Triple-negative breast cancers (TNBC) comprise a heterogeneous group of tumors characterized by poor survival and lack of targeted therapeutics. In recent years, androgen receptor (AR) has been demonstrated to play an important role in the genesis and development of TNBC. There has been increased interest in the role of AR in TNBC and AR-targeting has been introduced as a novel therapeutic option for TNBC. This review offers an overview of the relationship between AR expression and TNBC, and provides insights into the novel drugs in the development for targeting this signaling pathway.

Objective To explore the inhibitory effects of sorafenib combined with cisplatin (DDP) on human hepatocellular carcinoma cells HepG2 in vitro, and the possible underlying mechanisms. Methods The HepG2 cells were divided to 4 groups as control group, sorafenib group, cisplatin group and sorafenib-cisplatin group. Sorafenib and cisplatin were used in single agent or in combination against HepG2 in vitro. The inhibitory effects of sorafenib and/or cisplatin on proliferation of HepG2 were determined by MTT assay at 24h, 48h, 72h and 96h after the addition of the drugs to HepG2 culture. Cell cycle at 24h time point and apoptosis at 48h time point were examined by flow cytometry (FCM). At 24h time point, cells were labeled by Rhodamine123 and mitochondrial transmembrane potential (??m) was determined by FCM, while caspase-3 activity was assessed by caspase-3 colorimetric assay. Results MTT assay showed that sorafenib and cisplatin, when used as a single agent or in combination, could inhibit the growth of HepG2 cells and induce apoptosis in vitro, while synergistic effect was noted when lower doses of sorafenib and DDP were used in combination. It was also found that combined use of sorafenib and cisplatin arrested HepG2 cells at G0/G1 and G2 phase as shown by cell cycle analysis, and the highest apoptosis rate appeared in sorafenib-cisplatin combination group (P

Objective To compare the dosemetry between helical tomotherapy (HT) and intensity-modulated radiotherapy (IMRT) for early-stage postoperative breast cancer and provide more valuable evidences to the clinical researches. Methods Clinical trails of dosimetric comparing between HT and IMRT for early-stage breast cancer were obtained from PubMed, Embase, Sciencedirect, CNKI, VIP and Wanfang databases, evaluated and analyzed with the Cochrane Collaboration's RevMan 5.2 software. Results 10 studies were included with a total of 135 patients. Compared to IMRT plans, HT plans provided a significantly better conformity index (P<0.000 1), mean (P<0.000 01) and maximal dose (P=0.003) of the planning target volume (PTV). HT plans had a lower heart maximal dose (P=0.005), V20 (P=0.05), V30 (P=0.003), and ipsilateral lung maximal dose (P=0.003), V20 (P=0.02), as while as had a higher contralateral breast V5 (P=0.01), mean (P=0.05) and maximal dose (P<0.000 01). There was no significantly difference between HT and IMRT plans for homogeneity index of PTV, heart V5, V10, mean dose, ipsilateral lung V5, V10, V30, mean dose, contralateral breast V10, contralateral lung mean and maximal dose (all P >0.05). Conclusion Compared to IMRT plans, HT plans have the dosimetry superiority for early-stage breast cancer with significantly better coverage and dose conformity while maintaining lower doses to high risk organs.

Objective To investigate the mechanisms and effects of Sorafenib on cytotoxic sensitivity of allo-reactive natural killer(Allo-NK) cells against human multi-drug resistant nasopharyngeal carcinoma CNE2/DDP cells which expressing highly ATP-binding cassette superfamily G member 2(ABCG2)(abbr.as ABCG2HighCNE2/DDP cells).Methods ABCG2HighCNE2/DDP and Allo-NK cells were isolated by magnetic bead technique.The target cells were divided into 3 groups: a) treated group(ABCG2HighCNE2/DDP cells incubated with 10 ng/ml sorafenib for 4h);b) untreated group(conventionally cultured ABCG2HighCNE2/DDP cells);and c) control group(conventionally cultured K562 cells).Expression rates of ABCG2 in treated and untreated groups,and of five NKG2D-ligands(MICA,MICB,ULBP1,ULBP2,ULBP3) were evaluated by flow cytometry.The cytotoxic effects of NK cells against different groups of target cells were detected with LDH releasing assay.Results Expression rate of ABCG2 in isolated CNE2/DDP cells was 91.40%?2.32%.The purity of sorted CD3-CD16+CD56+ Allo-NK cells was 90% and higher.The expression rates of NKG2D-ligands(MICA,MICB,ULBP1,ULBP2 and ULBP3) in untreated group were 2.92%?0.33%,4.27%?0.33%,5.80%?0.62%,11.10%?3.15% and 7.75%?1.14%,respectively,which were remarkablely higher than that in treated group(10.38%?1.23%,10.68%?1.26%,11.62%?1.22%,43.24%?4.42% and 11.91%?0.88%,respectively,P

Objective To correlate the chemokine score with disease activity,organ damages and clinical features in systemic lupus erythematosus (SLE) patients.Methods Peripheral blood cells obtained from 60 SLE patients,20 rheumatoid arthritis (RA) patients and 23 healthy donors (HDs) were subjected to real-time PCR to measure the transcriptional levels of seven chemokines (RANTES,MCP-1,CCL19,MIG,IP-10,CXCL11,and IL-8).Chemokine scores were calculated and were compared between various groups of SLE patients as well as between patients and controls.Results Chemokine scores were significantly elevated in SLE patients compared with RA patients and HDs (P=0.0112 and P=0.0019,respectively).Chemokine scores were correlated positively with SLEDAI (P=0.0061) and negatively with C3 levels (P=0.003).Compared to patients without lupus nephritis (LN),chemokine scores were elevated in SLE patients with active LN,especially when their daily prednisone dosage was less than 30 mg (P=0.0418 and P=0.002,respectively).Chemokine scores were also associated with cumulative organ damage (SLICC damage index [SDI]＞0) and positive anti-Sm and anti-RNP autoantibodies.Conclusion The chemokine score may serve as a new biomarker for disease activity and organ damage in SLE patients.

Objective To correlate the expression levels of interferon inducible genes (IFIGs) with disease activity and clinical features in systemic lupus erythematosus (SLE) patiems,.Methods Peripheral blood cells obtained from 67 SLE patients and 23 healthy donors (HDs) were subjected to real-time PCR to measure the transcriptional levels of five IFIGs (OAS-1,Mx-1,Ly6e,IFIT1 and IFIT4).Interferon scores were calculated and were compared between various groups of SLE patients as well as between patients and controls;ISRE lucife:rase reporter gene activity was measured in 17 of 67 patients and correlated with interferon score.Results Interferon scores were strongly correlated with ISRIE reporter gene aetivity,which represented for the type Ⅰ interferon activity in serum.The expression.levels of IFIGs and jinterferon scores were significantly elevated in SLE patients compared with HDs (P＜0.0001).Interferon scores were correlated positively with SLEDAI-2K(P=0.0006) and negatively with C3 levels(P=0.0162).Interferon scores were also significantly elevated in SLE patients with a positive anti-Sm or anti-RNP autoantibodies.Clonclusion The interferon score may be regarded as a good indicator for serum type I interferon activity in SLE and serves as a new hiomarker for disease activity in SLE patients.

This study was aimed to investigate the effects of different doses of dexamethasone (Dex) on bone quality in rats. Thirty-one SD rats were randomly divided into 4 groups, Control (7 with saline), Dex-L (8 with 1 mg Dex. / kg), Dex-M (8 with Dex. 2.5 mg/kg), Dex-H (8 with Dex. 5 mg/kg), with tail injection, twice per week for 8 weeks. All the rats were killed then. Their proximal tibia were processed into undecalcified sections and measured for bone histomorphometry. The content of Ca2+ and hydroxyproline in their left ulnars were tested. Bone mineral density (BMD) and biomechanical property of the thigh bone were tested to observe the qualities of bone. Compared to the control group, the bodyweights of the rats in different Dex treatment Groups decreased remarkably. Percent labeled perimeter (%L. Pm), Mineral apposition rate(MAR), Bone formation rate (BFR/BV) and so on reduced significantly. Percent trabecular area (%Tb. Ar) and Trabecular number (Tb. N) were obviously higher while Trabecular separation (Tb. sp) was remarkablely lower than those of the control group. BMD in Dex-L and the content of hydroxyproline in Dex-M reduced notablely. Biomechanical property of Dex groups decreased significantly. Dex suppressed bone formation and reduced bone turnover significantly. As the increase doses of Dex, %Tb. Ar increased, and, on the contrary, BMD and biomechanical property decreased with the reduced matrix in bone at the same time. It suggested that non-mineralized bone formation increased and biomechanical property deceased. The doses of 1 mg/kg Dex had the most obvious effect on bone quality. This dose slightly increased %Tb. Ar, however, bone formation, bone biomechanical property and matrix in bone decreased obviously. Diffferent doses of Dex have different effects on bone qualities. However the dose has no direct influcing ratio to the bone qualities.
Animals ; Bone Density ; drug effects ; Dexamethasone ; administration & dosage ; adverse effects ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Osteoporosis ; chemically induced ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tibia ; metabolism ; pathology

Objective:To understand the etiology and clinical characteristics of hospitalized severe community-acquired pneumonia(SCAP) in Changchun, and provide scientific basis for its etiology diagnosis and targeted treatment.Methods:The study subjects included 618 children with clinical diagnosis of SCAP who were hospitalized from January 2016 to December 2019.We collected pharyngeal swabs and alveolar lavage fluid from children.Virus isolation, bacterial culture, time-of-flight mass spectrometry, PCR/RT-PCR, colloidal gold method and Optochin test were used to detect the antigen, nucleic acid and protein profiles in the specimen.Results:There were more boys than girls in hospitalized children with SCAP.The peak age of onset was 7 to 12 months.Most cases occurred in winter and spring.The highest detection rate of SCAP virus was 56.15%(347/618); 73.49%(255/347) were positive for one virus, among which the top five were respiratory syncytial virus (27.8%), influenza A virus (23.9%), influenza B virus (16.1%), rhinovirus (12.2%) and metapneumovirus (10.2%). Two viruses were positive for 19.88%(69/347); three viruses were positive for 4.32%(15/347); four viruses were positive for 2.31%(8/347). Atypical microbial infections were 29.77%(184/618), of which Mycoplasma pneumoniae accounted for 95.65%(176/184). Bacterial infections were 17.31%(107/618), mainly Streptococcus pneumoniae(39.25%, 42/107) and Staphylococcus aureus(24.30%, 26/107). The mixed infection of multiple pathogens was 7.61%(47/618), among which the mixed infection rates of Mycoplasma pneumonia with Streptococcus pneumoniae, virus were 40.43% and 34.04%, respectively.High fever, faster breathing, and perioral cyanosis were risk factors for SCAP, with OR and 95% CI of 7.71 and 4.56-13.04, 2.43 and 2.02-2.93, 3.53 and 2.56-4.86, respectively.Viral co-infection occurred in 36.96%(34/92) of complications such as heart failure, toxic encephalopathy, and myocardial damage; Mycoplasma pneumoniae and other pathogens co-infected 35.29% of children with pleural effusion. Conclusion:The pathogens of SCAP in Changchun are mainly viruses notably, respiratory syncytial virus is the dominant pathogen, followed by Mycoplasma pneumoniae.The bacterial pathogen is mainly Streptococcus pneumoniae.High fever, faster breathing, and cyanosis around the mouth are risk factors for severe pneumonia.Multi-pathogen mixed infection is prone to serious complications.

BACKGROUND: MicroRNAs (miRNAs) are non-coding small molecule RNAs that are widely found in eukaryotic organisms, although some miRNAs have been found in tumors, the expression and effects of miR-665 on small cell lung cancer (SCLC) are unclear. The aim of this study was to analyze the effects of miR-665 on proliferation, cycle, invasion and migration of SCLC cells, and to explore the role of miR-665 in SCLC and its working mechanism. METHODS: The expression of miR-665 in SCLC tissues and adjacent normal tissues was detected by qRT-PCR. TargetScan predicted potential target genes for miR-665 and validated with dual luciferase reporter assays, qRT-PCR and Western blot. CCK8 assay, flow cytometry, Transwell and wound healing assay to detect the effects of miR-665 and LLGL1 on proliferation, invasion, migration and S-phase fraction of SCLC cell line NCI-H446, NCI-H1688. A nude mouse xenograft model of SCLC was constructed and the effect of miR-665 on tumor growth in mice was observed. RESULTS: The expression of miR-665 in SCLC tissues was significantly higher than that in non-tumor normal tissues. MiR-665 could target 3'-UTR of LLGL1 and inhibit its expression. Compared with non-tumor normal tissues, the expression of LLGL1 was significantly lower in SCLC tissues. Inhibition of miR-665 expression could inhibit proliferation, S-phase fraction, invasion and migration ability of SCLC NCL-H446 cells, and interference LLGL1 expression could reverse this inhibition effect. Up-regulation of miR-665 expression could promoted proliferation, S-phase fraction, invasion and migration ability of SCLC NCI-H1688 cells, but this promotion effect was also reversed by overexpression of LLGL1. In a nude mouse xenograft model of SCLC, inhibition of miR-665 expression could up-regulate LLGL1 protein expression and inhibit tumor growth, while up-regulation of miR-665 expression could produce opposite results. CONCLUSIONS The expression of miR-665 is closely related to SCLC. miR-665 can promote the biological behavior of SCLC cells by inhibiting the expression of target gene LLGL1, and miR-665 play a role in tumor-promoting genes in SCLC.

Objective: To detect the expression of miR-133a-3p in gastric cancer (GC) tissues and plasma of GC patients, and to investigate its effect on the proliferation of GC cells as well as its correlation toprognosis of GC patients. Methods: 52 cases of cancertissues (non-necrosis part) and corresponding adjacent tissues as well as the pre-operative peripheral blood samples from GC patients, who underwent surgery at Department of General Surgery, the Forth Hospital of Hebei Medical University(Shijiazhuang, China) between May 2012 and May 2013, were collected for this study. The plasma sample (n=35) from healthy donors were obtained during their physical examination. RT-qPCR was adopted to detect the expression of miR-133a-3p in gastric cancer tissues, adjacent tissuesand plasma samples of GC patients and healthy volunteers. The relationships between miR-133a-3p expression and the median DFS as well as clinicopathological parameters were also analyzed. CCK-8 assay was adopted to detect the effect of miR-133a-3p silence or over-expression on proliferation of gastric cancer SGC7901 cells. Results: miR-133a-3p was dramatically decreased in gastric cancer tissues (P<0.01), and its expression was associated with TNM stage, tumor infiltration (T), lynphonode metastasis (N), and vascular tumor thrombus (all P<0.01); miR-133a-3p was significantly increased in the plasma of GC patients (P<0.01), and its expression was associated with TNM stage, lynphonode metastasis (N), and vascular tumor thrombus (all P<0.05). miR-133a-3p expression was positively correlated with serum CA199 level of GC patients (P<0.01). The median DFS of patients with high miR-133a-3pexpression in cancer tissues was significantly longer than that of the patients with low expression(20.8 vs 14.8 months, P<0.05); The median DFS of patients with high plasma miR-133a-3p expression was significantly shorter than that of the patients with low expression (14.4 vs 20.3 months, P<0.05). Over-expression of miR-133a-3p could significantly inhibit the proliferation of gastric cancer SGC7901 cells, while miR-133a-3p silence could significantly promote the proliferation (all P<0.05). Conclusion: miR-133a-3p could significantlyinhibit the proliferation of SGC7901 cells; miR-133a-3p aberrantlyexpressed in gastric cancer tissues and plasma, and obviously correlated with prognosis of gastric cancer patients, which may be used as a potential clinical bio-maker for early diagnosis and treatment as well as the prognosis prediction of gastric cancer.