thyroid hormone, was reported to protect myocardium from ischemia/reperfusion (I/R) injury when given before sustained ischemia, but its cardioprotective effects when given at the onset of reperfusion (postconditioning), a protocol with more clinical impact is unknown. Therefore, the present study was designed to determine whether T3 postconditioning (THPostC) is able to protect the heart from reperfusion injury and its underlying mechanisms. Isolated Sprague-Dawley rat hearts were subjected to 30 min ischemia/45 min reperfusion, triiodothyronine was delivered at the first 5 min of reperfusion. Our data shown that T3 from 1 to 10 µM during the first 5-min of reperfusion concentration-dependently improved post-ischemic myocardial function. A similar protection was observed in isolated rat cardiomyocytes characterized by the alleviation of I/R-induced loss of mitochondrial membrane potential and exacerbated cell death. Moreover, mitophagy (selectively recognize and remove damaged mitochondria) was significantly stimulated by myocardial I/R, which was enhanced with THPostC. Meanwhile, we found that THPostC stimulated PINK1/Parkin pathway, a critical regulator for mitophagy. Then, adenoviral knockdown of PINK1 and Parkin conformed its roles in the THPostC-mediated cardioprotection. Our results suggest that THPostC confers cardioprotection against I/R injury at least in part by reinforcing PINK1-dependent mitophagy. These findings reveal new roles and mechanisms of triiodothyronine in the cardioprotection against I/R injury.

miR-215 suppresses papillary thyroid cancer proliferation, migration, and invasion through the AKT/GSK-3ß/Snail signaling by targeting ARFGEF1.

The incidence of papillary thyroid cancer (PTC) has been rapidly increasing in recent years. PTC is prone to lymph node metastasization, which further increases the recurrence rate and mortality of thyroid cancer. However, the underlying mechanisms of this process remain elusive. Several reports have shown that the microRNA miR-215 plays an important role in cancer metastasis. Here, we investigated, for the first time, the potential association between miR-215 and metastasis in PTC. The results of qPCR analysis demonstrated that miR-215 was downregulated in PTC cell lines and tissues, and lower levels of miR-215 correlated with lymph node metastasis of PTC. In vitro and in vivo assays revealed that restoration of miR-215 dramatically inhibited PTC cell proliferation and metastasis. We identified ADP ribosylation factor guanine nucleotide-exchange factor 1 (ARFGEF1) as the target, which mediated the function of miR-215. The expression of ARFGEF1 was inhibited by miR-215, and the effects of miR-215 were abrogated by re-expression of ARFGEF1. Moreover, we found that miR-215 suppressed PTC metastasis by modulating the epithelial-mesenchymal transition via the AKT/GSK-3ß/Snail signaling. In summary, our study proves that miR-215 inhibits PTC proliferation and metastasis by targeting ARFGEF1 and indicates miR-215 as a biomarker for PTC prognosis.

KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and metastasis of hepatocellular carcinoma via gankyrin/AKT signaling.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. The poor survival may be due to a high proportions of tumor recurrence and metastasis. Kinesin family member C1 (KIFC1) is highly expressed in a variety of neoplasms and is a potential marker for non-small cell lung cancer or ovarian adenocarcinoma metastasis. Nevertheless, the role of KIFC1 in HCC metastasis remains obscure. We investigated this in the present study using HCC cell lines and clinical specimens. Our results indicated that increased levels of KIFC1 were associated with poor prognosis and metastasis in HCC. In addition, KIFC1 induced epithelial-to-mesenchymal transition (EMT) and HCC metastasis both in vitro and in vivo. This tumorigenic effect depended on gankyrin; inhibiting gankyrin activity reversed EMT via activation of protein kinase B (AKT)/Twist family BHLH transcription factor 1 (AKT/TWIST1). We also found that KIFC1 was directly regulated by the microRNA miR-532-3p, whose downregulation was associated with metastatic progression in HCC. These results denote that a decrease in miR-532-3p levels results in increased KIFC1 expression in HCC, leading to metastasis via activation of the gankyrin/AKT/TWIST1 signaling pathway.

CircRNA circRNA_102171 promotes papillary thyroid cancer progression through modulating CTNNBIP1-dependent activation of ß-catenin pathway.

BACKGROUND: As a type of recently discovered noncoding RNA, circular RNAs (circRNAs) exert pivot biological functions in diverse cancers. However, the role of circRNA_102171 in papillary thyroid cancer (PTC) has not been investigated. Our study was focused on the functional investigation toward circRNA_102171 in PTC progression. And we also aimed to reveal its potential molecular mechanism. METHODS: The expression pattern of circRNA_102171 was determined using quantitative polymerase chain reaction (qPCR) in PTC samples and cell lines. Cell proliferation was examined utilizing CCK8, colony formation and EdU incorporation assays. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. Cell migration and invasion was measured using Transwell assay. Tumor growth in vivo was determined through a xenograft assay. RNA-pulldown, RNA-IP (RIP) and RNA-EMSA were used to analyze the interaction between circRNA_102171 and CTNNBIP1. RESULTS: CircRNA_102171 expression was upregulated in tumor tissues and cell lines. CircRNA_102171 silencing suppressed PTC cell proliferation, migration and invasion while promoting apoptosis. CircRNA_102171 knockdown inhibited PTC growth in vivo. CircRNA_102171 interacted with CTNNBIP1 to block its interaction with the ß-catenin/TCF3/TCF4/LEF1 complex, leading to activation of Wnt/ß-catenin pathway. CONCLUSIONS: CircRNA_102171 overexpression promotes PTC progression through activating Wnt/ß-catenin pathway in a CTNNBIP1-dependent way.

Deregulated AJAP1/ß-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis.

Adherens junctions-associated protein 1 (AJAP1) is an integral membrane protein that is thought to function as a tumor suppressor in various malignancies. Downregulation of AJAP1 mRNA levels may predict recurrence in hepatocellular carcinoma (HCC) patients, but the underlying molecular mechanism is unknown. This was addressed in the present study by examining the role of AJAP1 in HCC cell proliferation, migration, and invasion in vitro as well as in human specimens and mouse xenograft model. We found that AJAP1 expression was reduced in HCC cells and human HCC tissue, which was associated with metastasis. AJAP1 overexpression inhibited HCC progression and metastasis, while its silencing had the opposite effect both in vitro and in vivo. Furthermore, AJAP1 blocked epithelial-to-mesenchymal transition by interacting with ß-catenin and inhibiting its nuclear translocation, which suppressed zinc finger E-box binding homeobox 1 (ZEB1) transcription. These results indicate that AJAP1 inhibits HCC metastasis, and is thus a potential therapeutic target for HCC treatment.

Targeted delivery of adipose-derived stem cells via acellular dermal matrix enhances wound repair in diabetic rats.

Cell-based therapeutic intervention has emerged as a new approach to accelerate wound closure. Adipose-derived stem cells (ASCs), as a fascinating cell source, have received much attention in tissue repair and regeneration. In this study we evaluated the potential of acellular dermal matrix (ADM) scaffold serving as a carrier for the delivery of ASCs and investigated its therapeutic effects on wound healing. First, ASCs were isolated and characterized for multidifferentiation potential. ASCs-ADM grafts were then prepared, and ADM scaffold was shown to support the in vitro growth and proliferation of ASCs. Next, we analysed paracrine factors in conditioned medium and found that ASCs-ADM grafts secreted various cytokines, including VEGF, HGF, TGFß and bFGF. Moreover, ASCs-ADM conditioned medium notably stimulated the migration and proliferation of fibroblasts. In vivo, we established an excisional wound model in diabetic rats which received phosphate-buffered saline (PBS), ADM or ASCs-ADM grafts, respectively. Our results demonstrated that implantation of ASCs-ADM significantly enhanced tissue regeneration and increased epithelialization, resulting in accelerated wound closure. Immunofluorescence analysis further indicated that capillary density was evidently increased in the ASCs-ADM group compared with the control or ADM group. In addition, western blot analysis showed that ASCs-ADM significantly increased the expression of angiogenic factors, which was consistent with in vitro data. Taken together, our results suggest that targeted delivery of ASCs via ADM scaffold accelerate diabetic wound healing through a paracrine mechanism, with enhanced granulation tissue formation and increased re-epithelialization and neovascularization.

Thyrotropin-releasing hormone and its analogs accelerate wound healing.

BACKGROUND: Thyrotropin-releasing hormone (TRH) is a classical hormone that controls thyroid hormone production in the anterior pituitary gland. However, recent evidence suggested that TRH is expressed in nonhypothalamic tissues such as epidermal keratinocytes and dermal fibroblasts, but its function is not clear. This study aimed to investigate the effects of TRH and its analogs on wound healing and explore the underlying mechanisms. MATERIALS AND METHODS: A stented excisional wound model was established, and the wound healing among vehicle control, TRH, and TRH analog taltirelin treatment groups was evaluated by macroscopic and histologic analyses. Primary fibroblasts were isolated from rat dermis and treated with vehicle control, TRH or taltirelin, cell migration, and proliferation were examined by scratch migration assay, MTT, and 5-ethynyl-2'- deoxyuridine (EdU) assay. The expression of α-Smooth muscle actin in fibroblasts was detected by Western blot and immunocytochemical analysis. RESULTS: TRH or taltirelin-treated wounds exhibited accelerated wound healing with enhanced granulation tissue formation and increased re-epithelialization and tissue formation. Furthermore, TRH or taltirelin promoted the migration and proliferation of fibroblasts and induced the expression of α-Smooth muscle actin in fibroblasts. CONCLUSIONS: TRH is important in upregulating the phenotypes of dermal fibroblasts and plays a role in accelerating wound healing.

Locally administered adipose-derived stem cells accelerate wound healing through differentiation and vasculogenesis.

Despite advances in wound closure techniques and devices, there is still a critical need for new methods of enhancing the healing process to achieve optimal outcomes. Recently, stem cell therapy has emerged as a new approach to accelerate wound healing. Adipose-derived stem cells (ASCs) hold great promise for wound healing, because they are multipotential stem cells capable of differentiation into various cell lineages and secretion of angiogenic growth factors. The aim of this study was to evaluate the benefit of ASCs on wound healing and then investigate the probable mechanisms. ASCs characterized by flow cytometry were successfully isolated and cultured. An excisional wound healing model in rat was used to determine the effects of locally administered ASCs. The gross and histological results showed that ASCs significantly accelerated wound closure in normal and diabetic rat, including increased epithelialization and granulation tissue deposition. Furthermore, we applied GFP-labeled ASCs on wounds to determine whether ASCs could differentiate along multiple lineages of tissue regeneration in the specific microenvironment. Immunofluorescent analysis indicated that GFP-expressing ASCs were costained with pan-cytokeratin and CD31, respectively, indicating spontaneous site-specific differentiation into epithelial and endothelial lineages. These data suggest that ASCs not only contribute to cutaneous regeneration, but also participate in new vessels formation. Moreover, ASCs were found to secret angiogenic cytokines in vitro and in vivo, including VEGF, HGF, and FGF2, which increase neovascularization and enhance wound healing in injured tissues. In conclusion, our results demonstrate that ASC therapy could accelerate wound healing through differentiation and vasculogenesis and might represent a novel therapeutic approach in cutaneous wounds.

[Expression of BRMS1 gene protein in nasal and paranasal sinus carcinomas].

OBJECTIVE: To investigate the role and clinical significance of the expression of BRMS1 gene in development and progression of nasal and paranasal sinus carcinomas. METHOD: The expression of BRMS1 protein was detected by immunohistochemistry method in the 53 nasal and paranasal sinus carcinomas and 24 nasal polyp tissues and 10 normal mucosa. The expression of BRMS1 was analyzed in nasal and paranasal sinus carcinomas with different clinicopathological parameters. RESULT: The expression of BRMS1 in normal tissues (90.0%) and nasal polyp tissues (79.2%) was statistically significantly higher than that in nasal and paranasal sinus carcinomas (39.6%) (P < 0.01). There was a positive correlation between BRMS1 expression and TNM staging and lymph node metastasis; but not associated with pathological grade. CONCLUSION: The loss of BRMS1 expression may be involved in the development and progression of nasal and paranasal sinus carcinomas.

[Immune responses against cancers in cervical lymph nodes of laryngeal carcinoma].

OBJECTIVE: Densities of dendritic cells (DC) and hyperplastic follicular response in cervical lymph nodes were performed to prove their roles in immune responses against cancers. METHODS: Paraffin blocks were prepared for staining with monoclonal antibodies against CD45RO, CD20 and S-100 proteins,in 157 lymph nodes obtained from elective cervical lymphadenectomy in 47 cases of laryngeal squamous cell carcinomas. RESULTS: Quantitative analysis showed that the patients who survived longer than 5 years had significant higher number of follicles and higher extent of infiltration by DCs in the lymph nodes than those who less than 5 years (P < 0.001). According to negative or positive lymph node metastasis, there were statistically significant differences between two groups (P < 0.001). The patients who possessed T cell increase type follicular reaction had significant higher five-year survival rate ( P < 0.01) and lower lymph node metastasis rate (P < 0.05) than those who possessed T cell decrease type reaction. CONCLUSION: DCs and hyperplastic follicular response may be more directly involved in the host immune reaction against tumor. The classification of follicular reaction, the densities of DCs and follicular reaction, can serve as important indicators in assessing prognosis of laryngeal carcinomas.