Two cerebral infarctions caused by thrombus and myxomatous embolus in a patient with cardiac myxoma: A case report.

An increasing number of cases of cerebral embolism caused by cardiac myxoma have been reported. However, cerebral infarction caused by different types of emboli obstructing different vascular regions within a short period of time has not been reported. This is the first report to histologically confirm cerebral infarctions independently caused by thrombus and myxomatous embolus in a patient with cardiac myxoma within a period of 23 days. The first cerebral infarction was due to embolization of thrombus to the right middle cerebral artery, whereas the second was due to embolization of tissue from a mucinous tumor to the left middle cerebral artery. Both cerebral infarctions underwent mechanical thrombectomy, but unfortunately, we ultimately failed to save the patient's life. Therefore, further attention should be paid to the surgical resection and treatment of cardiac myxoma.

A Novel circRNA hsa_circRNA_002178 as a Diagnostic Marker in Hepatocellular Carcinoma Enhances Cell Proliferation, Invasion, and Tumor Growth by Stabilizing SRSF1 Expression.

Background: Previous research studies have shown that the elevation of circular RNA (circRNA), hsa_circRNA_002178, was associated with the poor prognosis of breast cancer and colorectal cancer, while its molecular mechanisms underlying the effects on hepatocellular carcinoma (HCC) are still elusive. Methods: The microarray dataset GSE97332 was obtained from the Gene Expression Omnibus (GEO) database and calculated by using the GEO2R tool to identify differentially expressed circRNAs. Differentially expressed hsa_circRNA_002178, in 7 HCC tissue samples and paracancerous tissues, as well as in HCC cell lines and normal hepatocytes, was checked by RT-qPCR. Cell proliferation, invasion, migration, and epithelial-to-mesenchymal transition (EMT)-related proteins were tested in hsa_circRNA_002178-overexpressed or hsa_circRNA_002178-knocked down HCC cells. Subsequently, we identified whether hsa_circRNA_002178 binds to serine- and arginine-rich splicing factor 1 (SRSF1) and then analyzed their function in regulating HCC cell behavior. The effect on HCC cell xenograft tumor growth was observed by the knockdown of hsa_circRNA_002178 in vivo. Results: GEO2R-based analysis displayed that hsa_circRNA_002178 was upregulated in HCC tissues. Overexpression or knockdown of hsa_circRNA_002178 encouraged or impeded HCC cell proliferation, migration, invasion, and EMT program. Mechanically, hsa_circRNA_002178 bound to SRSF1 3'-untranslated region (UTR) and stabilized its expression. SRSF1 weakening eliminated the effects of pcDNA-hsa_circRNA_002178 on cell malignant behavior. Finally, the knockdown of hsa_circRNA_002178 was confirmed to prevent xenograft tumor growth. Conclusions: hsa_circRNA_002178 overexpression encouraged the stability of SRSF1 mRNA expression, and it may serve as an upstream factor of SRSF1 for the diagnosis of HCC.

Circ_0067934 reduces JNK phosphorylation through a microRNA-545-3p/PPA1 axis to enhance tumorigenesis and cisplatin resistance in ovarian cancer.

BACKGROUND: Circular RNA 0067934 (circ_0067934) has been revealed as a cancer driver in multiple human malignancies, whereas its action in the pathogenesis of ovarian cancer (OC) remains unclear. This study focuses on the function of circ_0067934 in tumorigenesis and cisplatin (DDP) resistance in OC and the molecular mechanism. METHODS: Expression of circ_0067934 in OC tissues and cells was examined, and its correlation with the clinical characteristics of patients was analyzed. Candidate targets of circ_0067934 were predicted using bioinformatics systems. Binding relationships between circ_0067934 and microRNA (miR)-545-3p and between miR-545-3p and inorganic pyrophosphatase 1 (PPA1) were validated via luciferase assays. Gain- and loss-of functions of circ_0067934, miR-545-3p and PPA1 were performed to determine their functions in proliferation, invasion, apoptosis and DDP resistance of OC cells in vitro and in vivo. RESULTS: Circ_0067934 was overexpressed in OC samples and associated with advanced tumor staging and lymph node metastasis. Downregulation of circ_0067934 reduced DDP resistance of the DDP-resistant A2780/DDP cell line and reduced cell proliferation and invasion, but the malignant behaviors of OC cells were restored after further miR-545-3p downregulation. Circ_0067934 served as a sponge for miR-545-3p and diminished its suppressive effect on PPA1 translation. Artificial upregulation of PPA1 enhanced proliferation, invasion and DDP resistance of A2780/DDP cells, and it reduced phosphorylation of the pro-apoptotic JNK signaling. Similar results were found in vivo. CONCLUSION: This study suggests that circ_0067934 sequesters miR-545-3p and enhances PPA1 expression to promote tumorigenesis and DDP resistance in OC. This study may provide novel approaches in the management of OC.

LINC01420 Serves as a Novel Prognostic Biomarker and Promotes Cell Proliferation, Migration, and Invasion by Suppressing miR-149-5p in Gastric Cancer.

Gastric cancer (GCa) is the most common human health-threatening malignancy, and its high incidence and poor prognosis. Previous studies have shown that long non-coding RNAs (lncRNAs) are aberrantly expressed in a variety of tumors and are involved in tumor progression. This study aimed to investigate the regulatory role of LINC01420 in GCa cell proliferation migration and invasion, and search for new prognostic biomarkers for GCa. The expression levels of LINC01420 and miR-149-5p in GCa cells were analyzed with reverse transcription-quantitative PCR. Kaplan Meier survival analysis and Cox regression were used to analyze the prognostic value. Luciferase reporter assay was used to detect the interaction between LINC01420 and miR-149-5p. The effects of LINC01420/miR-149-5p axis on GCa cell proliferation, migration and invasion were assessed by CCK-8 and Transwell assays. LINC01420 expression levels were significantly increased in tissues and cell lines of GCa. Kaplan Meier curve results showed that overexpression of LINC01420 predicted poor prognosis. Silencing LINC01420 could inhibit the proliferation migration and invasion of GCa cells. The luciferase reporter assay results indicated that miR-149-5p might be a target of LINC01420 and mediate the effects of LINC01420 on GCa cell proliferation and migration and invasion. In conclusion, this study demonstrates an important regulatory role of the LINC01420/miR-149-5p axis in GCa progression and it provides a novel and significant biomarker for GCa treatment and prognosis.

Up-regulation of miR-204 inhibits proliferation, invasion and apoptosis of gallbladder cancer cells by targeting Notch2.

Gallbladder carcinoma (GC) is an extremely malignant gastrointestinal tumor, but relevant mechanisms are still under investigation. MicroRNA (miR) is differentially expressed in a variety of tumors. Here we explored miR-204 in patients with GC and related mechanisms. A GSE104165 chip was downloaded from the gene expression omnibus (GEO) for analysis. The qRT-PCR assay was used for quantifying miR-204 and Notch2 in the serum and tissues of the patients, and the patients were followed up for 3 years to analyze independent factors of prognosis. The CCK8, transwell, and flow cytometry assays were applied for analyzing proliferation, invasion, as well as apoptosis of cells, and the dual luciferase reporter (DLR) assay was adopted for determining the association of miR-204 with Notch2. MiR-204 was low in patients with GC, and it might serve as a diagnostic indicator for GC. In addition, patients with low e MiR-204 usually faced high rates of III+IV stage, distant metastasis, and low differentiation, and also showed a poor prognosis. DLR assay verified the targeted binding of miR-204 to Notch2 mRNA.

MicroRNA-221 promotes breast cancer resistance to adriamycin via modulation of PTEN/Akt/mTOR signaling.

As a prevalent tumor among women, breast cancer is still an incurable disease due to drug resistance. In this study, we report microRNA-221 to have a significant effect on breast cancer resistance to adriamycin. The microRNA-221 is elevated in tumor tissue compared with nearby nontumor samples, as well as in breast cancer cell line with adriamycin resistance (MCF-7/ADR) compared to its parental line (MCF-7) and the normal breast epithelial cell line (MCF-10A). Enforced level of microRNA-221 promotes cancer resistance to adriamycin, which in turn sustains cell survival and exacerbates malignant formation. Reciprocally, the silence of microRNA-221 in cancer cells augments the sensitivity to chemotherapy, thereby resulting in enhanced apoptosis of MCF-7/ADR cells. Mechanistically, we identify PTEN as a direct target of microRNA-221, which was conversely associated with a microRNA-221 level in breast tumors. The knock-down of PTEN partially reversed the stimulatory role of microRNA-221 in the modulation of the Akt/mTOR signaling. Taken together, these findings suggest microRNA-221 suppresses PTEN transcription and activates Akt/mTOR pathway, which in turn enhances breast cancer resistance to adriamycin and promotes cancer development. Our data thus illuminate the microRNA-221/PTEN axis may act as a promising strategy for the treatment of chemotherapy-resistant breast tumors.

Aneurysms Arising From the Fenestrated Middle Cerebral Artery.

Intracranial artery fenestration is segmental duplication of the lumen into 2 distinct channels and is known to have a low angiographical incidence of 0.3 to 0.9%. Intracranial artery fenestration is frequently associated with aneurysms, and aneurysms arising at the site of fenestrated middle cerebral artery (MCA) is extremely rare. To our best knowledge, there are only 10 such patients have been reported. Herein, the authors describe the 11th case of aneurysm arising from the fenestrated MCA. As the characteristics of fenestrated MCA aneurysms has not been well determined until now, these interesting patients are investigated and summarized.

Oxytocin involves in chronic stress-evoked melanoma metastasis via ß-arrestin 2-mediated ERK signaling pathway.

Stress is associated with an increased risk of lung metastasis in melanoma. However, the underlying mechanism is elusive. Oxytocin (OXT), a neurohormone produced by the hypothalamus, plays a vital role in laboring induction and lactation. Emerging evidence suggests that OXT also regulates human emotions, social cognition, social behaviors and stress-related disorders. Here, we reported that a significant up-regulation of oxytocin receptors (OXTRs) was observed in malignant melanoma. The activation of OXTRs dramatically promoted migration, invasion and angiogenesis but not the proliferation of melanoma cells in vitro and in vivo via ß-arrestin 2-dependent ERK-VEGF/MMP-2 pathway. Next, chronic restraint stress significantly elevated the plasma level of OXT. Notably, 21 days chronic restraint stress facilitated lung metastasis of melanoma and reduced overall survival in mice, which were largely abrogated by knocking down either OXTR or ß-arrestin 2. These findings provide evidence that chronic stress hormone-OXT promotes lung metastasis of melanoma via a ß-arrestin 2-dependent mechanism and suggest that OXT, a novel pro-metastasis factor, is a potential therapeutic target for melanoma.

TIPE1 promotes cervical cancer progression by repression of p53 acetylation and is associated with poor cervical cancer outcome.

Previous studies have shown that TIPE1 inhibits tumor proliferation and metastasis in certain cancers; however, increased expression of TIPE1 is observed in cervical cancer cell lines and tissues, indicating it might exert a distinctive role in cervical cancer. Cell and xenograft tumorigenicity assays showed that TIPE1 facilitates cervical cancer progression in this study. Further investigation demonstrated that TIPE1 binds to p53 and impairs its activity via inhibition of its acetylation. In addition, TIPE1 promoted cell proliferation and suppressed cisplatin susceptibility in a p53-dependent manner, indicating that TIPE1 facilitates cervical cancer progression primarily through the p53 pathway. TIPE1 expression in clinical samples also demonstrated that its upregulation predicts poor prognosis in patients with cervical cancer. Taken together, the results of this study showed that TIPE1 serves as an oncogene by restricting p53 activity in the development of cervical cancer, suggesting that TIPE1 will provide a new potential target for cervical cancer therapy and can be used as a biomarker to predict patient prognosis.

TIPE2 sensitizes osteosarcoma cells to cis-platin by down-regulating MDR1 via the TAK1- NF-κB and - AP-1 pathways.

TIPE2 participates in multiple types of cancer development. However, its mechanism underlying chemoresistance in osteosarcoma has not been elucidated. Herein, we observed the expression of TIPE2 and MDR1 in cis-platin-resistant osteosarcoma tissues and cell lines. Compared to their matched sensitive cell lines and tissues, TIPE2 was downregulated while MDR1 expression was increased. Further investigation showed that overexpression of TIPE2 effectively inhibited MDR1 expression and greatly sensitized osteosarcoma cells to cis-platin, both in vivo and in vitro. Mechanistically, TIPE2 inhibited the transcription of the MDR1 promoter by interfering with the TAK1-NF-κB and -AP-1 pathways. Overall, our results elucidated for the first time that TIPE2 sensitizes osteosarcoma cells to cis-platin through downregulation of MDR1 and may be a novel target in osteosarcoma therapy.

Oxytocin inhibits ovarian cancer metastasis by repressing the expression of MMP-2 and VEGF.

Breastfeeding is associated with a decreased risk of ovarian cancer. However, the mechanism underlying this apparent clinical benefit is unknown. Oxytocin (OXT), a hypothalamic nonapetide, plays a crucial role in many reproductive and behavioural functions. In recent year, OXT acts as a growth regulator in many kind of tumor tissues, through the activation of a specific G-coupled transmembrane receptor, the oxytocin receptor (OXTR). OXT has been proved to inhibit the proliferation, migration and invasion of ovarian cancer SKOV3 cells in vitro. But, the underlying mechanisms remain unknown. Here, we found OXT inhibited proliferation, and critically migration and invasion of human ovarian cancer cells SKOV3 and A2780. Strikingly, OXT inhibited ovarian cancer metastasis by repressing the expressions of MMP-2 and VEGF. Moreover, OXT inhibited vascular endothelial cell tube formation by reducing the VEGF production from ovarian cancer cells. Our findings may provide a possible explanation for breastfeeding-associated protective effects and suggest new therapeutic opportunities for ovarian cancer.

Profiling of alternative polyadenylation sites in luminal B breast cancer using the SAPAS method.

Breast cancer (BC) is a leading cause of cancer-related mortality in females and is recognized as a molecularly heterogeneous disease. Previous studies have suggested that alternative messenger RNA (mRNA) processing, particularly alternative polyadenylation [poly(A)] (APA), can be a powerful molecular biomarker with prognostic potential. Therefore, in the present study, we profiled APA sites in the luminal B subtype of BC by sequencing APA sites (SAPAS) method, in order to assess the relation of these APA site-switching events to the recognized molecular subtypes of BC, and to discover novel candidate genes and pathways in BC. Through comprehensive analysis, the trend of APA site-switching events in the 3' untranslated regions (3'UTRs) in the luminal B subtype of BC were found to be the same as that in MCF7 cell lines. Among the genes involved in the events, a significantly greater number of genes was found with shortened 3'UTRs in the samples, which were samples of primary cancer with relatively low proliferation. These findings may provide novel information for the clinical diagnosis and prognosis on a molecular level. Several potential biomarkers with significantly differential tandem 3'UTRs and expression were found and validated. The related biological progresses and pathways involved were partly confirmed by other studies. In conclusion, this study provides new insight into the diagnosis and prognosis of BC from the APA site profile aspect.

Determination of alkaloids in Sinomenium acutum by field-amplified sample stacking in capillary electrophoresis with chemiluminescene detection.

A simple and rapid capillary electrophoresis (CE) with an acidic potassium permanganate chemiluminescence (CL) detection method was developed to determine three alkaloids (curine, sinomenine and magnoflorine) simultaneously. A laboratory-built CE-CL detection interface was used. The field-amplified sample stacking technique was applied to the online concentration of alkaloids. Experimental conditions for CE separation and CL detection were investigated in detail to acquire optimum conditions. Under optimal conditions, the three alkaloids were baseline separated within 6 min, and the detection limits (S/N = 3) ranged from 0.03 µg/mL to 0.49 µg/mL. This method was successfully applied to determine the above three alkaloids in Sinomenium acutum, and the result of the determination of sinomenine was in good agreement with those given by high-performance liquid chromatography and CE methods. In addition, a possible CL reaction mechanism of sinomenine-KMnO4-H2SO4 was proposed.

Correlation between chemosensitivity to anticancer drugs and telomerase reverse transcriptase mRNA expression in gastric cancer.

BACKGROUND: The determination of sensitive chemotherapy drugs for gastric cancer (GC) is one of the greatest challenges of adjuvant therapy. Here we evaluated the chemosensitivity of GC to anticancer drugs and the telomerase reverse transcriptase (hTERT) mRNA expression, and investigated the relationship of them. METHODS: The GC cells which were collected from 68 patients with primary GC were primary cultured. The chemosensitivity of GC cells to anticancer drugs was evaluated successfully using the MTT assay for 60 cases of GC cells, and the hTERT mRNA expression was examined in 60 cases of GC tissues and corresponding normal gastric mucosa and 6 cases of chronic superficial gastritis mucosa by in situ hybridization. RESULTS: Taxol, cisplatin and 5-fluorouracil were in general more effective than adriamycin and mitomycin for GC cells, and the chemosensitivity to anticancer drugs was associated with tumor histological types and a worse tumor grade. Compared to normal gastric mucosa tissues, hTERT mRNA expression was significantly increased in GC (P<0.05), which was related with a worse differentiation and drug-resistance to 5-fluorouracil or adriamycin in GC. CONCLUSIONS: These data demonstrate for the first time that examinations of hTERT mRNA expression as an important factor could be used to select the chemotherapeutic drugs for GC patients. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1793217009875483.

[Anti-tumor effect of chemotherapeutic drugs on human gastric cancer cells in vitro and the relationship with Bcl-2 expression].

OBJECTIVE: To evaluate in vitro anti-tumor effect of chemotherapeutic drugs on human gastric cancer cells, and investigate the relationship with Bcl-2 expression. METHODS: Single cell suspension was prepared from fresh gastric cancer tissue and exposed to taxol (Tax), 5-fluorouracil (5-FU), cisplatin (CDDP), adriamycin (ADM), mitomycin (MMC) respectively for 48 hours. Metabolic activity and inhibitory rate of cells were detected by MTT assay. Expression of Bcl-2 was examined with immunohistochemistry. RESULTS: The inhibitory rates of cancer cells exposed to chemotherapeutic drugs were different and Tax, 5-FU, CDDP had remarkably higher rates than ADM and MMC. The lower differentiated gastric cancer cells were more sensitive than the higher ones. Positive expression rate of Bcl-2 was 80% and the positive cells showed resistance to 5-FU, ADM and MMC. CONCLUSIONS: Chemosensitive testing by MTT assay can constitute the prediction for the application of chemotherapeutic drugs individually. Overexpression of Bcl-2 may contribute to multiple drug-resistance of tumors.

[Anti-tumor effects of chemotherapeutic drugs on human gastric cancer cells in vitro and the relationship with expression of hTERT mRNA].

OBJECTIVE: To evaluate in vitro antitumor effects of chemotherapeutic drugs, and investgate the relationship with expression of hTERT mRNA in human gastric cancer tissues. METHODS: Fresh samples of gastric cancer obtained from operation room were prepared to single-cell suspension (3 x 10(5) to 5 x 10(5) cells ml(-1)) and were separately exposed to taxol (TAX), cisplatin (CDDP), 5-fluorouracil (5-Fu), adriamycin (ADM), mitomycin (MMC) for 48 hours. Metabolic activity and inhibitory rate of the cells were determined by trypan blue exclusion and MTT assay. Expression of hTERT mRNA was detected by in situ hybridization (ISH). RESULTS: The inhibition rate of cancer cells exposed to chemotherapeutic drugs was different, and that of TAX, CDDP, 5-Fu was significantly higher than that of ADM and MMC. The positive rate of hTERT mRNA expression was 90.0% (54/60) and positive cells showed resistance to 5-Fu and ADM. CONCLUSION: Overexpression of hTERT mRNA may contribute to primary drug-resistance of tumors. Chemosensitivity tests by MTT assay may contribute to prediction of effectness in applying chemotherapeutic drugs and identify drug-resistant cases.