The role of DDX46 in breast cancer proliferation and invasiveness: A potential therapeutic target.

DDX46, a member of DEAD-box (DDX) proteins, is associated with various cancers, while its involvement in the pathogenesis of breast cancer hasn't been reported so far. The study demonstrated the overexpression of DDX46 in human breast cancer cells and tissue samples, and correlated with high histological grade and lymph node metastasis. Downregulation of DDX46 in the breast cancer cell lines inhibited their proliferation and invasiveness in vitro. Furthermore, the growth of MDA-MB-231 xenografts was suppressed in nude mice by DDX46 knockingdown. Taken together, our findings suggest that DDX46 is an oncogenic factor in human breast cancer, and a potential therapeutic target.

Augmentation of antitumor function of tumor-infiltrating lymphocytes against triple-negative breast cancer by PD-1 blockade.

T-cell-based immunotherapy and immune checkpoint blockade have been successfully used to treat several human solid cancers. The present study attempted to investigate the feasibility and efficacy of the antitumor effect of adoptive cell therapy along with programmed cell death protein 1 (PD-1) inhibitor on triple-negative breast cancer (TNBC). Tumor infiltration lymphocytes (TILs) from TNBC mouse tumor tissues were isolated and expanded, and TILs for adoptive cell therapy (TILs-ACT) were applied in combination with a PD-1 inhibitor to the TNBC mouse model. The pre- and post-therapy antitumor efficacy, cytokine secretion, and pathological changes were assessed both in vitro and in vivo. We found that TILs exhibited higher IFN-γ and TNF-α secretion than conventional T cells. The TILs-ACT combined with PD-1 inhibitor promoted active T-cell infiltration into the tumor tissue and exerted a strong antitumor effect in an in vivo model. Additionally, the strategy could downregulate the expression of inhibitory marker PD-1 on TILs. In conclusion, PD-1 blockade regulated T-cell exhaustion that synergized with adoptive TIL transfer immunotherapy, leading to eradication of established TNBC tumors. These findings might be useful in developing a feasible and effective therapeutic approach for TNBC.

Circular RNA 000554 represses epithelial-mesenchymal transition in breast cancer by regulating microRNA-182/ZFP36 axis.

Increasing evidence indicates that circular RNAs (circRNAs) play a crucial role in regulating microRNAs (miRs) and mRNAs during breast cancer (BC) progression. Based on the in silico analysis of circRNA/miR/mRNA in BC, we aim to define an important role of circRNA_000554 in BC in relation to miR-182 and zinc finger protein 36 (ZFP36). Low expression of circRNA_000554 and ZFP36, and high miR-182 expression were determined in the clinical BC tissues. CircRNA_000554 acted as a sponge of miR-182, and miR-182 directly targeted ZFP36. After that, in order to evaluate the effects of circRNA_000554, miR-182, and ZFP36 on cellular process, we evaluated in vitro epithelial-mesenchymal transition (EMT) and in vivo tumor growth after delivering a series of overexpression plasmids, mimic, inhibitor, or shRNAs into BC cells. Increasing circRNA_000554 suppressed EMT, cell invasion and migration during BC by depleting miR-182 and increasing ZFP36. The inhibitory effect of circRNA_000554 on tumor growth was validated in vivo. Taken together, the present study confirms that circRNA_000554 functioned as an inhibitor of EMT in BC and suggests a molecular mechanism that circRNA_000554 bound to miR-182 to upregulate ZFP36 in this process.

[Protective effect of ulinastatin on cerebral tissue in rats with lethal scald injury].

OBJECTIVE: To explore the protective effects of ulinastatin on cerebral tissue in rats following lethal burn injury and its relationship with the expression of protective protein. METHODS: A total of 40 male Sprague-Dawley rats were randomly divided into scald and ulinastatin groups (n = 20 each). Both groups were subjected to 50% total body surface area third-degree burns. Immediately after scalding, 1 ml normal saline was injected intravenously in scald group while 1 ml saline containing ulinastatin (40 000 U/kg) in ulinastatin group. Then cerebral tissue was harvested for measuring the activities of neuron-specific enolase (NSE) by enzyme-linked immunosorbent assay (ELISA) at 6 h and 24 h post-injury. And the level of acetylated histone H3 was detected by Western blot and heat shock protein 70 (HSP70) by ELISA. The rates of tissue water content in heart were determined by dry/wet weight. RESULTS: NSE and water content of cerebral tissue after 6 h injury in ulinastatin group were significantly lower than those in scald group ((146 ± 11) vs (156 ± 13) pg/ml, (77.3 ± 1.9)% vs (79.0 ± 2.2)%, both P < 0.05), the expressions of HSP70 and histone H3 after 6 h injury in ulinastatin group was significantly higher than those in scald group ((99 ± 19) vs (92 ± 13) pg/ml, (1.26 ± 0.37) vs (0.57 ± 0.23), both P < 0.05). The NSE content of cerebral tissue after 24 h injury in ulinastatin group was significantly lower than that in scald group ((141 ± 14) vs (159 ± 10) pg/ml, P < 0.05). And the water content of cerebral tissue, the expressions of HSP70 and histone H3 after 24 h injury had no significant inter-group differences ((75.9 ± 1.2)% vs (76.5 ± 1.4)%, (118 ± 17) vs (102 ± 16) pg/ml, (2.31 ± 0.27) vs (1.87 ± 0.31), both P > 0.05). CONCLUSIONS: Ulinastatin significantly alleviates cerebral tissue injury in early stage of burn injury. And its protective effects may be due to the up-regulations of histone H3 and HSP70.

Effects of two different immunotherapies on triple negative breast cancer in animal model.

The ability of immune system to react specifically against tumors inspirited the study of triple negative breast cancer (TNBC) immunotherapies. Sixty spontaneous breast cancer TA2 mice were randomly divided into three groups: GM-CSF group, with therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with breast cancer stem cells associated antigens and cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs); DC-CIK group, with infusions of dendritic cells/cytokine-induced killer (DC/CIK) cells; and PBS group as controls. After therapy, the cellular immunity of mice in GM-CSF group and DC-CIK group was obviously increased, especially for GM-CSF group (P<0.05), tumor regression was obviously observed in GM-CSF group. The survival rate of mice in GM-CSF group was significantly higher compared to DC-CIK group and PBS group. These results indicated that tumor immunotherapy manifested strong killing activity against TNBC. The therapeutic effect of GM-CSF combined with antigens and CpG was better than DC-CIK cells.

Mesothelial cells differentiate into fibroblast-like cells under the scirrhous gastric cancer microenvironment and promote peritoneal carcinomatosis in vitro and in vivo.

Peritoneal metastases are one reason for the poor prognosis of scirrhous gastric cancer (SGC), and myofibroblast provides a favorable environment for the peritoneal dissemination of gastric cancer. The aim of this study was to determine whether myofibroblast originates from peritoneal mesothelial cells under the influence of the tumor microenvironment. Immunohistochemical studies of peritoneal biopsy specimens from patients with peritoneal lavage cytological (+) status demonstrate the expression of the epithelial markers cytokeratin in fibroblast-like cells entrapped in the stroma, suggesting that these cells stemmed from local conversion of mesothelial cells. To confirm this hypothesis in vitro, we co-incubated mesothelial cells with SGC or non-SGC to investigate morphology and function changes. As we expected, mesothelial cells undergo a transition from an epithelial phenotype to a mesenchymal phenotype with loss of epithelial morphology and decrease in the expression of cytokeratin and E-cadherin when exposed to conditioned medium from HSC-39, and the induction of mesothelial cells can be abolished using a neutralizing antibody to transforming growth factor-beta1 (TGF-ß1) as well as by pre-treatment with SB431542. Moreover, we found that these mesothelial cells-derived cells exhibit functional properties of myofibroblasts, including the ability to increase adhesion and invasion of SGC. In summary, our current data demonstrated that mesothelial cells are a source of myofibroblasts under the SGC microenvironment which provide a favorable environment for the dissemination of gastric cancer; TGF-ß1 produced by autocrine/paracrine in peritoneal cavity may play a central role in this pathogenesis.

Associations of polymorphisms of rs693 and rs1042031 in apolipoprotein B gene with risk of breast cancer in Chinese.

BACKGROUND: Lipid synthesis is an integrated result of genetic, epigenetic and environmental factors, and also can promote growth and survival of cancer cells. Apolipoprotein B plays a central role in lipid metabolism as the major protein component of very-low-density lipoprotein and low-density lipoprotein. METHODS: We investigated the associations of polymorphisms of rs693 (-7673C>T) and rs1042031 (-12669 G>A) in the APOB gene with risk of breast cancer in 675 blood-unrelated Chinese patients with breast cancer and 712 healthy controls. RESULTS: Polymorphisms of -12669 G>A and -7673C>T in the APOB gene were significantly associated with an increased risk of breast cancer (P = 0.000), especially for postmenopausal women (P = 0.000, 0.023). The positive associations still remained after further analysis of the two polymorphisms' distribution according to body mass index. However, no statistical associations were found between -12669 G>A and -7673C>T polymorphisms and other clinical characteristics, including tumor size, lymph node metastasis, histological grade, estrogen and progesterone receptor status and Her-2 status. CONCLUSIONS: rs693 and rs1042031 polymorphisms in the APOB gene increased the risk of breast cancer in Chinese, and this role of the two polymorphisms in connection with breast cancer was not dependent on body mass index.

Efficacy of combined therapy of goserelin and letrozole on very young women with advanced breast cancer as first-line endocrine therapy.

Breast cancer in young women younger than 35 years old is rare, aggressive and associated with a poor prognosis. Endocrine therapy is a preferred treatment modality in hormone receptor-positive early stage and advanced breast cancer, combined therapy of goserelin and letrozole presents an option for premenopausal women. We reported the efficacy and safety of therapy of goserelin plus letrozole on very young women with advanced breast cancer as first-line endocrine therapy. Thirty-five patients with first diagnosed as advanced breast cancer, age younger than 35 years, were enrolled in the study. All patients received goserelin 3.6 mg by subcutaneous injection every 4 weeks along with letrozole 2.5mg daily by mouth as first-line endocrine therapy. The study endpoints were objective response rate (ORR), clinical benefit (CB), progression-free survival (PFS), overall survival (OS) and toxicity. The median duration of response to the therapy was 21 (range, 10-56) months, and median duration of follow-up was 44 (range, 5-79) months. The ORR was 25.7%, with one complete response (CR, 2.9%) and eight partial response (PR, 22.9%). Twenty-two patients had stable disease at 24 weeks, for a clinical benefit rate of 65.7%. The median PFS was 9.6 (range 5-58) months and median OS was 33 (range 6-72) months. During the therapy and follow-up, no serious toxicities were reported. Combined therapy of goserelin and letrozole appears to be an efficacious and well-tolerated therapy for very young women with advanced breast cancer. Further investigations involving more patients, combination of other therapies and longer follow-up are requisite.

Good neurologic recovery after cardiac arrest using hypothermia through continuous renal replacement therapy.

Therapeutic hypothermia (TH) is becoming a standard of care to mitigate neurologic injury in cardiac arrest survivors. Several cooling methods are available for use in TH. For maintaining a target temperature, intravascular cooling is superior to, more efficacious than, and safer than surface cooling methods. The use of an intravenous cooling catheter is independently associated with a higher odds ratio for survival. However, many techniques use commercially developed equipment that is expensive to purchase and use. The application and popularization of the intravascular cooling method have been difficult. In patients with pulmonary edema or cardiac insufficiency, liquid is restricted, so intravascular cooling systems cannot be used. Studies have shown abnormalities mimicking the immunologic and coagulation disorders observed in severe sepsis. Continuous renal replacement therapy has been widely used in the intensive care unit to improve clinical parameters and survival in patients with multiple-organ dysfunction of septic origin. Continuous renal replacement therapy can also be used as another type of core cooling method. We used continuous renal replacement therapy as a cooling method to induce TH in a patient who had a cardiac arrest, and the patient regained consciousness 52 hours later.

Synthesis and Application of Hybrid Aluminum Dialkylphosphinates as Highly Efficient Flame Retardants for Polyamides.

Hybrid aluminum dialkylphosphinates were synthesized from mixed diethyl-, ethylisobutyl-, and diisobutylphosphinates and Al3+ in water. The XRD, DSC, and TGA results of these Al phosphinates established that phosphinate ligands are randomly distributed in the species. The thermal and thermoxidative stabilities of the hybrid phosphinates were easily adjustable by varying the ratio of phosphinate ligands, a desirable feature for efficient flame retardants. The hybrid aluminum dialkylphosphinates with a relatively low ratio of diethylphosphinate demonstrated higher efficiency than Al diethylphosphinate and Al diisobutylphosphinate in flame-retarding polyamide 66. Detailed investigations on the thermal and thermoxidative stabilities of Al dialkylphosphinates and the morphologies of char obtained in UL-94 tests revealed that timely vaporization of degradation products of hybrid dialkylphosphinates at a temperature which closely matches the degradation temperature of polyamides and their ability to promote char formation of polyamides are two key factors which contribute to the excellent performance of hybrid aluminum dialkylphosphinates.

Erratum: [Corrigendum] Mesenchymal stem cells expressing interleukin­18 inhibit breast cancer in a mouse model.

[This corrects the article DOI: 10.3892/ol.2018.8166.].

Erratum: [Corrigendum] Mesenchymal stem cells expressing interleukin­18 suppress breast cancer cells in vitro.

[This corrects the article DOI: 10.3892/etm.2015.2286.].

Prognostic value and immunological role of Kruppel-like transcription factor 9 gene in pan-carcinoma.

OBJECTIVE: To investigate the correlation between the expression of Kruppel-like transcription factor 9 (KLF9) and the prognostic value of tumors as well as its relationship with tumor immune invasion. METHODS: A series of bioinformatics methods were used to analyze the relationship between KLF9 and tumor prognosis, tumor mutation burden, microsatellite instability (MSI), and immune cell infiltration in multiple carcinomas. RESULTS: In multiple tumor tissues, the expression of KLF9 was lower compared with paracancerous tissues. Therefore, KLF9 can serve as a protective factor to improve the prognosis of carcinoma patients with certain tumor types. KLF9 was closely related to the clinical staging of various carcinomas. The expression of KLF9 was not only associated with tumor mutation burden and MSI in some tumor types, but also positively correlated with immune and stromal cells in multiple tumors. Further studies have found that, the level of immune cell infiltration was significantly related to the expression of KLF9. CONCLUSION: KLF9 can affect the prognosis of pan-carcinoma, which is related to immune invasion. Therefore, KLF9 can be used as a potential biomarker for the prognosis of pan-carcinoma.

Clinical Characteristics and Death Risk Factors of Severe Sepsis in Children.

Sepsis is a systemic inflammatory response syndrome caused by viral infection. The circulatory dysfunction caused by sepsis is also called septic shock or septic shock. The main characteristics are rapid onset, rapid changes, and involvement. Multiple organs in the body make diagnosis difficult, which seriously threatens the survival of patients. As many as one million people worldwide die every year because of SIRS, it is also the leading cause of death among children in hospital ICUs. This article is aimed at studying the clinical characteristics of severe sepsis in children and the risk factors for death. Based on the analysis of the pathogenesis of sepsis and the treatment of septic shock, 65 cases of children with PICU sepsis admitted to a hospital were selected. Data, to study its clinical characteristics and risk factors for death. The results of the study showed that despite the interaction among the removal factors of the three indexes of serum lactic acid value, PCIS level, and the number of organs involved in MODS, they are still related to the mortality of children with severe sepsis.

Hormone receptor-positive, HER2-negative, metastatic breast cancer responded well to abemaciclib and exemestane after palbociclib and fulvestrant failure: A case report and literature review.

There is uncertainty regarding the usefulness of CDK4/6-inhibitor-based therapy for hormone receptor positive (HR+), human epidermal grow factor receptor 2 negative (HER2-), metastatic breast cancer (MBC), when CDK4/6 inhibitor treatment had previously failed. Furthermore, a biomarker for abemaciclib resistance has not been identified. Herein, we reported outcomes for an HR+/HER2- MBC patient diagnosed with multiple myeloma and treated with abemaciclib and exemestane, who had cancer progression after treatment with palbociclib and fulvestrant. Thalidomide was used in conjunction with all treatments. The patient had a good response to abemaciclib and exemestane, with progression-free survival much longer than previously reported. PIK3CA and TP53 mutations were identified after cancer progression following abemaciclib treatment. It is unclear whether thalidomide increased the effectiveness of abemaciclib. Whether benefit can be derived by the use of PI3K inhibitors, after cancer progression, requires further investigation, and this may be best accomplished by the use of next-generation sequencing.

Interfacial silicon­nitrogen aerogel raise flame retardancy of bamboo fiber reinforced polylactic acid composites.

A triazine derivative containing nitrogen and silicon (SiN) was synthesized and the SiN hybrid aerogel was covered on the surface of bamboo fiber (BF). The modified BF was identified as MBF. The MBF and ammonium polyphosphate (APP) were used to regulate the flame retardancy and mechanical properties of polylactic acid (PLA). The PLA/BF composites were investigated using limiting oxygen index (LOI), UL-94 vertical combustion, cone calorimetry, thermogravimetric analysis linked with infrared spectra (TG-IR) etc. The char residue of MBF at 800 °C is as high as 43.5 % which is 200 % more than that of BF. Incorporating 9 wt% APP generates a PLA9 which displays the UL-94 V2 rating and a LOI value of 28.0 vol%. PLA9/MBF composites display the UL-94 V0 rating and increased LOI values while PLA9/BF composites obtain the UL-94 V2 rating and decreased LOI. The MBF reduces the release of flammable gases during combustion, enhances charring ability and decreases the thermal conductivity of composites. Besides, the tensile and impact strength of PLA9/20MBF is 20 % and 37 % more than that of PLA9/20BF due to stronger interfacial adhesion. This work provides a good method to regulate the flame retardancy and mechanical properties of PLA/BF composites.

Using Cellulose-graft-Poly(L-lactide) Copolymers as Effective Compatibilizers for the Preparation of Cellulose/Poly(L-lactide) Composites with Enhanced Interfacial Compatibility.

Cellulose-grafte-poly(L-lactide) (C-g-PLLA) copolymers synthesized in a CO2-switchable solvent are proposed for use as effective compatibilizers for the preparation of cellulose-PLLA composites with enhanced interfacial compatibility. The effect of the molar substitution (MSPLLA) of the grafted PLLA side chain in the C-g-PLLA copolymer and the feeding amount of this copolymer on the mechanical and thermal properties and hydrophilicity of the composites was investigated. The composites had a largely increased impact strength with the incorporation of the compatibilizer. With the increasing of MSPLLA and the feeding amount of the copolymer, the resulting composites had an increased impact strength. When 5 wt% C-g-PLLA with MSPLLA of 4.46 was used as a compatibilizer, the obtained composite containing 20 wt% cellulose presented an impact strength equal to that obtained for the neat PLLA. The composites had a slightly decreased melting temperature and thermal decomposition temperature, but increased hydrophilicity due to the incorporation of the compatibilizer. This work suggests an effective method to improve the interfacial compatibility between cellulose and PLLA for the fabrication of fully bio-based composites with high performance.

Combining use of a panel of ssDNA aptamers in the detection of Staphylococcus aureus.

In this article, a panel of ssDNA aptamers specific to Staphylococcus aureus was obtained by a whole bacterium-based SELEX procedure and applied to probing S. aureus. After several rounds of selection with S. aureus as the target and Streptococcus and S. epidermidis as counter targets, the highly enriched oligonucleic acid pool was sequenced and then grouped under different families on the basis of the homology of the primary sequence and the similarity of the secondary structure. Eleven sequences from different families were selected for further characterization by confocal imaging and flow cytometry analysis. Results showed that five aptamers demonstrated high specificity and affinity to S. aureus individually. The five aptamers recognize different molecular targets by competitive experiment. Combining these five aptamers had a much better effect than the individual aptamer in the recognition of different S. aureus strains. In addition, the combined aptamers can probe single S. aureus in pyogenic fluids. Our work demonstrates that a set of aptamers specific to one bacterium can be used in combination for the identification of the bacterium instead of a single aptamer.

Clusterin confers gemcitabine resistance in pancreatic cancer.

OBJECTIVE: To measure clusterin expression in pancreatic cancer tissues and cell lines and to evaluate whether clusterin confers resistance to gmcitabine in pancreatic cancer cells. METHODS: Immunohistochemistry for clusterin was performed on 50 primary pancreatic cancer tissues and 25 matched backgrounds, and clusterin expression in 5 pancreatic cancer cell lines was quantified by Western blot and PT-PCR. The correlation between clusterin expression level and gmcitabine IC50 in pancreatic cancer cell lines was evaluated. The effect of an antisense oligonucleotide (ASO) against clusterin (ASO-CLU) [corrected] on gmcitabine resistance was evaluated by MTT assays. Xenograft model was used to demonstrate tumor growth. RESULTS: Pancreatic cancer tissues expressed significantly higher levels of clusterin than did normal pancreatic tissues (P < 0.01). Clusterin expression levels were correlated with gmcitabine resistance in pancreatic cancer cell lines, and ASO-CLU [corrected] significantly decreased BxPc-3 cells resistance to gmcitabine (P < 0.01). In vivo systemic administration of AS clusterin and gmcitabine significantly decreased the s.c. BxPC-3 tumor volume compared with mismatch control ODN plus gmcitabine. CONCLUSION: Our finding that clusterin expression was significantly higher in pancreatic cancer than in normal pancreatic tissues suggests that clusterin may confer gmcitabine resistance in pancreatic cancer cells.