Chemotherapy combined with endocrine neoadjuvant therapy for hormone receptor-positive local advanced breast cancer: a case report and literature review.

Background: Early studies have revealed antagonistic effects associated with stacking chemotherapy (CT) and endocrine therapy (ET), thereby conventional wisdom does not advocate the simultaneous combination of these two treatment modalities. Limited clinical studies exist on the combined use of neoadjuvant CT (NACT) and neoadjuvant ET (NET), and there are no reported instances of concurrent neoadjuvant treatment for locally advanced breast cancer (LABC) using capecitabine and fulvestrant (FUL). Case presentation: We reported a 54-year-old woman who was diagnosed with hormone receptor-positive (HR+) LABC at our hospital. After neoadjuvant treatment involving two distinct CT regimens did not lead to tumor regression. Consequently, the patient was transitioned to concurrent capecitabine and FUL therapy. This change resulted in favorable pathological remission without any significant adverse events during treatment. Conclusions: A novel approach involving concurrent neoadjuvant therapy with CT and endocrine therapy may offer a potentially effective treatment avenue for some cases with HR+ LABC.

Detection of thyroglobulin for diagnosis of metastatic lateral cervical lymph nodes in papillary thyroid carcinoma: accuracy and application in clinical practice.

Background: Accurate assessment of lateral cervical lymph node metastasis (LLNM) involvement is important for treating papillary thyroid carcinoma (PTC). Thyroglobulin is associated with LLNM, but there may be differences in the diagnostic value of serum thyroglobulin (sTg) and fine needle aspiration washout fluid thyroglobulin (FNA-Tg). Herein, we investigated the optimal cutoff value (OCV) of sTg and FNA-Tg and their diagnostic performance. Methods: We enrolled 116 PTC patients who underwent radical resection of thyroid carcinoma with lateral cervical lymph node dissection at the Affiliated Hospital of Zunyi Medical University from June 2018 to July 2022. We used the receiver operating characteristic (ROC) curve analysis to determine the OCV for sTg and FNA-Tg to diagnose LLNM in PTC patients. We also evaluated the performance of FNA-Tg, sTg, fine needle aspiration cytology (FNAC), and their combinations for diagnosis. Pathological results were the gold standard. Results: We performed 125 lymph node dissections, 106 had metastasis, and 19 did not. The OCV for sTg was 17.31 ng/mL [area under the curve (AUC) =0.760, sensitivity =78.30%, specificity =73.68%, and accuracy =77.60%]. Meanwhile, the OCV for FNA-Tg was 4.565 ng/mL (AUC =0.948, sensitivity =89.62%, specificity =100%, and accuracy =91.20%). The combination of FNAC and FNA-Tg presented the greatest diagnostic performance for LLNM detection in PTC patients. Moreover, serum antithyroglobulin antibody (TgAb) was not correlated with sTg or FNA-Tg levels. Conclusions: The cutoff value for the diagnosis of LLNM in PTC are sTg >17.31 ng/mL or FNA-Tg >4.565 ng/mL. The combination method of FNA-Tg and FNAC is the most optimal choice for the diagnosis of LLNM and is highly recommended for further clinical application.

LCN2: Versatile players in breast cancer.

Lipocalin 2 (LCN2) is a secreted glycoprotein that is produced by immune cells, including neutrophils and macrophages. It serves various functions such as transporting hydrophobic ligands across the cellular membrane, regulating immune responses, keeping iron balance, and fostering epithelial cell differentiation. LCN2 plays a crucial role in several physiological processes. LCN2 expression is upregulated in a variety of human diseases and cancers. High levels of LCN2 are specifically linked to breast cancer (BC) cell proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, chemotherapy resistance, and prognosis. As a result, LCN2 has gained attention as a potential therapeutic target for BC. This article offered an in-depth review of the advancement of LCN2 in the context of BC occurrence and development.

Isolated soft tissue tuberculosis: a case report and literature review.

Soft tissue tuberculosis is a rare extrapulmonary form of tuberculosis with limited experience in diagnosis and treatment. Soft tissue tuberculosis is an extrapulmonary infection with atypical clinical symptoms that can be easily misdiagnosed. In this article, we report a case of a female patient with isolated soft tissue tuberculosis who presented with a progressively enlarging subcutaneous mass as the primary symptom, and was suspected of having a subcutaneous lipoma after ultrasonography. A review of the literature revealed that soft tissue tuberculosis is insidious and mainly occurs in muscles and subcutaneous tissues. It was indicated by histopathology and qPCR testing for Mycobacterium tuberculosis complex. There is no standard treatment protocol for soft tissue tuberculosis, and a comprehensive regimen of surgical debridement of the lesion combined with chemotherapy can be used following the guidelines for treating extrapulmonary tuberculosis. Early diagnosis and standardized anti-tuberculosis treatment can significantly improve the prognosis of patients.

The glycoside hydrolase 28 member VdEPG1 is a virulence factor of Verticillium dahliae and interacts with the jasmonic acid pathway-related gene GhOPR9.

Glycoside hydrolase (GH) family members act as virulence factors and regulate plant immune responses during pathogen infection. Here, we characterized the GH28 family member endopolygalacturonase VdEPG1 in Verticillium dahliae. VdEPG1 acts as a virulence factor during V. dahliae infection. The expression level of VdEPG1 was greatly increased in V. dahliae inoculated on cotton roots. VdEPG1 suppressed VdNLP1-mediated cell death by modulating pathogenesis-related genes in Nicotiana benthamiana. Knocking out VdEPG1 led to a significant decrease in the pathogenicity of V. dahliae in cotton. The deletion strains were more susceptible to osmotic stress and the ability of V. dahliae to utilize carbon sources was deficient. In addition, the deletion strains lost the ability to penetrate cellophane membrane, with mycelia showing a disordered arrangement on the membrane, and spore development was affected. A jasmonic acid (JA) pathway-related gene, GhOPR9, was identified as interacting with VdEPG1 in the yeast two-hybrid system. The interaction was further confirmed by bimolecular fluorescence complementation and luciferase complementation imaging assays in N. benthamiana leaves. GhOPR9 plays a positive role in the resistance of cotton to V. dahliae by regulating JA biosynthesis. These results indicate that VdEPG1 may be able to regulate host immune responses as a virulence factor through modulating the GhOPR9-mediated JA biosynthesis.

Overexpression of cotton Trihelix transcription factor GhGT-3b_A04 enhances resistance to Verticillium dahliae and affects plant growth in Arabidopsis thaliana.

Verticillium wilt is a soil-borne fungal disease that severely affects cotton fiber yield and quality. Herein, a cotton Trihelix family gene, GhGT-3b_A04, was strongly induced by the fungal pathogen Verticillium dahliae. Overexpression of the gene in Arabidopsis thaliana enhanced the plant's resistance to Verticillium wilt but inhibited the growth of rosette leaves. In addition, the primary root length, root hair number, and root hair length increased in GhGT-3b_A04-overexpressing plants. The density and length of trichomes on the rosette leaves also increased. GhGT-3b_A04 localized to the nucleus, and transcriptome analysis revealed that it induced gene expression for salicylic acid synthesis and signal transduction and activated gene expression for disease resistance. The gene expression for auxin signal transduction and trichome development was reduced in GhGT-3b_A04-overexpressing plants. Our results highlight important regulatory genes for Verticillium wilt resistance and cotton fiber quality improvement. The identification of GhGT-3b_A04 and other important regulatory genes can provide crucial reference information for future research on transgenic cotton breeding.

VdERG2 was involved in ergosterol biosynthesis, nutritional differentiation and virulence of Verticillium dahliae.

The ergosterol biosynthesis pathway plays an important role in model pathogenic bacteria Saccharomyces cerevisiae, but little is known about the biosynthesis of ergosterol in the pathogenic fungus Verticillium dahliae. In this study, we identified the VdERG2 gene encoding sterol C-8 isomerase from V. dahliae and investigated its function in virulence by generating gene deletion mutants (ΔVdERG2) and complemented mutants (C-ΔVdERG2). Knockout of VdERG2 reduced ergosterol content. The conidial germination rate and conidial yield of ΔVdERG2 significantly decreased and abnormal conidia were produced. In spite of VdERG2 did not affect the utilization of carbon sources by V. dahliae, but the melanin production of ΔVdERG2 was decreased in cellulose and pectin were used as the sole carbon sources. Furthermore, the ΔVdERG2 mutants produced less microsclerotia and melanin with a significant decrease in the expression of microsclerotia and melanin-related genes VaflM, Vayg1, VDH1, VdLAC, VdSCD and VT4HR. In addition, mutants ΔVdERG2 were very sensitive to congo red (CR), sodium dodecyl sulfate (SDS) and hydrogen peroxide (H2O2) stresses, indicating that VdERG2 was involved in the cell wall and oxidative stress response. The absence of VdERG2 weakened the penetration ability of mycelium on cellophane and affected the growth of mycelium. Although ΔVdERG2 could infect cotton, its pathogenicity was significantly impaired. These phenotypic defects in ΔVdERG2 could be complemented by the reintroduction of a full-length VdERG2 gene. In summary, as a single conservative secretory protein, VdERG2 played a crucial role in ergosterol biosynthesis, nutritional differentiation and virulence in V. dahliae.

Two Metalloproteases VdM35-1 and VdASPF2 from Verticillium dahliae Are Required for Fungal Pathogenicity, Stress Adaptation, and Activating Immune Response of Host.

Verticillium dahliae is a soilborne fungus that causes destructive vascular wilt diseases in a wide range of plant hosts. In this study, we identified two M35 family metalloproteinases: VdM35-1 and VdASPF2, and investigated their function in vitro and in vivo. The results showed that VdM35-1 and VdASPF2 were located in the cell membrane, as secreted proteins depended on signal peptide, and two histidine residues (H) induced cell death and activated plant immune response. VdM35-1 depended on membrane receptor proteins NbBAK1 and NbSOBIR1 in the process of inducing cell death, while VdASPF2 did not depend on them. The deletion of VdM35-1 and VdASPF2 led to the decrease of sporulation and the slow shortening of mycelial branch growth, and the spore morphology of VdM35-1-deficient strain became malformed. In addition, ΔVdM35-1 and ΔVdASPF2 showed more sensitive to osmotic stress, SDS, Congo red (CR), and high temperature. In terms of the utilization of carbon sources, the knockout mutants exhibited decreased utilization of carbon sources, and the growth rates on the medium containing sucrose, starch, and pectin were lower than the wild type strain, with significantly limited growth, especially on galactose-containing medium. Furthermore, ΔVdM35-1 and ΔVdASPF2 showed a significant reduction in pathogenicity. Collectively, these results suggested that VdM35-1 and VdASPF2 were important multifunction factors in the pathogenicity of V. dahliae and relative to stress adaptation and activated plant immune response. IMPORTANCE Verticillium wilt, caused by the notorious fungal pathogen V. dahliae, is one of the main limiting factors for agricultural production. Metalloproteases played an important role in the pathogenic mechanism of pathogens. Our research found that M35 family metalloproteases VdM35-1 and VdASPF2 played an important role in the development, adaptability, and pathogenicity of V. dahliae, providing a new perspective for further understanding the molecular mechanism of virulence of fungal pathogens.

Significant efficacy of paclitaxel plus carboplatin (TP) as a neoadjuvant regimen for metaplastic squamous cell carcinoma of the breast: a rare case report and literature review.

Background: Metaplastic squamous cell carcinoma of the breast (MSCCB) is a rare and aggressive type of cancer. So far, no standard treatment regimen has been established due to the absence of clinical data. Case Description: We report a case of a 48-year-old female admitted to our hospital as a result of a left breast mass with skin rupture. Core needle biopsy under ultrasonic guidance confirmed MSCCB. Immunohistochemistry revealed negative staining for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2/neu). After receiving 4 cycles of paclitaxel and carboplatin neoadjuvant chemotherapy, the patient was treated with modified radical mastectomy. Postoperative pathology revealed a Miller-Payne score of 4 and no metastasis in the axillary lymph nodes (0/13), indicating a good response to neoadjuvant chemotherapy. She recovered well post-surgery and was discharged to home after admission. No recurrence was identified during the 2 years post-surgery follow-up. Conclusions: MSCCB is a rare and aggressive type of cancer. However, the treatment of MSCCB has not been standardized due to its rarity. Given the observation that the majority of patients with MSCCB had ER, PR, HER2-negative neoplasms, we refer to the triple negative breast cancer (TNBC) treatment protocol. TP regimen was demonstrated to be an effective treatment for TNBC. The results of this case suggest that the TP regimen is effective in neoadjuvant chemotherapy of MSCCB.

Icariside II Restores Vascular Smooth Muscle Cell Contractile Phenotype by Enhancing the Focal Adhesion Signaling Pathway in the Rat Vascular Remodeling Model.

Vascular smooth muscle cell (VSMC) phenotypic transition represents the fundamental pathophysiological alteration in the vascular remodeling process during the initiation and progression of cardiovascular diseases. Recent studies have revealed that Icariside II (ICS-II), a flavonol glycoside derived from the traditional Chinese medicine Herba Epimedii, exhibited therapeutic effects in various cardiovascular diseases. However, the therapeutic efficacy and underlying mechanisms of ICS-II regarding VSMC phenotypic transition were unknown. In this study, we investigated the therapeutic effects of ICS-Ⅱ on vascular remodeling with a rat's balloon injury model in vivo. The label-free proteomic analysis was further implemented to identify the differentially expressed proteins (DEPs) after ICS-II intervention. Gene ontology and the pathway enrichment analysis were performed based on DEPs. Moreover, platelet-derived growth factor (PDGF-BB)-induced primary rat VSMC was implemented to verify the restoration effects of ICS-II on the VSMC contractile phenotype. Results showed that ICS-II could effectively attenuate the vascular remodeling process, promote SMA-α protein expression, and inhibit OPN expression in vivo. The proteomic analysis identified 145 differentially expressed proteins after ICS-II intervention. Further, the bioinformatics analysis indicated that the focal adhesion signaling pathway was enriched in the ICS-II group. In vitro studies showed that ICS-II suppressed VSMC proliferation and migration, and promoted VSMC contractile phenotype by modulating the focal adhesion signaling pathway. Taken together, our results suggest that ICS-II attenuates the vascular remodeling process and restores the VSMC contractile phenotype by promoting the focal adhesion pathway.

Sentinel Lymph Node Biopsy Mapped With Carbon Nanoparticle Suspensions in Patients With Breast Cancer: A Systematic Review and Meta-Analysis.

Background: The mapping method represents a crucial factor affecting the rate of sentinel lymph node detection in breast cancer. We carried out this meta-analysis to assess the clinical utility of carbon nanoparticle suspensions (CNSs) in guiding sentinel lymph node biopsy (SLNB) for breast cancer patients. Methods: Electronic databases, which comprised the China National Knowledge Infrastructure, the Wanfang electronic database, the Cochrane Library, EMBASE, and PubMed, were explored to identify relevant studies from database inception to July 2021 that studied the detection rate of CNSs-guided SLNB. A meta-analysis was performed to generate pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), a summary receiver operator characteristic curve (SROC), and a diagnostic odds ratio (DOR). Results: A total of 33 publications that enrolled 2,171 patients were analyzed. The pooled sensitivity, specificity, PLR, and NLR were 0.93 (95% CI: 0.91-0.95, I2 = 0.0%), 0.99 (95% CI: 0.98-0.99, I2 = 56.5%), 42.85 (95% CI: 29.73-61.77, I2 = 47.0%), and 0.09 (95% CI: 0.07-0.11, I2 = 0.0%), respectively. The area under the curve (AUC) of the SROC curve was 0.98. There were no significant differences when analyzed based on the dose and site of CNS injection. There was significant publication bias among the included publications based on Deeks' funnel plot [Slope (Bias) = -7.35, P = 0.00]. Nonetheless, the sensitivity analysis identified the results to be reliable and stable. Conclusion: This meta-analysis highlights the accuracy and feasibility of using CNSs for SLNB in patients with breast cancer. Clinically, the identification and predictive values of CNSs as an optimal tracer for SLNB remains undisputed.

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis.

ABSTRACT: Angioplasty often fails due to the abnormal proliferation of vascular smooth muscle cells (VSMCs). Success rates of angioplasty may increase following the administration of an agent that effectively ameliorates aberrant vascular remodeling. Icariside II (ICS-II) is a natural flavonol glycoside extract from the Chinese herbal medicine Epimedii that possesses several medicinal qualities that are beneficial in humans. Nevertheless, the role of ICS-II in addressing aberrant vascular remodeling have yet to be clarified. The current investigation studies the molecular effects of ICS-Ⅱ on balloon-inflicted neointimal hyperplasia in rats in vivo and on platelet-derived growth factor-induced vascular proliferation in primary rat aortic smooth muscle cells (VSMCs) in vitro. ICS-II was found to be as effective as rapamycin, the positive control used in this study. ICS-II inhibited neointimal formation in injured rat carotid arteries and notably reduced the expression of Wnt7b. ICS-Ⅱ significantly counteracted platelet-derived growth factor-induced VSMCs proliferation. Cell cycle analysis showed that ICS-II triggered cell cycle arrest during the G1/S transition. Western blot analysis further indicated that this cell cycle arrest was likely through Wnt7b suppression that led to CCND1 inhibition. In conclusion, our findings demonstrate that ICS-II possesses significant antiproliferative qualities that counteracts aberrant vascular neointimal hyperplasia. This phenomenon most likely occurs due to the suppression of the Wnt7b/CCND1 axis.

Therapeutic efficacy of mesenchymal stem cells for abdominal aortic aneurysm: a meta-analysis of preclinical studies.

BACKGROUND: Abdominal aortic aneurysm (AAA) is life-threatening, surgical treatment is currently the only clinically available intervention for the disease. Mesenchymal stem cells (MSCs) have presented eligible immunomodulatory and regenerative abilities which showed favorable therapeutic efficacy in various cardiovascular diseases. However, current evidence summarizing the effectiveness of MSCs for AAA is lacking. Thus, a meta-analysis and systematic review was necessary to be performed to assess the therapeutic efficacy of MSCs for AAA in preclinical studies. METHODS: Comprehensive literature search restricted in English was conducted in PubMed, Cochrane Library, EBSCO, EMBASE and Web of Science from inception to Oct 2021. The primary outcomes were parameters about aortic diameter change during MSCs intervention. The secondary outcomes included elastin content and expression level of inflammatory cytokines, matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). Data were extracted and analyzed independently by two authors. The meta package with random effects model was used to calculate the pooled effect size and 95% confidence intervals in R (version 4.0.2). RESULTS: Meta-analysis of 18 included studies demonstrated that MSCs intervention has significant therapeutic effects on suppressing aortic diameter enlargement compared with the control group (diameter, SMD = - 1.19, 95% CI [- 1.47, - 0.91]; diameter change ratio, SMD = - 1.36, 95% CI [- 1.72, - 1.00]). Subgroup analysis revealed differences between MSCs and control group regarding to cell type, intervention route and cell compatibility. Moreover, the meta-analysis also showed that MSCs intervention had a significant effect on preserving aortic elastin content, reducing MCP-1, TNF-α, IL-6, MMP-2/9 and increasing TIMP-1/2 expression level compared with control group. CONCLUSION: Our results suggested that MSC intervention is effective in AAA by suppressing aortic diameter enlargement, reducing elastin degradation, and modulating local immunoinflammatory reactions. These results are important for the systemic application of MSCs as a potential treatment candidate for AAA in further animal experiments and clinical trials.

Oncotype DX 21-gene test has a low recurrence score in both pure and mixed mucinous breast carcinoma.

The Oncotype DX 21-gene test can be used to predict chemotherapy efficacy in patients with estrogen receptor (ER)-positive and HER2-negative breast cancer; however, the data on the 21-gene recurrence score (RS) for mucinous breast carcinoma (MBC) are limited. The present study aimed to evaluate the distribution pattern and clinical value of the 21-gene RS in patients with MBC. A total of 38 pure MBC (PMBC) and 11 mixed MBC (MMBC) cases were retrospectively analyzed, and a total of 29 ER-positive and HER2-negative MBCs underwent the Oncotype DX 21-gene test. There were no statistically significant differences between the PMBCs and MMBCs in age, tumor size and molecular subtype; however, patients with MMBC showed a significantly higher incidence rate of nodal metastases compared with that in patients with PMBC (72.7 vs. 16.2%, respectively). Following surgery, 87.8 and 59.2% of the enrolled patients received endocrine therapy and chemotherapy, respectively. With a median follow-up of 65.6 months, the 5-year disease-free survival and overall survival rates were 97.0 and 100.0%, respectively. The 21-gene test revealed that the proportions of patients with MBC categorized into low (RS <18), intermediate (RS ≥18-30) and high (RS ≥30) risk groups were 51.7, 44.8 and 3.5%, respectively, and there was no statistically significant difference between the PMBC and MMBC cases. Notably, among the genes in the 21-gene RS testing, the expression levels of cathepsin V, progesterone receptor (PR) and CD68 were significantly higher in the PMBC group compared with that in the MMBC group. In conclusion, the current study demonstrated that patients with MBC had a favorable prognosis, and both PMBC and MMBC cases had a low- and intermediate-risk RS, which suggests that a considerable proportion of patients may be able to avoid chemotherapy. In addition, the high expression level of PR, based on the 21-gene test in PMBCs, indicated that they may have a more favorable response to endocrine therapy than MMBCs.

Potential Target miR-455 Delaying Arterial Stenosis Progression Through PTEN.

Background: Vascular smooth muscle cells (VSMC) underwent phenotypic switching upon stimulation signals, and this is the prerequisite for their proliferation and migration. Previous work revealed that miR-455 may be involved in vascular stenosis. Thus, this study aimed to explore potential targets and mechanisms underlying the dynamics of miR-455 in vascular stenosis. Methods: miR-455 and PTEN expression levels were studied in normal and stenosis tissue, as well as in VSMC in proliferation model. Manipulating miR-455 expression levels was achieved by transfection of either miR-455 mimic or inhibitor, and its effect on cell proliferation was studied by CCK-8 assay. Its effect on gene expression was studied by RT-qPCR and western blot. The expression regulation mechanism was studied by luciferase reporter system. Finally, the effect of miR-455 on regulating vascular stenosis was studied using a rat balloon-injured carotid artery stenosis model. Results: High expression levels of miR-455 were detected in both stenosis arterial tissues and VSMC proliferation models. In contrast, the expression levels of PTEN were downregulated in these systems. miR-455 transfected VSMC showed higher levels of proliferation and decreased levels of PTEN. Potential binding sites between miR-455 and PTEN 3'UTR were predicted and confirmed. NF-kB p65 was found to bind directly on miR-455 promoter region and regulate its transcription. The progression of arterial stenosis could be delayed by introducing miR-455 antagomir. Conclusions: The p65/miR-455/PTEN signaling pathway plays a crucial role in regulating VSMC proliferation and vascular stenosis. This indicated that miR-455 is a novel target that would help improve treatment outcomes in patients suffering from vascular stenosis.

Application of carbon nanoparticles combined with intraoperative neuromonitoring in papillary thyroid microcarcinoma surgery.

PURPOSES: To improve the lymph node dissection as well as protect parathyroid gland and recurrent laryngeal nerve, the carbon nanoparticles and intraoperative neuromonitoring were applied in papillary thyroid microcarcinoma surgery. METHODS: Carbon nanoparticles and intraoperative neuromonitoring were used in the experimental group, whereas the control group were not. Routine pathological examination was performed. RESULTS: The lymph nodes dissected was significantly higher in the experimental group, but the metastatic lymph nodes were not. The number of mistakenly dissected parathyroid gland and postoperative hypoparathyroidism were 3 and 13 in the experimental group respectively, significantly less than 10 and 25 in the control group. The incidences of overall, transient and persistent recurrent laryngeal nerve palsy in the experimental group were 5.5%, 5.5% and 0% respectively, whereas in the control group were 8.6%, 6.9% and 1.7%. CONCLUSIONS: Carbon nanoparticles can improve lymph node dissection in papillary thyroid microcarcinoma surgery, and the combination of carbon nanoparticles with intraoperative neuromonitoring can reduce surgical complications and improve patient quality of life.

Mediastinal liposarcoma masquerading as penetrating aortic ulcer in the descending aorta: a case report.

A 56-year-old woman with a history of hypertension and cerebral infarction was admitted to the hospital complaining of progressive and severe chest pain for 1 day. CT scan revealed a descending penetrating ulcer. Accordingly, she underwent an uneventful endovascular repair with a thoracic endograft. One month later the patient presented to our clinic with chest and back pain again. The contrast CT indicated that the periaortic mass grew larger, which interpreted as hematoma resulting from endoleak. But no endoleak was found by angiography. CT-guided needle biopsy was carried out, the histology of the mass revealed a pleomorphic liposarcoma. Liposarcomas are malignant fat-containing tumors derived from mesenchymal cells that typically occur in the extremities and retroperitoneum, mediastinal liposarcoma account for less than 1% in mediastinal malignancies; pleomorphic liposarcoma is the least common liposarcomas. Cases of liposarcoma invading vascular system are seldom, to our knowledge, it is the first case of mediastinal pleomorphic liposarcoma invaded the descending aorta. It is worth mentioning that in the modern endovascular era, the majority of aortic diseases are being repaired by endovascular techniques. When patients with growing periaortic mass post endovascular repair and endograft-related causes have been excluded, the rare possibility of mediastinal liposarcoma should arise as a differential diagnosis. Promptly CT-guided biopsy help establish an early diagnosis.

Osthole Alleviates Neointimal Hyperplasia in Balloon-Induced Arterial Wall Injury by Suppressing Vascular Smooth Muscle Cell Proliferation and Downregulating Cyclin D1/CDK4 and Cyclin E1/CDK2 Expression.

Percutaneous coronary intervention (PCI) is the most widely used therapy for treating ischemic heart disease. However, intimal hyperplasia and restenosis usually occur within months after angioplasty. Modern pharmacological researchers have proven that osthole, the major active coumarin of Cnidium monnieri (L.) Cusson, exerts potent antiproliferative effects in lung cancer cells, the human laryngeal cancer cell line RK33 and TE671 medulloblastoma cells, and its mechanism of action is related to cell cycle arrest. The goal of the present study was to observe the effect of osthole on vascular smooth muscle cell (VSMC) proliferation using platelet-derived growth factor-BB (PDGF-BB)-stimulated VSMCs isolated from rats and vascular balloon injury as models to further elucidate the molecular mechanisms underlying this activity. We detected the relative number of VSMCs by the MTT assay and EdU staining and examined cell cycle progression by flow cytometry. To more deeply probe the mechanisms, the protein expression levels of PCNA, the cyclin D1/CDK4 complex and the cyclin E1/CDK2 complex in balloon-treated rat carotid arteries and the mRNA and protein expression levels of the cyclin D1/CDK4 and cyclin E1/CDK2 complexes in VSMCs were detected by real-time RT-PCR and western blotting. The data showed that osthole significantly inhibited the proliferation of VSMCs induced by PDGF-BB. Furthermore, osthole caused apparent VSMC cycle arrest early in G0/G1 phase and decreased the expression of cyclin D1/CDK4 and cyclin E1/CDK2. Our results demonstrate that osthole can significantly inhibit PDGF-BB-induced VSMC proliferation and that its regulatory effects on cell cycle progression and proliferation may be related to the downregulation of cyclin D1/CDK4 and cyclin E1/CDK2 expression as well as the prevention of cell cycle progression from G0/G1 phase to S phase. The abovementioned mechanism may be responsible for the alleviation of neointimal hyperplasia in balloon-induced arterial wall injury by osthole.

Osthole inhibits cell proliferation by regulating the TGF-ß1/Smad/p38 signaling pathways in pulmonary arterial smooth muscle cells.

Pulmonary artery smooth muscle cell (PASMC) proliferation contributes to pulmonary vascular remodeling, which ultimately leads to pulmonary arterial hypertension (PAH). Osthole has been previously shown to inhibit tumor cell growth. Our previous experiments demonstrated that osthole could prevent monocrotaline-induced PAH and pulmonary artery remodeling in rats and that its effects might be associated with inhibiting PASMC proliferation. However, the exact mechanism remains unclear. In this study, we observed the inhibitory effect of osthole on platelet-derived growth factor (PDGF)-BB-induced rat PASMC growth, cell cycle progression and proliferating cell nuclear antigen (PCNA) expression, as measured by CCK-8 assay, flow cytometric analysis and western blotting, respectively. We also detected the expression and activities of the cell cycle regulators cyclin D1/CDK4, cyclin E1/CDK2, p53, p27 and p21 and the TGF-ß1/Smad/p38 signaling pathways in rat PASMCs by western blotting. Our results show that osthole effectively suppressed PDGF-BB-stimulated proliferation, PCNA protein expression, and cell cycle progression in rat PASMCs in vitro. We further demonstrated that treatment with osthole significantly induced cell cycle arrest at the G0/G1 phase in PASMCs, which was supported by the finding that osthole significantly decreased cyclin D1/CDK4 and cyclin E1/CDK2 protein levels and increased p53, p27 and p21 protein levels. These effects may partly be attributed to the downregulation of TGF-ß1/Smad/p38 signaling pathway activation. Our findings suggest that osthole is a potential therapeutic candidate that warrants further investigation regarding its potential use for the treatment of PAH.

JAZF1 Suppresses Papillary Thyroid Carcinoma Cell Proliferation and Facilitates Apoptosis via Regulating TAK1/NF-κB Pathways.

PURPOSE: Juxtaposed with another zinc finger gene 1 (JAZF1) is involved in gluconeogenesis, insulin sensitivity, cell differentiation, lipid metabolism and inflammation, but its role in carcinoma remains inexplicit. PATIENTS AND METHODS: We explored the JAZF1 expression in human papillary thyroid cancer (PTC) tissues, adjacent normal thyroid tissues and nodular goitre tissues, as well as Ki67 expression in PTC tissues, using immunohistochemistry staining. Western blotting and RT-qPCR were performed to explore the JAZF1 expression levels in Nthy-ori 3-1, BCPAP and TPC-1 cells. BCPAP cells overexpressing JAZF1 were constructed using an Adv-JAZF1-GFP recombinant adenovirus vector. Next, the cell proliferation assay, colony formation assay, cell cycle analysis, apoptosis and immunofluorescence were performed. The mRNA expression level of nuclear factor-κB p65 (NF-κB p65) was examined using RT-qPCR. The expression of Bcl-2, Bax, transforming growth factor beta-activated kinase 1 (TAK1), NF-κB p65 and NF-κB p-p65 were examined using Western blotting. RESULTS: The expression of JAZF1 in human PTC tissues was downregulated compared with adjacent thyroid tissues or nodular goitre. Additionally, JAZF1 expression was associated with the location and lymph node metastasis of PTC. The expression level of JAZF1 had a negative correlation with Ki67 labelling index (LI). Compared to Nthy-ori 3-1 cells and TPC-1 cells, BCPAP cells expressed the lowest JAZF1. JAZF1 overexpressed significantly inhibited proliferation, caused G0/G1 cell cycle arrest and promoted apoptosis in BCPAP cells. Furthermore, JAZF1 overexpressed in BCPAP cells clearly upregulated the expression level of Bax protein, whereas decreased the expression of Bcl-2, TAK1, NF-κB but did not affect the mRNA or protein expression level of NF-κB p65. CONCLUSION: JAZF1 inhibits proliferation and induces apoptosis in BCPAP cells by suppressing the activation of TAK1/NF-κB signalling pathways, suggesting that JAZF1 may serve as a reliable molecular marker in PTC.