Enforced expression of hsa-miR-125a-3p in breast cancer cells potentiates docetaxel sensitivity via modulation of BRCA1 signaling.

Epigenetic gene inactivation by microRNAs (miRNAs) plays a key role in malignant transformation, prevention of apoptosis, drug resistance and metastasis. It has been shown that miR-125a is down-regulated in HER2-amplified and HER2-overexpressing breast cancers (BCa), and this miRNA is believed to serve as an important tumor suppressor. miR-125a has two mature forms: hsa-miR-125a-3p and hsa-miR-125a-5p. However, the functional details of these miRNAs in BCa, particularly during pathogenesis of drug resistance, remain largely unexplored. Herein, we reported that hsa-miR-125a-3p expression was significantly reduced in chemoresistant BCa tissues and in experimentally established chemoresistant BCa cells. hsa-miR-125a-3p knockdown promoted cell proliferation and compromised docetaxel (Dox)-induced cell death, whereas overexpression of hsa-miR-125a-3p attenuated Dox chemoresistance in BCa cells. From a mechanistic standpoint, hsa-miR-125a-3p directly targeted 3'-untranslated regions (3'-UTRs) of breast cancer early onset gene 1 (BRCA1) and inhibits its protein expression via translational repression mechanism. In addition, suppression of BRCA1 expression by siRNA treatment effectively improved hsa-miR-125a-3p deficiency-triggered chemoresistance in BCa cells. Collectively, these findings suggest that hsa-miR-125a-3p may function as a tumor suppressor by regulating the BRCA1 signaling, and reintroduction of hsa-miR-125a-3p analogs could be a potential adjunct therapy for advanced/chemoresistant BCa.

Predictive value of HLA-G and HLA-E in the prognosis of colorectal cancer patients.

HLA-G and HLA-E are non-classical HLA Ib molecules. Recently, increasingly more reports have shown that HLA-G is highly expressed in different malignancies. In this article, we detected the expression levels of HLA-G and HLA-E in primary colorectal cancer patients. Our results showed that 70.6% and 65.7% of the colorectal cancer tissues had positive HLA-G or HLA-E expression, respectively, and that 46.1% positively expressed both molecules. We also analyzed the correlations between the expression levels of HLA-G, HLA-E or both combined and the clinical outcomes of the patients. Kaplan-Meier analysis results showed that the expression levels of HLA-G or HLA-E alone and the combined expression of both molecules were all statistically correlated with the overall survival of colorectal cancer patients. Cox multivariate analysis showed that only HLA-G expression can serve as independent factor for OS. Our results also showed that the expression of HLA-E was significantly correlated with tumor metastasis.

A subanesthetic dose of isoflurane during postconditioning ameliorates zymosan-induced neutrophil inflammation lung injury and mortality in mice.

Anesthetic isoflurane (ISO) has immunomodulatory effects. In the present study, we investigated whether a subanesthetic dose of ISO (0.7%) protected against zymosan (ZY) induced inflammatory responses in the murine lung and isolated neutrophils. At 1 and 6 hrs after ZY administration intraperitoneally, ISO was inhaled for 1 hr, and 24 hrs later, lung inflammation and injury were assessed. We found that ISO improved the survival rate of mice and mitigated lung injury as characterized by the histopathology, wet-to-dry weight ratio, protein leakage, and lung function index. ISO significantly attenuated ZY-induced lung neutrophil recruitment and inflammation. This was suggested by the downregulation of (a) endothelial adhesion molecule expression and myeloperoxidase (MPO) activity in lung tissue and polymorphonuclear neutrophils (b) chemokines, and (c) proinflammatory cytokines in BALF. Furthermore, ZY-induced nuclear translocation and DNA-binding activity of NF- κ B p65 were also reduced by ISO. ISO treatment inhibited iNOS expression and activity, as well as subsequent nitric oxide generation. Consistent with these in vivo observations, in vitro studies confirmed that ISO blocked NF- κ B and iNOS activation in primary mouse neutrophils challenged by ZY. These results provide evidence that 0.7% ISO ameliorates inflammatory responses in ZY-treated mouse lung and primary neutrophils.

Recombination and natural selection in hepatitis E virus genotypes.

To gain new insights into the evolutionary processes that created the genetic diversity of the hepatitis E virus (HEV), the Recombination Detection Program (RDP) and SimPlot program were employed to detect recombination events in the genome, then the fixed-effects likelihood (FEL) method was used to detect natural selection effects on viral proteins. Recombination analysis provided strong evidence for both intergenotype and intragenotype recombination events in the sequences analyzed. Recombination events were found to be distributed non-randomly, with the highest frequency in the X domain and the helicase. Strain DQ450072 was identified as intergenotype-recombinant. Natural selection analysis revealed that codons under both negative selection and positive selection were distributed non-randomly. ORF1 and ORF2 have experienced strong purifying selection across genotypes. Furthermore, potentially important sites were also found under positive selection in the N-terminal end of ORF2 and the C-terminal end of ORF3. No significant difference was found among the selective pressures on different genotypes.

Rectal carcinoma metastatic to the male breast after 7 years: case report.

BACKGROUND: Colorectal cancer metastasis to a mammary location is very rare. CASE REPORT: A 38-year-old male, who had undergone anterior resection of an advanced rectal carcinoma 7 years earlier, presented with a right mammary mass. Core needle biopsy of the mass indicated cytology consistent with breast adenocarcinoma. After neoadjuvant chemotherapy and modified radical mastectomy, pathology identified the mass as rectal carcinoma. CONCLUSION: The authors highlight the difficulty of making an accurate diagnosis of rectal cancer metastasis to the breast of a male.

Theoretical evaluation of burns to the human respiratory tract due to inhalation of hot gas in the early stage of fires.

A transient two-dimensional mathematical model for heat and water vapor transport across the respiratory tract of human body was established and applied to predict the thermal impact of inhaled hot gas to the nasal tissues during the early stage of fires. Influences of individual's physiological status and environment variables were comprehensively investigated through numerical calculations. Burn evaluation was performed using the classical Henriques model to predict the time for thermal injury to occur. It was shown that decreasing the air velocity and increasing the respiratory rate is helpful to minimize the burn over the respiratory tract. The effect of relative humidity of surrounding dry hot air could be ignored in predicting burns for short duration exposures. Due to evaporation cooling on the mucousal membrane, the burn often occurs at certain positions underneath the skin of the tract near the inlet of the respiratory tract. Most of the tissues near the surface suffer injury immediately after exposure to fire, while in the deeper tissues, serious damage occurs after a relatively longer time period. The method presented in this paper may suggest a valuable approach to theoretically evaluate the injury of hot air to the human respiratory tract under various fire situations.

Establishment and Clinical Application of an Electronic Database for Breast Cancer in China.

PURPOSE: To establish a database for breast cancer patients to save and manage clinical data and to preliminarily investigate its clinical application. MATERIALS AND METHODS: Information on breast cancer patients hospitalized in our department from 2008.01 to 2013.01 were input into our breast cancer management system. SPSS 16.0 software was used as a convenient reference to evaluate the accuracy of the newly built database. RESULTS: A database of 2403 breast cancer patients was successfully established. Information in the database clearly displayed capabilities of storage, addition, retrieval, statistical analysis and other functions. As the continuously updated database showed, the distribution of age, sex, nationality, allergy history, pausimenia and marriage of patients was identical to that achieved by SPSS analysis, indicating reliable and accurate data analysis. CONCLUSIONS: The described database is easy and convenient to operate and manage, and should prove suitable for application in clinical research and treatment.

3-D numerical study on the induced heating effects of embedded micro/nanoparticles on human body subject to external medical electromagnetic field.

Advancement of the recent micro/nanotechnology stimulates the renaissance of using magnetic micro/nanoparticles embedded in tissues for the target tumor hyperthermia. However, there is a strong lack of quantitative understanding of the temperature profiles thus induced by the applied external electromagnetic (EM) field, which may impede the successful operation of this therapy. In the current study, the three-dimensional quasi-steady-state EM field and transient tissue temperature behavior induced by two planar electrodes were numerically investigated. Detailed computations indicated that nanoparticles exhibit an extraordinary highly focused heating on target tumor tissue, which is much stronger than that in the surrounding areas. This heating effect depends heavily on the properties of the magnetic nanoparticles, which may vary appreciably for different samples depending on their particle sizes and microstructures. The effect of micro/nanoparticle concentration, heating area, and the frequency and strength of the external alternating EM field were also tested. Moreover, a criterion to determine the appropriate particle concentration thermally important for medical treatment was established. Given accurate thermal and EM parameters for cancerous tissue embedded with nanoparticles, the current model could possibly be applied in the hyperthermia treatment planning and help optimize the surgical procedures.

Subanesthetic isoflurane reduces zymosan-induced inflammation in murine Kupffer cells by inhibiting ROS-activated p38 MAPK/NF-κB signaling.

Volatile anesthetic isoflurane (ISO) has immunomodulatory effects. The fungal component zymosan (ZY) induces inflammation through toll-like receptor 2 or dectin-1 signaling. We investigated the molecular actions of subanesthetic (0.7%) ISO against ZY-induced inflammatory activation in murine Kupffer cells (KCs), which are known as the resident macrophages within the liver. We observed that ISO reduced ZY-induced cyclooxygenase 2 upregulation and prostaglandin E2 release, as determined by western blot and radioimmunoassay, respectively. ISO also reduced the production of tumor necrosis factor-α, interleukin-1ß, IL-6, high-mobility group box-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 as assessed by enzyme-linked immunosorbent assays. ISO blocked the ZY-induced nuclear translocation and DNA-binding activity of nuclear factor- (NF)-κB p65. Moreover, ISO attenuated ZY-induced p38 mitogen-activated protein kinase (MAPK) activation partly by scavenging reactive oxygen species (ROS); the interregulation that ROS activated p38 MAPK followed by NF-κB activation was crucial for the ZY-induced inflammatory responses in KCs. An in vivo study by peritoneal injection of ZY into BALB/C mice confirmed the anti-inflammatory properties of 0.7% ISO against ZY in KCs. These results suggest that ISO ameliorates ZY-induced inflammatory responses in murine KCs by inhibiting the interconnected ROS/p38 MAPK/NF-κB signaling pathways.

The prevalence and trends of transfusion-transmissible infectious pathogens among first-time, voluntary blood donors in Xi'an, China between 1999 and 2009.

OBJECTIVES: The prevalence of infectious diseases is increasing in developing countries, and this may threaten the biological safety of donated blood. This study analyzed trends in the prevalence of transfusion-transmissible infectious pathogens among Chinese, first-time, voluntary blood donors from 1999 to 2009 to evaluate the potential for disease transmission. METHODS: From 1999 to 2009, all first-time donors at the Xi'an Blood Service (XBS) were screened for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis infections using enzyme-linked immunosorbent assays (ELISA); results were confirmed using alternative commercial kits. The prevalence and temporal trends were analyzed using the Cochran-Armitage trend test and other appropriate methods. RESULTS: From 1999 to 2009, 263 299 first-time blood donors were analyzed. The overall prevalence rates were 1.16% for HBV, 0.51% for HCV, 0.02% for HIV, and 0.31% for syphilis. There was a significant decrease in the trend for HBV and HCV infections, while a significant increase was found for syphilis. The prevalence of HIV infection remained low and stable during the study period. CONCLUSIONS: These findings suggest that HBV infection is the primary threat to blood safety, while the increasing prevalence of syphilis might also be a potential threat.

Lysosome-membrane fusion mediated superoxide production in hyperglycaemia-induced endothelial dysfunction.

Lysosomal exocytosis and fusion to cellular membrane is critical in the oxidative stress formation of endothelium under apoptotic stimulus. We investigated the role therein of it in hyperglycaemia-induced endothelial dysfunction. The lysosome-membrane fusion was shown by the expression of lamp1, the lysosomal membrane marker, on cellular membrane and the transportation of lysosomal symbolic enzymes into cultural medium. We also examined the ceramide production, lipid rafts (LRs) clustering, colocalization of gp91(phox), a NADPH oxidase subunit (NOX) to LRs clusters, superoxide (O2·â») formation and nitric oxide (NO) content in human umbilical vein endothelial cells (HUVEC) and the endothelium-dependent NO-mediated vasodilation in isolated rat aorta. As compared to normal glucose (5.6 mmol/l, Ctrl) incubation, high glucose (22 mmol/l, HG) exposure facilitated the lysosome-membrane fusion in HUVEC shown by significantly increased quantity of lamp1 protein on cellular membrane and enhanced activity of lysosomal symbolized enzymes in cultural medium. HG incubation also elicited ceramide generation, LRs clustering and gp91(phox) colocalization to LRs clusters which were proved to mediate the HG induced O2·â» formation and NO depletion in HUVEC. Functionally, the endothelium-dependent NO-mediated vasodilation in aorta was blunted substantially after HG incubation. Moreover, the HG-induced effect including ceramide production, LRs clustering, gp91(phox) colocalization to LRs clusters, O2·â» formation and endothelial dysfunction could be blocked significantly by the inhibition of lysosome-membrane fusion. We propose that hyperglycaemia-induced endothelial impairment is closely related to the lysosome-membrane fusion and the following LRs clustering, LRs-NOX platforms formation and O2·â» production.

The distribution of genetic diversity of KIR genes in the Chinese Mongolian population.

Killer cell immunoglobulin-like receptors (KIRs) are expressed on natural killer cells and as such regulate their response against infection and malignancy. KIR genes are variable in gene content and type, which results in different KIR haplotypes, and can be used to discriminate individuals and populations from different regions or ethnic groups. In the present study, we represent the first report on the KIR gene frequency and content diversities of 14 KIR genes (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and 2 pseudogenes (KIR3DP1 and 2DP1) in the Chinese Mongolian population. The 16 detected KIR genes were all observed. All the individuals were typed positive for the four framework genes KIR3DL3, 3DL2, 2DL4 and the pseudogene KIR3DP1, as well as for the pseudogene KIR2DP1. The observed carrier gene frequencies (OF) of the other KIR genes ranged from 16% at the KIR2DL2 locus to 93% at the KIR3DL1 locus. Over all, 48 different gene profiles were found in the study population and the most commonly observed KIR gene profile with a frequency of 14% consisted of KIR2DL4, 3DL2, 3DL3, 2DP1, 3DP1, 2DL1, 2DL3 and 3DL1 which belongs to the AA genotype. Principal component analysis (PCA) and the dendrogram illustrated the genetic distances between our study population and previously published populations from other ethnic groups or regions. The results of the present study show that the KIR gene family is highly polymorphic and can be a valuable tool for enriching the Chinese ethnical gene information resources, for anthropological studies, as well as for KIR gene related disease research.

[Association between polymorphisms of interleukin-6 gene promoter and breast cancer].

AIM: To study possible association between three single nucleotide polymorphisms (-597G/A, -572C/G and -174G/C) of interleukin-6 (IL-6) gene promoter and breast cancer. METHODS: Genomic DNA was isolated from the venous blood leukocytes from 176 unrelated patients with breast cancer and 200 healthy unrelated females (control group). Polymorphisms of -597G/A, -572C/G and -174G/C, were genotyped by PCR-restriction fragment length polymorphisms (PCR-RFLP). SPSS 11.5 software was employed for statistical analysis and the association of IL-6 polymorphisms with breast cancer was evaluated by x(2); test. RESULTS: There was significant differences in both allele and genotype frequencies of -572C/G in case group compared with control group. The allele G of -572C/G was significantly higher in cancer patients than the controls(x(2);=15.438, P<0.01). CONCLUSION: There is an association between -572C/G polymorphism and breast cancer risk. The females with G allele of -572C/G are susceptible to breast cancer compared with non-carrying females.

The role of survivin in diagnosis, prognosis and treatment of breast cancer.

Survivin is a cancer gene that is silenced in differentiated tissues, while overexpressed at high levels in vast majority of tumors. It has garnered great interests in recent years. Some essential properties characterizing it as an ideal target involve inhibiting apoptosis, promoting mitosis, stimulating vessel growth thus inducing chemo-resistance. These functions touch the full gamut of tumorigenesis, including proliferation, migration, and invasion, and collectively facilitate malignant behavior. In the case of breast cancer, survivin detection independent or combined in serum and/or urine has emerged as a measure for diagnosis. Moreover, many studies indicated aberrant expression of survivin is associated with poor prognosis and drug/radiation resistance. Strategies targeting survivin to treat breast cancer have got promising initial results. In this review, we summarize its role in breast cancer's diagnosis, prognosis, and treatment, with the intention to explain why this interesting molecule plays a conflicting role.

T-vector and in vivo recombination as tools to construct a large antibody library of breast cancer.

The emergence of phage antibody libraries is an important advance in the field of antibody engineering. It provides a useful methodology to produce human antibodies and has the potential to replace traditional hybridoma technology. In our research, we used T-vector and in vivo recombination to construct a large antibody library from breast cancer patients. The use of T-vector considerably increased the cloning efficiency, and the diversity of the library could be increased easily using in vivo recombination. Taken together, a combination of these two techniques might be valuable in constructing a large antibody library.

Capacity of brain cooling via ventilating oxygen at low temperature over respiratory tract.

Cerebral hypothermia is a rather useful way to improve outcome after brain injury. In this paper, the capacity of cooling oxygen ventilation (COV) during cerebral circulation arrest was theoretically evaluated. A transient two-dimensional mathematical model for the heat and water vapor transport through the respiratory tract of human body was established to predict the temperature response of the brain tissue. Calculation results indicate that COV will help in some extent to reduce the inner temperature of patient brain subject to cerebral circulation arrest. However, its capacity on lowering the deep brain temperature is very limited. Therefore more powerful cooling strategies should be investigated to realize an efficient cooling on the target cerebral tissue.