Antitumor effects of helenalin in doxorubicin-resistant leukemia cells are mediated via mitochondrial mediated apoptosis, loss of mitochondrial membrane potential, inhibition of cell migration and invasion and downregulation of PI3-kinase/AKT/m-TOR signalling pathway.

Retraction of: 'Antitumor effects of helenalin in doxorubicin-resistant leukemia cells are mediated via mitochondrial mediated apoptosis, loss of mitochondrial membrane potential, inhibition of cell migration and invasion and downregulation of PI3-kinase/AKT/m-TOR signalling pathway', by Jingxin Liu, Yanan Zhao, Zhangzhen Shi, Yuansong Bai, JBUON 2019;24(5):2068-2074; PMID:31786877. Following the publication of the above article, readers drew to our attention that part of the data was unreliable. The authors were requested to provide the raw data to prove the originality, but were unable to do so. After an investigation, the Editors of JBUON decided to retract this article. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Antitumor effects of helenalin in doxorubicin-resistant leukemia cells are mediated via mitochondrial mediated apoptosis, loss of mitochondrial membrane potential, inhibition of cell migration and invasion and downregulation of PI3-kinase/AKT/m-TOR signalling pathway.

PURPOSE: The main purpose of the current study was to investigate the antitumor effects of helenalin - a plant derived sesquiterpene lactone, against doxorubicin-resistant acute myeloid leukemia HL60 cells, along with evaluating its effects on apoptosis induction, mitochondrial membrane potential (MMP), cell migration and inhibition and PI3K/AKT/M-TOR signalling pathway. METHODS: Antiproliferative effects were evaluated with CCK8 cell viability assay and colony formation assay. Cell apoptotic effects were studied by (acridine orange) AO/ethidium bromide (EB) staining assay. To further estimate the extent of apoptosis, flow cytometry using annexin V assay was used. Effects on MMP were estimated by flow cytometry, while transwell migration assay was used to study the effects on cell migration and invasion. Protein expression was estimated by western blot method. RESULTS: The results showed that helenalin inhibits the growth of the HL60 cells significantly and exhibited an IC50 of 23.5 µM. In addition, it was observed that the anticancer effects of helenalin are due to induction of mitochondrial-mediated apoptosis which was also associated with enhancement of the expression of Bax and decrease in the expression of Bcl-2. Helenalin also caused loss of MMP in the doxorubicin-resistant HL-60 cells and also inhibited their migratory and invasive properties via modulation of the PI3K/AKT/M-TOR signalling pathway. CONCLUSIONS: In conclusion, the present study reveals that helenalin sesquiterpene lactone exhibits significant antitumor activity in doxorubicin-resistant acute myeloid leukemia HL60 cells by targeting some key pathways and as such this molecule could prove to be a potential drug candidate for future investigations.

HOXA11-AS promotes the migration and invasion of hepatocellular carcinoma cells by inhibiting miR-124 expression by binding to EZH2.

The objective of this study was to examine the function of the long non-coding RNA (lncRNA) HOXA11-AS in hepatocellular carcinoma (HCC). In total, samples from liver tumor and surrounding normal liver tissues were collected from 66 cases of HCC patients. Normal liver cell line HL-7702 and HCC cell lines HepG2, Hep3B, MHCC-97H and BEL7402 were used. Cells were transfected with different small interference RNAs or vectors. Then, transwell assay, qRT-PCR, CHIP, RIP and Western blot experiments were performed. We found that the HOXA11-AS expression level was higher in HCC samples than surrounding normal liver tissues. And the higher expression level of HOXA11-AS in HCC patients indicated a lower 5-year survival rate. Knockdown of HOXA11-AS in HepG2 and Hep3B cells caused impaired cell invasion and migration abilities. Otherwise, upregulation of HOXA11-AS in MHCC-97H and BEL7402 cells displayed higher invasion and migration capabilities. We also demonstrated that HOXA11-AS could inhibit miR-124 expression by binding to EZH2. Furthermore, overexpression of miR-124 or knockdown EZH2 expression could reverse the HOXA11-AS-induced migration and invasion effects in HCC cells. In summary, the high HOXA11-AS expression in HCC patients is associated with the poor outcome. HOXA11-AS could inhibit miR-124 expression by binding to EZH2 and thus promoted the migration and invasion of HCC cells.

Prognostic significance of systemic immune-inflammation index in triple-negative breast cancer.

Introduction: The prognostic significance of the systemic immune-inflammation index (SII) in breast cancer is unknown. Here, we aimed to explore the connection between pretreatment SII and the survival of patients with triple-negative breast cancer (TNBC). Methods: We enrolled 160 TNBC patients treated in our hospital between May 2000 and June 2012. We employed the Kaplan-Meier curve and log-rank test to assess overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS). We identified the prognostic significance of SII using the Cox regression model. Results: The Kaplan-Meier curve revealed the median OS as 44.2 and 82.4 months in high and low SII TNBC patients, respectively (P<0.001). According to univariate and multivariate analyses, increased SII correlated with poor OS (HR =2.91, 95% CI: 2.00-4.23, P<0.001; HR =2.60, 95% CI: 1.74-3.88, P<0.001). The DFS and DMFS of patients with high SII were 18.8 and 23.8 months, respectively, while those of patients with low SII were 29 and 45.2 months, respectively, (P<0.001). Further univariate analyses showed a significant correlation between SII and DFS and DMFS (P<0.01), while results from multivariate analyses suggested that SII is an independent prognostic factor for DFS (P=0.045), but not for DMFS (P=0.078). The area under the receiver operating characteristics curves for SII to differentiate between long and short OS, DFS, and DMFS were 0.69, 0.60, and 0.64, respectively. Conclusion: Our findings may point to SII having an independent prognostic significance in TNBC patients. Prospective in-depth studies, using a larger sample size, are required to further investigate the precise role of SII in TNBC before clinical use.

Exploring the molecular pathogenesis associated with T-cell prolymphocytic leukemia based on a comprehensive bioinformatics analysis.

As a rare hematological malignancy, T-cell prolymphocytic leukemia (T-PLL) has a high mortality rate. However, the comprehensive mechanisms of the underlying pathogenesis of T-PLL are unknown. The purpose of the present study was to investigate the pathogenesis of T-PLL based on a comprehensive bioinformatics analysis. The differentially expressed genes (DEGs) between T-PLL blood cell samples and normal peripheral blood cell samples were investigated using the GSE5788 Affymetrix microarray data from the Gene Expression Omnibus database. To investigate the functional changes associated with tumor progression, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used on the identified DEGs, followed by protein-protein interaction (PPI) and sub-PPI analysis. Transcription factors and tumor-associated genes (TAGs) were investigated further. The results identified 84 upregulated genes and 354 downregulated genes in T-PLL samples when compared with healthy samples. These DEGs featured in various functions including cell death and various pathways including apoptosis. The functional analysis of DEGs revealed 17 dysregulated transcription factors and 37 dysregulated TAGs. Furthermore, the PPI network analysis based on node degree (a network topology attribute) identified 61 genes, including the core downregulated gene of the sub-PPI network, signal transducer and activator of transcription 3 (STAT3; degree, 13) and the core upregulated gene, insulin receptor substrate-1 (IRS1; degree, 5), that may have important associations with the progression of T-PLL. Alterations to cell functions, including cell death, and pathways, including apoptosis, may contribute to the process of T-PLL. Candidate genes identified in the present study, including STAT3 and IRS1, should be targets for additional studies.

Lutein Inhibits Cell Growth and Activates Apoptosis via the PI3K/AKT/mTOR Signaling Pathway in A549 Human Non-Small-Cell Lung Cancer Cells.

Cancer, the uncontrolled growth of cells, is a major disease that threatens the worldwide population. Among all cancer types, lung cancer has the highest morbidity rate, with a survival rate of less than 5%. Various studies have focused on discovering a potent anticancer drug that will increase the survival rate of lung cancer patients. Lutein (3,3'-dihydroxy-ß, ε-carotene), a carotenoid present in fruits and vegetables, is one such compound that possesses excellent antioxidant properties. The present study was designed to determine the anticancer effect of lutein against A549, a non-small-cell lung cancer cell line. The cytotoxic effect of lutein against lung cancer cells (A549 and HCC827) and normal cells (BEAS-2B) was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The Transwell assay was performed to detect the inhibitory potential of lutein against cell invasion and migration of A549 cells. The induction of apoptosis by lutein in A549 was analyzed by a double-staining technique using TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling) and DAPI (4',6-diamidino-2-phenylindole) staining assays to confirm the molecular mechanism exhibited by lutein to induce apoptosis through regulating the phosphoinositide 3-kinase (PI3K)/AKT signaling molecules that are often deregulated in cancerous condition. The results show that lutein inhibits the PI3K/AKT signaling pathway and induces apoptosis in A549, which may therefore be used as a potent natural anticancer drug with no side effects to treat lung cancer.

Review of Rosai-Dorfman Disease: New Insights into the Pathogenesis of This Rare Disorder.

Rosai-Dorfman disease (RDD) is a rare histiocytosis typically with bilateral painless cervical lymphadenopathy. Laboratory data are nonspecific, and the presence of emperipolesis in large foamy S-100+ CD1a- histiocytes is the prominent histologic feature. The pathogenesis of RDD still remains elusive. According to published studies, we propose that RDD cells might represent intermediate recruiting monocytes with differentiation blockade. Both disturbance of homoeostasis and inherent genomic alterations could contribute to initiation of the disorder through signal transduction. Several inflammatory molecules such as macrophage colony-stimulating factor, IL-1ß, IL-6, and tumor necrosis factor-α also play a pivotal role in the development of this rare entity. Additional studies are needed to further elucidate the essence of the disease.

RNA-Seq analysis of non-small cell lung cancer in female never-smokers reveals candidate cancer-associated long non-coding RNAs.

We aimed to elucidate the potential mechanisms of long non-coding RNAs (lncRNAs) in the progression of non-small cell lung cancer (NSCLC). The microarray datasets of GSE37764, including 3 primary NSCLC tumors and 3 matched normal tissues isolated from 6 Korean female never-smokers, were downloaded from Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNA in NSCLC samples were identified using NOISeq package. Co-expression network of differentially expressed lncRNAs and mRNA was established. Gene Ontology (GO) and pathway enrichment analysis were respectively performed. Finally, lncRNAs related to NSCLC were predicted by blasting the differentially expressed lncRNAs with all predicted lncRNAs related to NSCLC. A total of 182 and 539 differentially expressed lncRNAs and mRNA (109 up- and 73 down-regulated lncRNAs; 307 up- and 232 down-regulated mRNA) were respectively identified. Among them, 4 up-regulated lncRNAs, like lnc-geranylgeranyl diphosphate synthase 1 (GGPS1), lnc-zinc finger protein 793 (ZNF793) and lnc-serine/threonine kinase 4 (STK4), and 4 down-regulated lncRNAs including lnc-LOC284440 and lnc-peptidylprolyl isomerase E-like pseudogene (PPIEL), and lnc-zinc finger protein 461 (ZNF461) were predicted related to NSCLC. lncSSPS1, lnc-ZNF793 and lnc-STK4 were co-expressed with linker for activation of T cells (LAT) and Lck interacting transmembrane adaptor 1 (LIME1). Lnc-LOC284440, lnc-PPIEL and lnc-ZNF461 were co-expressed with Src-like-adaptor 2 (SLA2) and defensin beta 4A (DEFB4A). Our study indicates that immune response may be a crucial mechanism involved in NSCLC progression. Lnc-GGPS1, lnc-ZNF793, lnc-STK4, lnc-LOC284440, lnc-PPIEL, and lnc-ZNF461 may be involved in immune response for promoting NSCLC progression via co-expressing with LAT, LIME1, SLA2 and DEFB4A.

Male accessory breast cancer successfully treated with endocrine therapy: A case report.

Male accessory breast cancer is an extremely rare tumor. Several risk factors have been identified, including genetic and hormonal abnormalities. Accessory breast carcinoma usually occurs under the axilla or in the inguinal region. Clinical diagnosis is frequently delayed due to the general lack of awareness among physicians and patients. In the present study, the case of a 63-year-old male patient who was diagnosed with accessory breast cancer at a local advanced stage was reported. However, the patient was successfully treated with endocrine therapy.

Langerhans cell histiocytosis with multisystem involvement in an infant: A case report.

Langerhans cell histiocytosis (LCH) is a proliferative disease of histiocyte-like cells, with a wide range of clinical presentations that vary from a solitary lesion to more severe multifocal or disseminated lesions. The disease can affect any age group; however, the peak incidence rate is in infants aged between 1 and 3 years-old. Diagnosis of LCH should be based on the synthetical analysis of clinical presentations, in addition to features of imaging and histopathology. Although certain cases regress spontaneously, other patients require systemic chemotherapy together with the administration of steroids. The present study reports the case of an infant with LDH with multisystem involvement, including that of the bone, skin, orbit, spleen and lungs. The patient received chemotherapy and obtained rapid improvement in the involved systems. A total of 2.5 years after completion of the therapy, the patient still remains in follow-up and no evidence of active disease has been noted.

[Influence of gene transduction mediated by lentivirus vector on gene expression of human CD34+ cord blood cells].

OBJECTIVE: To investigate the influence of gene transduction mediated by lentivirus vector on human CD34+ cord blood cell (CBCs) gene expression. METHODS: CD34+ cells were isolated and transduced with the third-generation self-inactivating ( SIN) lentiviral vector carrying green fluorescent protein (GFP). The total RNA from transduced cells was extracted and the differences of genotypes between the transduced and non-transduced CD34+ cells were determined with cDNA microarray analysis. RESULTS: In 23000 genes two were upregulated and six downregulated. These changes were not confirmed by semi-quantitative RT-PCR method. CONCLUSIONS: Lentiviral vector used in this study do not influence significantly on the gene expression of CD34+ CBCs, and the vector system may be a useful and safe one in clinical gene therapy.