Testing and Analysis of Ultra-High Toughness Cementitious Composite-Confined Recycled Aggregate Concrete under Axial Compression Loading.

In order to analyze the axial compressive properties of ultra-high-toughness cementitious composite (UHTCC)-confined recycled aggregate concrete (RAC), a batch of UHTCC-confined RAC components was designed and manufactured according to the requirements of GB/T50081-2002 specifications. After analyzing the surface failure phenomenon, load-displacement curves, scanning electron microscope (SEM), and parameter analysis of the specimen, the result shows that UHTCC-confined RAC is an effective confinement method, which can effectively improve the mechanical properties and control the degree of surface failure of RAC structures. Compared with the unconfined specimen, the maximum peak load of the UHTCC confinement layer with a thickness of 10 mm and 20 mm increased by 44.61% and 79.27%, respectively, meeting the requirements of engineering practice. Different fiber mixing amounts have different effects on improving the mechanical performance of RAC structural. The specific rule was steel fiber (SF) > polyvinyl alcohol fiber (PVAF) > polyvinyl alcohol fiber (PEF) > no fiber mixture, and the SF improves the axial compression properties of UHTCC most significantly. When there are strict requirements for improving the mechanical properties of the structure, SF should be added to UHTCC. On the contrary, PVAF should be added to UHTCC.

ACT001 can prevent and reverse tamoxifen resistance in human breast cancer cell lines by inhibiting NF-κB activation.

Endocrine therapy is one of the main treatments for estrogen receptor-positive breast cancers. Tamoxifen is the most commonly used drug for endocrine therapy. However, primary or acquired tamoxifen resistance occurs in a large proportion of breast cancer patients, leading to therapeutic failure. We found that the combination of tamoxifen and ACT001, a nuclear factor-κB (NF-κB) signaling pathway inhibitor, effectively inhibited the proliferation of both tamoxifen-sensitive and tamoxifen-resistant cells. The tamoxifen-resistant cell line MCF7R/LCC9 showed active NF-κB signaling and high apoptosis-related gene transcription, especially for antiapoptotic genes, which could be diminished by treatment with ACT001. These results demonstrate that ACT001 can prevent and reverse tamoxifen resistance by inhibiting NF-κB activation.

[MicroRNAs Regulation of Cancer Stem Cells].

Cancer stem cells(CSCs) have been reported in many human tumors and are associated with tumor initiation and progression. CSCs share many biological properties with normal somatic stem cells, such as self-renewal, the propagation of differentiated progeny. However, they also have differences in their chemoresistance and tumorigenic and metastatic activity. CSCs have potential clinical importance, but the regulation at the molecular level is not well-understood. MicroRNAs(miRNAs) are a class of endogenous non-coding RNAs, and play important role in the regulation of several cellular processes. Varieties of evidence show that, miRNAs can regulates the CSCs at a molecular level and are associated with tumor initiation and progression. Better understanding of the regulation of CSCs gene expression by miRNAs could be used to identify the biomarkers and therapeutic targets. In the present review, we summarize the major development on the regulation of CSCs by miRNAs.

Potential role of pemetrexed in metastatic breast cancer patients pre-treated with anthracycline or taxane.

OBJECTIVES: This article reviews pharmacology, pharmacokinetic properties, clinical efficacy, and safety in metastatic breast cancer patients, as well as the predictive biomarkers for outcome of treatment with pemetrexed-based regimens. METHODS: PubMed, Embase, OVID, and the Cochrane Library databases were searched from the beginning of each database without any limitations to the date of publication. Search terms were ''pemetrexed'' or ''LY231514'' or "Alimta", "metastatic breast cancer", and "advanced breast cancer". RESULTS: There were 15 studies (n = 1002) meeting our criteria for evaluation. Eight single-agent trials (n = 551) and seven using combinations with other agents (n = 451) were identified that evaluated pemetrexed for use in patients with metastatic breast cancer. Response rates to pemetrexed as a single agent varied from 8% to 31%, and with combination therapy have been reported to be between 15.8% and 55.7%. With routine supplementation of patients with folic acid, dexamethasone, and vitamin B12, the toxicity profile of these patients was mild, including dose-limiting neutropenia and thrombocytopenia, as well as lower grades of reversible hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase (TS) and other biomarkers are associated with the prognosis and sensitivity for pemetrexed in breast cancer. CONCLUSION: Pemetrexed has shown remarkable activity with acceptable toxicities for treatment of metastatic breast cancer patients. Translational research on pemetrexed in breast cancer identified biomarkers as well as additional genes important to its clinical activity and toxicity. Further research is needed to clarify the role of pemetrexed in breast cancer treatment in order to guide oncologists.

RIP3 overexpression sensitizes human breast cancer cells to parthenolide in vitro via intracellular ROS accumulation.

AIM: Receptor-interacting protein 3 (RIP3) is involved in tumor necrosis factor receptor signaling, and results in NF-κB-mediated prosurvival signaling and programmed cell death. The aim of this study was to determine whether overexpression of the RIP3 gene could sensitize human breast cancer cells to parthenolide in vitro. METHODS: The expression of RIP3 mRNA in human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435 and T47D) was detected using RT-PCR. Both MDA-MB-231 and MCF-7 cells were transfected with RIP3 expression or blank vectors via lentivirus. Cell viability was measured with MTT assay; intracellular ROS level and cell apoptosis were analyzed using flow cytometry. RESULTS: RIP3 mRNA expression was not detected in the four human breast cancer cell lines tested. However, the transfection induced higher levels of RIP3 protein in MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of RIP3 decreased the IC50 values of parthenolide from 17.6 to 12.6 µmol/L in MCF-7 cells, and from 16.6 to 9.9 µmol/L in MDA-MB-231 cells. Moreover, overexpression of RIP3 significantly increased parthenolide-induced apoptosis and ROS accumulation in MCF-7 and MDA-MB-231 cells. Pretreatment with N-acetyl-cysteine abrogated the increased sensitivity of RIP3-transfected MCF-7 and MDA-MB-231 cells to parthenolide. CONCLUSION: Overexpression of RIP3 sensitizes MCF-7 and MDA-MB-231 breast cancer cells to parthenolide in vitro via intracellular ROS accumulation.

Progression of solitary and multifocal papillary thyroid carcinoma - a retrospective study of 368 patients.

BACKGROUND: Papillary thyroid carcinoma (PTC) represents one of the most frequent endocrine malignancies. Several factors have been found to be involved in determining the outcome of treatment for patients with PTC. Large tumor size, diagnosis at an early age, extra-thyroidal invasion, aggressive histological variants, and distant metastases are the most important determinants of a poor outcome. BRAF(V600E) mutation has been found to be a major genetic alteration in PTC. This study aimed to evaluate progression in patients with multifocal and solitary PTC. METHODS: We performed a retrospective study to analyze 368 patients with PTC who underwent surgery, including 282 patients with solitary PTC and 86 patients with multifocal PTC. The status of BRAF(V600E) mutation in all tumor foci from multifocal PTC was detected. RESULTS: Our study suggested that multifocal PTC was more related to lymph node metastasis and vascular invasion than solitary PTC. However, the distant metastasis rate and 10-year survival rate showed no difference between these two groups. The number of tumor foci did not affect progression of disease in multifocal PTC patients. Lymph node metastasis in multifocal PTC patients was associated with larger tumors, diagnosis at early stage, and extra-thyroidal invasion. CONCLUSION: The status of BRAF(V600E) mutation was more frequent in multifocal PTC patients with lymph node metastasis and diagnosis at later age.

Enhanced antitumor effects of BPD-MA-mediated photodynamic therapy combined with adriamycin on breast cancer in mice.

AIM: Photodynamic therapy (PDT) is an emerging treatment used to eradicate premalignant and early-stage cancers and to reduce tumor size in end-stage cancers. In this study, we investigated the effects of a combination of benzoporphyrin derivative monoacid ring A (BPD-MA)-mediated PDT with adriamycin (ADM) on 4T1 breast carcinoma cells in vivo and the mechanisms underlying this effect. METHODS: Normal BALA/c female mice bearing 4T1 breast carcinoma xenografts were tested. The animals were treated with PDT (BPD-MA 1 mg/kg, iv, plus single-dose laser irradiation) or ADM (5 mg/kg, iv) alone, or a combination of PDT with ADM. The tumor growth rate was determined by measuring the tumor weight. Cell apoptosis was measured with flow cytometry, and the expression of apoptosis-related molecules was assessed using Western blot. Microvessel density (MVD) was determined with immunohistochemical staining. RESULTS: Compared to PDT or ADM alone, PDT plus ADM produced a combined inhibition on the tumor growth, prolonged life span, and enhanced apoptosis in the mice bearing 4T1 subcutaneously xenografted tumors. The combination of PDT and ADM exerted additive effects on the upregulation of Bax and the downregulation of Bcl-2, and on the reduction of MVD in 4T1 xenografted tumors. CONCLUSION: Our results demonstrate that PDT plus ADM exerts enhanced in vivo antitumor effect on breast cancer, which is closely associated with the cooperative regulation of extrinsic apoptotic pathways and the inhibition of tumor angiogenesis. Thus, PDT plus ADM is a promising combined treatment strategy for breast carcinoma.

Involvement of tissue transglutaminase in endothelin 1-induced hypertrophy in cultured neonatal rat cardiomyocytes.

A potential link between tissue-type transglutaminase (tTG) and cardiac hypertrophy was suggested recently. However, whether tTG is implicated in hypertrophic agonist-induced cardiac hypertrophy is not yet known. The purpose of this study was to investigate the effects of tTG on cardiomyocyte hypertrophy induced by endothelin (ET) 1. Real-time quantitative RT-PCR and Western blot analysis demonstrated that ET-1 increased the expression of tTG mRNA and protein in cardiomyocytes by activating ET(A) receptors. ET-1 failed to cause increases in cell size and [(3)H]leucine uptake, sarcomere reorganization, and gene induction of the atrial natriuretic factor when cardiomyocytes were treated with monodansylcadaverine, a competitive inhibitor of tTG. Furthermore, the effects of ET-1 on multifunctional activities of tTG were determined by evaluating the incorporation of [(3)H]putrescine into N,N'-dimethylated casein and charcoal absorption, respectively. The results showed that ET-1 did not influence the basal transglutaminase activity of cardiomyocytes but significantly inhibited the 0.1-mmol/L Ca(2+)-stimulated transglutaminase activity. Otherwise, ET-1 elevated the activity of GTPase in a concentration- and time-dependent manner. In vivo, right ventricular hypertrophy induced by 2 weeks of chronic hypoxia was depressed by the tTG inhibitor cystamine (10 to 30 mg/kg, 2 times per day, IP) in a dose-dependent manner. Taken together, our data strongly supported the notion that tTG may act as a positive regulator of the hypertrophic program in response to ET-1. This is probably attributable to the signaling activity of tTG rather than transglutaminase activity.

[Yin-yang relationship between oncogene and antioncogene].

OBJECTIVE: Oncogene and antioncogene play contrary effects on the cell growth and proliferation controlling process, and cancer occurs when the presence of imbalance expression between them. That means there is yin-yang relationship between oncogene (yang) and antioncogene (yin), and also inside both of them. Taking the oncogene myc and antioncogene p53 for example, the yin gene p53 acts, in the yin side, to promote cell apoptosis and inhibit cell growth, while in the yang side, it facilitates for repairing the injured DNA to keep cell survival; the yang gene myc, promoting cell growth and proliferation in the yang side and inducing cell apoptosis in the yin side. To elucidate the yin-yang reactions between oncogene and antioncogene would be of important significance in the all-round and profound research of cancer.

Silencing of herg gene by shRNA inhibits SH-SY5Y cell growth in vitro and in vivo.

Overexpression of human ether-à-go-go (eag) related gene (herg) contributes to the progression and metastasis of a variety of tumors of different histogenesis, which implies that the herg gene could provide a promising target on tumor therapy. In the present study, plasmid-mediated expression of shRNA-herg1 and shRNA-herg1/1b was employed to silence the herg gene expression in human neuroblastoma SH-SY5Y cell lines. The inhibition of the target gene expression was confirmed by RT-PCR and Western blot. It was found that shRNA-herg1 or shRNA-herg1/1b depressed the cellular growth rate, inhibited cell viability and reduced colony formation of SH-SY5Y cells. The flow cytometry assay revealed that SH-SY5Y cells were retarded in G0-G1 after herg1 or herg1/1b gene was silenced by shRNA-herg1 or shRNA-herg1/1b. In vivo, intra-tumor injection of shRNA-herg1/1b inhibited the growth of SH-SY5Y tumors inoculated subcutaneously in nude mice. The result suggested that the herg played an important role in regulating the growth and proliferation of SH-SY5Y cells. The block of the HERG channel might be a potential therapeutic strategy for neuroblastoma and some other tumors with overexpression of the herg gene.

[Ion channels and tumor].

This review illuminates the current approaches of ion channels and tumor. Potassium, calcium, chloride channnels and others are abnormally expressed in the membrane of tumor cells. They are crucial for tumor development and growth. By the regulation of membrane voltage, cell cycle, cell volume, Ca2+ signaling and cytosolic pH, they can adjust the cell proliferation and apoptosis. With further study, ion channels will become a new target for cancer therapy and diagnosis.