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Teratomas originate from pluripotent cells and can differentiate along one or more embryonic germ lines. Renal teratoma is infrequent and malignant renal teratoma is even rarer. Experience in the diagnosis and treatment of this uncommon malignancy is seriously limited. In this report, we described the case of a 64-year-old female who complained of right flank pain for 4 months. Computed tomography (CT) revealed a hypodense mass (50 mm in maximum diameter) with slow contrast enhancement and obscure boundary located in the lower pole of the right kidney. CT also showed multiple retroperitoneal lymphadenectasis. Retroperitoneal laparoscopic right radical nephrectomy along with regional lymphadenectomy was successfully performed, and postoperative pathological examination confirmed malignant teratoma of the kidney. After surgery, the patient received adjuvant chemotherapy with BEP (bleomycin, etoposide, and cisplatin) protocol. At the 6-month follow-up, pulmonary and liver metastases were discovered by CT and the patient refused any further treatment. Unfortunately, she died at 16 months postoperatively. Although primary renal malignant teratoma is extremely rare, this kind of tumor should be taken into consideration. Currently, there is no therapeutic standard consensus for this disease and the prognosis remains unclear. Early detection and surgical intervention is critical, and more research on postoperative adjuvant therapy should be performed.

In the majority of acute promyelocytic leukemia (APL) cases, translocons produce a promyelocytic leukemia protein-retinoic acid receptor α (PML-RARα) fusion gene. Studies have reported that neutrophil elastase (NE) cleaves bcr-1-derived PML-RAα in early myeloid cells, leaving only the nuclear localization signal (NLS) of PML attached to RARα. NLS-RARα promotes cell growth and inhibits differentiation in response to ATRA. However, the mechanisms by which NLS-RARα affects cell biological characteristics are yet to be fully elucidated. The present study found that the location of RARαwas altered after it was cleaved by NE. Firstly, NE was overexpressed during the preparation of recombinant plasmid NB-4/pCMV6-NE-Myc to cleave PML-RARα. The total protein expression levels of myc and NE and expression levels of NLS-RARα in nucleoprotein were detected by western blotting. Location of NLS-RARα protein was detected by immunofluorescence and confocal laser scanning. Secondly, a nude mice model was constructed and NE protein, NLS-RARα and RARα protein assays, and the location of NLS-RARα and RARα proteins were assessed as described. The present results showed that, compared with the control groups, the location of NLS-RARα protein was predominantly detected in the nucleus, whereas RARα was mainly distributed in the cytoplasm. These findings were consistent with those of the nude mice model, and these may be used as a foundation to explain the occurrence mechanism of APL.

Neutrophil elastase (NE) is a neutrophil-derived serine proteinase with specificity for a broad range of substrates. NE has been reported to be associated with the pathogenesis of several conditions, particularly that of pulmonary diseases. Previous studies have shown that NE can cleave the pro-myelocyte - retinoic acid receptor-alpha chimeric protein and is important for the development of acute pro-myelocytic leukemia. To further elucidate the role of NE in acute pro-myelocytic leukemia, the present study successfully constructed a lentiviral vector containing the NE gene (LV5-NE), which was transfected into NB4 acute pro-myelocytic leukemia cells. The effects of NE overexpression in NB4 cells were detected using a Cell-Counting Kit-8 assay, flow cytometry and western blot analysis. The results showed that NE significantly promoted the proliferation of NB4 cells, inhibited cell apoptosis and apoptotic signaling, and led the activation of Akt. In an additional experiment, a vector expressing small hairpin RNA targeting NE was constructed to assess the effects of NE knockdown in U937 cells. Western blot analysis revealed that apoptotic signaling was increased, while Akt activation was decreased following silencing of NE. The results of the present study may indicate that NE activates the phosphoinositide-3 kinase/Akt signaling pathway in leukemia cells to inhibit apoptosis and enhance cell proliferation, and may therefore represent a molecular target for the treatment of pro-myelocytic leukemia.

Recently, the long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified as an oncogenic gene in multiple human tumor entitles, and dysregulation of UCA1 was tightly linked to carcinogenesis and cancer progression. However, whether the aberrant expression of UCA1 in non-small cell lung cancer (NSCLC) is associated with malignancy, metastasis or prognosis has not been characterized. In this study, we found that UCA1 was upregulated in NSCLC tissues. Higher expression of UCA1 led to a significantly poorer survival time, and multivariate analysis revealed that UCA1 was an independent risk factor of prognosis. UCA1 overexpression enhanced, whereas UCA1 silencing impaired the proliferation and colony formation of NSCLC cells. Moreover, mechanistic investigations showed that UCA1 upregulated the expression of miR-193a-3p target gene ERBB4 through competitively 'spongeing' miR-193a-3p. Overall, we concluded that UCA1 functions as an oncogene in NSCLC, acting mechanistically by upregulating ERBB4 in part through 'spongeing' miR-193a-3p.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). With the application of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), APL becomes one of best prognosis of leukemia. However, ATRA and ATO are not effective against all APLs. Therefore, a new strategy for APL treatment is necessary. Here, we investigated whether lithium chloride (LiCl), a drug used for the treatment of mental illness, could promote apoptosis in human leukemia NB4 cells. We observed that treatment with LiCl significantly accelerated apoptosis in NB4 cells and led to cell cycle arrest at G2/M phase. Moreover, LiCl significantly increased the level of Ser9-phosphorylated glycogen synthase kinase 3β(p-GSK-3β), and decreased the level of Akt1 protein in a dose-dependent manner. In addition, LiCl inhibition of c-Myc also enhanced cell death with a concomitant increase in β-catnin. Taken together, these findings demonstrated that LiCl promoted apoptosis in NB4 cells through the Akt signaling pathway and that G2/M phase arrest was induced by increase of p-GSK-3β(S9).

Neutrophil elastase (NE) is an early myeloid-specific serine protease, which is predominantly produced by promyelocytes. A previous study demonstrated that NE has an important role in the development of acute promyelocytic leukemia (APL). The process of APL was shown to be accelerated in animals that expressed abundant NE, whereas NE‑deficient mice were protected from APL development; thus suggesting an important role for NE in the development of APL. The present study aimed to investigate the effects and possible mechanisms of NE. Up- and downregulation of NE in various leukemia cell lines was conducted in order to explore its significance in the occurrence and procession of leukemia, with the aim of identifying novel targeted therapeutic drugs for the treatment of leukemia. NE was overexpressed in cells following infection with an adenovirus, and Cell Counting kit‑8 and flow cytometry results demonstrated that cell proliferation was promoted, and cell apoptosis was inhibited, as compared with the untreated cells. NE was downregulated in the cells by both RNA interference and treatment with GW311616A, a specific inhibitor of NE, following which cell growth was shown to be inhibited and apoptosis was induced. These results suggested that NE may promote the development of APL, therefore, NE may be a therapeutic target and its inhibitor GW311616A may be a potential therapeutic drug for leukemia. Furthermore, the apoptosis‑associated protein B‑cell lymphoma 2 (Bcl‑2)‑associated X protein was significantly increased, whereas Bcl‑2 was markedly decreased in the cells with downregulated NE. Further experiments revealed that the probable apoptosis‑associated signaling pathway was the phosphoinositide 3‑kinase/AKT pathway. The present study is the first, to the best of our knowledge, to demonstrate that GW311616A, a specific NE inhibitor, may act as a potential targeted drug for leukemia, which may have a profound impact on the future of leukemia-targeted therapy.

This study aimed to explore the effect of MED27 on the expression of epithelial-mesenchymal transition (EMT)-related proteins and β-catenin in adrenal cortical carcinoma (ACC). The functional mechanism of MED27 on ACC processes was also explored. The expression of MED27 was assessed by quantitative real-time polymerase chain reaction (qRT-PCR). siRNA was utilized to knockdown the expression of MED27. CCK8 assays were performed to evaluate SW-13 cell proliferation. Transwell assays were performed to assess the invasion ability, and wound healing assays were utilized to detect migration. A tumor xenograft mouse model was established to investigate the impact of silencing MED27 on tumor growth and metastasis. MED27 was highly expressed in ACC tissues and cells. Down-regulation of MED27 induced ACC cell apoptosis, and significantly attenuated ACC cell proliferation, invasion and metastasis in vivo and in vitro. MED27 knockdown regulated the expression of EMT-related proteins and Wnt/β-catenin signaling pathway-related proteins. Our study investigated the function and mechanism of MED27 and validated that MED27 plays a negative role in ACC occurrence and progression and could be utilized as a new therapeutic target in ACC prevention and treatment.

Aberrant DNA methylation has been implicated in prostate carcinogenesis. The one-carbon metabolism pathway and related metabolites determine cellular DNA methylation and thus is thought to play a pivotal role in PCa occurrence. This study aimed to investigate the contribution of genetic variants in one-carbon metabolism genes to prostate cancer (PCa) risk and the underlying biological mechanisms. In this hospital-based case-control study of 1817 PCa cases and 2026 cancer-free controls, we genotyped six polymorphisms in three one-carbon metabolism genes and assessed their association with the risk of PCa. We found two noncoding MTR variants, rs28372871 T > G and rs1131450 G > A, were independently associated with a significantly increased risk of PCa. The rs28372871 GG genotype (adjusted OR = 1.40, P = 0.004) and rs1131450 AA genotype (adjusted OR = 1.64, P = 0.007) exhibited 1.40-fold and 1.64-fold higher risk of PCa, respectively, compared with their respective homozygous wild-type genotypes. Further functional analyses revealed these two variants contribute to reducing MTR expression, elevating homocysteine and SAH levels, reducing methionine and SAM levels, increasing SAH/SAM ratio, and promoting the invasion of PCa cells in vitro. Collectively, our data suggest regulatory variants of the MTR gene significantly increase the PCa risk via decreasing methylation potential. These findings provide a novel molecular mechanism for the prostate carcinogenesis.

Acute promyelocytic leukemia (APL) is characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid receptor-α (RAR-α) fusion protein. PML-RARα can be cleaved by neutrophil elastase (NE) in several positions in cells in the promyelocytic stage, nuclear location signal (NLS)-negative PML and NLS-RARα may be the products of PML-RARα by NE. The function of NLS-RARα may be affected by the addition of NLS, which would alter its localization in cells, as the role of NLS is to identify proteins for transport to the nucleus. Preliminary experiments demonstrated that the overexpression of NLS-RARα in HL-60 cells could promote cellular proliferation and inhibit cellular differentiation. Following treatment with all-trans retinoic acid (ATRA), the degree of cellular differentiation was enhanced. In the present study, the localization of NLS-RARα was identified and its activity as a novel transcriptional factor was assessed, which may be critical in the development of APL. The location of NLS-RARα was detected in the nucleus and cytoplasm by indirect immunofluorescence and western blot analysis, with expression in the nucleus revealed to be increased compared with that in the cytoplasm. Next, native-PAGE was performed and NLS-RARα and RXRα were revealed to form heterodimers in the nucleus. In addition, co-immunoprecipitation revealed an interaction between NLS-RARα and retinoid X receptor-α (RXRα). An electrophoresis mobility shift assay (EMSA) indicated that NLS-RARα could bind retinoic acid response elements (RAREs) in the presence of ATRA. Indeed, NLS-RARα could bind RAREs just as WTRARα could, including the RAREs direct repeat-2 (DR-2) and DR-5. In addition, results from a luciferase reporter gene assay demonstrated that NLS-RARα could mediate the activity of RAREs that it bound. Together, these results indicated that NLS-RARα may be a novel transcription factor that contributes to leukemogenesis by competitively binding RAREs as heterodimers with RXRα, just as PML-RARα does, thus repressing the gene transcription essential for myeloid differentiation. These findings indicate the potential role of NLS-RARα targeted therapy in APL.

Accumulating evidence demonstrates that lncRNAs play important roles in regulating gene expression and are involved in various pathological processes. In the present study, we screened the lncRNAs profile in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) database, and got linc00152, a differentially expressed lncRNA that haven’t been reported in ccRCC. To further explore its role in ccRCC, the level of Linc00152 was detected in 77 paired ccRCC tissues and renal cancer cell lines by qRT-PCR, and its association with overall survival was assessed by statistical analysis. Linc00152 expression was significantly up-regulated in cancerous tissues and cell lines compared with normal counterparts, and high Linc00152 expression was closely associated with advanced TNM stage. Moreover, Linc00152 was found to be able to serve as an independent predictor of overall survival. Further experiments demonstrated that overexpression of Linc00152 can significantly promote cell proliferation and invasion, inhibit cell cycle arrest in G1 phase and dramatically decrease apoptosis in both 786O and Caki-2 cell lines, whereas the opposite results were observed with attenuated Linc00152 expression. Our data suggest that Linc00152 is a novel molecule involved in ccRCC progression as well as a potential prognostic biomarker and therapeutic target.

Urothelial carcinoma (UC) comprises a heterogeneous group of epithelial neoplasms with diverse biological behaviors and variable clinical outcomes. Distinguishing UC histological subtypes has become increasingly important because prognoses and therapy can dramatically differ among subtypes. In clinical work, overlapping morphological findings between low-grade noninvasive UC (LGNUC), which exhibits an inverted growth pattern, and inverted urothelial papilloma (IUP) can make subclassification difficult. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping these clinical entities. In our study, tissue microarray immunohistochemical profiles of Ki-67, p53, cytokeratin 20 (CK20) and cyclinD1 were assessed. Molecular genetic alterations such as the gain of chromosomes 3, 7 or 17 or the homozygous loss of 9p21 were also assessed for their usefulness in differentiating these conditions. Based on our analysis, Ki-67 and CK20 may be useful for the differential diagnosis of these two tumor types. Fluorescence in situ hybridization (FISH) can also provide important data in cases in which the malignant nature of an inverted urothelial neoplasm is unclear. LGNUC with an inverted growth pattern that is negative for both Ki-67 and CK20 can be positively detected using FISH.

There has been a rapid increase in the incidence of prostate cancer in China, especially in areas with boosted economic development. In this study, we analyzed the pathological features of a contemporary series of radical prostatectomy cases. A total of 230 consecutive, whole-mounted radical prostatectomy specimens collected from 2012 to 2014 were reviewed. The median age of the patients was 68 years, and 64.3% of patients presented with prostate specific antigen alone. Pathological examination indicated that a high proportion (77.4%) of patients had intermediate- or high-risk disease according to the Cancer of the Prostate Risk Assessment Post-Surgical score. After surgery, only 28 patients met the criteria for active surveillance (organ-confined Gleason ≥6 disease). The Prostate Cancer Research International Active Surveillance criteria achieved a sensitivity of 57.1% and a specificity of 98.0% for identifying candidates. The probability of Gleason score upgrading was 24.8% in the entire group and 59.0% in biopsy-confirmed Gleason ≥6 disease. The predominant tumor was located in the transition zone in 14.8% of cases, while only three patients (1.3%) had a predominant tumor located in the anterior region. Patients with transition zone-predominant tumor were likely to have been referred with urinary symptoms and high prostate specific antigen levels. The results of this study highlight the contemporary pathological features of localized prostate cancer in urban China. There was an increased trend towards asymptomatic cases, though most patients had intermediate- or high-risk disease and were suitable for definitive treatment. The low prevalence of dominant cancer in the anterior region may reflect race-based pathological differences.

Hepatic stem cells (HSCs) are involved in repair of liver injury. Stem cells may have inhibitory effects on tumor cell growth and apoptosis. However, it is unknown whether HSCs regulate the biological functions of hepatocarcinoma cells, especially tumor cell growth and apoptosis. The present study was designed to determine the effects of hepatocytic precursor (stem-like) WB-F344 cells on the growth and apoptosis of hepatoma CBRH-7919 cells. Using a Transwell chamber culture system, we co-cultured WB-F344 cells and CBRH-7919 cells in serum-free conditioned medium at 3 different ratios: 1:1 (2 x 10(5): 2 x 10(5) cells/well), 1:5 (4 x 10(4): 2 x 10(5) cells/well), and 5:1 (2 x 10(5): 4 x 10(4) cells/well). We determined the effects of stem cells on tumor cells using in vivo xenograft assay in nude mice and determining gene expression by RT-PCR and Western blot analyses. With the increment proportion of the WB-F344 cells in the co-culture system, tumor formation was inhibited in nude mice. Moreover, down-regulation of bone morphogenetic protein 4 (BMP4), Bcl-2, and c-Myc and upregulation of PTEN also occurred along with the inhibitory effects. Western blotting showed that the TGF-beta/Smad pathway played a prominent role in tumor inhibition, which may have been mediated by the cytokines released from the stem cells. In conclusion, hepatocytic precursor (stem-like) WB-F344 cells inhibit the tumorigenicity of hepatoma CBRH-7919 cells, and the effect is mediated by TGF-beta/Smad signaling pathway.

Effects of the enzymes in Actinomucor elegans extract and the enzyme Alcalase 2.4L on debittering the soybean protein hydrolysates were investigated. When the protein was treated only with the latter, a strong bitterness formed; but it decreased if the protein was treated with both the enzymes. The more the enzymes were used, weaker was the bitterness tasted. SDS-PAGE profile and ESI-MS spectrum of the hydrolysates evidenced that the Alcalase could convert the protein into peptides rapidly, while the enzymes in the A. elegans extract were able to further degrade some peptides which were difficult or unable to be hydrolyzed by the Alcalase. Further systematic analysis of the peptidases showed that the Alcalase exhibited a significant endopeptidase activity towards NBZ-Phe-pNA substrate (p