Sentinel lymph node metastasis diagnosis using ultrasound plus magnetic resonance lymphangiography in breast cancer.

Background: Ultrasound diagnosis is a highly specific tool and widely applied, but is associated with low sensitivity in detection of sentinel lymph nodes (SLNs). The diagnostic value of routine ultrasound combining magnetic resonance lymphangiography (MRL) for the detection of SLNs in breast cancer metastasis is still unclear. This study used ultrasound combined with MRL to explore the diagnostic value of detecting SLN metastasis in breast cancer. Methods: This study included female breast cancer patients who received modified radical mastectomy at the Department of Breast Surgery, the First Affiliated Hospital of Zhengzhou University between January 2016 and January 2019. The gold standard of SLNs is pathological results. The patients were divided into three groups: (I) Group A: an ultrasound plus MRL (contrast agent injected outside the areola) group; (II) Group B: an ultrasound plus MRL (contrast agent injection around the areola) group; and (III) Group C: an ultrasound plus MRL group (this group comprised patients from the two aforementioned groups). Results: A total of 432 patients were included. The overall detection rate and overall diagnostic accuracy of SLNs in breast cancer differed significantly among the three groups (all P<0.05). Ultrasound plus MRL showed a best overall detection rate 56.02%, and a best diagnostic accuracy 95.83%. The detection rate and diagnostic accuracy of axillary SLNs varied markedly among the three groups (P<0.05). The detection rate and diagnostic accuracy when the internal mammary node was the SLN differed notably between the ultrasound plus MRL (contrast agent injected outside the areola) and ultrasound plus MRL (contrast agent injection around the areola) groups and between the ultrasound plus MRL (contrast agent injection around the areola) and ultrasound plus MRL groups (all P<0.05). Conclusions: Ultrasound plus MRL may be advantageous for the detection of SLN metastasis in breast cancer and predicting breast cancer prognosis.

Identification of Moldy Peanuts under Different Varieties and Moisture Content Using Hyperspectral Imaging and Data Augmentation Technologies.

Aflatoxins in moldy peanuts are seriously toxic to humans. These kernels need to be screened in the production process. Hyperspectral imaging techniques can be used to identify moldy peanuts. However, the changes in spectral information and texture information caused by the difference in moisture content in peanuts will affect the identification accuracy. To reduce and eliminate the influence of this factor, a data augmentation method based on interpolation was proposed to improve the generalization ability and robustness of the model. Firstly, the near-infrared hyperspectral images of 5 varieties, 4 classes, and 3 moisture content gradients with 39,119 kernels were collected. Then, the data augmentation method called the difference of spectral mean (DSM) was constructed. K-nearest neighbors (KNN), support vector machines (SVM), and MobileViT-xs models were used to verify the effectiveness of the data augmentation method on data with two gradients and three gradients. The experimental results show that the data augmentation can effectively reduce the influence of the difference in moisture content on the model identification accuracy. The DSM method has the highest accuracy improvement in 5 varieties of peanut datasets. In particular, the accuracy of KNN, SVM, and MobileViT-xs using the data of two gradients was improved by 3.55%, 4.42%, and 5.9%, respectively. Furthermore, this study provides a new method for improving the identification accuracy of moldy peanuts and also provides a reference basis for the screening of related foods such as corn, orange, and mango.

Hsa_circ_0048674 facilitates hepatocellular carcinoma progression and natural killer cell exhaustion depending on the regulation of miR-223-3p/PDL1.

BACKGROUND: Circular RNAs (circRNAs) play vital regulatory roles in human cancers, including hepatocellular carcinoma (HCC). In this study, we aimed to explore the functions of hsa_circ_0048674 in HCC development. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect hsa_circ_0048674, ubiquitin-like with PHD and RING finger domains 1 (UHRF1), microRNA-223-3p (miR-223-3p) and programmed death ligand 1 (PDL1). RNase R assay and Actinomycin D assay were employed to analyze the stability of hsa_circ_0048674. Cell Counting Kit-8 (CCK-8) assay, colony formation assay and 5-ethynyl-2'- deoxyuridine (EdU) assay were conducted to assess cell proliferation. Flow cytometry analysis, transwell assay and tube formation assay were carried out for cell apoptosis, migration, invasion and angiogenesis, respectively. Western blot assay was adopted for protein levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to analyze the relationship between miR-223-3p and hsa_circ_0048674 or PDL1. Murine xenograft model assay was conducted for the function of hsa_circ_0048674 in vivo. Immunohistochemistry (IHC) assay was used to detect Ki-67 level in tumor tissues. Enzyme linked immunosorbent assay (ELISA) kits were employed for the concentrations of inflammatory factors. RESULTS: Hsa_circ_0048674 was highly expressed in HCC tissues and cells. Silencing of hsa_circ_0048674 repressed cell growth, migration, invasion and angiogenesis and promoted apoptosis in HCC cells in vitro and hampered tumor growth in vivo. Hsa_circ_0048674 served as an miR-223-3p sponge to alter PDL1 expression. MiR-223-3p inhibition or PDL1 overexpression restored the impacts of hsa_circ_0048674 silencing on HCC malignant behaviors. In addition, hsa_circ_0048674 knockdown promoted natural killer (NK) cell-mediated cytotoxicity to HCC cells. CONCLUSION: Hsa_circ_0048674 knockdown decelerated HCC progression through the mediation of the miR-223-3p/PDL1 axis.

ß-glucan from Aureobasidium pullulans augments the anti-tumor immune responses through activated tumor-associated dendritic cells.

Dendritic cells (DCs) are recognized as the most potent antigen-presenting cells, capable of priming both naïve and memory T cells. Thus, tumor-resident DCs (tumor-associated DCs: TADCs) play a crucial role in the immune response against tumors. However, TADCs are also well known as a "double-edged sword" because an immunosuppressive environment, such as a tumor microenvironment, maintains the immature and tolerogenic properties of TADCs, resulting in the deterioration of the tumor. Therefore, it is essential to maintain and enhance the anti-tumoral activity of TADCs to aid tumor elimination. This study demonstrated the potential for tumor growth inhibition of Aureobasidium pullulan-derived ß-glucan (AP-BG). Administration of AP-BG dramatically limited the development of different types of tumor cell lines transplanted into mice. Examination of the tumor-infiltrating leukocytes revealed that AP-BG caused high expression of co-stimulatory molecules on TADCs and enhanced the production of cytolytic granules as well as pro-inflammatory cytokines by the tumor-resident T cells. Furthermore, the syngeneic mixed lymphoid reaction assay and popliteal lymph node assay showed the significant ability of AP-BG to improve DCs' antigen-specific priming of T cells in vitro and in vivo. Taken together, ß-glucan might be an immune-potentiating adjuvant for cancer treatment. This highly widely-used reagent will initiate a new way to activate DC-targeted cancer immune therapy.

Prognostic and clinicopathological significance of systemic immune-inflammation index in pancreatic cancer: a meta-analysis of 2,365 patients.

The prognostic value of the systemic immune-inflammation index (SII) in patients with pancreatic cancer is conflicting according to previous investigations. Therefore, we performed a meta-analysis to explore the association between SII and pancreatic cancer prognosis. Electronic databases were searched for studies exploring the association of SII with prognostic outcomes in pancreatic cancer. The endpoints were overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and clinicopathological parameters. The prognostic value of SII was estimated by hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Nine studies containing 11 cohorts with 2,365 subjects in total were included in this meta-analysis. Elevated SII was associated with poor OS (HR=1.50, 95% CI=1.15-1.96, p=0.002), RFS/PFS/DFS (HR=1.52, 95% CI=1.01-2.28, p=0.045), and CSS (HR=2.60, 95% CI=1.65-4.09, p < 0.001) in patients with pancreatic cancer. Additionally, there was no significant association between SII and other parameters in pancreatic cancer such as sex, tumor location, lymph node metastasis, tumor-node-metastasis stage, vascular invasion, and grade. This meta-analysis suggested that elevated SII was a significant prognostic marker for short-term and long-term survival outcomes in patients with pancreatic cancer.

Effect of Rongchang capsule on seizure behavior, cognitive impairment, and hippocampal DNA damage and inflammatory factors in epileptic rat.

OBJECTIVE: To observe the behavioral changes and changes in DNA fragments and related inflammatory factors in the hippocampus of epileptic rats pretreated with Rongchang capsule (). METHODS: Eighty Sprague-Dawley rats were randomly divided into the normal group (NG), model group (MG), sodium valproate group (VG), and Rongchang capsule group (RG) (n = 20 in each group). Pentylentetrazol was administered to the MG, VG, and RG to induce epilepsy. The VG and RG were pretreated with 1/2 the therapeutic dose of sodium valproate and Rongchang capsule, respectively. Changes in convulsion behavior and water maze learning were observed. Single cell gel electrophoresis was used to detect changes in the DNA in the hippocampus. The tail length (TL) and Olive tail moment (OTM) of cells were analyzed by GASP software. The expression of interleukin-1ß (IL-1ß), high mobility group box 1 (HMGB1), transforming growth factor-ß (TGF-ß), and CCL4 in the hippocampus was determined by Western blotting. RESULTS: Rongchang capsule had a weaker effect on convulsive latency than sodium valproate, but significantly reduced seizure susceptibility. The spatial learning ability of the RG was better than that of the VG (P ≤ 0.01). The TL and OTM were significantly higher in the MG than the NG (P < 0.01). The RG had a better TL and OTM than the VG (P < 0.01). Combined with the microscopy results, DNA damage was most pronounced in the MG. Drug intervention decreased the DNA damage in the VG and RG. The expressions of IL-1ß, CCL4, and HMGB1 in the hippocampus were significantly greater in the MG than the NG (P < 0.01), and were significantly reduced in the RG and VG compared with the MG (P < 0.01); however, there was no intergroup difference in the expression of TGF-ß. The average values for the expression of inflammatory factors in the hippocampus were higher in the RG than in the VG; thus, Rongchang capsule may have a weaker effect on reducing the expression of inflammatory factors in the hippocampus than sodium valproate. CONCLUSION: Pretreatment with Rongchang capsule prevents or delays cognitive impairment in rats with induced epilepsy, reduces hippocampal DNA damage, and decreases the hippocampal expressions of IL-1ß, CCL4, and HMGB1.

lncRNA GAS5-promoted apoptosis in triple-negative breast cancer by targeting miR-378a-5p/SUFU signaling.

PURPOSE: Long-chain noncoding RNAs (lncRNAs) are involved in regulating the sensitivity of cancer cells to chemotherapeutic drugs, but the specific mechanism of action is not well understood. The aim of this study was to investigate the effect of lncRNA growth-stasis specific transcript 5 (GAS5) on triple-negative breast cancer (TNBC). METHODS: Quantitative real-time polymerase chain reaction and flow cytometry were used to screen lncRNA associated with tumor resistance. Double luciferase reporter gene assay, flow cytometry, and Western blot assay were used to determine whether miRNA 378a-5p and SUFU were involved in tumor cell apoptosis induced by lncRNA GAS5. A mouse model of subcutaneous xenografts was established to investigate the relationship between lncRNA GAS5 and tumor resistance in vivo. RESULTS: In this study, the expression of lncRNA GAS5 was significantly downregulated in cells treated with paclitaxel (PTX) or cisplatin (CIS). Furthermore, TNBC cells with low expression of lncRNA GAS5 had a lower percentage of apoptosis under stress conditions, especially in serum-free medium. More interestingly, the expression level of lncRNA GAS5 in TNBC patients was associated with tumor resistance to PTX and CIS. In addition, RNA immunoprecipitation experiments confirmed that lncRNA GAS5 and miR-378 could directly bind to each other. Moreover, the miR-378a-5p target of SUFU could promote lncRNA GAS5-induced apoptosis of TNBC cells. Finally, lncRNA GAS5 overexpressed MDA-231R could enhance the sensitivity of TNBC to PTX. CONCLUSION: The above results confirmed that lncRNA GAS5 could induce apoptosis in TNBC cells by targeting miR-378a-5p/SUFU signaling.

SNHG1 contributes to proliferation and invasion by regulating miR-382 in breast cancer.

Introduction: Long non-coding RNAs (lncRNAs) are key regulators in multiple cancers. lncRNA, SNHG1, was shown to be associated with tumorigenesis. However, little is known about the role SNHG1 plays in breast cancer. The aim of the study was to study the role and underlying mechanism of SNHG1 regulation in breast cancer. Methods: Quantitative real-time PCR was used to measure the levels of SNHG1, miR-382 and ZEB1 levels in breast cancer tissue or cells. The proliferation, colony formation, migration and invasion of breast cancer cells, under SNHG1 knockdown achieved by transfection of SNHG1-specific siRNAs, were assessed by Cell Counting Kit-8, colony forming, scratch wound and transwell assays. Bioinformatical analysis and luciferase assay were used to explore the interaction between SNHG1 and its potential miRNA target. Western blot was used to evaluate the expression of epithelial-to-mesenchymal transition (EMT) markers. MDA-MB-231 cells with or without SNHG1 knockdown were used to initiate tumor xenografts in vivo. Tumor growth and expression of SNHG1, miR-382-5p and EMT markers were evaluated. Results: SNHG1 upregulation was observed in breast cancer tissues and cells. Knockdown of SNHG1 attenuated breast cancer proliferation, colony formation, migration and invasion. A miRNA, miR-382-5p, was identified as the target of SNHG1. A reciprocal negative regulation was found between SNHG1 and miR-382-5p. SNHG1 knockdown attenuated EMT both in vitro and in vivo. miR-382-5p transfection reversed the tumor-promoting role by SNHG1. In vivo, SNHG1 knockdown decreased breast tumor growth. Conclusion: SNHG1 promotes breast cancer through the regulation of miR-382-5p and EMT markers. Our results report SNHG1 as a novel miRNA that govern the progression of breast cancer, providing a potential new therapeutic target in breast cancer.

Silencing of the long non-coding RNA RHPN1-AS1 suppresses the epithelial-to-mesenchymal transition and inhibits breast cancer progression.

Breast cancer (BC) is a frequently diagnosed malignancy in women. Increasing evidence implicates mis-expression of the long non-coding RNA (lncRNA) RHPN1 antisense RNA 1 (RHPN1-AS1) in the development of multiple cancer types. However, little is known about the expression pattern and function of lncRNA RHPN1-AS1 in the pathobiology of BC. We evaluated the expression of RHPN1-AS1 in The Cancer Genome Atlas dataset, and analyzed associations between RHPN1-AS1 expression and clinicopathologic features of BC patients. Additionally, we compared the expression of RHPN1-AS1 between BC and breast non-tumor samples via quantitative real-time polymerase chain reaction, and in situ hybridization, and evaluated the prognostic value of RHPN1-AS1 in a BC tissue microarray. We examined the impact of RHPN1-AS1 knockdown on proliferation, migration, and invasion of BC cells in vitro, and tumor growth in vivo. Bioinformatics analyses were used to predict the function of RHPN1-AS1 in BC. RHPN1-AS1 expression was upregulated in BC and elevated RHPN1-AS1 expression was strongly associated with poor prognosis of BC patients. Moreover, both univariate and multivariate analyses revealed that RHPN1-AS1 was a significant and independent predictor of BC prognosis. Functionally, RHPN1-AS1 silencing attenuated BC cell proliferation, migration, and invasion in vitro, and reduced tumor growth in xenograft models. Furthermore, RHPN1-AS1 silencing was associated with a decrease in the expression of epithelial-to-mesenchymal transition (EMT) markers in the xenograft tumors, suggesting that RHPN1-AS1 promotes invasion in BC cells by enhancing EMT. These findings suggest that RHPN1-AS1 is a potential prognostic biomarker and therapeutic target for BC.

Overexpression of CBX2 in breast cancer promotes tumor progression through the PI3K/AKT signaling pathway.

Breast cancer is the second leading cause of cancer-related death among women worldwide. Emerging evidence suggests that chromobox homolog 2 (CBX2) is overexpressed in breast cancer and plays an essential role in tumor progression. However, its expression and functional roles in breast cancer development and progression require further exploration. Here, we evaluated CBX2 expression in breast cancer using mRNA expression data from the TCGA database; CBX2 expression was upregulated in breast cancer. Furthermore, upregulated CBX2 expression was significantly associated with poorer overall survival (OS) and progression-free survival (PFS) of breast cancer patients. Immunohistochemical analysis of CBX2 expression in a tissue microarray (TMA) cohort yielded concordant results. Univariate and multivariate analyses showed that elevated CBX2 expression was significantly and independently associated with poorer OS of patients in this TMA cohort. Additionally, we performed in vitro functional assays to evaluate the proliferation, migration, and invasion abilities of breast cancer cell lines wherein CBX2 was knocked down using short hairpin RNA (shRNA). CBX2 silencing inhibited cell proliferation, migration, and invasion in vitro. Furthermore, knockdown of CBX2 markedly reduced breast tumorigenesis in xenograft mouse models. Functional and pathway enrichment analyses indicated a positive correlation between high CBX2 expression and activation of the PI3K/AKT pathway, which were further confirmed by western blot and immunohistochemical analyses of mouse tumors. Our findings indicate that CBX2 is a potential prognostic biomarker and therapeutic target for breast cancer.

Dual-Targeting of miR-124-3p and ABCC4 Promotes Sensitivity to Adriamycin in Breast Cancer Cells.

AIMS: Increasing evidence links the abnormal expression of microRNAs and ATP-binding cassette subfamily C member 4 (ABCC4) with tumor development and progression, as well as with chemoresistance. Our aims were to determine the therapeutic potential of targeting both miR-124-3p and ABCC4 in breast cancer cells and to determine if duel targeting increased their sensitivity to chemotherapeutic drugs, in vitro. MATERIALS AND METHODS: The expression of the ABCC4 protein and miR-124-3p were detected, respectively, by immunohistochemical staining and quantitative real-time polymerase chain reaction in breast cancer tumor tissue, MCF-7 and MCF-7-ADR cell lines. Suppression of ABCC4 expression and miR-124-3p overexpression were performed in MCF-7-ADR cell lines. Western blot assays were used to detect expression of ABCC4 and permeability glycoprotein 1/multi-drug resistance protein 1 (P-gp) in cells. Cell Counting Kit-8, flow cytometry, transwell, and scratch assays were conducted to detect cell proliferation, cell cycle, invasion, and migration of cells. RESULTS: We found that ABCC4 protein expression was significantly increased, while the miR-124-3p level was significantly decreased in breast cancer tissue and cell lines. Tumor size and clinical tumor node metastasis stage were significantly correlated with elevated expression of ABCC4 and decreased expression of miR-124-3p. Interestingly, ABCC4 expression was significantly increased in MCF-7-ADR cells, while miR-124-3p level was significantly decreased compared with MCF-7 cells. The inhibition of ABCC4 and miR-124-3p overexpression both led to a significant decrease in cell proliferation, invasion, and migration of MCF-7-ADR cells, and combination of suppression of ABCC4 with miR-124-3p overexpression had a synergistic inhibitory effect. Our results further demonstrated that inhibition of ABCC4 expression and overexpression of miR-124-3p significantly enhanced the sensitivity to adriamycin (ADR) in MCF-7-ADR cells, and that simultaneous dual-targeting of miR-124-3p and ABCC4 had a stronger promotive effect on the sensitivity to ADR in MCF-7-ADR cells. Moreover, western blot analysis showed that miR-124-3p overexpression significantly inhibited P-gp expression in MCF-7-ADR cells. CONCLUSION: Our data demonstrate that the combination of downregulation of ABCC4 with overexpression of miR-124-3p significantly increased sensitivity to ADR in MCF-7-ADR cells. This finding suggests that similar dual targeting may serve as a means to enhance therapies for drug-resistant breast cancers.

Treatment patterns for adjuvant docetaxel-based chemotherapy in early-stage breast cancer in China: A pooled retrospective analysis of four observational studies.

OBJECTIVE: Adjuvant docetaxel-based chemotherapy is frequently used for operable early breast cancer (EBC). This study investigated patterns of use of docetaxel (T) in real-life clinical practice in China. METHODS: This was a retrospective pooled analysis of the Asia-Pacific Breast Initiatives (APBI) I (2006-2008) and II (2009-2011) registries, and two Chinese observational studies; BC STATE (2011-2014) and BC Local Registry (2007-2010). Female Chinese adults (≥18 years) with operable breast cancer treated with docetaxel-based adjuvant chemotherapy were included in the analysis. Patients with metastatic disease were excluded. The primary endpoint was assessment of treatment patterns and patient profiles. A logistic regression analysis was conducted to identify factors associated with choice of adjuvant chemotherapy regimen. RESULTS: Data from 3,020 patients were included. The most frequently used adjuvant regimen was docetaxel/anthracycline combination [n=1,421 (47.1%); of whom 52.0% received T/epirubicin (E)/cyclophosphamide (C)], followed by docetaxel/other [n=705 (23.3%); of whom 72.8% received TC], docetaxel/anthracycline sequential [n=447 (14.8%); of whom 40.9% and 39.6% received 5-Fu/EC-T and EC-T, respectively], and " other" [n=447 (14.8%); of whom 91.5% received T]. A significant association was found between adjuvant therapy with docetaxel/anthracycline combination and patient weight, menopausal status and estrogen receptor status. CONCLUSIONS: Real-world data revealed that docetaxel/anthracycline combination is the most commonly used category of docetaxel-based adjuvant therapy for patients with operable breast cancer in China; of which TEC is the most frequently used regimen.

BCA3 contributes to the malignant progression of hepatocellular carcinoma through AKT activation and NF-κB translocation.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide with elusive molecular mechanisms. The aim of this study is to investigate the clinical significance and biological roles of breast cancer-associated protein 3 (BCA3) in HCC. Our investigation demonstrated that BCA3 expression was up-regulated in primary HCC tissues, and BCA3 levels were positively correlated with tumor size, TNM stage, microvascular invasion and poor prognosis. BCA3 promoted tumor growth, metastasis and angiogenesis of HCC in vitro and in vivo. Moreover, we found that BCA3 induced aggressive behaviors were mediated by AKT activation, which in turn activated mTOR signalling pathway and induced cytoplasm-nuclear translocation of NF-κB p65. Blockage of AKT signalling pathway by a specific AKT inhibitor LY294002 impaired BCA3 mediated phenotypes. Collectively, our current study indicated the pleiotropic effects of BCA3 in HCC progression, and blockage of BCA3-AKT pathway might contribute to development of therapeutic measures for HCC.

S100A4 participates in epithelial-mesenchymal transition in breast cancer via targeting MMP2.

Numerous studies have shown that S100A4 acquires its metastasis-promoting effects via inducing epithelial-mesenchymal transition (EMT). However, its role and mechanism in EMT in breast cancer had not been clearly elucidated. Herein, we showed that the knockdown of S100A4 expression in breast cancer cell lines, MDA-MB-231 and MDA-MB-468, inhibited not only cell invasion ability greatly, but also the occurrence of EMT significantly. In addition, S100A4 knockdown could also decrease the expression of MMP2, a promoter and a mediator of the EMT processes in cancer. Above all, restoring the expression of MMP2 in MDA-MB-231 and MDA-MB-468 could not only rescue the invasion ability inhibited by knockdown of S100A4, but also reverse the EMT suppressed by knockdown of S100A4. In summary, our results indicated that S100A4 could promote the invasion ability of breast cancer cells via EMT, more importantly, it could participate in EMT via regulating MMP2 in breast cancer. Therefore, S100A4 could be a candidate biomarker for defining breast cancer metastasis and useful target for therapy.

[Value of FOXP3 Tregs predicting the effectiveness of neoadjuvant chemotherapy in patients with breast cancer].

OBJECTIVE: To explore the predictive significance of FOXP3 Tregs in patients with breast cancer on neoadjuvant chemotherapy (NACT). METHODS: A total of 78 newly diagnosed and untreated patients with invasive breast cancer were recruited for this retrospective study.FOXP3 Tregs were assessed by immunohistochemistry. The relationship between clinicopathological factors, FOXP3+ Tregs and pathological complete response (pCR) rate was analyzed. RESULTS: Among 78 patients with TAC neoadjuvant chemotherapy, the pCR rate was 19.2%. The pCR rate of patients with high expressions of FOXP3+ Tregs was significantly lower than that of those with low expressions of FOXP3+ Tregs (9.5% vs 30.5%, P = 0.023). FOXP3+ Tregs expression in breast cancer and efficacy of NACT were negatively correlated. CONCLUSION: FOXP3+ Tregs may serve as a predictor for assessing the efficacy of NACT.

Cellular and molecular mechanisms in vascular smooth muscle cells by which total saponin extracted from Tribulus terrestris protects against artherosclerosis.

BACKGROUND/AIMS: Total saponin extracted from Tribulus terrestris (TSETT) has been reported to protect against atherosclerosis. We here investigate the cellular and molecular mechanisms of TSETT underlying protection against atherosclerosis. METHODS: Cell proliferation was measured with Methyl thiazolyl tetrazolium (MTT); Intracellular H2O2 was measured with DCFH-DA, a fluorescent dye; Intracellular free Ca(2+) was measured with a confocal laser scanning microscopy; Genes expression was measured with gene array and real-time quantitative polymerase chain reaction (RT-PCR); Phosphorylation of extracellular signal-regulated kinase 1/2 (phospho-ERK1/2) was measured with cell-based enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: TSETT significantly suppressed the increase in cells proliferation induced by angiotensin II, significantly suppressed the increase in the intracellular production of H2O2 induced by angiotensin II, significantly inhibited the increase in intracellular free Ca(2+) induced by H2O2, significantly inhibited the increase in phospho-ERK1/2 induced by angiotensin II; significantly inhibited the increase in mRNA expression of c-fos, c-jun and pkc-α induced by angiotensin II. CONCLUSION: These findings provide a new insight into the antiatherosclerotic properties of TSETT and provide a pharmacological basis for the clinical application of TSETT in anti-atherosclerosis.

[Effects of all trans retinoic acid on the expression alterations of beta-protein 1 in human breast cancer cell lines of MDA-MB-468 and MCF-7].

OBJECTIVE: To explore the effects of all trans retinoic acid (ATRA) on the cell proliferation and expression alterations of beta-protein 1 (BP1) in human breast cancer cells lines of MDA-MB-468 and MCF-7. METHOD: The proliferation changes were detected by thiazolyl blue tetrazolium bromide (MTT) after the treatment of ATRA. At the dose of 10(-5) mol/L ATRA, the expression of BP1 was measured by reverse transcription-polymerase chain reaction (RT-PCR) and immunochemistry. RESULTS: After the treatment of ATRA, the proliferation of cells and the expression of BP1 decreased. Optical density ratio (ODR) of each group decreased from 0.85 ± 0.01, 0.71 ± 0.01 to 0.75 ± 0.02, 0.72 ± 0.06 at 24 h, 0.55 ± 0.01, 0.52 ± 0.05 at 48 h and 0.34 ± 0.02, 0.48 ± 0.03 at 72 h. Significant differences existed among different time groups (P < 0.01). The mean optical density (MOD) of each group decreased from 0.509 ± 0.081, 0.826 ± 0.015 to 0.509 ± 0.081, 0.826 ± 0.015 at 24 h, 0.270 ± 0.022, 0.641 ± 0.041 at 48 h and 0.145 ± 0.019 and 0.206 ± 0.179 at 72 h. Significant differences existed among different time groups (P < 0.01). CONCLUSION: ATRA can inhibit the proliferation and the expression of BP1 in breast cancer cells. And BP1 gene may become a therapeutic target for the ATRA-mediated inhibited growth of breast cancer cells.

[Clinical comparative study of neoadjuvant chemotherapy outcome in locally advanced breast cancer: docetaxel versus paclitaxel plus pirarubicin hydrochloride and cyclophosphamide].

OBJECTIVE: To compare the efficacy and toxicity of neoadjuvant chemotherapy of docetaxel with paclitaxel plus pirarubicin hydrochloride (THP) and cyclophosphamide (CTX) in locally advanced breast cancer (LABC). METHODS: A total of 97 LABC cases were randomly divided into 2 groups: docetaxel group (n = 49, taxotere plus THP & CTX) and paclitaxel group (n = 48, paclitaxel plus THP & CTX). Neoadjuvant chemotherapy had four cycles of 21 days each. RESULTS: The clinical and pathological complete remission rates of docetaxel group was 28.6% and 26.5% respectively. They were significantly higher than those of paclitaxel group (10.4% and 8.3%). Furthermore the pathological negative rate of regional lymph node in docetaxel group was also significantly higher than that of paclitaxel group (40.6% vs. 12.9%). However, grade III-IV blood system toxic reaction was found in 71.4% cases, grade II-IV liver dysfunction in 53.1% cases and edema in 24.5% cases among docetaxel group. They were higher than those among paclitaxel group (46.9%, 27.1% & 4.2%). CONCLUSION: Compared with paclitaxel, the combined regimen of docetaxel plus THP and CTX offers better outcomes for locally advanced breast cancer.

[Application of guide wire location under mammography for a resection of subclinical breast lesions].

OBJECTIVE: To investigate the value of guide wire location under mammography for a resection of subclinical breast lesions. METHODS: A total of 79 patients presenting with abnormal mammography but unpalpable lesions received a guide wire pre-operative location under mammography. And 82 lesions were successfully located and resected for pathological examination. RESULTS: All 82 lesions were located with a high accuracy. The pathological examination revealed breast fibroma (n = 4), mammary gland hyperplasia with calcification (n = 58), intraductal papilloma (n = 2), fat necrosis with calcification (n = 3), mammary atypical hyperplasia (n = 5), breast inflammation (n = 1) and breast cancer (n = 9). CONCLUSION: The technique of guide wire location under mammography is highly accurate for pre-operative location of subclinical breast lesions. It is valuable for an early diagnosis of unpalpable breast lesions.

Detection and identification of potential biomarkers of breast cancer.

PURPOSE: Noninvasive and convenient biomarkers for early diagnosis of breast cancer remain an urgent need. The aim of this study was to discover and identify potential protein biomarkers specific for breast cancer. METHODS: Two hundred and eighty-two (282) serum samples with 124 breast cancer and 158 controls were randomly divided into a training set and a blind-testing set. Serum proteomic profiles were analyzed using SELDI-TOF-MS. Candidate biomarkers were purified by HPLC, identified by LC-MS/MS and validated using ProteinChip immunoassays and western blot technique. RESULTS: A total of 3 peaks (m/z with 6,630, 8,139 and 8,942 Da) were screened out by support vector machine to construct the classification model with high discriminatory power in the training set. The sensitivity and specificity of the model were 96.45 and 94.87%, respectively, in the blind-testing set. The candidate biomarker with m/z of 6,630 Da was found to be down-regulated in breast cancer patients, and was identified as apolipoprotein C-I. Another two candidate biomarkers (8,139, 8,942 Da) were found up-regulated in breast cancer and identified as C-terminal-truncated form of C3a and complement component C3a, respectively. In addition, the level of apolipoprotein C-I progressively decreased with the clinical stages I, II, III and IV, and the expression of C-terminal-truncated form of C3a and complement component C3a gradually increased in higher stages. CONCLUSIONS: We have identified a set of biomarkers that could discriminate breast cancer from non-cancer controls. An efficient strategy, including SELDI-TOF-MS analysis, HPLC purification, MALDI-TOF-MS trace and LC-MS/MS identification, has been proved very successful.