Neutron-Absorption Properties of B/Cu Composites.

Copper has high electrical and thermal conductivity, which is frequently employed in structural and functional materials. In this research, powder metallurgy was used to incorporate boron nanosheets into metal matrix composites to create boron dispersion-enhanced copper matrix composites. The neutron-absorption characteristics of composite materials were investigated, as well as the link between neutron-absorption cross-section and neutron energy. The results told us that the morphology of the second phase on the particle surface is closely related to the size of Cu-B particles, copper and boron correspond atomically to each other on the interface without dislocation or lattice distortion, forming a completely coherent interface, and that the neutron absorption cross-section decreases exponentially as neutron energy increases. In low-energy neutrons with energies less than 0.1 eV, the increase of boron content and 10B abundance in Cu-B alloy will enhance the neutron-absorption capacity of the alloy. Boron dispersion-strengthened copper matrix composites have good neutron-absorption capacity, and the microstructure and size of boron do not affect the neutron-absorption performance of composites with the same content of boron. The hardness of the B-dispersion-strengthened Cu matrix composite obtained by nanoindentation test is about 3.04 GPa. Copper matrix composites with boron dispersion reinforcement exhibit high hardness and neutron-absorption characteristics.

Preliminary study on establishing the discriminant equation in pathological grading of hepatocellular carcinoma using immunohistochemical marker parameters.

Context: Identifying the pathological diagnosis for patients with primary hepatocellular carcinoma (HCC) depends on recognizing the microscopic cytological morphology and pathological molecular marker expressions. However, there are nearly 100 markers of primary HCC, most of which are discretely distributed. Thus, the diagnostical process lacks certainty. Aims: Settings and Design: A preliminary study. Methods and Material: A total of 37,012 pathological molecular markers were selected in this study from 1,034 randomly selected patients with primary HCC from January 2014 to June 2019. Patient information included demographic and pathological characteristics, immunohistochemical and blood biochemical indicators, and other biological laboratory data. Statistical Analysis Used: The discriminant analysis method (parametric and non-parametric) was used in two-thirds of the dataset to quantitatively establish the discriminant equation of gender, age, and positive variables determined by the Cochran-Armitage trend test for pathologic grading. The remaining one-third dataset was used to verify the discriminative ability. Results: According to the fitted discriminant equation, only CD34, CD68, Glypican-3, HepPar-1, and Ki-67 (%) exhibited high sensitivity for the diagnosis of primary HCC. Among these five indicators, glypican-3 demonstrated a relatively high correlation with Ki-67 (%). CK19 and CK7 were highly correlated. Glypican-3 demonstrated a higher positive rate in poorly differentiated tumors, whereas HepPar-1 exhibited a higher positive rate in well-differentiated tumors. Conclusions: Gender, age, HepPar-1, Ki-67 (%), and Glypican-3 demonstrated higher accuracy in discriminating the pathological grades of I/II, but the ability to discriminate pathological grades III/IV was insufficient. Additionally, other factors were found to affect pathological grading.

Erratum: FBXO22 Suppresses Metastasis in Human Renal Cell Carcinoma via Inhibiting MMP-9-Mediated Migration and Invasion and VEGF-Mediated Angiogenesis.

[This corrects the article DOI: 10.7150/ijbs.31293.].

Hemoglobin, albumin, lymphocyte, and platelet score and neutrophil-to-lymphocyte ratio are novel significant prognostic factors for patients with small-cell lung cancer undergoing chemotherapy.

OBJECTIVE: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are the important prognostic markers in some tumor types. This study aimed to evaluate the prognostic impact of pretreatment using HALP, NLR, and PLR for patients with small-cell lung cancer (SCLC), who were undergoing chemotherapy. MATERIALS AND METHODS: In this retrospective study, 335 patients with SCLC were included between 2016 and 2018. The cutoff values for HALP, NLR, and PLR were defined using X-tile software. Survival was analyzed by the Kaplan-Meier method, with differences analyzed through the log-rank test. The multivariate Cox proportional hazard model was used to evaluate the prognostic significance of HALP, NLR, and PLR for SCLC. RESULTS: The median follow-up period was 27.1 months (range: 0.5-46.2 months). Based on the Kaplan-Meier curve analysis, it was noticed that the low pretreatment HALP (≤18.6), high pretreatment NLR (>2.4), and high PLR (>191.6) were significantly associated with worse overall survival (OS) (P = 0.009, 0.001, and 0.033, respectively). Cox multivariate analysis demonstrated that low pretreatment HALP and high pretreatment NLR were the independent prognostic factors for worse OS (hazard ratio [HR] = 1.468, 95% confidence interval [CI]: 1.004-2.146, P = 0.047; HR = 0.722, 95% CI: 0.542-0.960, P = 0.025, respectively). CONCLUSION: HALP and NLR were the independent prognostic factors of OS for SCLC patients undergoing chemotherapy.

Associations of MTA1 expression with CT features, pathology and prognosis of elderly patients with non-small cell lung cancer.

Associations of metastasis-associated protein 1 (MTA1) expression with computed tomography (CT) features, pathology and prognosis of elderly patients with non-small cell lung cancer (NSCLC), and its clinical significance were explored. A total of 98 elderly patients with NSCLC were selected and underwent CT examination. The expression of MTA1 in carcinoma tissues and para-carcinoma normal tissues was detected via immunohistochemistry, and its associations with CT features, pathology and prognosis were analyzed. The results manifested that the expression of MTA1 in carcinoma tissues was significantly higher than that in para-carcinoma normal tissues, and it was associated with the degree of differentiation, stage and lymph node metastasis (P<0.05). Besides, the high expression of MTA1 was also related to the spicule sign, pleural indentation and lymph node metastasis (P<0.05) as well as the CT perfusion parameter capillary permeability (PMB) (P<0.05), but not to blood volume (BV), blood flow (BF) or time to peak (TTP). Moreover, the patients with high expression of MTA1 had significantly shorter survival time and a remarkably lower 5-year survival rate than those with low expression of MTA1 (P<0.05). In conclusion, MTA1 plays a certain role in the occurrence and development of NSCLC in elderly patients and has an association with their prognosis, which can provide references for the treatment and prognosis of NSCLC, with important clinical significance.

Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression.

We investigated the influence of the long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) on the malignant phenotype of non-small cell lung cancer (NSCLC) cells in vitro and in vivo. We also explored the mechanisms by which VPS9D1-AS1 exerts its oncogenic action during NSCLC progression. VPS9D1-AS1 expression was upregulated in NSCLC; the extent of its upregulation significantly correlated with patients' adverse clinicopathological characteristics and shorter overall survival. When VPS9D1-AS1 was knocked down in NSCLC cells, their proliferation, colony-forming capacity, migration, and invasiveness were lower, whereas their apoptosis rate was higher, compared to the control. VPS9D1-AS1 knockdown attenuated tumor growth of NSCLC cells in vivo. Mechanistically, VPS9D1-AS1 directly interacted with microRNA-532-3p (miR-532-3p) in NSCLC cells; the impact of VPS9D1-AS1 knockdown on NSCLC cells was attenuated by miR-532-3p inhibition. Furthermore, VPS9D1-AS1 knockdown decreased the expression of high mobility group AT-hook 2 (HMGA2) in NSCLC cells via miR-532-3p sponging. Recovery of HMGA2 expression partially reversed the inhibitory effects of VPS9D1-AS1 knockdown on NSCLC cells. Thus, VPS9D1-AS1 functions as a competing endogenous RNA that positively regulates HMGA2 expression by sponging miR-532-3p in NSCLC cells, suggesting that the VPS9D1-AS1-miR-532-3p-HMGA2 pathway can be a potential diagnostic and/or therapeutic target in NSCLC.

Genomic based analyses reveal unique mutational profiling and identify prognostic biomarker for overall survival in Chinese small-cell lung cancer.

OBJECTIVE: As an aggressive subtype of lung cancer, small-cell lung cancer (SCLC) presents a poor prognosis. Although molecular and clinical characteristics have been established for SCLC, limited investigation has been performed for predicting survival of SCLC patients. METHODS: Genomic alterations were profiled in Chinese SCLC patients (N = 37) using targeted sequencing. Clonal mutation burden (CMB) integrated the number of mutations with the clonal structure of the tumor. Specific pathways involving DNA damage repair (DDR) and cell cycle as well as CMB were studied as potential biomarkers for prognosis of SCLC. RESULTS: TP53 and RB1 gene mutations were the most common alterations (91.9% and 83.8%, respectively), followed by LRP1B, FAM135B, SPTA1, KMT2D, FAT1, and NOTCH3. Survival analysis revealed that mutation status of the DDR pathway was associated with worse OS in our cohort. Importantly, patients with higher CMB exhibited worse OS in our cohort and this observation was successfully validated in the cBioportal cohort. Moreover, multivariate analysis demonstrated CMB as a promising independent prognostic factor for OS in Chinese SCLC patients. Interestingly, patients with loss of function of RB1, validated by immunohistochemistry staining, appeared to have worse OS. CONCLUSIONS: The mutational profiling of Chinese SCLC patients signified an ethnicity dependent component. CMB was firstly found to be associated with OS of Chinese SCLC patients and could be regarded as a prognostic marker for SCLC.

The oncogenic role of NKAP in the growth and invasion of colon cancer cells.

It has been reported that NF­κB activating protein (NKAP) is a transcriptional repressor of the Notch signaling pathway and is involved in the proliferation and survival of hematopoietic stem cells. In the present study, we aimed to investigate the effect of NKAP on the progression and metastasis of colon cancer. The results of immunohistochemical staining and western blot analysis showed that NKAP was upregulated in colon cancer tissues, and its expression was associated with colon cancer stages. CCK­8, colony formation, Transwell, and flow cytometry assays were used to demonstrate that NKAP knockdown significantly suppressed the proliferation and invasion of HCT116 and HT­29 cells, and also induced apoptosis and autophagy. By contrast, NKAP overexpression markedly promoted the proliferation and invasion of HCT­15 cells, and inhibited cell apoptosis and autophagy. Moreover, we observed that NKAP knockdown inhibited the epithelial­mesenchymal transition (EMT) process in HCT116 and HT­29 cells, while NKAP overexpression promoted EMT in HCT­15 cells. Furthermore, NKAP knockdown inhibited activation of the Akt/mTOR signaling pathway by downregulating the phosphorylation of Akt and mTOR, as well as their downstream proteins, whereas NKAP overexpression promoted the Akt/mTOR signaling pathway. Additionally, expression of P65 was downregulated by silencing of NKAP and upregulated by NKAP overexpression. These data suggest that NKAP functions as an oncogene in the growth and invasion of colon cancer in vitro.

Long noncoding RNA OIP5-AS1 in cancer.

Long noncoding RNAs (lncRNAs) can be over two hundred nucleotides in length and lack an obvious open reading frame (ORF). Interestingly, these RNAs form a group of nucleic acids involved in a variety of diverse cellular mechanisms involving proliferation, differentiation, apoptosis,and senescence. Given these characteristics, it is not unexpected that the aberrant expression of certain lncRNAs is strongly linked to oncogenesis and tumor advancement. OIP5-AS1, a prominent tumor-associated lncRNA, contributes to intricate cellular mechanisms during the evolution of malignant tumors. For example, it not only represses cyclin G-associated kinase (GAK) expression thus impacting mitosis, but also regulates cell proliferation and apoptosis in many cancers, including lung adenocarcinoma, breast, glioma and hepatoblastoma. In this paper, we review our current understanding of OIP5-AS1 in carcinogenesis and its potential application as a clinical biomarker or therapeutic target in malignancy.

Cytokines derived from innate lymphoid cells assist Helicobacter hepaticus to aggravate hepatocellular tumorigenesis in viral transgenic mice.

BACKGROUND: Recently, intestinal microbiome has been involved in hepatic diseases due to the immunologic and metabolic communication between liver and intestine. Initiation of hepatocellular carcinoma (HCC) frequently attributes to conspiracy between immune cells and infectious carcinogens. Here, the hypothesis that the tumorigenesis of HCC with HBV infection will be aggravated by specific intestinal bacteria was verified in viral transgenic mouse models. METHODS: Comparative 16S rRNA sequencing was adopted to observe the intestinal enrichment of Helicobacter hepaticus in HCC. Oral administration of Helicobacter hepaticus was carried out to evaluate its hepatic carcinogenic effect in HBV transgenic mice or wildtype C57BL/6. The livers of experimental mice were collected and examined for the degree of tumorigenesis. RESULTS: We found that Helicobacter hepaticus more likely colonized at lower colon of HBV-infected mice with HCC, compared with C57BL/6 and HBV-infected mice without neoplasm. Pretreatment of Helicobacter hepaticus in transgenic mice aggravated tumor formation, with higher incidence, more tumor nodule and higher serum AFP. Then, a cytokines expression patterns with inclined IFN-γ, IFN-γR1, IL-17 and IL-23 was found in HBV-infected mice with Helicobacter hepaticus. Furthermore, innate lymphoid cells, especially Th17 and NK cells which can secret IL-17 and IFN-γ respectively, might be recruited by Helicobacter hepaticus cooperated with HBV. Besides, increased expression of CD69, NKG2D and IFN-γ showed activation of cytokine production in intrahepatic NK cells. Finally, IFN-γ decreased E-cadherin expression through p-STAT1 pathway, resulting in epithelial-mesenchymal transition with inclined expression of Snail2, SIP1 and CXCR4 in vitro. p-STAT1 inhibitor was able to reverse the expression of E-cadherin and EMT resulted from IFN-γ function on HBsAg-positive hepatocytes. CONCLUSIONS: Helicobacter hepaticus generate a detrimental immune microenvironment by IFN-γ/p-STAT1 axis which can promote the tumorigenesis of hepatitis B via recruiting innate lymphoid cells.

FBXO22 Suppresses Metastasis in Human Renal Cell Carcinoma via Inhibiting MMP-9-Mediated Migration and Invasion and VEGF-Mediated Angiogenesis.

F-box only protein 22 (FBXO22), a substrate receptor of the SKP1-Cullin 1-F-box protein (SCF) E3 ubiquitin ligase that targets key regulators of cellular activities for ubiquitylation and degradation, plays important roles in the progression of human cancer. However, little is known about the role of FBXO22 in renal cell carcinoma (RCC). This study aims to explore the biological function of FBXO22 in RCC progression and its specific regulation mechanism. We performed immunohistochemistry analysis and found that the expression level of FBXO22 was significantly lower in RCC tissues than in normal renal tissues. Reduced FBXO22 expression in RCC tissues is related to tumor size and TNM stage and to worse overall and disease-free survival. Through an in vitro assay, we demonstrated that FBXO22 has no effect on renal cancer cells proliferation, whereas FBXO22 remarkably restricted RCC cell migration and invasion, thereby reversing EMT transition and elevating the activity of tissue inhibitor of matrix metalloproteinase-1, which subsequently inhibited metalloproteinase-9 (MMP-9) expression and activity in vitro. We also found that FBXO22 suppresses tube formation by disrupting the secretion of vascular endothelial growth factor. Meanwhile, in vivo studies verified that FBXO22 suppresses RCC metastasis. These findings suggested that FBXO22 is a novel prognostic indicator and plays an important role in RCC metastasis.

Expression profile analysis identifies a two-gene signature for prediction of head and neck squamous cell carcinoma patient survival.

AIM: The aim of this study is to identify a gene prognostic signature for the head-and-neck squamous cell carcinoma (HNSCC). HNSCC is one of the most common malignancies worldwide; however, the molecular mechanisms underlying the malignancy are unclear. MATERIALS AND METHODS: We analyzed the gene expression profiles of GSE2379, GSE53819, and GSE59102 derived from the gene expression omnibus, and the cancer genome atlas (TCGA) HNSC databases. The R software was used to identify the differentially expressed genes (DEGs) between HNSCC tissues and normal controls. Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, protein-protein interactions network, and survival analyses of common DEGs were also performed. RESULTS: A total of 52 upregulated and 31 downregulated DEGs were identified. Functional analyses demonstrated that these DEGs were mainly enriched in extracellular matrix-receptor interaction, focal adhesion, tyrosine metabolism, and cytokine-cytokine receptor interaction. According to the survival analyses, PLAU and SERPINE1 could predict the overall survival of HNSCC patients from the TCGA cohort. Multivariable Cox regression analyses showed that the PLAU and SERPINE1 were independent prognostic factors for HNSCC patients. The prediction power of this two-gene signature was evaluated through receiver operating characteristic curve analysis and achieved a better prognostic value than PLAU (area under curve 0.613 [95% confidence interval 0.569-0.656] vs. 0.577 [0.533-0.621]; P = 0.008) or SERPINE1 (0.613 [0.569-0.656] vs. 0.586 [0.541-0.629]; P = 0.043) when considered alone. CONCLUSIONS: The study has identified a set of novel genes and pathways that play significant roles in the carcinogenesis and progression of HNSCC. This two-gene signature may prove to be a useful therapeutic target for HNSCC.

Dehydrocostus Lactone Enhances Chemotherapeutic Potential of Doxorubicin in Lung Cancer by Inducing Cell Death and Limiting Metastasis.

BACKGROUND Natural compounds have been utilized in inhibiting metastasis alone or in combination with other anti-tumor agents. Dehydrocostus lactone (DHC), a natural sesquiterpene lactone, was used to investigate its effect on proliferation of lung cancer cells and on the anti-angiogenic efficacy of doxorubicin. MATERIAL AND METHODS Cell proliferation was assessed by MTT assay and clonogenic assay. Apoptosis and migration were assessed by flow cytometry and wound-healing assay, respectively. Western blotting and qPCR were performed for gene and protein expression analysis. Matrigel plug assay was performed for angiogenesis assessment. RESULTS Results of the study show that DHC inhibited the survival and proliferation of lung cancer cells (A549 and H460) and enhanced the growth-inhibitory properties of DOX. Cotreatment of DHC enhanced the apoptosis-inducing effects of DOX by activating caspase-9 and caspase-3 followed by cleavage of PARP. Treatment of A549 and H460 cells with DHC caused suppression of HIF-1α, Akt and pAkt, GSK-3ß and pGSK-3ß, as well as ERK, pERK, mTOR, and p-mTOR. DHC enhanced the effect of DOX by inhibiting migration of A549 cells as observed by wound-healing assay. DHC caused synergistic inhibition of MMP-2 and MMP-9 genes when treated in combination with DOX. DHC further enhanced the anti-angiogenic properties of DOX in mice implanted with Matrigel plugs. DHC suppressed the proliferation of lung cancer cells and enhanced the anti-angiogenic properties of DOX. CONCLUSIONS The putative mechanism behind the metastasis-limiting effects of DHC may involve the suppression of Akt/GSK-3ß and inhibition of MMP-2 and MMP-9 in lung cancer cells.

Effect of low-frequency rotary magnetic fields on advanced gastric cancer: Survival and palliation of general symptoms.

OBJECTIVE: The tumor inhibition by magnetic fields (MFs) has been reported in many in vivo and in vitro studies, while clinical trials have been rare. This report aimed to evaluate the improvement of survival and general symptoms in advanced cancer patients treated with MFs. SUBJECTS AND METHODS: In this study, we investigated 21 patients with advanced gastric cancer (AGC) treated with 420 r/min, 0.4-T low-frequency rotary MFs. The treatment area encompassed the primary tumor sites, metastatic sites, and metastatic lymph nodes. In addition, the patients were treated 2 h per day, 5 days per week for 6-12 weeks. The toxicity pilot human study was approved by the competent ethical committee. Toxicity and side effects were assessed according to the WHO criteria. The changes of general symptoms were analyzed during low-frequency rotary MFs treatment and 2 weeks after the end of therapy. Electrocardiogram, chest X-ray, physical examination, blood cell count and complete blood chemistry, biochemical, and kidney function tests were performed before and after the end of the treatment. All 21 patients were followed up by outpatient service or telephone interview. RESULTS: Our results demonstrated that low-frequency rotary MFs improved abdominal pain in 9/21 (42.9%), nausea/vomiting in 4/21 (19.0%), weight loss in 11/21 (52.4%), ongoing blood loss in 2/21 (9.5%), physical strength in 5/21 (23.8%), and sleep quality in 4/21 (19.0%) patients. No severe toxicity and side effect were observed in our trial. The median survival time was 8.0 months (95% confidence interval, 5.190-10.810). The 1-year survival rate was 25.8%. CONCLUSION: Low-frequency rotary MFs may prolong survival and improve general symptom of AGC patients, as an effective, well-tolerated, and safe treatment choice.

High scavenger receptor class B type I expression is related to tumor aggressiveness and poor prognosis in lung adenocarcinoma: A STROBE compliant article.

Scavenger receptor class B type I (SR-B1) is highly expressed in a variety of cancers, including prostate, breast and ovarian. However, the relationship between SR-B1 and lung adenocarcinoma is unknown. We analyzed the expression of SR-B1 in a well-characterized lung adenocarcinoma tissue microarray by immunohistochemistry, in 90 cancerous and 90 adjacent normal lung tissues. Results showed that the positive expression rate of SR-B1 in cancer tissues (86/90, 96%) was significantly higher than that of adjacent tissues (50/90, 56%) (P < .001). And SR-B1 overexpression in lung adenocarcinoma tissue was significantly higher than that of adjacent normal tissue (P < .001), accounting for 67% of cases. This elevated SR-B1 expression was associated with AJCC stage (P < .001), T stage (P = .012), N stage (P = .002), and lymph node positivity (P < .001). The Kaplan-Meier survival analysis indicated that patients with high SR-B1 expression had a shorter overall survival (P < .001). On the multivariate analysis, SR-B1 was an independent prognostic factor for outcomes after adjustment for other prognostic factors (P = .038). In conclusion, high SR-B1 expression is associated with conventional pathologic parameters that represent tumor aggressiveness and may purport a poor clinical prognosis in lung adenocarcinoma.

MicroRNA-124-3p directly targets PDCD6 to inhibit metastasis in breast cancer.

Breast cancer (BC) is the leading cause of cancer-associated mortality among women worldwide, with a poor 5-year survival rate, particularly among patients with metastatic BC. Previous studies have indicated that the dysregulation of microRNAs (miRNAs/miRs) is associated with carcinogenesis and metastasis. Thus, investigating the underlying molecular mechanisms by which miRNAs mediate their effects may aid in the improvement of BC treatment. In the present study, reverse transcription-quantitative polymerase chain reaction analyses were performed to investigate miR-124-3p expression in BC tissues. The expression of miR-124-3p was significantly decreased in primary BC tissues compared with that in adjacent non-tumor tissues. Downregulated miR-124-3p was correlated with lymph node metastasis and a low overall survival time. Wound-healing and Transwell assays revealed that MDA-MB-231 and MCF-7 cell motility was inhibited by miR-124-3p, but was promoted by a miR-124-3p inhibitor. Overexpression of miR-124-3p increased levels of E-cadherin, and decreased levels of N-cadherin and Vimentin, indicating that miR-124-3p inhibits the epithelial-mesenchymal transition. In addition, a bioinformatics analysis and subsequent in vitro experiments identified programmed cell death protein 6 (PDCD6) as a direct target of miR-124-3p. Restoration of PDCD6 expression impaired the metastasis inhibitor role of miR-124-3p by promoting cell invasion. Furthermore, the expression of miR-124-3p was inversely associated with PDCD6 mRNA levels in clinical breast tumors. Taken together, these data suggest that miR-124-3p inhibits tumor metastasis by inhibiting PDCD6 expression, and that the miR-124-3p/PDCD6 signaling axis may be a potential target for novel treatments in patients with advanced BC.

Loss of ß-arrestin-2 and Activation of CXCR2 Correlate with Lymph Node Metastasis in Non-small Cell Lung Cancer.

Background : Although ß-arrestin-2 (ß-arr2) and CXCR2 have been shown to affect various malignant tumors, their exact roles in lung cancer remain unclear. We investigated expression of ß-arr2 and CXCR2 in patients with non-small cell lung cancer (NSCLC) and their correlation with lymph node metastasis and prognosis. Methods : We reviewed medical records of 136 patients with NSCLC who underwent surgical resection, and assessed their specimens immunohistochemically for expression of ß-arr2 and CXCR2 in primary tumors and metastatic lymph nodes (MLNs), respectively. Results: High ß-arr2 expression was seen in 63 specimens (46.3%), and was significantly associated with male patients (P=0.011), squamous cell carcinoma (P=0.003), and lymph node metastasis (P<0.001). High CXCR2 expression was seen in 62 specimens (45.6%), and was significantly correlated only with lymph node metastasis (P<0.001). Expression of ß-arr2 was significantly lower at MLNs than at primary lesions (Z=-2.315; P=0.021; Wilcoxon signed-rank), whereas CXCR2 expression was significantly higher in MLNs than in primary lesions (Z=-3.712; P<0.001; Wilcoxon signed-rank). No relationship was seen between ß-arr2 and CXCR2 expression in primary lesions (r=-0.065, P=0.548; Spearman rank coefficient), but they were inversely related in MLNs (r=-0.263, P=0.012). Kaplan-Meier survival curve was shown that low ß-arr2 and high CXCR2 expressions was associated with poor survival (log-rank: χ2=5.926, P=0.015). Conclusions : ß-arr2 may promote lymph node metastasis in NSCLC by modulating CXCR2 activation.

Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function.

Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. BCAA catabolism is a conserved regulator of physiological aging and participates in diverse physiological and pathological processes, including carcinoma development. The roles of BCAA catabolism in human breast cancer remains unknown. Here we provide evidence that BCAA catabolism is involved in human breast cancer. The plasma and tissue levels of BCAAs are increased in breast cancer, which is accompanied by the elevated expression of the catabolic enzymes, including branched-chain amino acid transaminase 1 (BCAT1). Knockdown of BCAT1 represses the growth rate and colony formation capacity of breast cancer cells, opposing results are observed when BCAT1 is overexpressed. BCAT1 can promote mitochondrial biogenesis, ATP production and repress mitochondrial ROS in breast cancer cells by regulating the expression of related genes. Mechanism study reveals that BCAT1 activates the mTOR, but not AMPK or SIRT1, signaling to promote mitochondrial biogenesis and function, and subsequently facilitates growth and colony formation of breast cancer cells. Taken together, we demonstrate that BCAA catabolism is activated in human breast cancer, and abolishment of BCAA catabolism by knocking down BCAT1 inhibits breast cancer cell growth by repressing mTOR-mediated mitochondrial biogenesis and function.

Effect of BIM on advanced non-small cell lung cancer / 中国肿瘤临床

Lung cancer displays the highest morbidity and mortality worldwide. Non-small cell lung cancer (NSCLC) is the most com-mon type of lung cancer. In-depth research was performed on the pathogenesis and biological behavior of lung cancer and the im-provement of genetic testing level. The discovery of drugs targeting epidermal growth factor receptor and anaplastic lymphoma kinase plays a significant role in individual treatment of advanced NSCLC. BIM is a protein in the Bcl-2 family that promotes apoptosis, which leads to cell death. The BIM expression level and polymorphism can influence the therapeutic effect of targeted therapy and chemo-therapy on advanced NSCLC. Therefore, this review summarizes BIM and its effects on targeted therapy and chemotherapy for ad-vanced NSCLC.