• Androgen receptor
• Breast cancer
• Prostate cancer
• Signaling pathway

• Humans
• Receptors, Androgen/metabolism
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Breast Neoplasms/metabolism
• Female
• Signal Transduction/drug effects
• Biomarkers, Tumor/metabolism
• Drug Discovery/methods

• deer antler
• immunomodulatory mechanisms
• molecular docking
• molecular dynamics simulation
• network pharmacology

• No.20200404024YY Jilin Province Science and Technology Development Plan Project
• No. JJKH20210363KJ Research Foundation of the Education Department of Jilin Province

Pleomorphic adenoma gene like-2 (PLAGL2) has been implicated in the development and progression of diverse malignancies, including glioblastoma. An increasing number of studies have reported that dysregulated expression of PLAGL2 is a common phenomenon in different malignancies. However, the mechanism and biological functions of PLAGL2 in patients with high-grade glioma (HGG) remain unclear. In addition, the expression and clinical significance of PLAGL2 in HGG have not yet been reported. Herein, we investigated the expression patterns and prognostic values of PLAGL2 in patients with HGG by using various databases, including Tumor Immune Estimation Resource 2.0 (TIMER2.0), GENT2, ONCOMINE, GEPIA, Human Protein Atlas, and Gene Expression Omnibus datasets. In the present study, we analyzed the relationship between PLAGL2 mRNA expression and clinical parameters in 184 HGG cases and found that PLAGL2 presented positively high expression and was relevant to poor prognosis. Immunohistochemistry analysis confirmed the overexpression of PLAGL2 protein, which is mainly expressed in the nucleus of glioma. Additionally, a high level of expression of the PLAGL2 gene was associated with lower survival in progression-free survival and overall survival in GBM patients. The correlation analysis between PLAGL2 and immune infiltration related to the abundance of B cells, CD8⁺ T cells, CD4⁺ T cells, macrophages, DCs, and neutrophils was also performed using TIMER2.0. GSEA results showed that high PLAGL2 expression was associated with cell migration, proliferation, actin cytoskeletal, and angiogenesis. To sum up, our findings indicated that PLAGL2 could serve as an independent prognostic biomarker and might be a potential therapeutic target for HGG, which should be further investigated.

Crescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN.

One hundred IgAN patients with various proportions of crescents—24 with 1%–24%, 27 with 25%–49%, 21 with 50%–74% 12 with more than 75%, and 16 without crescents—were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry.

IgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652–62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0–1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127–66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859–2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058–1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916–11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents.

Excess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.

• complement
• crescent
• immunoglobulin A nephropathy (IgAN)
• lectin pathway
• urinary C4d

We aimed to explore the cardiovascular characteristics of patients who were initially diagnosed with breast cancer.

A total of 600 patients who were diagnosed with primary breast cancer were included in this retrospective study. The data of fasting blood glucose, total cholesterol, total triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein (a) (LP (a)) and serum uric acid were collected. Univariate analysis was used to evaluate the cardiovascular risk factors (CVRFs) in patients with breast cancer. The arteriosclerotic cardiovascular disease (ASCVD) risk assessment was performed. Multivariate analysis was used to identify the factors that influenced axillary lymph node metastasis (ALNM).

Compared with the premenopausal group, the prevalence of overweight/obesity (47.6% vs. 35.2%), diabetes (12.8% vs. 4.3%) and hypertension (49.7% vs. 26.3%) were significantly increased in the postmenopausal group (p < 0.05). Comparisons of rural patients and urban patients showed that there were significant differences in the diagnostic age (49.94 ± 9.92 vs. 52.59 ± 11.13) in the rural patients was notably younger in comparison with the urban patients (p < 0.05). However, the number of menopausal patients (44.3% vs. 53.3%) in the rural group were decreased in comparison with the urban group (p < 0.05). In ASCVD risk stratification, the proportion of low-risk patients (56.4% vs. 90.8%), medium-risk patients (20.6% vs 0.3%) and high-risk patients (19.3% vs. 6.6%) were significantly different between the postmenopausal group and premenopausal group (p < 0.05). Residence (OR 0.735; 95% CI 0.516–1.046; p = 0.087), the number of children (OR 1.250; 95% CI 0.990–1.578; p = 0.061) and LP (a) of ≥ 500 mg/L (OR 0.603; 95% CI 0.342–1.063; p = 0.080) were independent influencing factors of ALNM.

Postmenopausal patients have more CVRFs and higher risks of ASCVD than premenopausal patients initially diagnosed with breast cancer. There was a correlation between CVRFs and ALNM in patients with breast cancer.

• Axillary lymph node metastasis
• Breast cancer
• Cardiovascular risk factors
• Initial diagnosis

• AR/ER ratio
• androgen receptor
• breast cancer
• pre-menopausal
• testosterone

• Breast Neoplasms/blood
• Breast Neoplasms/metabolism
• Breast Neoplasms/mortality
• Breast Neoplasms/pathology
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Prognosis
• Receptors, Androgen/metabolism
• Receptors, Estrogen/metabolism
• Retrospective Studies
• Survival Rate
• Testosterone/blood

• IA/CPHI/18/1/503938 DBT-Wellcome Trust India Alliance
• Wellcome Trust

Microarray profiles of hepatocellular carcinoma (HCC) identified that long intergenic noncoding RNA 00221 (LINC00221) was upregulated. Herein, we aimed to identify the functional significance and underlying mechanisms of LINC00221 in HCC.

Human HCC samples had increased expression of LINC00221. Effects of LINC00221 on HCC cellular functions were analyzed using gain- and loss-function approaches. LINC00221 knockdown repressed HCC cell growth, migration, and invasion and enhanced their apoptosis. This anti-tumor effect was validated in vivo. Online prediction showed the potential binding relationship between LINC00221 and let-7a-5p, as well as that between let-7a-5p and matrix metalloproteinase 11 (MMP11). The results of luciferase, RNA immunoprecipitation, and RNA pull-down assays identified that LINC00221 interacted with let-7a-5p to increase expression of MMP11. Furthermore, we demonstrated that LINC00221 silencing increased let-7a-5p and inhibited MMP11 expression, thereby delaying the progression of HCC in vitro.

Silencing of LINC00221 could prevent HCC progression via upregulating let-7a-5p and downregulating MMP11. As such, LINC00221 inhibition presents a promising antitumor strategy for the treatment of HCC.

• Cell cycle
• Cell migration
• Hepatocellular carcinoma
• Let-7a-5p
• Long noncoding RNA LINC00221
• Matrix metalloproteinase-11

• benefits versus risks
• estrogens
• global index
• hazard ratio
• menopausal hormone therapy
• multivariate failure times
• progestin

• Coronary Disease/epidemiology
• Estrogen Replacement Therapy/statistics & numerical data
• Estrogens, Conjugated (USP)/administration & dosage
• Female
• Hip Fractures/epidemiology
• Humans
• Medroxyprogesterone Acetate/administration & dosage
• Middle Aged
• Neoplasms/epidemiology
• Postmenopause
• Proportional Hazards Models
• Pulmonary Embolism/epidemiology
• Stroke/epidemiology

• HHSN268201600002C NHLBI NIH HHS
• R01 CA210921 NCI NIH HHS
• HHSN268201100046C NHLBI NIH HHS
• HHSN271201600004I NIDA NIH HHS
• HHSN268201600004C NHLBI NIH HHS
• HHSN268201600003C NHLBI NIH HHS
• HHSN271201600004C NIDA NIH HHS
• R01 CA119171 NCI NIH HHS

We explored the therapeutic and prognostic effect of YAP/TAZ intensityinHER2-positive breast cancer patients. We also investigated the relationship between YAP/TAZ expression and Trastuzumab-resistance.

We collected clinicopathological information from 397 cases. We evaluated therapeutic and prognostic effect of YAP/TAZ and other variables. We also cultivated Trastuzumab-resistance cell lines and explored relationship between YAP/TAZ and Trastuzumab-resistance.

Over-expression of YAP/TAZ was remarkable in Trastuzumab-resistant cells, and so did HER3 and HER2/HER3 heterodimer. Inhibition of YAP/TAZ expression reversed Trastuzumab-resistance.YAP/TAZ deficiency contributed to favorable therapeutic response, and so did hormone receptor insufficiency and chemotherapy dosage inferiority. Deficient YAP/TAZ intensity and abundant hormone receptor intensity contributed to better survival. Over-expression of YAP/TAZ was obvious in recurrent cases in comparison with their matching primary lesions. Prognostic superiority of insufficient YAP/TAZ intensity was more outstanding in hormone receptor negative cases. Over-expression of YAP/TAZ and HER3 was generally synchronous. Absence of HER3 expression in residual lesions might correlate with better breast cancer-free survival.

Over-expression of YAP/TAZ as well as HER-3 and HER2/HER3 heterodimer was synchronously remarkable in Trastuzumab-resistant cell lines. Inhibition of YAP/TAZ expression reversed Trastuzumab resistance. Deficient YAP/TAZ intensity as well as insufficient hormone receptor intensity and high chemotherapy dosage contributed to favorable therapeutic response. Deficient YAP/TAZ intensity and abundant hormone receptor intensity contributed to better survival, and so did absence of HER3expression in residual lesions. Prognostic superiority of YAP/TAZ expression depended on hormone receptor status. Cases with synchronous over-expression of YAP/TAZ and HER3 suffered poor survival, which revealed the potential effect of YAP/TAZ-HER2/HER3 crosstalk in prognosis of HER2-positive patients.

• HER2/HER3 heterodimer
• SKBR-3 cell lines
• Trastuzumab-based neoadjuvant therapy
• YAP/TAZ
• breast cancer-free interval

• Cox model
• cancer
• cardiovascular disease
• diabetes
• dual outcomes
• fractures
• hazard ratio
• menopausal hormone therapy

• Aged
• Cardiovascular Diseases/epidemiology
• Estrogen Replacement Therapy
• Estrogens, Conjugated (USP)/administration & dosage
• Female
• Fractures, Bone/epidemiology
• Gallbladder Diseases/epidemiology
• Humans
• Incidence
• Intention to Treat Analysis
• Medroxyprogesterone Acetate/administration & dosage
• Middle Aged
• Postmenopause
• Randomized Controlled Trials as Topic
• Risk Factors
• United States/epidemiology

• HHSN268201600002C NHLBI NIH HHS
• R01 CA210921 NCI NIH HHS
• HHSN268201100046C NHLBI NIH HHS
• HHSN271201600004I NIDA NIH HHS
• HHSN268201600004C NHLBI NIH HHS
• HHSN268201600001C NHLBI NIH HHS
• HHSN268201600003C NHLBI NIH HHS
• HHSN271201600004C NIDA NIH HHS
• R01 CA119171 NCI NIH HHS
• National Cancer Institute
• National Heart, Lung and Blood Institute

Rectal cancer (RC) is one of the most common diagnosed cancers, and one of the major causes of cancer-related death nowadays. Majority of the current guidelines rely on TNM classification regarding therapy regiments, however recent studies suggest that additional histopathological findings could affect the disease course.

To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival (OS) of RC patients.

A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic, Clinical Center of Serbia, between the years of 2014–2016. All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification. In addition, the patient’s demographics, surgical details, postoperative pathological details, differentiation degree and their correlation with OS was investigated.

Of 245 included patients with stage I-III RC, lymphovascular invasion (LVI) was identified in 92 patients (38%), whereas perineural invasion (PNI) was present in 46 patients (19%). Using Kaplan-Meier analysis for overall survival rate, we have found that both LVI and PNI were associated with lower survival rates (P < 0.01). Moreover when Cox multiple regression model was used, LVI, PNI, older age, male gender were predictors of poor prognosis (HR = 5.49; 95%CI: 2.889-10.429; P < 0.05).

LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients, hence more aggressive therapy should be reserved for these patients after curative resection.

• Lymphovascular invasion
• Perineural invasion
• Rectal cancer

Si-Wu-Tang (SWT), a traditional Chinese herbal formula, has shown an effect on antibreast cancer. However, the mechanisms and bioactive components of SWT are still unclear. Fortunately, cell type-specific molecular network has provided an effective method. This study integrated the data of formula components, all types of biomolecules in the human body, and nonexpressed protein in breast cancer cells and constructed the breast cancer cell network and the biological network that SWT acted on the breast cancer-related targets by Entity Grammar System (EGS). Biological network showed 59 bioactive components acting on 15 breast cancer-related targets. The antibreast cancer mechanisms were summarized by enrichment analysis: regulation of cell death, response to hormone stimulation, response to organic substance, regulation of phosphorylation of amino acids, regulation of cell proliferation, regulation of signal transmission, and affection of gland development. In addition, we discovered that verbascoside played the role of antibreast cancer by inhibiting cell proliferation, but there was not a report on this effect. The results of CCK8 and western blot were consistent with the antibreast cancer effect of verbascoside based on biological network. Biological network modeling by EGS and network analysis provide an effective way for uncovering the mechanism and identifying the bioactive components of SWT.

• Obesity
• Parity
• Premenopausal
• breast cancer
• postmenopausal

• Adult
• Aged
• Body Mass Index
• Breast Neoplasms/etiology
• Breast Neoplasms/pathology
• Case-Control Studies
• Factor Analysis, Statistical
• Female
• Follow-Up Studies
• Humans
• India
• Middle Aged
• Obesity/complications
• Overweight/complications
• Parity
• Postmenopause
• Pregnancy
• Premenopause
• Prognosis
• Risk Factors

• Notch-1
• breast cancer
• microRNA 34a
• rhamnetin

• Adult
• Aged
• Aged, 80 and over
• Cardiovascular Diseases/chemically induced
• Cardiovascular Diseases/mortality
• Cause of Death
• Estrogen Replacement Therapy/adverse effects
• Estrogen Replacement Therapy/methods
• Estrogens/adverse effects
• Estrogens/therapeutic use
• Female
• Hot Flashes/drug therapy
• Humans
• Middle Aged
• Neoplasms/chemically induced
• Neoplasms/mortality
• Perimenopause
• Postmenopause
• Progesterone/adverse effects
• Progesterone/therapeutic use
• Randomized Controlled Trials as Topic
• Venous Thromboembolism/chemically induced

• breast cancer
• conjugated equine estrogen
• estrogen deprivation
• estrogen-induced apoptosis
• glucocorticoid activity
• inflammatory response
• medroxyprogesterone acetate
• menopausal hormone therapy

• P30 CA016672 NCI NIH HHS

• breast cancer
• obesity
• postmenopausal women
• women’s health initiative

• Aged
• Body Mass Index
• Breast Neoplasms/diagnostic imaging
• Breast Neoplasms/epidemiology
• Breast Neoplasms/mortality
• Breast Neoplasms/therapy
• Female
• Humans
• Incidence
• Life Style
• Mammography
• Middle Aged
• Multivariate Analysis
• Neoplasm Invasiveness
• Obesity/diagnosis
• Obesity/epidemiology
• Obesity/mortality
• Overweight/diagnosis
• Overweight/epidemiology
• Overweight/mortality
• Postmenopause
• Prognosis
• Proportional Hazards Models
• Risk Assessment
• Risk Factors
• Time Factors
• United States/epidemiology
• Weight Gain

• HHSN268201100001I NHLBI NIH HHS
• HHSN268201100004I NHLBI NIH HHS
• HHSN268201100046C NHLBI NIH HHS
• HHSN268201100003C WHI NIH HHS
• HHSN271201100004C NIA NIH HHS
• HHSN268201100002C WHI NIH HHS
• HHSN268201100003I NHLBI NIH HHS
• HHSN268201100001C WHI NIH HHS
• HHSN268201100004C WHI NIH HHS
• HHSN268201100002I NHLBI NIH HHS
• K07 CA136969 NCI NIH HHS

• Cancer
• Estrogen alone
• Estrogen plus progestin
• Menopausal hormone therapy

• Breast Neoplasms/epidemiology
• Breast Neoplasms/etiology
• Estrogen Replacement Therapy/adverse effects
• Estrogens/adverse effects
• Estrogens/therapeutic use
• Female
• Hormone Replacement Therapy/adverse effects
• Humans
• Postmenopause
• Progestins/adverse effects
• Progestins/therapeutic use
• Randomized Controlled Trials as Topic

• N01WH42129-32 WHI NIH HHS
• N01WH32119 WHI NIH HHS
• N01WH32100-2 WHI NIH HHS
• N01WH32108-9 WHI NIH HHS
• N01WH42107-26 WHI NIH HHS
• N01WH32118 WHI NIH HHS
• N01WH32122 WHI NIH HHS
• N01WH32105-6 WHI NIH HHS
• N01WH32111-13 WHI NIH HHS
• N01 WH042120 WHI NIH HHS
• N01WH22110 WHI NIH HHS
• N01WH24152 WHI NIH HHS
• N01WH32115 WHI NIH HHS
• N01WH44221 WHI NIH HHS