The effects of the prognostic biomarker SAAL1 on cancer growth and its association with the immune microenvironment in lung adenocarcinoma.

BACKGROUND: Inhibition of Serum Amyloid A-like 1 (SAAL1) expression could inhibit cancer progression and improve the prognosis of cancer patients. At present, the correlation between SAAL1 and lung adenocarcinoma (LAC) remains unclear. Therefore, this study surveyed the worth and pathway of SAAL1 in LAC progression and immunity. METHODS: Bioinformatics and immunohistochemistry were used to identify the SAAL1 expression in LAC. The roles of SAAL1 expression in the existence values of LAC patients were explored, and the nomograms were constructed. Clinical values of SAAL1 co-expressed genes were evaluated by COX regression, survival, and Receiver operating characteristic (ROC) analysis. EDU and western blotting methods were used to inquiry the functions and pathways of the SAAL1 in cell growths. The correlation between the SAAL1 level and immune microenvironment was visualized using correlation research. RESULTS: SAAL1 level was elevated in LAC tissues, and was observed in cancer tissues of dead patients. SAAL1 overexpression had something to do with shorter overall survival, progression-free interval, and disease-specific survival in LAC. The area under the curve of SAAL1 was 0.902 in normal tissues and cancer tissues. Inhibition of SAAL1 expression could inhibit cancer cell proliferation, which may be related to the decreased expression of cyclin D1 and Bcl-2 proteins. In LAC, SAAL1 level had something to do with stromal, immune, and estimate scores, and correlated with macrophages, T cells, Th2 cells, CD8 T cells, NK CD56dim cells, DC, eosinophils, NK CD56bright cells, pDC, iDC, cytotoxic cells, Tgd, aDC cells, B cells, Tcm, and TFH levels. SAAL1 overexpression had something to do with existence values and the immunity in LAC. CONCLUSIONS: Inhibition of SAAL1 expression could regulate cancer growth via cyclin D1 and Bcl-2. SAAL1 is a promising prognostic biomarker in LAC patients.

A positive feedback loop of heparanase/syndecan1/nerve growth factor regulates cancer pain progression.

Background: The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)/nerve growth factor (NGF) on cancer pain from melanoma. Methods: The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. Results: HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. Conclusions: The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

Association between monocyte lymphocyte ratio and abdominal aortic calcification in US adults: A cross-sectional study

Abstract Background This study aimed to evaluate the association between Monocyte Lymphocyte Ratio (MLR) and Abdominal Aortic Calcification (AAC) in adults over 40 years of age in the United States. Methods Data were collected from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). AAC was quantified by the Kauppila score system based on dual-energy X-Ray absorptiometry. Severe AAC was defined as a total AAC score > 6. The lymphocyte count and monocyte count can be directly obtained from laboratory data files. Multivariable logistic regression models were used to determine the association between MLR and the AAC score and severe AAC. Results A total of 3,045 participants were included in the present study. After adjusting for multiple covariates, MLR was positively associated with higher AAC score (β = 0.21, 95% CI 0.07, 0.34, p = 0.0032) and the odds of severe AAC increased by 14% per 0.1 unit increase in the MLR (OR = 1.14, 95% CI 1.00, 1.31, p = 0.0541). The Odds Ratio (OR) (95% CI) of severe AAC for participants in MLR tertile 3 was 1.88 (1.02, 3.47) compared with those in tertile 1 (p for trend = 0.0341). Subgroup analyses showed that a stronger association was detected in the elderly compared with non-elderly (p for interaction = 0.0346) and diabetes compared with non-diabetes (borderline significant p for interaction = 0.0578). Conclusion In adults in the United States, MLR was associated with higher AAC scores and a higher probability of severe AAC. MLR may become a promising tool to predict the risk of AAC.

Downregulation of T-cell cytotoxic marker IL18R1 promotes cancer proliferation and migration and is associated with dismal prognosis and immunity in lung squamous cell carcinoma.

Immunotherapy can improve the survival of patients with advanced lung squamous cell carcinoma (LUSC). T cytotoxic cells are one of the main members of the immune microenvironment. Herein, we aimed to identify the roles of T-cell cytotoxic markers interleukin 18 (IL18) receptor 1 (IL18R1) in the LUSC progression using bioinformatics, clinical tissue specimen, and cell experiment. We assessed the association between the IL18R1 expression and immune infiltration and IL18R1-related competing RNA network. The IL18R1 expression was downregulated in the LUSC tissues. The IL18R1 expression downregulation was associated with diagnosis and short overall survival and disease-specific survival, and it was also an independent risk factor for dismal survival time in LUSC. IL18R1-related nomograms predicted the survival time of patients with LUSC. IL18R1 overexpression inhibited the proliferation, migration, and invasion of LUSC cells. The IL18R1 expression was significantly associated with the microenvironment (stromal, immune, and estimate scores), immune cells (such as the T cells, cytotoxic cells, CD8 T cells), and immune cell markers (such as the CD8A, PD-1, and CTLA4) in LUSC. AC091563.1 and RBPMS-AS1 downregulation was positively associated with the IL18R1 expression, negatively associated with the miR-128-3p expression, and associated with short disease-specific survival and progression in LUSC. In conclusion, IL18R1 was significantly downregulated and associated with the prognosis and immune microenvironment. IL18R1 overexpression inhibits the growth and migration of cancer cells in LUSC. Furthermore, AC091563.1 and RBPMS-AS1 might compete with IL18R1 to bind miR-128-3p for participating in LUSC progression. These results showed that IL18R1 is a biomarker for evaluating the prognosis of patients with LUSC.

TRAT1 overexpression delays cancer progression and is associated with immune infiltration in lung adenocarcinoma.

The roles and mechanisms of T-cell receptor (TCR)-associated transmembrane adaptor 1 (TRAT1) in lung adenocarcinoma (LAC) have not yet been reported in the relevant literature. Therefore, this study aimed to understand the roles and mechanisms of TRAT1 in LAC using bioinformatics and in vitro experiments. TRAT1 expression levels in LAC samples were analysed using various databases. TRAT1 co-expressed genes were acquired by the correlation analysis of LAC tissues. The functional mechanisms and protein network of TRAT1 co-expressed genes were analysed using bioinformatics analysis. The expression of TRAT1 was activated in LAC cells, and the roles of TRAT1 overexpression in the growth and migration of cancer cells was investigated using flow cytometry, Cell Counting Kit-8 (CCK-8), and migration and invasion assays. The relationship between TRAT1 overexpression, the immune microenvironment, and RNA modification was evaluated using correlation analysis. TRAT1 expression levels were significantly abnormal at multiple mutation sites and were related to the prognosis of LAC. TRAT1 co-expressed genes were involved in cell proliferation, adhesion, and differentiation, and TRAT1 overexpression significantly inhibited cell viability, migration, and invasion and promoted apoptosis of A549 and H1299 cells, which might be related to the TCR, B cell receptor (BCR), MAPK, and other pathways. TRAT1 expression levels were significantly correlated with the ESTIMATE, immune, and stromal scores in the LAC microenvironment. Additionally, TRAT1 expression levels were significantly correlated with the populations of B cells, CD8 T cells, cytotoxic cells, and other immune cells. TRAT1 overexpression was significantly correlated with the expression of immune cell markers (such as PDCD1, CD2, CD3E) and genes involved in RNA modification (such as ALKBH1, ALKBH3, ALKBH5). In conclusions, TRAT1 overexpression inhibited the growth and migration of LAC cells, thereby delaying cancer progression, and was correlated with the LAC microenvironment and RNA modifications.

The Roles and Mechanisms of TRAT1 in the Progression of Non-Small Cell Lung Cancer.

OBJECTIVE: T cell receptor-associated transmembrane adaptor 1 (TRAT1) is one of the hub genes regulating T cell receptors (TCRs). Herein, the roles of TRAT1 in the prognosis and immune microenvironment of non-small cell lung cancer (NSCLC) were investigated. METHODS: The expression and prognosis values of TRAT1 in NSCLC, and the relationship between TRAT1 expression levels and cancer immune cell infiltration was identified via the TIMER, UALCAN, TISIDB, and other databases. The mechanism of TRAT1 in NSCLC was analyzed using gene set enrichment analysis (GSEA). RESULTS: The expression level of TRAT1 was decreased in NSCLC tissues. Low TRAT1 expression was associated with shorter overall survival of patients with NSCLC and was related to gender, smoking, and tumor grade. TRAT1 was involved in regulating immune response, TCR signaling pathway, PI3K/AKT, and other processes. TRAT1 expression levels were positively correlated with immune cell infiltration in NSCLC. CONCLUSION: Down-regulation of TRAT1 expression was associated with an unfavorable prognosis and immune infiltration of NSCLC.

Clinical Roles of Risk Model Based on Differentially Expressed Genes in Mesenchymal Stem Cells in Prognosis and Immunity of Non-small Cell Lung Cancer.

The tumor microenvironment (TME) plays an important regulatory role in the progression of non-small cell lung cancer (NSCLC). Mesenchymal stem cells (MSCs) in the TME might contribute to the occurrence and development of cancer. This study evaluates the role of differentially expressed genes (DEGs) of MSCs and the development of NSCLC and develops a prognostic risk model to assess the therapeutic responses. The DEGs in MSCs from lung tissues and from normal tissues were analyzed using GEO2R. The functions and mechanisms of the DEGs were analyzed using the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Additionally, the Cancer Genome Atlas (TCGA) database was used to determine the expression levels of the DEGs of MSCs in the NSCLC tissues. The prognostic factors of NSCLC related to MSCs were screened by survival analysis, meta-analysis, Cox regression analysis, and a prognostic risk model and nomogram was developed. The signaling mechanisms and immune roles that risk model participate in NSCLC development were determined via Gene Set Enrichment Analysis and CIBERSORT analysis. Compared to the normal tissues, 161 DEGs were identified in the MSCs of the lung tissues. These DEGs were associated with mechanisms, such as DNA replication, nuclear division, and homologous recombination. The overexpression of DDIT4, IL6, ITGA11, MME, MSX2, POSTN, and TRPA1 were associated with dismal prognosis of NSCLC patients. A high-risk score based on the prognostic risk model indicated the dismal prognosis of NSCLC patients. The nomogram showed that the age, clinical stage, and risk score affected the prognosis of NSCLC patients. Further, the high-risk model was associated with signaling mechanisms, such as the ECM-receptor interaction pathways, cytokine-cytokine receptor interaction, and MAPK pathways, involved in the progression of NSCLC and was also related to the components of the immune system, such as macrophages M0, T follicular helper cells, regulatory T cells. Therefore, the risk model and nomogram that was constructed on the basis of MSC-related factors such as POSTN, TRPA1, and DDIT4 could facilitate the discovery of target molecules that participate in the progression of NSCLC, which might also serve as new candidate markers for evaluating the prognosis of NSCLC patients.

Suture anchors for primary deltoid ligament repair associated with acute ankle fractures.

The aim of the study is to evaluate the clinical effect of primary suture anchors repair in the treatment of deltoid ligament rupture associated with ankle fractures. 34 patients with acute deltoid ligament rupture associated with ankle fractures were selected between 2011 and 2014. Medial clear space (MCS), American Orthopaedic Foot and Ankle Society (AOFAS) scores, visual analog scale (VAS) were noted. The mean follow-up was 28.4 (range, 22-35) months. The mean AOFAS score was 92.6 (range, 90-95) and the mean VAS score was 1.06±0.65 (range 0 to 2) points at the final follow-up. The mean MCS is (9.10±4.99) mm before and (3.71±0.33) mm after surgery in radiographs. At the postoperative final follow-up, the mean MCS of injured ankle is (3.74±0.32) mm in radiographs, and (3.65±0.17) mm of uninjured contralateral ankle. Using suture anchors for the primary repair of deltoid ligament rupture during the treatment of ankle fractures can achieve satisfactory outcomes.

Deregulation of lncRNA-AC078883.3 and microRNA-19a is involved in the development of chemoresistance to cisplatin via modulating signaling pathway of PTEN/AKT.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. As a platinum-based chemotherapeutic drug, cisplatin has been used in the NSCLC treatment for over 30 years, and its effects are impaired by drug resistance. This study aimed to investigate the potential role of lncRNA-AC078883.3 in the development of chemoresistance against cisplatin. Real-time PCR, Western blot analysis, Immunohistochemistry (IHC) assay, bioinformatic analysis, and luciferase assay were collaboratively used to establish the lncRNA-AC078883.3/miR-19a/PTEN/AKT pathway. Also, the effect of cisplatin on cell proliferation was observed via an MTT assay. Furthermore, Cox regression and Kaplan-Meier analyses were used to study whether lncRNA-AC078883.3 is involved in the survival of NSCLC. Compared with the Cisplatin-Sensitive group, the Cisplatin-Resistance group exhibited lower levels of lncRNA-AC078883.3 and PTEN and higher levels of miR-19a and p-Akt. The growth rate of A549 and H460 cells and the IC 50 of DPP in the Cisplatin-Resistance group were higher than those in the Cisplatin-S group. miR-19a contains a putative binding site of lncRNA-AC078883.3, which enabled the luciferase activity of wild-type lncRNA-AC078883.3 to be reduced by miR-19a. In addition, by directly targeting PTEN 3'-untranslated region (UTR), miR-19a repressed the luciferase activity of wild-type PTEN 3'-UTR. The median OS of patients with reduced lncRNA-AC078883.3 expression was longer than that of patients with higher lncRNA-AC078883.3 expression. Finally, compared with low lncRNA-AC078883.3-expression patients, the high lncRNA-AC078883.3-expression patients were associated with lower miR-19a expression and higher PTEN expression. Therefore, we suggested for the first time that the low expression of lncRNA-AC078883.3 contributed to the development of chemoresistance against cisplatin.

Direct anterior approach for mini plate fixation of Regan-Morrey type II comminuted ulnar coronoid process fracture.

BACKGROUND: The goal of this study was to evaluate the clinical effect of Regan-Morrey type II comminuted coronoid process fracture treated with mini plate through the direct anterior approach (DAA). METHODS: Ten patients who underwent open reduction and internal fixation (ORIF) with mini plate through the DAA between February 2013 and August 2016 was included. There were three women and seven men, with an average age of 34.4 ± 7.5 years. At the final follow-up, the Mayo Elbow Performance Index (MEPS), Visual Analogue Scale (VAS) score, Disability of the Arm, Shoulder, and Hand (DASH) score, and the elbow range of motion were noted. RESULTS: The mean follow-up was 26.3 ± 2.2 (range 24-31) months. The mean elbow arc of motion was 118.5° with a mean arc of extension of 4° ± 5.2° and flexion of 122.5° ± 7.2°.The mean forearm pronation was 72° ± 7.2°, and the mean supination was 68° ± 6.3° with a mean forearm rotation arc of 140°. The average postoperative score according to the MEPS was 91 ± 5.7 points (range 80-100 points), and all patients achieved satisfactory scores (8 excellent and 2 good). The final average VAS score was 0.6 ± 1 (range 0-3). The final average DASH score was 4.0 ± 1.6 (range 2.3-7.4). None of the patients complained about elbow instability that required secondary surgery. No complications of infection, joint incongruency, fracture nonunion, median nerve palsy, or implant failure were reported. CONCLUSIONS: ORIF with mini plate through the DAA for the treatment of the type II comminuted coronoid process fractures can achieve satisfactory outcomes.

Relationship Between Apoptosis of Endplate Microvasculature and Degeneration of the Intervertebral Disk.

OBJECTIVE: To explore the relationship between intervertebral disk degeneration and endplate microvasculature, and to determine the role of apoptosis in the pathophysiology underlying end plate microvasculature. METHODS: Twelve 6-month-old rabbits were randomly divided into group A (control group where animals underwent a sham operation, in which the loading device was implanted but without loading) and group B (degeneration group, where a calibrated spring within the loading device would immediately create static shear force of 50 N to the disk of L4-5). Paraffin-embedded midsagittal sections of the L4-5 disk were obtained 4 weeks after surgery in the both groups. Sections were stained with cluster of differentiation (CD) 31 immunohistochemistry to measure the blood vessel density in the endplate, with CD31 immunofluorescence and terminal dUTP nick-end labeling (TUNEL) to detect the apoptosis of vascular endothelial cells in the endplate. RESULTS: After 4 weeks, the microvasculature density was 91 ± 8 vessels/mm2 in group A and 47 ± 2 vessels/mm2 (P < 0.001) in group B, demonstrating that vessels were reduced in the endplate of intervertebral disk degeneration. CD31 immunofluorescence and TUNEL showed that apoptosis of vascular endothelial cells exists in the endplate of intervertebral disk degeneration. CONCLUSIONS: The results of this study suggest that apoptosis of vascular endothelial cells results in a decrease in endplate microvasculature density, further affecting the pathologic process of intervertebral disk degeneration.

Unusual case of extracutaneous pyoderma gangrenosum with myelodysplastic syndrome.

Pyoderma gangrenosum (PG) is a rare, noninfectious, inflammatory disease characterized by neutrophilic infiltration and destruction of tissue. Extracutaneous involvement in PG is unusual. Myelodysplastic syndrome (MDS) is the most frequent hematologic disease associated with PG. We present a case diagnosed with MDS-EB-I. He had a large ulcer in his buttocks. Tissue culture and microscopy showed no evidence of fungi, bacteria, or mycobacteria. Histology showed granulation tissue, inflammatory infiltrate, abscess formation, and focal necrotizing vasculitis. Dermatology opinion confirmed PG. The skin lesions responded well to corticosteroid treatment at first, but it relapsed quickly with involvement of skin and lungs. In the meantime, MDS progressed to acute myeloid leukemia. The patient received chemotherapy and immunosuppressive therapy at the same time. After achievement of complete remission (CR), he had allogeneic hematopoietic stem cell transplantation. Two years later, the patient is still in CR status with no sign of PG relapse.

The selective Nlrp3 inflammasome inhibitor Mcc950 attenuates lung ischemia-reperfusion injury.

Lung ischemia-reperfusion (IR) occurs in many circumstances and leads to impaired lung function. The NACHT, LRR and PYD domains-containing protein 3 (Nlrp3) inflammasome is reportedly activated during lung IR. Mcc950 is a recently developed Nlrp3 inhibitor. The aim of our study was to test the efficacy of Mcc950 on lung IR injury and to investigate the role of reactive oxygen species (ROS) in Nlrp3 inflammasome activation using a murine lung IR model. The results of the current study confirmed that Nlrp3 was upregulated and activated during lung IR, and inhibiting oxidative stress by the ROS scavenger edaravone attenuated Nlrp3 inflammasome activation. Mcc950 pretreatment significantly alleviated IR-induced lung injury by reducing production of the proinflammatory cytokines Il-1ß and Il-18 and inhibiting neutrophil infiltration and cell apoptosis. Protein coimmunoprecipitation revealed that Mcc950 partially blocked the interaction between Nlrp3 and Nek7 (NimA-related protein kinase 7). Therefore, we conclude that ROS-dependent activation of the Nlrp3 inflammasome contributed to lung IR injury. Mcc950 significantly reduced lung IR injury by blocking Nlrp3 inflammasome activation, and the mechanism was partially attributed to inhibition of the interaction between Nlrp3 and Nek7. Thus, Mcc950 is a promising treatment for the prevention of lung IR injury.

14-3-3ζ promotes esophageal squamous cell carcinoma invasion by repressing S1PR2 protein expression through NF-κB signaling.

14-3-3ζ is overexpressed in several cancers, including esophageal squamous cell carcinoma (ESCC), and plays an important role in tumorigenesis. However, the mechanisms underlying its tumorigenesis remain unclear. Here we report that 14-3-3ζ was upregulated in ESCC tumors, compared with adjacent normal tissues; 14-3-3ζ levels were positively correlated with ESCC lymph node metastasis and recurrence. Overexpression of 14-3-3ζ promoted the tumor growth and invasion of ESCC in vitro and in vivo, whereas depletion of 14-3-3ζ suppressed these effects. Moreover, 14-3-3ζ reduces expression of genes mediating S1P/S1PR2 signaling, and this effect is mediated through activation of NF- κ B. Taken together, 14-3-3ζ contributes to ESCC tumorigenesis and progression through repressing S1PR2 signaling and may act as a new therapeutic target for ESCC.

Increased risk of severe infections in non-small-cell lung cancer patients treated with pemetrexed: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Infections related to pemetrexed have been reported in clinical trials. It is not yet clear whether this drug increases infection risk or not. This meta-analysis assessed the overall incidence and risk of severe infections (≥ grade 3) associated with the use of pemetrexed in non-small-cell lung cancer patients. METHODS: The databases of PubMed, Embase, and the Cochrane Library were searched for relevant studies published up to December 2015. Eligible studies included randomized controlled trials (RCTs) of pemetrexed for non-small-cell lung cancer patients that reported grade 3-5 infection and febrile neutropenia. Summary incidence rates, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random-effects or fixed-effects models, according to the heterogeneity of the included studies. RESULTS: Seven randomized controlled trials were included, comprising 1848 patients. The incidence of severe infection and febrile neutropenia due to pemetrexed was 5.7% (95% CI: 3.2-8.3%) and 1.3% (95% CI: 0.7-2.0%), respectively. The use of pemetrexed was associated with an increased risk of severe infection (RR 1.61, 95% CI: 1.07-2.44, P = .02) and febrile neutropenia (RR 4.28, 95% CI: 1.08-17.01, P = .04). CONCLUSION: The use of pemetrexed was associated with an increased risk of developing severe infections and febrile neutropenia in non-small-cell lung cancer patients. Frequent clinical monitoring and management of infections should be emphasized during pemetrexed treatment. More studies are needed to reveal the mechanism of the increased risk of severe infections.

XBP1 induces MMP-9 expression to promote proliferation and invasion in human esophageal squamous cell carcinoma.

X-box binding protein 1 (XBP1) was found to be overexpressed in glioma and breast cancers, suggesting that XBP1 might act as a potent oncogenic protein. However, the clinical significance and biological role of XBP1 in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we report that XBP1 is markedly overexpressed in ESCC cell lines and clinical samples. XBP1 overexpression was significantly correlated with ESCC tumor stage, lymph node metastasis and poor outcome. A functional study demonstrated that XBP1 promoted cell growth and cell invasion both in vitro and in vivo. Further study found that the XBP1-mediated invasion and proliferation of cancer cells requires the up-regulation of matrix metalloproteinase-9 (MMP-9). Importantly, a significant correlation between XBP1 and MMP-9 levels was observed in ESCC clinical samples. Our findings demonstrate that XBP1 is an oncogene that plays an important role in the development of ESCC by activating MMP-9 expression.

14-3-3ζ promotes lung cancer cell invasion by increasing the Snail protein expression through atypical protein kinase C (aPKC)/NF-κB signaling.

14-3-3ζ has been identified as a putative oncogene in several cancers, including non-small cell lung cancer (NSCLC). However, the mechanisms underlying its functions remain undefined. In this study, we show that overexpression of 14-3-3ζ was frequently detected in lung adenocarcinoma (LuAC) tissues and was significantly associated with lymph node metastasis and poor outcome. Functional studies demonstrated that 14-3-3ζ promoted migration and invasion in A549 cells, both of which were effectively inhibited when 14-3-3ζ was silenced with short hairpin RNA (shRNA). Furthermore, 14-3-3ζ-mediated invasion of cancer cells was found to upregulate Snail through the activation of atypical protein kinase C (aPKC). Activation of aPKCζ mediates this effect by stimulating NF-κB signaling. Our results identify a specific pathway by which 14-3-3ζ induces tumor invasion and provide insight into potential therapeutic approaches to target 14-3-3ζ-associated lung adenocarcinoma.

Genome-Wide Association Mapping for Female Infertility in Inbred Mice.

The genetic factors underlying female infertility in humans are only partially understood. Here, we performed a genome-wide association study of female infertility in 25 inbred mouse strains by using publicly available SNP data. As a result, a total of four SNPs were identified after chromosome-wise multiple test correction. The first SNP rs29972765 is located in a gene desert on chromosome 18, about 72 kb upstream of Skor2 (SKI family transcriptional corepressor 2). The second SNP rs30415957 resides in the intron of Plce1 (phospholipase C epsilon 1). The remaining two SNPs (rs30768258 and rs31216810) are close to each other on chromosome 19, in the vicinity of Sorbs1 (sorbin and SH3 domain containing 1). Using quantitative RT-PCR, we found that Sorbs1 is highly expressed in the mouse uterus during embryo implantation. Knockdown of Sorbs1 by siRNA attenuates the induction of differentiation marker gene Prl8a2 (decidual prolactin-related protein) in an in vitro model of decidualization using mouse endometrial stromal cells, suggesting that Sorbs1 may be a potential candidate gene for female infertility in mice. Our results may represent an opportunity to further understand female infertility in humans.

Circulating Tumor Cells and Tumor Stem Cells Detection in the Peripheral Blood Mononuclear Cells of Breast Cancer.

BACKGROUND: Our aim was to retrospectively analyze the relationships between circulating tumor cells (CTCs) and the development of breast cancer, for elucidating the role of CTCs in breast cancer. METHODS: A total of 107 female patients with primary breast cancer and 48 matched healthy female volunteers were recruited. After blood collection, isolation of peripheral blood mononuclear cells (PBMC) was performed followed by the detection of cytokeratin 19 positive (CK19(+) ) and CD44(+) /CD24(-/low) cells, as well as estrogen receptor (ER), progesterone, and CerbB2. Data were analyzed with the SPSS 20.0 software. RESULTS: None of the 48 volunteers were detected with CK19(+) cells in their PBMC, while in 77 patients, 72% of 107 female patients with primary breast cancer, the CK19(+) cells were detected. CK19(+) could also be detected among patients in each grouping by different clinical staging and lymph node metastasis, with statistical differences (all P < 0.05). Further, among the 83 CK19(+) specimens, 32 were also detected with CD44(+) /CD24(-/low) cells. Comparisons of CK19(+) and CD44(+) /CD24(-/low) cells in patients with different clinical features (ER positive vs. ER negative, C-erbB2 positive vs. C-erbB2 negative) and molecular subtypes (triple-negative breast cancer, ER positive, and C-erbB2 positive) showed no obvious difference (all P > 0.05). CONCLUSIONS: Both CTCs and tumor stem cells (TSCs) could be detected in the PBMC of breast cancer patients; besides, positive expression rate of CTCs might be obviously associated with the clinical stage and metastasis. Positive relationship of TSCs and the clinical stage of breast cancer was also proved in this study.

Differential regulation of receptivity in two uterine horns of a recipient mouse following asynchronous embryo transfer.

Receptivity is a limited time in which uterine endometrium can establish a successful dialogue with blastocyst. This study was to investigate the effect of asynchronous embryo transfer on uterine receptivity in mice. Embryos under different stages were transferred into two oviduct sides of a recipient mouse on day 1 of pseudopregnancy. Our results showed the asynchronously transferred embryos can implant in all groups. Compared to zygote-transfer group, the length of implanted embryos is longer in 8-cell embryo- or blastocyst-transfer group. The levels of Snail and COX-2 immunostaining in blastocyst-transfer group are significantly stronger than that in zygote-transfer group. Embryos in blastocyst-transfer group migrate faster than that in zygote-transfer group within uterus. Blastocysts are in a state of developmental delay after they are transferred into oviducts, and they are reactivated and implanted rapidly in uterus. The developmental rate to newborn in zygote-transfer group is obviously higher than that in blastocyst-transfer group, suggesting that a delay in embryo development and implantation will lead to a decrease of litter size. These results indicated that the window of implantation is differentially regulated in two uterine horns of a recipient by embryos at different stages.