Prediction of Follicular Thyroid Neoplasm and Malignancy of Follicular Thyroid Neoplasm Using Multiparametric MRI.

The study aims to evaluate multiparametric magnetic resonance imaging (MRI) for differentiating Follicular thyroid neoplasm (FTN) from non-FTN and malignant FTN (MFTN) from benign FTN (BFTN). We retrospectively analyzed 702 postoperatively confirmed thyroid nodules, and divided them into training (n = 482) and validation (n = 220) cohorts. The 133 FTNs were further split into BFTN (n = 116) and MFTN (n = 17) groups. Employing univariate and multivariate logistic regression, we identified independent predictors of FTN and MFTN, and subsequently develop a nomogram for FTN and a risk score system (RSS) for MFTN prediction. We assessed performance of nomogram through its discrimination, calibration, and clinical utility. The diagnostic performance of the RSS for MFTN was further compared with the performance of the Thyroid Imaging Reporting and Data System (TIRADS). The nomogram, integrating independent predictors, demonstrated robust discrimination and calibration in differentiating FTN from non-FTN in both training cohort (AUC = 0.947, Hosmer-Lemeshow P = 0.698) and validation cohort (AUC = 0.927, Hosmer-Lemeshow P = 0.088). Key risk factors for differentiating MFTN from BFTN included tumor size, restricted diffusion, and cystic degeneration. The AUC of the RSS for MFTN prediction was 0.902 (95% CI 0.798-0.971), outperforming five TIRADS with a sensitivity of 73.3%, specificity of 95.1%, accuracy of 92.4%, and positive and negative predictive values of 68.8% and 96.1%, respectively, at the optimal cutoff. MRI-based models demonstrate excellent diagnostic performance for preoperative predicting of FTN and MFTN, potentially guiding clinicians in optimizing therapeutic decision-making.

Super-Assembled Multilayered Mesoporous TiO2 Nanorockets for Light-Powered Space-Confined Microfluidic Catalysis.

In the field of sustainable chemistry, it is still a significant challenge to realize efficient light-powered space-confined catalysis and propulsion due to the limited solar absorption efficiency and the low mass and heat transfer efficiency. Here, novel semiconductor TiO2 nanorockets with asymmetric, hollow, mesoporous, and double-layer structures are successfully constructed through a facile interfacial superassembly strategy. The high concentration of defects and unique topological features improve light scattering and reduce the distance for charge migration and directed charge separation, resulting in enhanced light harvesting in the confined nanospace and resulting in enhanced catalysis and self-propulsion. The movement velocity of double-layered nanorockets can reach up to 10.5 µm s-1 under visible light, which is approximately 57 and 119% higher than that of asymmetric single-layered TiO2 and isotropic hollow TiO2 nanospheres, respectively. In addition, the double-layered nanorockets improve the degradation rate of the common pollutant methylene blue under sustainable visible light with a 247% rise of first-order rate constant compared to isotropic hollow TiO2 nanospheres. Furthermore, FEA simulations reveal and confirm the double-layered confined-space enhanced catalysis and self-propulsion mechanism.

MRI Manifestations of Breast Cancer Stroma and their Role in Predicting Molecular Subtype: A Case-control Study.

OBJECTIVE: This study explored whether breast MRI manifestations could be used to predict the stroma distribution of breast cancer (BC) and the role of tumor stroma-based MRI manifestations in molecular subtype prediction. METHODS: 57 patients with pathologically confirmed invasive BC (non-special type) who had lumpy BC on MRI within one week before surgery were retrospectively collected in the study. Stroma distributions were classified according to their characteristics in the pathological sections. The stromal distribution patterns among molecular subtypes were compared with the MRI manifestations of BC with different stroma distribution types (SDTs). RESULTS: SDTs were significantly different and depended on the BC hormone receptor (HR) (P<0.001). There were also significant differences among five SDTs on T2WI, ADC map, internal delayed enhanced features (IDEF), marginal delayed enhanced features (MDEF), and time signal intensity (TSI) curves. Spiculated margin and the absence of type-I TSI were independent predictors for BC with star grid type stroma. The appearance frequency of hypo-intensity on T2WI in HR- BCs was significantly lower (P=0.043) than in HR+ BCs. Star grid stroma and spiculated margin were key factors in predicting HR+ BCs, and the AUC was 0.927 (95% CI: 0.867-0.987). CONCLUSION: Breast MRI can be used to predict BC's stromal distribution and molecular subtypes.

Integration of scRNA and bulk RNA-sequence to construct the 5-gene molecular prognostic model based on the heterogeneity of thyroid carcinoma endothelial cell.

Thyroid cancer (TC) is a kind of cancer with high heterogeneity, which leads to significant difference in prognosis. The prognostic molecular processes are not well understood. Cancer cells and tumor microenvironment (TME) cells jointly determine the heterogeneity. However, quite a little attention was paid to cells in the TME in the past years. In this study, we not only reveal that endothelial cells (ECs) are strongly associated with the progress of papillary thyroid cancer (PTC) using single-cell RNA-seq (scRNA-seq) data downloaded from Gene Expression Omnibus (GEO) and WGCNA, but also screen 5 crucial genes of ECs: CLDN5, ABCG2, NOTCH4, PLAT, and TMEM47. Furthermore, the 5-gene molecular prognostic model is constructed, which can predict how well a patient will do on PD-L1 blockade immunotherapy for TC and evaluate prognosis. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrates that PLAT is decreased in TC and the increase of PLAT can restrain the migratory capacity of TC cells. Meanwhile, in TC cells, PLAT suppresses VEGFa/VEGFR2-mediated human umbilical vascular endothelial cell (HUVEC) proliferation and tube formation. Totally, we construct the 5-gene molecular prognostic model from the perspective of EC and provide a new idea for immunotherapy of TC.

Proteomics Analysis of Polyphyllin D-Treated Triple-Negative Breast Cancer Cells Reveal the Anticancer Mechanisms of Polyphyllin D.

Polyphyllin D (PD), one of the important steroid saponins in traditional medicinal herb Paris polyphylla, has been demonstrated to have anticancer activity both in vitro and in vivo. However, the mechanisms through which PD exerts its anticancer effects in triple-negative breast cancer (TNBC) remain unclear. Our study was presented to evaluate the anticancer effect and the potential mechanisms of PD in two TNBC cell lines, BT-549 and MDA-MB-231. Through comprehensively comparing the liquid chromatography-tandem mass spectrometry (LC-MS/MS) data of PD-treated and untreated BT-549 and MDA-MB-231 cells, we found that PD could induce apoptosis of TNBC cells by activating oxidative phosphorylation pathway in BT-549 cells, as well as inhibiting spliceosome function alteration in MDA-MB-231 cells. These results suggested that the mechanisms underlying the pro-apoptotic effect of PD on TNBC may be cell type-specificity-dependent. Moreover, we found that nodal modulator 2/3 (NOMO2/3) were downregulated both in PD-treated BT-549 and MDA-MB-231 cells, suggesting that NOMO2/3 may be the potential target of PD. Verification experiments revealed that PD deceased NOMO2/3 expression at protein level, rather than mRNA level. Whether NOMO2/3 are the upstream modulators of oxidative phosphorylation pathway and spliceosome needs further validation. In conclusion, a comprehensive proteomics study was performed on PD-treated or untreated TNBC cells, revealing the anticancer mechanisms of PD.

Circular forms of dedicator of cytokinesis 1 promotes breast cancer progression by derepressing never in mitosis related kinase 2 via sponging miR-128-3p.

The conjecture of breast cancer is uncertain because of its explosive growth and the complicated molecular mechanisms. Circular RNAs (circRNAs) are regulatory RNA sequences present in the genome and their regulatory mechanism involves the sponging of microRNAs (miRNAs). In this study, we explored the regulation between circular forms of dedicator of cytokinesis 1 (circDOCK1) (hsa_circ_0007142) and miR-128-3p, and its implication on the pathogenesis of breast cancer modulated by never in mitosis (NIMA) related kinase 2 (NEK2). We revealed an increase in circDOCK1 and NEK2 expression, and a decrease in miR-128-3p expression in breast cancer tissues and cell lines. Bioinformatics analysis and experimental validation indicated a positive correlation between circDOCK1 and NEK2 expression but a negative correlation was recorded between miR-128-3p and circDOCK1 or NEK2, respectively. Furthermore, inhibition of circDOCK1 expression was followed by an increase in miR-128-3p and a decrease in NEK2 levels in vitro and in vivo. The luciferase assay concluded that miR-128-3p was a direct target of circDOCK1 while NEK2 was the direct target of miR-128-3p. Furthermore, circDOCK1 inhibition hindered breast cancer development by repressing NEK2 and thus promoting the increased expression of miR-128-3p both in vitro and in vivo. We therefore conclude that circDOCK1 promotes breast cancer progression by targeting miR-128-3p-mediated downregulation of NEK2 and that the circDOCK1/hsa-miR-128-3p/NEK2 axis may be a novel therapeutic target for breast cancer treatment.

Thermally driven phase transition of halide perovskites revealed by big data-powered in situ electron microscopy.

Halide perovskites are promising light-absorbing materials for high-efficiency solar cells, while the crystalline phase of halide perovskites may influence the device's efficiency and stability. In this work, we investigated the thermally driven phase transition of perovskite (CsPbIxBr3-x), which was confirmed by electron diffraction and high-resolution transmission electron microscopy results. CsPbIxBr3-x transitioned from δ phase to α phase when heated, and the γ phase was obtained when the sample was cooled down. The γ phase was stable as long as it was isolated from humidity and air. A template matching-based data analysis method enabled visualization of the thermally driven phase evolution of perovskite during heating. We also proposed a possible atomic movement in the process of phase transition based on our in situ heating experimental data. The results presented here may improve our understanding of the thermally driven phase transition of perovskite as well as provide a protocol for big-data analysis of in situ experiments.

MRI-Based Texture Analysis for Preoperative Prediction of BRAF V600E Mutation in Papillary Thyroid Carcinoma.

Purpose: BRAF V600E mutation can compensate for the low detection rate by fine-needle aspiration (FNA) and is related to aggressiveness and lymph node metastasis. This study aimed to investigate the relationship between texture analysis features based on magnetic resonance imaging (MRI) and mutations. Methods: Retrospective analysis was performed on patients with postoperative pathology confirmed papillary thyroid carcinoma (PTC) from 2017 to 2021. One thousand one hundred and thirty-two texture features were extracted from T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CE-T1WI) separately by outlining the tumor volume of interest (VOI). Univariate, minimum redundancy maximum relevance (mRMR), and multivariate analyses were used for feature selection to construct 3 models (T2WI, CE-T1WI, and combined model) to predict mutation. The reproducibility between observers was evaluated by intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) analysis was used to assess the performance of models. The diagnostic performance of the optimal cut-off value of models were calculated and validated by 10-fold cross-validation. Results: A total of 80 PTCs (22 BRAF V600E wild-type and 58 BRAF V600E mutant) were included in our study. Good interobserver agreement was found on texture features we selected (all ICCs >0.75). The area under the ROC curves (AUCs) for the T2WI model, CE-T1WI model, and combined model were 0.83 (95% CI: 0.75-0.91), 0.83 (95% CI: 0.73-0.90), and 0.88 (95% CI: 0.81-0.94), respectively. The accuracy, sensitivity, specificity, PPV, and NPV were 0.776, 0.679, 0.905, 0.905, and 0.679 for the T2WI model at a cut-off value of 0.674; 0.755, 0.750, 0.762, 0.808, and 0.696 for the CE-T1WI model at a cut-off value of 0.573; 0.816, 0.893, 0.714, 0.806, and 0.833 for the combined model at a cut-off value of 0.420. Conclusion: MRI-based texture analysis could be a potential method for predicting BRAF V600E mutation in PTC preoperatively.

Acute effects of ambient air pollution exposure on lung function in the elderly in Hangzhou, China.

Evidence of an association between acute air pollution exposure and lung function in the elderly is limited. This study is cross-sectional. We quantified the effects of air pollution exposure on lung function among 256 elderly by using a linear mixed model. The results revealed that air pollutants had lag effects on lung function after adjusting for confounders. PM2.5 (Lag03, Lag 03 was defined three-day moving average, and so forth), PM10, NO2 (Lag04-Lag05) were significantly associated with reduced FEV1. PM2.5 (Lag01-Lag02), PM10 (Lag0-Lag07), NO2 (Lag0, Lag04), and SO2 (Lag0) were significantly associated with reduced Forced vital capacity (FVC). PM2.5 (Lag04-Lag07) and NO2 (Lag01-Lag07) were significantly associated with reduced FEF25%-75%. The results showed the adverse change was stronger after adjusting for other pollutants in the PM models, and women were more susceptible to air pollutants. Therefore, we should pay attention to the problem of air pollution in the elderly, especially in women.

Analysis of the key ligand receptor CADM1_CADM1 in the regulation of thyroid cancer based on scRNA-seq and bulk RNA-seq data.

Introduction: Advanced papillary thyroid cancer (PTC) has a poor prognosis, 60~70% of which become radio iodine refractory (RAI-R), but the molecular markers that assess PTC progress to advanced PTC remain unclear. Meanwhile, current targeted therapies are badly effective due to drug resistance and adverse side effects. Ligand-receptor pairs (L/R pairs) play an important role in the interactions between tumor cells and other cells in the tumor microenvironment (TME). Nowadays, therapies targeting ligand-receptor pairs in the TME are advancing rapidly in the treatment of advanced cancers. However, therapies targeting L/R pairs applied to advanced PTC remains challenging because of limited knowledge about L/R pairs in PTC. Methods: We screened the critical L/R pair: CADM1-CADM1 using 65311 single-cell RNA sequencing (scRNA-seq) samples from 7 patients in different stage of PTC and bulk RNA-seq datasets containing data from 487 tumor samples and 58 para-carcinoma samples. Moreover, the expression levels of CADM1-CADM1 was assessed by quantitative real time polymerase chain reaction (qRT-PCR) and the function was analyzed using Transwell immigration assay. Results: We found that CADM1_CADM1 could be regarded as a biomarker representing a good prognosis of PTC. In addition, the high expression of CADM1_CADM1 can strongly increase the sensitivity of many targeted drugs, which can alleviate drug resistance. And the results of qRT-PCR showed us that the expression of CADM1_CADM1 in PTC was down-regulated and overexpression of CADM1 could suppresses tumor cell invasion migration. Conclusion: Our study identified that CADM1_CADM1 played an essential role in the progression of PTC for the first time and our findings provide a new potential prognostic and therapeutic ligand-receptor pair for advanced PTC.

Docetaxel-resistant triple-negative breast cancer cell-derived exosomal lncRNA LINC00667 reduces the chemosensitivity of breast cancer cells to docetaxel via targeting miR-200b-3p/Bcl-2 axis.

Development of docetaxel (TXT) resistance is a major obstacle for triple-negative breast cancer (TNBC) treatment. Additionally, chemoresistant cell-derived exosomes were able to change the chemo-response of chemosensitive recipient cells via transportation of lncRNAs. It has been shown that lncRNA LINC00667 level was significantly elevated in breast cancer tissues. Therefore, we explored whether LINC00667 level is increased in TXT-resistant TNBC cell-derived exosomes. In addition, whether exosomal LINC00667 derived from TXT-resistant TNBC cell could affect TXT sensitivity in TXT-sensitive TNBC cells was investigated as well. In the present study, exosomes were isolated from the TXT-resistant TNBC cells and from TXT-sensitive TNBC cells. Next, the level of LINC00667 in the isolated exosomes was detected with RT-qPCR. We found that LINC00667 expression was obviously elevated in TXT-resistant TNBC cell-derived exosomes compared to that in TXT-sensitive TNBC cell-derived exosomes. In addition, LINC00667 could be transferred from TXT-resistant TNBC cells to TNBC cells via exosomes. Moreover, TXT-resistant TNBC cell secreted exosomal LINC00667 markedly reduced the sensitivity of TNBC cells to TXT via upregulation of Bcl-2. Meanwhile, downregulation of LINC00667 notably enhanced the sensitivity of TXT-resistant TNBC cells to TXT through downregulation of Bcl-2. Additionally, LINC00667 was considered to be a ceRNA to sponge miR-200b-3p, thereby elevating Bcl-2 expression. Collectively, TXT-resistant TNBC cell-derived exosomal LINC00667 could decrease the chemosensitivity of TNBC cells to TXT via regulating miR-200b-3p/Bcl-2 axis. These findings suggested that LINC00667 might serve as a promising target for enhancing sensitivity of TNBC cells to TXT therapy.

Hypoxia induces docetaxel resistance in triple-negative breast cancer via the HIF-1α/miR-494/Survivin signaling pathway.

Cytotoxic chemotherapy is the major strategy to prevent and reduce triple-negative breast cancer (TNBC) progression and metastasis. Hypoxia increases chemoresistance and is associated with a poor prognosis for patients with cancer. Based on accumulating evidence, microRNAs (miRNAs) play an important role in acquired drug resistance. However, the role of miRNAs in hypoxia-induced TNBC drug resistance remains to be clarified. Here, we found that hypoxia induced TNBC docetaxel resistance by decreasing the miR-494 level. Modulating miR-494 expression altered the sensitivity of TNBC cells to DTX under hypoxic conditions. Furthermore, we identified Survivin as a direct miR-494 target. Hypoxia upregulated survivin expression. In a clinical study, the HIF-1α/miR-494/Survivin signaling pathway was also active in primary human TNBC, and miR-494 expression negatively correlated with HIF-1α and survivin expression. Finally, in a xenograft model, both miR-494 overexpression and the HIF-1α inhibitor PX-478 increased the sensitivity of TNBC to DTX by suppressing the HIF-1α/miR-494/Survivin signaling pathway in vivo. In conclusion, treatments targeting the HIF-1α/miR-494/Survivin signaling pathway potentially reverse hypoxia-induced drug resistance in TNBC.

A Radiomics Nomogram for Distinguishing Benign From Malignant Round-Like Breast Tumors.

Objective: The objective of this study is to develop a radiomics nomogram for the presurgical distinction of benign and malignant round-like solid tumors. Methods: This retrospective trial enrolled patients with round-like tumors who had received preoperative digital mammography (DM) no sooner than 20 days prior to surgery. Breast tumors were segmented manually on DM images in order to extract radiomic features. Four machine learning classification models were constructed, and their corresponding areas under the receiver operating characteristic (ROC) curves (AUCs) for differential tumor diagnosis were calculated. The optimal classifier was then selected for the validation set. After this, predictive machine learning models that employed radiomic features and/or patient features were applied for tumor assessment. The models' AUC, accuracy, negative (NPV) and positive (PPV) predictive values, sensitivity, and specificity were then derived. Results: In total 129 cases with benign and malignant tumors confirmed by pathological analysis were enrolled in the study, including 91 and 38 in the training and test sets, respectively. The DM images yielded 1,370 features per patient. For the machine learning models, the Least Absolute Shrinkage and Selection Operator for Gradient Boosting Classifier turned out to be the optimal classifier (AUC=0.87, 95% CI 0.76-0.99), and ROC curves for the radiomics nomogram and the DM-only model were statistically different (P<0.001). The radiomics nomogram achieved an AUC of 0.90 (95% CI 0.80-1.00) in the test cohort and was statistically higher than the DM-based model (AUC=0.67, 95% CI 0.51-0.84). The radiomics nomogram was highly efficient in detecting malignancy, with accuracy, sensitivity, specificity, PPV, and NPV in the validation set of 0.868, 0.950, 0.778, 0.826, and 0.933, respectively. Conclusions: This radiomics nomogram that combines radiomics signatures and clinical characteristics represents a noninvasive, cost-efficient presurgical prediction technique.

Self-Assembly of Au-Ag Alloy Hollow Nanochains for Enhanced Plasmon-Driven Surface-Enhanced Raman Scattering.

In this paper, Au-Ag alloy hollow nanochains (HNCs) were successfully prepared by a template-free self-assembly method achieved by partial substitution of ligands. The obtained Au-Ag alloy HNCs exhibit stronger enhancement as surface-enhanced Raman scattering (SERS) substrates than Au-Ag alloy hollow nanoparticles (HNPs) and Au nanochains substrates with an intensity ratio of about 1.3:1:1. Finite difference time domain (FDTD) simulations show that the SERS enhancement of Au-Ag alloy HNCs substrates is produced by a synergistic effect between the plasmon hybridization effect associated with the unique alloy hollow structure and the strong "hot spot" in the interstitial regions of the nanochains.

miR-466 Contributes to the Enhanced Antitumor Effect of Bortezomib on Non-Small-Cell Lung Cancer by Inhibiting CCND1.

INTRODUCTION: Changes in microRNAs (miRs) contribute to the alternative chemo-resistance of cancers. Bortezomib (BTZ) is a well-characterized anticancer agent that inhibits proteasome, and its effect is associated with the function of miRs. Based on the data of microarray assay and comprehensive bioinformatics analyses, in the current study, we explored the role of miR-466 and its downstream effector CCND1 in the BTZ-resistance of non-small-cell lung cancer (NSCLC) cells. METHODS: miR expression profiles in NSCLC tissues and paratumor tissues were determined with microarray assay. The potential miR involved in the chemo-resistance of NSCLC cells was explored via a series of bioinformatics analyses, and miR-466 was selected. Afterward, levels of miR-466 and CCND1 were investigated in NSCLC samples and analyzed by clinicopathologic parameters, including age, sex, stage of NSCLC, tumor size, tumor differentiation status, and lymphocytic infiltration status. The expression of CCND1 and miR-466 was then modulated in vitro to explore the influence on cell phenotypes, which was then verified with mouse models. RESULTS: Based on microarray detection, 287 miRs were dysexpressed between NSCLC tissues and paratumor tissues, including 90 upregulated members and 197 downregulated members. After bioinformatics analyses and reverse transcription quantitative PCR validation, miR-466 and CCND1 were selected. Following clinical investigations, miR-466 was downregulated, while CCND1 was upregulated in NSCLC samples, contributing to the advanced cancer progression. The overexpression of CCND1 increased cell viability, suppressed cell apoptosis, decreased p21 and induced N-cadherin, CCND2, and CDK4 under BTZ treatment. The induced expression of miR-466 re-sensitized NSCLC cells to BTZ treatment. In the animal model, the overexpression of CCND1 impaired the inhibitory effect of BTZ on the growth and metastasis of solid tumor, which was restored by miR-466 induction. CONCLUSION: The findings showed that the interaction between BTZ, miR-466, and CCND1 determined the antitumor effect of BTZ on NSCLC.

Downregulation of PDGF-D Inhibits Proliferation and Invasion in Breast Cancer MDA-MB-231 Cells.

BACKGROUND: The platelet derived growth factor-D (PDGF-D) plays an important role in breast tumor aggressiveness. However, limited study has investigated the effect of silencing PDGF-D on the biological function of breast cancer. The purpose of this study is to clarify the potential value of PDGF-D as a target for breast cancer treatment. METHODS: Reverse transcription-polymerase chain reaction and western blot were used to detect PDGF-D expression in 5 different breast cancer cells. The lentiviral vector was usd to silence PDGF-D in MDA-MB-231 cells. Then, Methyl Thiazolyl Tetrazolium was used to detect cell viability, 5-Ethynyl-2'- deoxyuridine and a soft agar assay were used to detect cell proliferation and clonality. Additionally, cell apoptosis after PDGF-D knockdown was measured by Annexin V/ Prodium Iodide staining, and cell migration was detected by trans-well assay. Survival rate and tumor size were measured by nude mice transplantation. RESULTS: The MDA-MB-231 and SK-BR-3 cell lines showed higher PDGF-D expression than the MCF7 cell lines (P<.05). After the PDGF-D gene was silenced, the growth and colony forming abilitys ignificantly decreased (P<.05) together with the induction of apoptosis in MDA-MB-231 cells (P<.05). Moreover, MDA-MB-231 cells with PDGF-D silencing showed significantly diminished aggressive migration and invasion potential compared to other cells (P<.05). In vivo experiments also indicated that PDGF-D silencing inhibited tumor growth and improved the survival rate of tumor-bearing mice. CONCLUSION: Downregulation of PDGF-D had dramatic effects on breast cancer cell proliferation, apoptosis and migration, which indicates that it plays an important role in breast cancer development and progression.

Polyphyllin D induces apoptosis and protective autophagy in breast cancer cells through JNK1-Bcl-2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyphyllin D (PD), an active component from rhizome of Paris polyphylla Sm, root and rhizome, shows a strong anti-cancer activity in several cancers. However, whether autophagy is involved in PD-induced cell death in breast cancer cells and its molecular mechanism has not yet been elucidated. AIM OF THE STUDY: To explore the anti-tumor effects of PD in breast cancer and the underlying mechanisms. MATERIALS AND METHODS: PD was isolated from P. polyphylla Sm and confirmed by HPLC and NMR. The role of PD in cell viability, apoptosis, autophagy in breast cancer cells were determined. RESULTS: PD shows significant anti-tumor activity by inhibit cell proliferation and induce caspase-dependent apoptosis in breast cancer cells. Moreover, PD treatment could induce autophagy by activation of JNK1/Bcl-2 pathway. Importantly, blocking of autophagy by using autophagy inhibitor 3-methyladenine (3-MA) dramatically increase PD-induced apoptosis as evidence by the increased percentage of apoptotic cell death. The anti-tumor effects of PD also investigated in vivo. The results showed that the combinatory treatment of PD with autophagy inhibitor significantly promote PD-induced apoptosis. CONCLUSION: PD could induce caspase-dependent apoptosis and cyto-protectvie autophagy by activation of JNK1/Bcl-2 pathway in breast cancer cells. Combination with an autophagy inhibitor significantly enhance cytotoxic effect of PD and this combination may be a promising candidate for breast cancer therapy.

In Vitro and In Vivo of Triphenylamine-Appended Fluorescent Half-Sandwich Iridium(III) Thiosemicarbazones Antitumor Complexes.

Half-sandwiched structure iridium(III) complexes appear to be an attractive organometallic antitumor agents in recent years. Here, four triphenylamine-modified fluorescent half-sandwich iridium(III) thiosemicarbazone (TSC) antitumor complexes were developed. Because of the "enol" configuration of the TSC ligands, these complexes formed a unique dimeric configuration. Aided by the appropriate fluorescence properties, studies found that complexes could enter tumor cells in an energy-dependent mode, accumulate in lysosomes, and result in the damage of lysosome integrity. Complexes could block the cell cycle, improve the levels of intrastitial reactive oxygen species, and lead to apoptosis, which followed an antitumor mechanism of oxidation. Compared with cisplatin, the antitumor potential in vivo and vitro confirmed that Ir4 could effectively inhibit tumor growth. Meanwhile, Ir4 could avoid detectable side effects in the experiments of safety evaluation. Above all, half-sandwich iridium(III) TSC complexes are expected to be an encouraging candidate for the treatment of malignant tumors.