circ-0000512 inhibits PD-L1 ubiquitination through sponging miR-622/CMTM6 axis to promote triple-negative breast cancer and immune escape.

BACKGROUND: This study reported the function and mechanism of circ-0000512 in the progression of triple-negative breast cancer (TNBC). METHODS: circ-0000512 expression in TNBC tissues and paired adjacent normal tissues and cells was examined by qRT-PCR. Moreover, circ-0000512 expression in TNBC cells was modulated by transfection. Thereafter, colony formation assay, Transwell assay and flow cytometry were conducted to observe cell proliferation, migration and apoptosis. TNBC cells were treated with cycloheximide and the protease inhibitor MG132. Later, ubiquitination assay was performed to detect programmed cell death ligand 1 (PD-L1) ubiquitination in TNBC cells. The T cell killing ability was assessed by the T cell-mediated tumor cell killing assay. IFNγ and IL-2 levels were detected by ELISA. The percentage of activated T cells was detected with a flow cytometer. In addition, dual luciferase reporter gene assay and RNA immunoprecipitation assay were carried out to evaluate the binding between two genes. In vivo study was conducted on mice. CD8+ T cells in xenograft tumors were detected by immunohistochemistry. RESULTS: circ-0000512 was upregulated in patients with TNBC. circ-0000512 knockdown attenuated the proliferation and migration of TNBC cells and enhanced their apoptosis. circ-0000512 overexpression had opposite effects. circ-0000512 knockdown enhanced the PD-L1 protein ubiquitination in TNBC cells by inhibiting CMTM6. Meanwhile, circ-0000512 promoted CMTM6 expression by sponging miR-622. circ-0000512 knockdown increased the ratio of CD8+T cells and the lethality of T cells against TNBC cells. Besides, circ-0000512 knockdown inhibited the growth of TNBC cells in immunodeficient nude mice and normal immune mice and increased the ratio of CD8+T cells in xenograft tumors of normal immune mice. CONCLUSIONS: circ-0000512 inhibited PD-L1 ubiquitination by sponging the miR-622/CMTM6 axis, thus promoting TNBC progression and immune escape.

Phylogeny-Related Variations in Venomics: A Test in a Subset of Habu Snakes (Protobothrops).

We conducted a comparative analysis to unveil the divergence among venoms from a subset of Old World habu snakes (Protobothrops) in terms of venomic profiles and toxicological and enzymatic activities. A total of 14 protein families were identified in the venoms from these habu snakes, and 11 of them were shared among these venoms. The venoms of five adult habu snakes were overwhelmingly dominated by SVMP (32.56 ± 13.94%), PLA2 (22.93 ± 9.26%), and SVSP (16.27 ± 4.79%), with a total abundance of over 65%, while the subadult P. mangshanensis had an extremely low abundance of PLA2 (1.23%) but a high abundance of CTL (51.47%), followed by SVMP (22.06%) and SVSP (10.90%). Apparent interspecific variations in lethality and enzymatic activities were also explored in habu snake venoms, but no variations in myotoxicity were found. Except for SVSP, the resemblance of the relatives within Protobothrops in other venom traits was estimated to deviate from Brownian motion evolution based on phylogenetic signals. A comparative analysis further validated that the degree of covariation between phylogeny and venom variation is evolutionarily labile and varies among clades of closely related snakes. Our findings indicate a high level of interspecific variation in the venom proteomes of habu snakes, both in the presence or absence and the relative abundance of venom protein families, and that these venoms might have evolved under a combination of adaptive and neutral mechanisms.

Diagnostic performance of RASSF1A and SHOX2 methylation combined with EGFR mutations for differentiation between small pulmonary nodules.

BACKGROUND AND AIM: Aberrant methylation of Ras association domain family 1, isoform A (RASSF1A), and short-stature homeobox gene 2 (SHOX2) promoters has been validated as a pair of valuable biomarkers for diagnosing early lung adenocarcinomas (LUADs). Epidermal growth factor receptor (EGFR) is the key driver mutation in lung carcinogenesis. This study aimed to investigate the aberrant promoter methylation of RASSF1A and SHOX2, and the genetic mutation of EGFR in 258 specimens of early LUADs. METHODS: We retrospectively selected 258 paraffin-embedded samples of pulmonary nodules measuring 2 cm or less in diameter and evaluated the diagnostic performance of individual biomarker assays and multiple panels between noninvasive (group 1) and invasive lesions (groups 2A and 2B). Then, we investigated the interaction between genetic and epigenetic alterations. RESULTS: The degree of RASSF1A and SHOX2 promoter methylation and EGFR mutation was significantly higher in invasive lesions than in noninvasive lesions. The three biomarkers distinguished between noninvasive and invasive lesions with reliable sensitivity and specificity: 60.9% sensitivity [95% confidence interval (CI) 52.41-68.78] and 80.0% specificity (95% CI 72.14-86.07). The novel panel biomarkers could further discriminate among three invasive pathological subtypes (area under the curve value > 0.6). The distribution of RASSF1A methylation and EGFR mutation was considerably exclusive in early LUAD (P = 0.002). CONCLUSION: DNA methylation of RASSF1A and SHOX2 is a pair of promising biomarkers, which may be used in combination with other driver alterations, such as EGFR mutation, to support the differential diagnosis of LUADs, especially for stage I.

CycC1;1-WRKY75 complex-mediated transcriptional regulation of SOS1 controls salt stress tolerance in Arabidopsis.

SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.

Alcohol promotes epithelial mesenchymal transformation-mediated premetastatic niche formation of colorectal cancer by activating interaction between laminin-γ2 and integrin-ß1.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor. Alcohol consumption is positively correlated with CRC malignant metastasis; however, the mechanism is unclear. The interaction between laminin-γ2 (LAMC2) and integrin-ß1 (ITGB1) plays a role in premetastatic niche signaling, which may induce epithelial mesenchymal transformation (EMT) and lead to metastasis. AIM: To investigate the effects of alcohol on CRC metastasis from the molecular mechanism of the premetastatic niche. METHODS: The interaction between LAMC2 and ITGB1 was measured by Duolink assay, and the expression levels of LAMC2, ITGB1 and focal adhesion kinase (FAK), snail, fibronectin, N-cadherin and special AT-rich sequence binding protein 1 (SATB1) were measured by quantitative real-time polymerase chain reaction, immunohistochemistry and western blotting. Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-6 levels were measured via enzyme-linked immunosorbent assay, histopathological assessment via hematoxylin eosin staining, and determination of aberrant crypt foci via methylene blue. RESULTS: The lymph node metastasis rate was higher in the alcohol group than non-alcohol group. There was a significant increase in interaction signals between LAMC2 and ITGB1, and an increase in phosphorylate-FAK/FAK, snail, fibronectin, N-cadherin and SATB1, whereas E-cadherin was reduced in the alcohol group compared to the non-alcohol group in both animal and clinical samples. Serum IL-1ß, TNF-α and IL-6 were higher in alcohol group than in non-alcohol group. Alcohol may promote CRC metastasis by influencing the molecular mechanism of the premetastatic niche. CONCLUSION: Our study suggests that alcohol promotes EMT-mediated premetastatic niche formation of CRC by activating the early interaction between LAMC2 and ITGB1 and lead to CRC metastasis.

CycC1;1 negatively modulates ABA signaling by interacting with and inhibiting ABI5 during seed germination.

Regulation of seed germination is important for plant survival and propagation. ABSCISIC ACID (ABA) INSENSITIVE5 (ABI5), the central transcription factor in the ABA signaling pathway, plays a fundamental role in the regulation of ABA-responsive gene expression during seed germination; however, how ABI5 transcriptional activation activity is regulated remains to be elucidated. Here, we report that C-type Cyclin1;1 (CycC1;1) is an ABI5-interacting partner affecting the ABA response and seed germination in Arabidopsis (Arabidopsis thaliana). The CycC1;1 loss-of-function mutant is hypersensitive to ABA, and this phenotype was rescued by mutation of ABI5. Moreover, CycC1;1 suppresses ABI5 transcriptional activation activity for ABI5-targeted genes including ABI5 itself by occupying their promoters and disrupting RNA polymerase II recruitment; thus the cycc1;1 mutant shows increased expression of ABI5 and genes downstream of ABI5. Furthermore, ABA reduces the interaction between CycC1;1 and ABI5, while phospho-mimic but not phospho-dead mutation of serine-42 in ABI5 abolishes CycC1;1 interaction with ABI5 and relieves CycC1;1 inhibition of ABI5-mediated transcriptional activation of downstream target genes. Together, our study illustrates that CycC1;1 negatively modulates the ABA response by interacting with and inhibiting ABI5, while ABA relieves the CycC1;1 interaction with and inhibition of ABI5 to activate ABI5 activity for the ABA response, thereby inhibiting seed germination.

Abscisic acid facilitates phosphate acquisition through the transcription factor ABA INSENSITIVE5 in Arabidopsis.

Low phosphate (LP) in soil is a common nutrient stress that severely restricts agricultural production, but the role, if any, of the major stress phytohormone abscisic acid (ABA) in plant phosphate (Pi) starvation responses remains elusive. Here, we report that LP-induced ABA accumulation promotes Pi uptake in an ABA INSENSITIVE5 (ABI5)-dependent manner in Arabidopsis thaliana. LP significantly activated plant ABA biosynthesis, metabolism, and stress responses, suggesting a role of ABA in the plant response to Pi availability. LP-induced ABA accumulation and expression of two major high-affinity phosphate transporter genes PHOSPHATE TRANSPORTER1;1/1;4 (PHT1;1/1;4) were severely impaired in a mutant lacking BETA-GLUCOSIDASE1 (BG1), which converts conjugated ABA to active ABA, and the mutant had shorter roots and less Pi content than wild-type plants under LP conditions. Moreover, a mutant of ABI5, which encodes a central transcription factor in ABA signaling, also exhibited suppressed root elongation and had reduced Pi content under LP conditions. ABI5 facilitated Pi acquisition by activating the expression of PHT1;1 by directly binding to its promoter, while overexpression of PHT1;1 completely rescued its Pi content under LP conditions. Together, our findings illustrate a molecular mechanism by which ABA positively modulates phosphate acquisition through ABI5 in the Arabidopsis response to phosphate deficiency.

Gaze Tracking Based on Concatenating Spatial-Temporal Features.

Based on experimental observations, there is a correlation between time and consecutive gaze positions in visual behaviors. Previous studies on gaze point estimation usually use images as the input for model trainings without taking into account the sequence relationship between image data. In addition to the spatial features, the temporal features are considered to improve the accuracy in this paper by using videos instead of images as the input data. To be able to capture spatial and temporal features at the same time, the convolutional neural network (CNN) and long short-term memory (LSTM) network are introduced to build a training model. In this way, CNN is used to extract the spatial features, and LSTM correlates temporal features. This paper presents a CNN Concatenating LSTM network (CCLN) that concatenates spatial and temporal features to improve the performance of gaze estimation in the case of time-series videos as the input training data. In addition, the proposed model can be optimized by exploring the numbers of LSTM layers, the influence of batch normalization (BN) and global average pooling layer (GAP) on CCLN. It is generally believed that larger amounts of training data will lead to better models. To provide data for training and prediction, we propose a method for constructing datasets of video for gaze point estimation. The issues are studied, including the effectiveness of different commonly used general models and the impact of transfer learning. Through exhaustive evaluation, it has been proved that the proposed method achieves a better prediction accuracy than the existing CNN-based methods. Finally, 93.1% of the best model and 92.6% of the general model MobileNet are obtained.

[Impact of Enclosure Culture on Heavy Metal Content in Surface Sediments of Hongze Lake and Ecological Risk Assessment].

In order to explore the concentrations of heavy metals and the influence of fencing on Hongze lake, the content, source, and spatial distribution characteristics of heavy metals in surface sediments and ecological risks were analyzed in 2018 after part of the fence around Hongze Lake was removed. The results showed that the average contents of Cr, Ni, Cu, Zn, As, Cd, and Pb in the surface sediments in Hongze Lake were 66.78, 33.89, 25.35, 74.77, 16.55, 0.23, and 27.20 mg·kg-1, respectively. Cr, Ni, Cu, Zn, and Pb contents were at non-polluting levels, with As and Cd at the lowest level, based on the accumulation index evaluation. Except for Cd, all the elements showed low potential ecological risk. The results showed that the heavy metal content in the fenced, dismantled, and peripheral areas increased and accumulated towards the center of the lake. The removal of the fence did not significantly reduce the heavy metal content in the short-term. Overall, Hongze Lake presented a state of low ecological risk. In the future, environmental policies should include surface sediment accumulation areas and fencing culture in the north and northeast of Hongze Lake.

Potential prognostic factors in progression-free survival for patients with cervical cancer.

BACKGROUND: Cervical cancer continues to be one of the leading causes of cancer deaths among females in low and middle-income countries. In this study, we aimed to assess the independent prognostic value of clinical and potential prognostic factors in progression-free survival (PFS) in cervical cancer. METHODS: We conducted a retrospective study on 92 cervical cancer patients treated from 2017 to 2019 at the Zhuhai Hospital of Traditional Chinese and Western Medicine. Tumor characteristics, treatment options, progression-free survival and follow-up information were collected. Kaplan-Meier method was used to assess the PFS. RESULTS: Results showed that the number of retrieved lymph nodes had a statistically significant effect on PFS of cervical cancer patients (P = 0.002). Kaplan-Meier survival curve analysis showed that cervical cancer patients with initial symptoms age 25-39 had worse survival prognoses (P = 0.020). And the using of uterine manipulator in laparoscopic treatment showed a better prognosis (P < 0.001). A novel discovery of our study was to verify the prognostic values of retrieved lymph nodes count combining with FIGO staging system, which had never been investigated in cervical cancer before. According to the Kaplan-Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis, significant improvements were found after the combination of retrieved lymph nodes count and FIGO stage in predicting PFS for cervical cancer patients (P < 0.001, AUC = 0.826, 95% CI: 0.689-0.962). CONCLUSION: Number of retrieved lymph nodes, initial symptoms age, uterine manipulator, and retrieved lymph nodes count combining with FIGO staging system could be potential prognostic factors for cervical cancer patients.

Specific Gene Co-variation Acts Better Than Number of Concomitant Altered Genes in Predicting EGFR-TKI Efficacy in Non-small-cell Lung Cancer.

BACKGROUND: There occurs huge heterogeneity in clinical outcomes for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The purpose of this study was to indicate genetic biomarkers predicting primary resistance of EGFR-TKIs in these patients. PATIENTS AND METHODS: Using a next-generation sequencing panel with 168 cancer-related genes, matched tumor biopsy and plasma samples before treatments from patients with NSCLC were analyzed. Patients taking EGFR-TKIs were followed-up with imaging examination. Correlation of co-alterative genes with progression-free survival (PFS) was analyzed. RESULTS: Of the 48 patients treated with EGFR-TKIs, 46 (95.83%) had at least 1 genetic co-variant beyond EGFR mutation. Multivariate analysis indicated that RB1, PIK3CA, and ERBB2 co-alterations, rather than number of co-alterative genes, were independently associated with poorer PFS. Grouping patients by specific gene status showed best likelihood ratio χ2, Akaike information criterion, and Harrell concordance index. The median PFS for patients in group A (less genetic co-variations and wild specific genes), group B (more genetic co-variations and wild specific genes), group C (less genetic co-variations and altered specific genes), and group D (more genetic co-variations and altered specific genes) were 10.4, 9.13 (vs. group A; P = .3112), 6.33 (vs. group B; P = .0465), and 3.90 (vs. group C; P = .0309) months, respectively. CONCLUSIONS: This study revealed a high concomitant genetic alteration rate in patients with EGFR-mutated NSCLC. Specific gene variants were more important than number of altered genes in predicting poor PFS, and may help select patients needing new treatment strategies.

Fabrication of Magnetic Superstructure NiFe2O4@MOF-74 and Its Derivative for Electrocatalytic Hydrogen Evolution with AC Magnetic Field.

As an ideal hydrogen production route, electrolyzed water still faces the challenges of high cost of noble-metal electrocatalysts and low performance of non-noble-metal catalysts in scalable applications. Recently, introduction of external fields (such as magnetic fields, light fields, etc.) to improve the electrocatalytic water splitting performance of non-noble-metal catalysts has attracted great attention due to their simplicity. Here, a simple method for preparing magnetic superstructure (NiFe2O4@MOF-74) is described, and the hydrogen evolution reaction (HER) behavior of its carbonized derivative, a ferromagnetic superstructure, is revealed in a wide range of applied voltage under an AC magnetic field. The overpotential (@10 mA cm-2) required for the HER of the obtained ferromagnetic superstructure in 1 M KOH was reduced by 31 mV (7.7%) when a much small AC magnetic field (only 2.3 mT) is applied. Surprisingly, the promotion effect of the AC magnetic field is not monotonically increasing with the increase of the applied voltage or the strength of AC magnetic field, but increasing first, then weakening. This unusual behavior is believed to be mainly caused by the enhanced induced electromotive force and the additional energy by the applied AC magnetic field. This discovery provides a new idea for adjusting the performance of electrocatalytic reactions.

Energy metabolism in cancer stem cells.

Normal cells mainly rely on oxidative phosphorylation as an effective energy source in the presence of oxygen. In contrast, most cancer cells use less efficient glycolysis to produce ATP and essential biomolecules. Cancer cells gain the characteristics of metabolic adaptation by reprogramming their metabolic mechanisms to meet the needs of rapid tumor growth. A subset of cancer cells with stem characteristics and the ability to regenerate exist throughout the tumor and are therefore called cancer stem cells (CSCs). New evidence indicates that CSCs have different metabolic phenotypes compared with differentiated cancer cells. CSCs can dynamically transform their metabolic state to favor glycolysis or oxidative metabolism. The mechanism of the metabolic plasticity of CSCs has not been fully elucidated, and existing evidence indicates that the metabolic phenotype of cancer cells is closely related to the tumor microenvironment. Targeting CSC metabolism may provide new and effective methods for the treatment of tumors. In this review, we summarize the metabolic characteristics of cancer cells and CSCs and the mechanisms of the metabolic interplay between the tumor microenvironment and CSCs, and discuss the clinical implications of targeting CSC metabolism.

[Distribution and Risk Assessment of OCPs in Surface Water, Sediments, and Fish from Lake Gucheng and Inflow and Outflow Rivers].

To investigate the distribution, source, and ecological risk of organochlorine pesticides (OCPs) residues in Lake Gucheng, surface water, sediment, and biological samples were collected from 12 sampling sites of Lake Gucheng and its inlets and outlets during summer and winter, and the concentrations of 19 OCPs were analyzed. The results showed that the concentration (dry weight) of OCPs in Lake Gucheng ranged from 26.74 to 48.12 ng·L-1 in surface water, 9.01 to 35.34 ng·g-1 in sediment, and 13.39 to 124.29 ng·g-1 in organisms. The pollution characteristics of OCPs in surface water showed that the concentration was much higher in summer than in winter, and much higher at inflow and outflow rivers than in farming ponds and the central region of Lake Gucheng; the seasonal pollution characteristics in sediment were not obvious. All 19 kinds of OCPs in water, sediment, and organisms were detected in different degrees, and the dominant contaminants were HCHs and DDTs. α-HCH was the main pollutant at all sites in both surface water and sediment, with 21% to 42% of total HCHs in two seasons. p,p'-DDD was the main pollutant in surface water with 30% to 76% of total DDTs, whereas p,p'-DDT was the main pollutant in sediment with 68% to 93% of total DDTs in two seasons. Source analysis based on ratios of HCHs isomers and DDTs isomers indicated that there was a new input of OCPs under anaerobic conditions in the study area. The ecological risk assessment showed that the OCPs in surface water did not lead to significant health risks, but the OCPs in sediments might pose ecological risks to the Lake Gucheng ecosystem. The organisms were within the acceptable potential carcinogenic risk range.

Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China.

To gain more information on the prevalence of germline mutations in BRCA1/2 and PALB2 genes in the Chinese population, and to explore the effects of the mutation status of these genes on clinical outcomes in patients with breast cancer, we performed a screening for BRCA1/2 and PALB2 mutations in a consecutive series of unselected breast cancer patients in the Chinese population. A total of 2,769 cases were enrolled between June 1993 and September 2017. All of the exons and exon-intron boundaries of the BRCA1/2 and PALB2 genes were screened with next-generation sequencing. Of the 2,769 breast cancer patients, BRCA1, BRCA2 and PALB2 mutations accounted for 2.7% (n = 74), 2.7% (n = 76), and 0.9% (n = 24), respectively. The BRCA1 gene had the highest mutation frequency in patients with triple-negative breast cancer (TNBC), which was 9.6% (n = 42), while the BRCA2 gene had the highest mutation frequency in patients with Luminal, which was 3.2% (n = 58). The disease-free survival (DFS) of BRCA1 mutation carriers was significantly lower than that of noncarriers (adjusted HR = 2.20, 95% CI = 1.15-4.18, p = 0.017). The mutation status of the PALB2 gene was significantly associated with the decline in overall survival (OS) (adjusted HR = 8.38, 95% CI = 2.19-32.11, p = 0.002). No significant difference was found between BRCA2 pathogenic mutation carriers and noncarriers. These results demonstrate that BRCA1 mutation status may be associated with a worse disease progression in patients with breast cancer, and women who harbored a PALB2 mutation might be at a higher risk of death due to breast cancer compared to noncarriers.

Safety of axitinib and sorafenib monotherapy for patients with renal cell carcinoma: a meta-analysis.

We sought to investigate safety of axitinib or sorafenib in renal cell carcinoma (RCC) patients and compare toxicity of these two vascular endothelial growth factor receptor inhibitors. Databases of PubMed and Embase were searched. We included phase II and III prospective trials, as well as retrospective studies, in which patients diagnosed with RCC were treated with axitinib or sorafenib monotherapy at a starting dose of 5 mg and 400 mg twice daily, respectively. The overall incidence of high grade hypertension, fatigue, gastrointestinal toxicity and hand-foot syndrome, along with their 95% confidence intervals (CI), were calculated using fixed- or random- effects model according to heterogeneity test results. A total of 26 trials, including 4790 patients, were included in our meta-analysis. Among them, 6 arms were related to axitinib and 22 were associated with sorafenib. The incidences of hypertension (24.9% vs. 7.9%), fatigue (8.2% vs. 6.6%), and gastrointestinal toxicity (17.6% vs. 11.3%) were higher in patients receiving axitinib versus those receiving sorafenib, while the incidence of hand-foot syndrome was lower in patients receiving axitinib versus those receiving sorafenib (9.5% vs. 13.3%). In conclusion, axitinib showed noticeably higher risks of toxicity versus sorafenib. Close monitoring and effective measures for adverse events are recommended during therapy.

[Advances in study of macrophages in chemotherapy resistance of cancer].

As extremely important inflammatory cells in the tumor microenvironment, tumor-associated macrophages (TAMs) can secrete a variety of chemokines and cytokines, which play an important role in the occurrence of tumor growth and metastasis. Recent years, increasing studies have shown that macrophages are associated with tumor chemotherapy sensitivity. The chemical substances produced by macrophages affect the efficacy of chemotherapeutic agents. In addition, some chemotherapeutic agents have an effect on the recruitment and bioactivity of macrophages in the tumor issue, which influences the anti-tumor efficacy of chemotherapy drugs. In this review, we summarize the roles of macrophages in the chemotherapy resistance, including the regulatory mechanism and the strategy of targeting macrophages.

[Statins enhance anti-tumor effect of suberoylanilide hydroxamic acid on human non-small cell lung carcinoma cells].

OBJECTIVE: To evaluate the anti-tumor effect of the combination of suberoylanilide hydroxamic acid(SAHA) with statins(lovastatin or simvastatin) on non-small cell lung carcinoma(NSCLC) cells. METHODS: Human NSCLC A549 cells were treated with SAHA in combination of lovastatin or simvastatin. The cell growth was analyzed by SRB method, and the apoptosis of A549 cells was assessed by flow cytometer. The expression of cleaved poly-ADP-ribose polymerase(cleaved-PARP) and p21 protein was analyzed by Western-blotting when A549 cells were challenged with 2.5µmol/L SAHA and 5µmol/L lovastatin. RESULTS: Lovastatin and simvastatin synergized SAHA in the inhibition of A549 cells. SAHA induced apoptosis was also enhanced by lovastatin. Treatment with 2.5µmol/L SAHA significantly up-regulated the expression of p21 protein in 48 h, while the protein expression was reduced in combined treatment with 5µmol/L lovastatin. CONCLUSION: Statins can synergize the anti-tumor effect of SAHA in human NSCLC cells through a p21-dependent way.