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1.
Article En | MEDLINE | ID: mdl-38853649

Intervertebral disc degeneration (IDD) is a significant cause of low back pain, characterized by excessive senescence and apoptosis of nucleus pulposus cells (NPCs). However, the precise mechanisms behind this senescence and apoptosis remains unclear. This study aimed to investigate the role of Tbxt in IDD both in vitro and in vivo, using a hydrogen peroxide (H2O2)-induced NPCs senescence and apoptosis model, as well as a rat acupuncture IDD model. Firstly, the expression of p16 and cleaved-caspase 3 significantly increased in degenerated human NPCs, accompanied by a decrease in Tbxt expression. Knockdown of Tbxt exacerbated senescence and apoptosis in the H2O2-induced NPCs degeneration model. Conversely, upregulation of Tbxt alleviated these effects induced by H2O2. Mechanistically, bioinformatic analysis revealed that the direct downstream target genes of Tbxt were highly enriched in autophagy-related pathways and overexpression of Tbxt significantly activated autophagy in NPCs. Moreover, the administration of the autophagy inhibitor, 3-methyladenine, impeded the impact of Tbxt on the processes of senescence and apoptosis in NPCs. Further investigation revealed that Tbxt enhances autophagy by facilitating the transcription of ATG7 through its interaction with a specific motif within the promoter region. In conclusion, this study suggests that Tbxt mitigates H2O2-induced senescence and apoptosis of NPCs by activating ATG7-mediated autophagy.

2.
Am J Physiol Cell Physiol ; 326(5): C1384-C1397, 2024 May 01.
Article En | MEDLINE | ID: mdl-38690917

Metabolic dysfunction of the extracellular matrix (ECM) is one of the primary causes of intervertebral disc degeneration (IVDD). Previous studies have demonstrated that the transcription factor Brachyury (Bry) has the potential to promote the synthesis of collagen II and aggrecan, while the specific mechanism is still unknown. In this study, we used a lipopolysaccharide (LPS)-induced model of nucleus pulposus cell (NPC) degeneration and a rat acupuncture IVDD model to elucidate the precise mechanism through which Bry affects collagen II and aggrecan synthesis in vitro and in vivo. First, we confirmed Bry expression decreased in degenerated human nucleus pulposus (NP) cells (NPCs). Knockdown of Bry exacerbated the decrease in collagen II and aggrecan expression in the lipopolysaccharide (LPS)-induced NPCs degeneration in vitro model. Bioinformatic analysis indicated that Smad3 may participate in the regulatory pathway of ECM synthesis regulated by Bry. Chromatin immunoprecipitation followed by quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter gene assays demonstrated that Bry enhances the transcription of Smad3 by interacting with a specific motif on the promoter region. In addition, Western blot and reverse transcription-qPCR assays demonstrated that Smad3 positively regulates the expression of aggrecan and collagen II in NPCs. The following rescue experiments revealed that Bry-mediated regulation of ECM synthesis is partially dependent on Smad3 phosphorylation. Finally, the findings from the in vivo rat acupuncture-induced IVDD model were consistent with those obtained from in vitro assays. In conclusion, this study reveals that Bry positively regulates the synthesis of collagen II and aggrecan in NP through transcriptional activation of Smad3.NEW & NOTEWORTHY Mechanically, in the nucleus, Bry enhances the transcription of Smad3, leading to increased expression of Smad3 protein levels; in the cytoplasm, elevated substrate levels further lead to an increase in the phosphorylation of Smad3, thereby regulating collagen II and aggrecan expression. Further in vivo experiments provide additional evidence that Bry can alleviate IVDD through this mechanism.


Aggrecans , Extracellular Matrix , Fetal Proteins , Intervertebral Disc Degeneration , Nucleus Pulposus , Rats, Sprague-Dawley , Smad3 Protein , T-Box Domain Proteins , Smad3 Protein/metabolism , Smad3 Protein/genetics , Nucleus Pulposus/metabolism , Nucleus Pulposus/pathology , Animals , Extracellular Matrix/metabolism , T-Box Domain Proteins/genetics , T-Box Domain Proteins/metabolism , Humans , Rats , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Degeneration/pathology , Aggrecans/metabolism , Aggrecans/genetics , Male , Fetal Proteins/genetics , Fetal Proteins/metabolism , Collagen Type II/metabolism , Collagen Type II/genetics , Gene Expression Regulation , Female , Adult , Middle Aged , Cells, Cultured , Transcription, Genetic
4.
Diagn Pathol ; 18(1): 123, 2023 Nov 11.
Article En | MEDLINE | ID: mdl-37951919

BACKGROUND: With the continuous discovery of new borderline thyroid lesions and benign and malignant "gray areas", coupled with the limitations of traditional immune indicators, the differential diagnosis of papillary thyroid carcinoma (PTC) has become more difficult. Cyclin D1 and P21 are cell cycle regulators involved in the occurrence and metastasis of multiple tumors, including PTC, but their specific functions are unclear. METHODS: In our study, immunohistochemical staining was used to explore the expression of Cyclin D1 and P21 in PTC, paracancerous tissue, follicular adenoma (FA) and papillary thyroid hyperplasia. In addition, their relationship with the clinicopathological features of PTC and their differential diagnostic value in distinguishing between intralymph node PTC metastases and intralymph node ectopic thyroid tissue were studied. RESULTS: Among 200 primary PTC lesions, Cyclin D1 and P21 were found to be expressed in 186 (93.00%) and 177 (88.50%), respectively, and their expression levels were significantly higher in PTC tissue than in adjacent tissue, FA tissue and papillary thyroid hyperplasia tissue (P < 0.05). The expression levels of Cyclin D1 and P21 were positively correlated with tumor size and lymph node metastasis (P < 0.05) but not with sex, age, number of tumor lesions, histological subtype, chronic lymphocytic thyroiditis or TNM stage (P < 0.05). The expression levels of Cyclin D1 and P21 were significantly correlated (P < 0.05). The positivity rates of Cyclin D1 and P21 in intralymph node PTC metastases were 97.96% (48/49) and 89.80% (44/49), respectively, which were significantly higher than those in intralymph node ectopic thyroid tissue (P < 0.05). The sensitivity (Se) and negative predictive value (NPV) of Cyclin D1 and P21 detection alone or in combination were higher than those of the combined detection of the classical antibody markers CK19, HBME-1 and Galectin-3. Besides, the Se, Sp, PPV and NPV of Cyclin D1 and P21 in differentiating intralymph node PTC metastases and intralymph node ectopic thyroid tissue were higher. CONCLUSIONS: The results of our study show that Cyclin D1 and P21 are highly sensitive and specific markers for the diagnosis of PTC that are superior to traditional classical antibodies. And, these two markers are of great value in the differential diagnosis of intralymph node PTC metastases and intralymph node ectopic thyroid tissue.


Adenoma , Carcinoma, Papillary , Thyroid Dysgenesis , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/diagnosis , Cyclin D1 , Hyperplasia , Diagnosis, Differential , Carcinoma, Papillary/pathology , Biomarkers, Tumor/metabolism , Thyroid Neoplasms/pathology , Adenoma/pathology , Thyroid Dysgenesis/diagnosis
5.
Ultrasonics ; 134: 107087, 2023 Sep.
Article En | MEDLINE | ID: mdl-37406388

Recently, surface acoustic wave (SAW) based acoustofluidic separation of microparticles and cells has attracted increasing interest due to accuracy and biocompatibility. Precise control of the input power of acoustofluidic devices is essential for generating optimum acoustic radiation force to manipulate microparticles given their various parameters including size, density, compressibility, and moving velocity. In this work, an acoustophoretic system is developed by employing SAW based interdigital electrode devices. Power meters are applied to closely monitor the incident and reflected powers of the SAW device, which are associated with the separation efficiency. There exists a range of input powers to migrate the microparticles to the pressure node due to their random locations when entering the SAW field. Theoretical analysis is performed to predict a proper input power to separate mixtures of polystyrene microspheres, and the end lateral position of microspheres being acoustically separated. The separation efficiency of four sizes of microspheres, including 20 µm, 15 µm, 10 µm, and 5 µm, is calculated and compared with experimental results, which suggest the input power for separating the mixture of these microspheres. The study provides a practical guidance on operating SAW devices for bioparticle separation using the incident power as a control parameter.

6.
Front Endocrinol (Lausanne) ; 14: 1063774, 2023.
Article En | MEDLINE | ID: mdl-37361532

Background: Hysteroscopic metroplasty of the uterine septum has been the standard treatment strategy to improve reproductive outcomes, but there are still controversies about the appropriateness of metroplasty. In addition, there have been few studies of the factors related to reproductive outcomes of women after surgery. The study aimed to evaluate the reproductive outcomes and the associated risk factors that influence reproductive outcomes after hysteroscopic metroplasty of women with septate uterus and the desire to conceive. Methods: This study was an observational study. Cases were screened by searching electronic patient files, and demographic factors were collected. We conducted telephone follow-ups to collect the postoperative reproductive outcomes. The primary outcome of this study was live birth, and secondary outcomes were ongoing pregnancy, clinical pregnancy, early miscarriage, and preterm birth. Demographic variables included patients' age, body mass index (BMI), the type of septum, infertility and miscarriage history, and complications including intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were collected to perform univariate and multivariate analyses to predict the risk factors of reproductive outcomes after surgery treatment. Results: In total, 348 women were evaluated and followed up. There were 95 cases (27.3%, 95/348) with combined infertility, 195 cases (56.0%, 195/348) with miscarriage history, and cases combined with intrauterine adhesions, endometrial polyps, endometriosis, and adenomyosis were 107 (30.7%, 107/348), 53 (15.2%, 53/348), 28 (8.0%, 28/348), and 5 (1.4%), respectively. Following surgery, the live birth rate and clinical pregnancy rate were significantly higher than prior to surgery (84.6% vs 3.7%, p= 0.000; and 78.2% vs 69.5%, p= 0.01, respectively), early miscarriage rate and preterm delivery rate were significantly lower (8.8% vs 80.6%, p= 0.000; and 7.0% vs 66.7%, p=0.000, respectively). After adjusting for body mass index, miscarriage history, and complications, multivariable logistic regression analysis revealed age ≥ 35 years and primary infertility as independent factors that affected postoperative clinical pregnancy (OR 4.025, 95% CI 2.063-7.851, p= 0.000; and OR 3.603, 95% CI 1.903-6.820, p= 0.000; respectively) and ongoing pregnancy (OR 3.420, 95% CI 1.812-6.455, p= 0.000; and OR 2.586, 95% CI 1.419-4.712, p= 0.002; respectively). Conclusions: Hysteroscopic metroplasty could lead to improved reproductive outcomes of women with septate uterus. Both age and primary infertility were independent factors for postoperative reproductive outcomes. Trial registration: Chi ECRCT20210343.


Abortion, Spontaneous , Adenomyosis , Endometriosis , Infertility , Premature Birth , Septate Uterus , Uterine Diseases , Infant, Newborn , Pregnancy , Humans , Female , Adult , Hysteroscopy/adverse effects , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/etiology , Adenomyosis/complications , Endometriosis/complications , Premature Birth/epidemiology , Premature Birth/etiology , Uterus/surgery , Uterine Diseases/epidemiology , Uterine Diseases/etiology , Uterine Diseases/surgery , Infertility/etiology , Risk Factors
7.
FASEB J ; 37(6): e22976, 2023 06.
Article En | MEDLINE | ID: mdl-37227215

Nucleus pulposus (NP) degeneration is characterized by the decreased cellularity of nucleus pulposus cells (NPCs) and diminished content of hydrophilic extracellular matrix (ECM). Overexpression of brachyury has been reported to reverse the degenerated NPCs into healthy phenotypes. However, the direct correlation between brachyury and ECM has not been fully elucidated. This study revealed that brachyury expression decreased in human degenerated NP tissues and Lipopolysaccharide (LPS)-induced degenerated rat NPCs model. In vitro and in vivo experiments further showed that brachyury deficiency suppressed the synthesis of aggrecan and collagen II in NP. Mechanistically, ChIP-qPCR assays demonstrated that brachyury bound to the promoter region of aggrecan in NPCs. Furthermore, luciferase reporter assays revealed that brachyury transcriptionally activated aggrecan expression through binding with a novel specific motif. In rat in vivo model, brachyury overexpression partially reversed the degenerative phenotype. In conclusion, brachyury positively regulated ECM synthesis via directly promoting aggrecan transcription in NPCs. Accordingly, it may be helpful to be developed into a promising therapeutic target for NP degeneration.


Intervertebral Disc Degeneration , Nucleus Pulposus , Animals , Humans , Rats , Aggrecans/genetics , Aggrecans/metabolism , Extracellular Matrix/metabolism , Intervertebral Disc Degeneration/metabolism , Nucleus Pulposus/metabolism
8.
Front Microbiol ; 14: 1075900, 2023.
Article En | MEDLINE | ID: mdl-36744089

Introduction: The endometrial microbiota plays an essential role in the health of the female reproductive system. However, the interactions between the microbes in the endometrium and their effects on adenomyosis remain obscure. Materials and methods: We profile endometrial samples from 38 women with (n=21) or without (n=17) adenomyosis to characterize the composition of the microbial community and its potential function in adenomyosis using 5R 16S rRNA gene sequencing. Results: The microbiota profiles of patients with adenomyosis were different from the control group without adenomyosis. Furthermore, analysis identified Lactobacillus zeae, Burkholderia cepacia, Weissella confusa, Prevotella copri, and Citrobacter freundii as potential biomarkers for adenomyosis. In addition, Citrobacter freundii, Prevotella copri, and Burkholderia cepacia had the most significant diagnostic value for adenomyosis. PICRUSt results identified 30 differentially regulated pathways between the two groups of patients. In particular, we found that protein export, glycolysis/gluconeogenesis, alanine, aspartate, and glutamate metabolism were upregulated in adenomyosis. Our results clarify the relationship between the endometrial microbiota and adenomyosis. Discussion: The endometrial microbiota of adenomyosis exhibits a unique structure and Citrobacter freundii, Prevotella copri, and Burkholderia cepacia were identified as potential pathogenic microorganisms associated with adenomyosis. Our findings suggest that changes in the endometrial microbiota of patients with adenomyosis are of potential value for determining the occurrence, progression, early of diagnosis, and treatment oadenomyosis.

9.
Reprod Biomed Online ; 45(6): 1189-1196, 2022 12.
Article En | MEDLINE | ID: mdl-36184275

RESEARCH QUESTION: What is the efficacy of platelet-rich plasma (PRP) in reducing adhesion reformation in women with moderate to severe intrauterine adhesions (IUA)? DESIGN: In this randomized controlled trial, women with moderate-to-severe IUA were recruited between November 2019 and June 2021 from a university hospital and randomized into the PRP or control group. The PRP group was treated using an intrauterine-suitable balloon combined with PRP infusion following hysteroscopic adhesiolysis, whereas the control group received only the former intervention. The reductions in adhesion scores from before to after surgery and the adhesion reformation rate were analysed. RESULTS: A total of 123 participants successfully completed the study (PRP group, 63; control group, 60). Age, pregnancy history, menstrual score and American Fertility Society score before surgery were not significantly different between the two groups. At the second-look hysteroscopy, the PRP group had a significantly greater reduction in adhesion score than the control group (7 versus 6, respectively; P = 0.027). The postoperative adhesion reformation rates in the PRP group and the control group were 20.6% and 30.0%, respectively (risk ratio 0.69, 95% confidence interval 0.27-1.38, P = 0.232; number needed to treat 10.6). CONCLUSIONS: Intrauterine PRP infusion seems to be beneficial in reducing postoperative adhesion reformation following hysteroscopic adhesiolysis.


Intrauterine Devices , Platelet-Rich Plasma , Uterine Diseases , Pregnancy , Female , Humans , Tissue Adhesions/prevention & control , Tissue Adhesions/surgery , Hysteroscopy , Uterine Diseases/surgery , Uterine Diseases/prevention & control
11.
Int J Gynaecol Obstet ; 159(3): 875-881, 2022 Dec.
Article En | MEDLINE | ID: mdl-35574630

OBJECTIVE: To explore the impact of concomitant intrauterine adhesions (IUAs) on pregnancy outcomes and obstetric complications in women with a septate uterus. METHODS: This retrospective cohort included women with a septate uterus, with or without IUAs, between 2015 and 2019 in our hospital. The main outcomes were clinical pregnancy rate, live-birth rate, and obstetric complications. RESULTS: A total of 336 women with a septate uterus-105 women (31.3%) with IUAs and 231 (68.7%) women without IUAs-were analyzed. The rates of clinical pregnancy and live birth among women with moderate-to-severe IUAs were significantly decreased compared with those among women without IUAs (69.9% vs. 76.6%, odds ratio [OR] 0.51; 95% confidence interval [CI] 0.27-0.99, P = 0.046, and 57.0% vs. 67.1%, OR 0.53; 95% CI 0.30-0.95, P = 0.032, respectively). However, these rates were similar between women with mild IUAs and women without IUAs. Women with moderate-to-severe IUAs had a higher incidence of abnormal placentation than women with a septum only (13.2% vs. 1.3%, P = 0.001). CONCLUSION: Concomitant moderate-to-severe IUAs significantly reduce the rates of clinical pregnancy and live birth and increase the risk of abnormal placentation in subsequent pregnancies in women with a septate uterus.


Pregnancy Outcome , Uterine Diseases , Pregnancy , Female , Humans , Male , Retrospective Studies , Uterine Diseases/complications , Uterine Diseases/epidemiology , Tissue Adhesions/epidemiology , Tissue Adhesions/etiology , Uterus/pathology , Hysteroscopy
12.
Reprod Biomed Online ; 44(5): 881-887, 2022 05.
Article En | MEDLINE | ID: mdl-35361544

RESEARCH QUESTION: What are the prevalence and risk factors of intrauterine adhesions (IUA) in patients with a septate uterus? DESIGN: In this retrospective cohort study, patients with a septate uterus who underwent septum resection between 2015 and 2020 were analysed. Two-dimensional transvaginal ultrasonography plus hysteroscopy was used to diagnose uterine septum or IUA. The prevalence and risk factors for IUA in patients with a septate uterus were examined. RESULTS: Among 522 eligible patients with a septate uterus, 165 patients were diagnosed with IUA (prevalence 31.6% [95% CI 27.7 to 35.5%]). In the multivariable logistic regression analysis of risk factors for IUA, patients who had experienced one or more miscarriages were more likely to have IUA than patients who had not (OR 3.38, 95% CI 1.96 to 5.83, P < 0.001, and OR 2.55, 95% CI 1.24 to 5.23, P = 0.011, respectively). Patients who underwent one or more dilatation and curettage (D&C) procedures had a significantly increased risk of IUA compared with patients who did not (OR 3.42, 95% CI 1.87 to 6.26, P < 0.001, and OR 3.99, 95% CI 1.93 to 8.26, P < 0.001, respectively). For patients with a history of miscarriage or D&C, the prevalence rates of IUA were 46.5% (95% CI 40.6 to 52.4%) and 44.0% (95% CI 38.5 to 49.5%), respectively. CONCLUSION: Nearly one-third of patients with a septate uterus have concomitant IUA. A previous miscarriage or D&C is an important risk factor for IUA in patients with a septate uterus.


Abortion, Spontaneous , Uterine Diseases , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/etiology , Female , Humans , Hysteroscopy/methods , Pregnancy , Prevalence , Retrospective Studies , Risk Factors , Tissue Adhesions/epidemiology , Tissue Adhesions/etiology , Uterine Diseases/surgery , Uterus/diagnostic imaging , Uterus/surgery
13.
J Assist Reprod Genet ; 39(5): 1033-1043, 2022 May.
Article En | MEDLINE | ID: mdl-35332423

PURPOSE: The study aims to evaluate whether frozen embryo transfer can restore optimal receptivity leading to better assisted reproductive technology outcomes in women with endometriosis. METHODS: This systematic review and meta-analysis, conducted from January 10, 2021 to July 1, 2021, searched the Cochrane Library, PubMed, Embase, Web of Science, OVID, and Clinicaltrials.gov databases from inception to January 10, 2021. The search strategy combined search terms as follows: ("endometriosis" OR "deep endometriosis" OR "endometrioma") AND ("frozen-thawed embryo transfer" OR "frozen embryo transfer" OR "freeze-all strategy") AND ("pregnancy outcome" OR "live birth rate" OR "clinical pregnancy rate" OR "miscarriage rate"). No publication time or language limits were set during the searches. In addition, references of the related articles were searched by hand. Patients were included if they had a history of endometriosis and had received fresh or frozen embryo transfer. Only the first transfer cycle was included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to express outcomes, and data synthesis was conducted using RevMan, version 5.4 software. RESULTS: A total of six studies with moderate methodologic quality were retrieved in the meta-analysis. The studies included 3010 women with endometriosis who wanted to conceive; 1777 (59.0%) had frozen embryo transfer, and 1233 (41.0%) had fresh embryo transfer. There was a significantly higher frequency of live births in the frozen embryo group than in the fresh embryo group (OR, 1.53; 95% CI, 1.13-2.08; P = .007). Despite a similar clinical pregnancy rate in the two groups (OR, 1.26; 95% CI, 0.95-1.69; P = .11), the difference in miscarriage rate was significant (OR, 0.70; 95% CI, 0.50-0.97; P = .03). Evidence quality was considered moderate. CONCLUSION: Cryopreserved embryo transfer has resulted in preferable reproduction outcomes when compared with fresh embryo transfer in patients with endometriosis, but the evidence is not yet abundant. More strictly designed research is needed to evaluate whether frozen embryo transfer leads to better reproductive outcomes in women with endometriosis compared with those receiving fresh embryo transfer. REGISTRATION NUMBER: PROSPERO CRD42021248313.


Abortion, Spontaneous , Endometriosis , Infertility , Abortion, Spontaneous/etiology , Embryo Transfer/methods , Female , Humans , Infertility/etiology , Live Birth , Pregnancy , Pregnancy Rate
14.
Menopause ; 28(11): 1209-1213, 2021 09 07.
Article En | MEDLINE | ID: mdl-34469931

OBJECTIVES: The aim of this study was to examine the growth of uterine leiomyomas in postmenopausal women and evaluate the influencing factors associated with fibroid growth. METHODS: We retrospectively analyzed the medical records of postmenopausal women with fibroids between 2015 and 2020. All women received at least 2 transvaginal ultrasound examinations within a 6-month interval. All fibroids were verified via surgery. The postoperative pathology of all tumors was uterine fibroid. We calculated the fibroid volume using the ellipsoid volume formula and evaluated the growth rate of fibroids within 6 months simultaneously. Univariable analysis and a linear mixed-effects model were used to assess the factors influencing fibroid growth. RESULTS: A total of 102 postmenopausal women with a total of 132 fibroids were assessed. The median growth rate of surgically confirmed fibroids in postmenopausal women was 12.9% every 6 months (from -61.4% to 184.1%). Obesity was associated with fibroid growth (P < 0.05). Notably, the estimated growth rates of fibroids in obese and overweight women were 26.6% (95% confidence interval [CI]: 2.3-50.9) and 15.9% (95% CI: 0.4-31.4) higher than those in women of normal weight, respectively. The growth of fibroids varied by the initial tumor size (P < 0.05). The estimated growth rate of larger fibroids (≥5.0 cm diameter) was reduced 30.0% (95% CI: -52.4 to -7.5) compared with that of small fibroids (<3.0 cm diameter). CONCLUSIONS: Uterine fibroids continually grow in some postmenopausal women. Obesity and small fibroids (<3.0 cm diameter) may contribute to higher growth rates of fibroids.


Leiomyoma , Uterine Neoplasms , Female , Humans , Leiomyoma/diagnostic imaging , Leiomyoma/epidemiology , Leiomyoma/surgery , Postmenopause , Retrospective Studies , Ultrasonography , Uterine Neoplasms/diagnostic imaging , Uterine Neoplasms/epidemiology , Uterine Neoplasms/surgery
15.
BMC Cancer ; 21(1): 176, 2021 Feb 18.
Article En | MEDLINE | ID: mdl-33602172

BACKGROUND: Synchronous multifocal lung cancer (SMLC) is diagnosed with increasing frequency in clinical practice globally. Due to innate variation in clinical management and outcome, it is vital to properly distinguish between synchronous multifocal primary lung cancer (SMPLC) and intrapulmonary metastasis (IM). The pathologic features and principal classification criteria of multifocal lung cancer remain unclear. Our objective was to evaluate the diagnostic value of histological morphologic features and driver gene mutations in SMLC classification. METHODS: We collected a unique cohort of Chinese patients with SMLC, and fully explored the morphologic, immunohistochemical, and molecular features of the disease. Twenty-one SMLC patients with a total of 50 tumours were included in our study. The pathological features that were presented by these patients were analysed, including the tumours location, tumours size, pathological types, predominant pattern of adenocarcinoma, and immunohistochemical staining. We conducted molecular testing of nine driver oncogenes that are associated with lung cancer, namely, EGER, KRAS, BRAF, NRAS, ALK, ROS1, RET, HER2, and PIK3CA. RESULTS: According to the Martini-Melamed classification and refined standard, 8 and 17 patients, respectively, were considered to have SMPLCs. Gene mutations were identified in 18 tumours (36%). Twelve patients had different gene mutations. CONCLUSIONS: We demonstrate that conventional morphological assessment is not sufficient to clearly establish the clonal relationship of SMPLCs. Instead, the evaluation of histological subtypes, including nonmucinous adherent components, is required. Multiplex genotypic analysis may also prove to be a useful additional tool.


Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Adult , Aged , Aged, 80 and over , Asian People/genetics , China , Cohort Studies , Female , Genes, Neoplasm , Genetic Heterogeneity , High-Throughput Nucleotide Sequencing , Humans , Male , Middle Aged , Mutation , Neoplasm Grading
16.
Int J Surg Pathol ; 29(5): 520-523, 2021 Aug.
Article En | MEDLINE | ID: mdl-33605184

Ciliated muconodular papillary tumors (CMPTs) are rare peripheral lung lesions, characterized by papillary architecture and ciliated columnar cells admixed with mucous cells and basal cells. Only about 50 cases have been reported to date and is categorized as a benign neoplasm. In this article, we report an extremely rare case of 79-year-old man with a CMPT that developed in his right upper lobe. The central region of the tumor showed features of classic CMPT, while marginal area of the tumor showed the characteristics of invasive lung cancer. In central classic CMPT region, the ciliated, basal, and mucous cells were positive for thyroid transcription factor-1, cytokeratin 7 (CK7), and NapsinA. Basal cells were positive for CK5/6 and p40. Mucous cells were weakly positive for MUC2 and MUC5AC. However, CK5/6 and p40 were negative in the peripheral malignant area. Both of the benign and malignant regions had an EGFR driver mutation in exon 21. We concluded that this tumor was an extremely rare malignant case of CMPT.


Adenocarcinoma, Papillary/diagnosis , Biomarkers, Tumor/analysis , Lung Neoplasms/diagnosis , Lung/pathology , Adenocarcinoma, Papillary/pathology , Adenocarcinoma, Papillary/surgery , Aged , Diagnosis, Differential , Humans , Lung/diagnostic imaging , Lung/surgery , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Thoracic Surgery, Video-Assisted , Tomography, X-Ray Computed
17.
Carcinogenesis ; 41(5): 551-560, 2020 07 10.
Article En | MEDLINE | ID: mdl-31713604

The bone marrow has been long known to host a unique environment amenable to colonization by metastasizing tumor cells. Yet, the underlying molecular interactions which give rise to the high incidence of bone metastasis (BM) in breast cancer patients have long remained uncharacterized. In our study, in vitro and in vivo assays demonstrated that Brachyury (Bry) could promote breast cancer BM. Bry drives epithelial-mesenchymal transition (EMT) and promotes breast cancer aggressiveness. As an EMT driver, SOX5 involves in breast cancer metastasis and the specific function in BM. Chromatin immunoprecipitation (ChIP) assays revealed SOX5 is a direct downstream target gene of Bry. ChIP analysis and reporter assays identified two Bry-binding motifs; one consistent with the classic conserved binding sequence and the other a new motif sequence. This study demonstrates for the first time that Bry promotes breast cancer cells BM through activating SOX5. In clinical practice, targeting the Bry-Sox5-EMT pathway is evolving into a promising avenue for the prevention of bone metastatic relapse, therapeutic resistance and other aspects of breast cancer progression. Brachyury directly regulates the expression of SOX5 by binding to two motifs in its promoter region. The Bry-SOX5-EMT pathway may represent a potential target to develop treatments to prevent and treat bone metastasis from breast cancer.


Biomarkers, Tumor/metabolism , Bone Neoplasms/secondary , Breast Neoplasms/pathology , Fetal Proteins/metabolism , Gene Expression Regulation, Neoplastic , SOXD Transcription Factors/genetics , T-Box Domain Proteins/metabolism , Transcriptional Activation , Animals , Apoptosis , Biomarkers, Tumor/genetics , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Adhesion , Cell Movement , Cell Proliferation , Disease Progression , Epithelial-Mesenchymal Transition , Female , Fetal Proteins/genetics , Humans , Mice , Mice, Nude , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Prognosis , SOXD Transcription Factors/metabolism , Survival Rate , T-Box Domain Proteins/genetics , Tumor Cells, Cultured , Xenograft Model Antitumor Assays
18.
Cancer Biol Ther ; 17(3): 254-61, 2016.
Article En | MEDLINE | ID: mdl-26810818

SATB1, a global gene regulator, has been implicated in the growth and metastasis of multiple cancers, including colorectal cancer. While the understanding about the role of SATB1 in CRC remains limited. The aim of our study is to investigate the expression of SATB1 in CRC, and the relationship between SATB1 expression pattern and clinicopathological variables. A further aim is to analyze the correlation between SATB1 expression and epithelial-mesenchymal transition in CRC. Immunohistochemical expression of SATB1, ß-catenin, E-cadherin, CK20, Vimentin, SMA, and desmin were assessed in a cohort of 200 patients using tissue microarrays. SATB1 was expressed in 133 (66.5%) CRC primary lesions, 14 (28%) adjacent colorectal mucosa specimens, and 60 (75%) corresponding lymph node metastases. The expression level of SATB1 was significantly higher in lymph node metastases than in CRC primary lesions and normal mucosa (P = 0.000). High expression of SATB1 in CRC was strongly correlated with poor differentiation of tumor tissues (P = 0.000). High expression of SATB1 was significantly correlated with aberrant expression of ß-catenin (P = 0.0005), low expression of E-cadherin (P = 0.000) and CK20 (P = 0.000) and with high expression of Vimentin (P = 0.001). No SMA or desmin protein was expressed in the CRC cells. Our results suggested that high expression of SATB1 is significantly correlated with poor differentiation of CRC. SATB1 might promote the epithelial-mesenchymal transition by increasing the aberrant expression of ß-catenin.


Colorectal Neoplasms/metabolism , Matrix Attachment Region Binding Proteins/biosynthesis , beta Catenin/metabolism , Adult , Aged , Aged, 80 and over , Cohort Studies , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition , Female , Humans , Immunohistochemistry , Male , Matrix Attachment Region Binding Proteins/genetics , Matrix Attachment Region Binding Proteins/metabolism , Middle Aged
20.
Zhonghua Bing Li Xue Za Zhi ; 44(8): 578-81, 2015 Aug.
Article Zh | MEDLINE | ID: mdl-26705182

OBJECTIVE: To study the diagnostic value of SATB2, together with CK7 and CK20, in colorectal cancer. METHODS: Immunohistochemical study for SATB2, CK7 and CK20 was carried out in 210 cases of colorectal cancer tissue, 100 cases of non-colorectal cancer tissue, 90 cases of lymph node metastases and 50 cases of normal colorectal mucosa. RESULTS: The sensitivity and specificity of CK20+/CK7- immunophenotype for diagnosis of colorectal adenocarcinoma were 78.1% and 92.0%, respectively. When triple markers were used, the immunophenotype CK20+/CK7-/SATB2+ had a sensitivity of 57.1% and a specificity of 98.0%. When combining the immunophenotype of SATB2+/CK7- or CK20+/CK7-, the sensitivity was 85.7% and specificity was 90.0%. CONCLUSIONS: A panel of immunohistochemical markers SATB2, CK7 and CK20 could increase the specificity for diagnosis of colorectal adenocarcinoma significantly. SATB2 is considered as a useful adjunct in this respect.


Adenocarcinoma/diagnosis , Colorectal Neoplasms/diagnosis , Keratin-7/metabolism , Matrix Attachment Region Binding Proteins/metabolism , Transcription Factors/metabolism , Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Humans , Immunophenotyping , Keratin-20/metabolism , Lymphatic Metastasis , Sensitivity and Specificity
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