[Retracted] Sulforaphane regulates apoptosis­ and proliferation­related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer.

Following the publication of this paper, the authors realized that they had made an error in assembling the data shown in Fig. 6B on p. 2455, and requested the publication of a corrigendum to rectify this error. However, following an independent investigation of the data published in this paper made by the Editorial Office, it was noted that one set of the immunofluorescence assay images shown in Fig. 4A appeared to be strikingly similar to data appearing in different form in a paper published previously in the journal BMC Medicine by different authors at different research institutes [Jing Y­Y, Han Z­P, Sun K, Zhang S­S, Hou J, Liu Y, Li R, Gao L, Zhao X, Zhao Q­D et al: Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK­Mff signaling pathways. BMC Medicine 10: 98, 2012]. Owing to the fact that the abovementioned data in Fig. 4A had already been published prior to its submission to International Journal of Molecular Medicine, the Editor has chosen to decline the authors' request to publish a corrigendum, and decided that this paper should be retracted from the Journal instead. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 2447­2458, 2018; DOI: 10.3892/ijmm.2018.3860].

Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity.

PURPOSE: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. MATERIALS AND METHODS: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). RESULTS: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. CONCLUSIONS: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Contralateral S1 nerve root transfer for motor function recovery in the lower extremity among patients with central nervous system injury: study protocol for a randomized controlled trial.

BACKGROUND: Central nervous system injury (CNSI) comprises a series of common diseases that severely affect patients' motor function and quality of life and is associated with high disability and mortality rates. Previous studies have shown that contralateral lumbosacral nerve root transfer significantly improved the function of the paralyzed limb in rat models of CNSI. These studies showed that severing the sacral 1 nerve root (S1) did not damage the function of the ipsilateral lower extremity. Thus, we speculate that contralateral S1 nerve root transfer can improve the recovery of a paralyzed limb. Because no associated rigorously designed randomized controlled trial has evaluated the effectiveness of contralateral S1 nerve transfer thus far, we designed this clinical trial to compare the effects of this new treatment approach with those of traditional treatments in paralyzed patients after chronic CNSI. METHODS: This is a single-center, prospective, randomized controlled trial. Forty patients, who meet the inclusion criteria and have hemiplegia caused by chronic CNSI, will be randomly divided into the surgical or non-surgical group. The treatment effect in the 2 groups will be assessed before and 3, 6, 9, 12, 18, and 24 months after intervention by using numerous scales and resting-state functional magnetic resonance imaging. The primary outcome will be the Fugl-Meyer score for the lower limbs 24 months after treatment. The secondary outcomes include the modified Ashworth spasm scale, the modified Barthel scale, 10-m walking speed measurement results, three-dimensional gait analysis, muscle strength testing, electromyography, and resting-state functional magnetic resonance imaging findings. Safety outcomes and adverse events will be observed simultaneously. DISCUSSION: We expect that the surgery will improve the sensorimotor functions of the paralyzed limb, and the results of this trial will provide high-quality clinical evidence for a new efficient treatment strategy for disability after CNSI. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800014414, registration date: 12 January 2018.

Systematic tracking of altered modules identifies the key biomarkers involved in chronic lymphocytic leukemia.

Key genes in chronic lymphocytic leukemia (CLL) were investigated through systematically tracking the dysregulated modules from protein-protein interaction (PPI) networks. Microarray data of normal subjects and CLL patients recruited from ArrayExpress database were applied to extract differentially expressed genes (DEGs). Additionally, we re-weighted the PPI network of normal and CLL conditions by means of Pearsons correlation coefficient (PCC). Furthermore, clique-merging method was applied to extract the modules and then the altered modules were screened out. The intersection genes were selected from miss and add genes in the altered modules. The common genes were screened from the intersection genes and DEGs in CLL. A total of 734 DEGs were screened by statistical analysis. In this investigation, there were 1,805 and 703 modules in normal as well as disease PPI network. In addition, 875 altered modules were obtained which included 145 miss genes, 353 add genes and 85 intersection genes. Finally, in-depth analysis revealed 9 mutual genes between the intersection genes and DEGs in CLL. Our analysis revealed several key genes associated with CLL by systematically tracking the dysregulated modules, which might be candidate targets for diagnosis and management of CLL.

Sulforaphane regulates apoptosis- and proliferation­related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer.

Ovarian cancer is currently the most life­threatening type of gynecological malignancy with limited treatment options. Therefore, improved targeted therapies are required to combat ovarian cancer across the world. Sulforaphane is found in raw cruciferous vegetables. The chemotherapeutic and anti­carcinogenic properties of sulforaphane have been demonstrated, however, the underlying mechanisms remain to be fully elucidated, particularly in ovarian cancer. In the present study, the possibility of repurposing sulforaphane as an anti­ovarian cancer agent was examined. Cell viability and colony formation assay were used to test the anticancer efficiency of sulforaphane. Then wound healing assay, migration assay, cell cycle and apoptosis assays were used to detect how the drug worked on the cells. The mechanism of sulforaphane was investigated by western blot analysis. It was found that sulforaphane effectively suppressed the progression of human ovarian cancer cell proliferation, migration and cell cycle, and promoted apoptosis. Sulforaphane inhibited multiple cancer­associated signaling pathways, including B­cell lymphoma 2 (Bcl­2), Bcl­2­associated X protein, cytochrome c, Caspase­3, phosphorylated AKT, phosphorylated nuclear factor­κB, P53, P27, Cyclin­D1 and cMyc, and reduced the expression levels of human epidermal growth factor receptor 2 in human ovarian cancer cells. Sulforaphane synergized with cisplatin to suppress the cancer cell proliferation and enhance ovarian cancer cell apoptosis. Xenograft experiments in vivo confirmed that sulforaphane effectively suppressed tumor growth by inhibiting ovarian cancer cell proliferation through targeting tumor­related signals. The results indicated that sulforaphane may be repurposed as an effective anti­ovarian cancer agent, with further preclinical or clinical investigations required.

Targeting Human Poly(ADP-Ribose) Polymerase-1 with Natural Medicines and Its Potential Applications in Ovarian Cancer Therapeutics.

Targeting poly(ADP-ribose) polymerase-1 (PARP-1) has been established as an efficient therapeutics for advanced ovarian cancer. In this study, we describe an integrated procedure that combines virtual computer screening and an experimental enzyme assay to discover novel potent PARP-1 inhibitors from more than 130000 commercially available natural products. The protocol employed a stepwise strategy to fast exclude typical PARP-1 non-binders and then performing rigorous prediction to identify promising candidates with high potency against PARP-1. Consequently, eight natural products were hit and tested to determine their inhibitory activities against the PARP-1 catalytic domain. From these, four compounds, i.e., puerarin, phloretin, chlorogenic acid, and biochanin A, were found to have high or moderate potencies with inhibitory IC50 values of 6, 470, 25, and 86 nM, respectively. The values are comparable to that (IC50 = 1.94 nM) of the FDA-approved agent olaparib. Structural and energetic analyses of the modeled structures of the PARP-1 catalytic domain complexed with the newly identified inhibitors revealed a common binding mode in the complexes: the active site of PARP-1 is composed of a thin polar helix and a flat non-polar pocket; the inhibitors can form a number of hydrogen bonds and electrostatic forces with the helix, while tightly packing against the pocket to define chemical interactions.

Overexpression of Bmi-1 in uterine cervical cancer: correlation with clinicopathology and prognosis.

INTRODUCTION: B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is a member of polycomb group, which participates in axial patterning, hematopoiesis, cell cycle regulation, and senescence. Recently, overexpression of Bmi-1 has been reported in various human cancers and proved to be associated with poor survival. The aim of this study was to investigate the expression of Bmi-1 protein in human uterine cervical cancer (UCC) and explore its associations with clinicopathological factors and prognosis. METHODS: Western blot was used to detect the expression of Bmi-1 in 4 human cervical cancer cell lines (Hela, SiHa, CasKi, and C33A) and a normal cervical epithelial cell line. In addition, 152 UCC and 30 adjacent normal cervical paraffin-embedded samples were collected to detect Bmi-1 expression by immunohistochemistry. RESULTS: Western blot analysis showed Bmi-1 was overexpressed in 4 human UCC cell lines but not in the normal cervical epithelial cell line. Moreover, immunohistochemical staining revealed Bmi-1 was overexpressed in 63.2% UCC tissues (Bmi-1 ++ or +++), and the overexpression of Bmi-1 protein was significantly correlated with tumor size (P = 0.046), clinical stage (P = 0.021), and regional lymph nodes metastasis (P = 0.010). Survival analysis showed a significant difference between Bmi-1 protein overexpression and poor survival (P = 0.021). Cox proportional hazards risk analysis indicated that Bmi-1 protein overexpression was an independent prognostic factor for overall survival. CONCLUSIONS: B-cell-specific Moloney murine leukemia virus integration site 1 is overexpressed in UCC and correlated with adverse clinical characteristics and poor prognosis, which suggests that the Bmi-1 might participate in the development and progression of UCC and have clinical potential not only as a useful predictor of aggressive phenotype but also a promising prognostic predictor.