The clinicopathological significance of miR-149 and PARP-2 in hepatocellular carcinoma and their roles in chemo/radiotherapy.

Hepatocellular carcinomas (HCC) are commonly diagnosed at an advanced stage with unresectable tumors. Although numerous non-surgical approaches have been developed to treat HCC, the prognosis of patients with HCC is still poor. This study investigated the expression of miR-149 and PARP-2 in HCC tumor tissues and their roles in sensitizing chemo/radiotherapy. The expression of miR-149 was measured by real-time PCR, and PARP-2 protein was measured by immunohistochemistry and Western blot. The xenograft HCC mouse model was established by inoculating Hep G2 cells. Increased PARP-1 and decreased miR-149 expression was observed in HCC tissues compared to peritumoral tissues. Positive PARP-2 and low miR-149 expression correlated with larger tumor mass size (P < 0.001), capsular and vascular invasion (P < 0.001), lymph node metastasis (P = 0.02), high histological grade (P < 0.001), TNM (P < 0.001), and BCLC grade (P = 0.001). The Kaplan-Meier survival analysis showed a negative correlation between high PARP-2 expression or low miR-149 expression in HCC tissues with the survival of patients. High PARP-2 and low miR-149 correlated with a low 5-year survival rate and are poor prognosis factors. Overexpression of miR-149 or inhibition of PARP-2 expression could inhibit tumor growth but was more effective in sensitizing chemotherapy and radiotherapy in xenograft HCC animal models. Increased PARP-2 expression and loss of miR-149 expression are involved in the pathogenesis of HCC and are poor prognosis factors in patients with HCC. Although both miR-149 overexpression and PARP-2 inhibitor exert some antitumoral effect, PARP-2 inhibitor is a chemo/radio sensor and can be used to enhance chemotherapy and radiotherapy in patients with HCC.

Auditory evoked potentials in patients with major depressive disorder measured by Emotiv system.

In a previous study (unpublished), Emotiv headset was validated for capturing event-related potentials (ERPs) from normal subjects. In the present follow-up study, the signal quality of Emotiv headset was tested by the accuracy rate of discriminating Major Depressive Disorder (MDD) patients from the normal subjects. ERPs of 22 MDD patients and 15 normal subjects were induced by an auditory oddball task and the amplitude of N1, N2 and P3 of ERP components were specifically analyzed. The features of ERPs were statistically investigated. It is found that Emotiv headset is capable of discriminating the abnormal N1, N2 and P3 components in MDD patients. Relief-F algorithm was applied to all features for feature selection. The selected features were then input to a linear discriminant analysis (LDA) classifier with leave-one-out cross-validation to characterize the ERP features of MDD. 127 possible combinations out of the selected 7 ERP features were classified using LDA. The best classification accuracy was achieved to be 89.66%. These results suggest that MDD patients are identifiable from normal subjects by ERPs measured by Emotiv headset.

Antibacterial activity of silver nanoparticles target sara through srna-teg49, a key mediator of hfq, in staphylococcus aureus.

UNLABELLED: Attributed to its antimicrobial effect, Silver nanoparticles (AgNPs) is widely used in various fields, such as biomedicine, textiles, health care products and food, etc. However, the antibacterial mechanism of AgNPs in staphylococcus aureus (S. aureus) by regulating sRNA expression remains largely unknown. OBJECTIVES: This study was performed to investigate the involvement of the antibacterial mechanism of AgNPs through sRNA-TEG49, a key mediator of Hfq, in S. aureus. METHODS: Through the antimicrobial tests of AgNPs, its antibacterial laps and minimum inhibitory concentration was measured. A hierarchical cluster analysis of the differentially expressed sRNA in S. aureus was performed to investigate the relationship between AgNPs and sRNA. Expression of genes was analyzed by real-time PCR. RESULTS: In the present study we found that at the concentrations higher than 1 mg/L, AgNPs could completely restrain bacteria growth, and the antibacterial activity of AgNPs apparently declined at the concentrations lower than 1 mg/L. S. aureus exposure to AgNPs, the expression of sRNA-TEG49, Hfq and sarA was significantly up-regulated in wild-type S. aureus. Moreover, Hfq loss-of-function inhibited the expression of sRNA-TEG49 in mutant-type S. aureus. Furthermore, sRNA-TEG49 loss-of-function associated with down-regulation the expression of sarA in mutant-type S. aureus. CONCLUSIONS: It was reasonable that Hfq regulated a distinct underlying molecular and antibacterial mechanism of AgNPs by forming a positive feedback loop with sRNA-TEG49. These observations suggested that Hfq plays an important role in the antibacterial mechanism of AgNPs by regulating sRNA-TEG49 expression, via its target sarA.

Evaluation of the Antitumor Efficacy of RNAi-Mediated Inhibition of CDC20 and Heparanase in an Orthotopic Liver Tumor Model.

Over 90% of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage. This study investigated the antitumor efficacy of the inhibition of cell division cycle protein 20 (CDC20) and heparanase (HPSE) expression in Hepa1-6 mouse hepatoma cells. Cell viability was measured by the MTT assay. Cell cycle was analyzed by cytometry. The invasion assay was performed using the Transwell chamber. The orthotopic liver tumor model was established by inoculating the livers of immunocompetent Kunming mice with Hepa1-6 cells. The MTT assay showed that 50 and 100 nM CDC20 siRNA-1 and HPSE siRNA-2 significantly reduced Hepa1-6 cell viability with the combination of CDC20 and HPSE siRNA being the most effective. Silencing of CDC20 or both CDC20 and HPSE expression significantly induced G2/M phase cell cycle arrest in Hepa1-6 HCC cells. Silencing HPSE expression significantly inhibited the invasion ability of Hepa1-6 cells with the combination of CDC20 and HPSE silencing being more effective than HPSE alone. Silencing CDC20 and HPSE expression significantly inhibited HCC tumor growth in the orthotopic liver tumor model, but the combination was most effective. Silencing CDC20 and HPSE expression activated cell apoptosis and autophagy. In conclusion, targeting inhibition of both CDC20 and HPSE expression is an ideal strategy for HCC therapy.

Enhanced antiproliferative and apoptosis effect of paclitaxel-loaded polymeric micelles against non-small cell lung cancers.

Amphiphilic copolymer monomethoxy poly(ethylene glycol)-poly(caprolactone)-D-α-tocopheryl polyethylene glycol 1000 succinate (MPEG-PCL-TPGS) was prepared. In the present study, MPEG-PCL-TPGS was used as a novel nanovehicle for the delivery of paclitaxel (PTX) in the treatment of resistant lung cancers. The PTX-loaded MPEG-PCL-TPGS (PTX/MPT) micelles exhibited sustained release profile (168 h) with accelerated drug release at acidic pH conditions. The blank polymeric micelles showed excellent biocompatibility with cell viability of >85 %, making it suitable for all in vivo applications. PTX/MPT micelles displayed superior cytotoxicity in A-549 lung cancer cells than that of free PTX. The selective delivery of PTX to cancer cells resulted in enhanced cancer cell death. The PTX/MPT micelles showed higher cellular uptake via endocytosis pathways. The PTX-bound micelles preferentially arrested the cells at G2/M phase and showed a marked increase in sub G1 cell population (∼ 20 %). The pharmacokinetic study revealed a long blood circulation for PTX/MPT micelles. Finally, micellar formulation showed a remarkable tumor suppression effect in resistant A549/Taxol cells bearing xenograft nude mice along with no toxicity profile. The results indicate that the PTX-loaded biocompatible polymeric nanosystem could act as a potential delivery system for the treatment of lung carcinomas.

Tissue Engineering Applications of Three-Dimensional Bioprinting.

Recent advances in tissue engineering have adapted the additive manufacturing technology, also known as three-dimensional printing, which is used in several industrial applications, for the fabrication of bioscaffolds and viable tissue and/or organs to overcome the limitations of other in vitro conventional methods. 3D bioprinting technology has gained enormous attention as it enabled 3D printing of a multitude of biocompatible materials, different types of cells and other supporting growth factors into complex functional living tissues in a 3D format. A major advantage of this technology is its ability for simultaneously 3D printing various cell types in defined spatial locations, which makes this technology applicable to regenerative medicine to meet the need for suitable for transplantation suitable organs and tissues. 3D bioprinting is yet to successfully overcome the many challenges related to building 3D structures that closely resemble native organs and tissues, which are complex structures with defined microarchitecture and a variety of cell types in a confined area. An integrated approach with a combination of technologies from the fields of engineering, biomaterials science, cell biology, physics, and medicine is required to address these complexities. Meeting this challenge is being made possible by directing the 3D bioprinting to manufacture biomimetic-shaped 3D structures, using organ/tissue images, obtained from magnetic resonance imaging and computerized tomography, and employing computer-aided design and manufacturing technologies. Applications of 3D bioprinting include the generation of multilayered skin, bone, vascular grafts, heart valves, etc. The current 3D bioprinting technologies need to be improved with respect to the mechanical strength and integrity in the manufactured constructs as the presently used biomaterials are not of optimal viscosity. A better understanding of the tissue/organ microenvironment, which consists of multiple types of cells, is imperative for successful 3D bioprinting.

Bladder Cancer and Genetic Mutations.

The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder cancer need further research.

Radiolabeling in Biology.

Chemistry is the science of chemical reactions, the study of chemical properties, composition, and structure of a molecule. When the molecule under observation is of a biological origin (proteins, carbohydrates, lipids, or nucleic acids), the study of its chemical properties, reactions, and structure is known as biochemistry. Similarly, if the molecule or a biochemical under observation is radioactive, the science becomes radiochemistry or radio biochemistry. So, chemistry is the science which fuses these two diverse fields of applied sciences. Fusion of these two sciences on chemistry platform has enabled the development of various new radioactive formulations which are called as radiopharmaceuticals and are being used the world over for clinical as well as experimental purposes. For the successful development of radiopharmaceuticals, we require in-depth understanding of both biochemistry as well as radiochemistry. So, the present review article summarizes basic relevant details and experimental advances in both these sciences with regard to development of radiopharmaceuticals.

Octamer-binding protein 4 affects the cell biology and phenotypic transition of lung cancer cells involving ß-catenin/E-cadherin complex degradation.

Clinical studies have reported evidence for the involvement of octamer­binding protein 4 (Oct4) in the tumorigenicity and progression of lung cancer; however, the role of Oct4 in lung cancer cell biology in vitro and its mechanism of action remain to be elucidated. Mortality among lung cancer patients is more frequently due to metastasis rather than their primary tumors. Epithelial­mesenchymal transition (EMT) is a prominent biological event for the induction of epithelial cancer metastasis. The aim of the present study was to investigate whether Oct4 had the capacity to induce lung cancer cell metastasis via the promoting the EMT in vitro. Moreover, the effect of Oct4 on the ß­catenin/E­cadherin complex, associated with EMT, was examined using immunofluorescence and immunoprecipitation assays as well as western blot analysis. The results demonstrated that Oct4 enhanced cell invasion and adhesion accompanied by the downregulation of epithelial marker cytokeratin, and upregulation of the mesenchymal markers vimentin and N­cadherin. Furthermore, Oct4 induced EMT of lung cancer cells by promoting ß­catenin/E­cadherin complex degradation and regulating nuclear localization of ß­catenin. In conclusion, the present study indicated that Oct4 affected the cell biology of lung cancer cells in vitro through promoting lung cancer cell metastasis via EMT; in addition, the results suggested that the association and degradation of the ß­catenin/E­cadherin complex was regulated by Oct4 during the process of EMT.

MicroRNA-145 inhibits lung cancer cell metastasis.

Previous studies have identified a variety of microRNAs (miRNAs) that have important roles in cancer progression, particularly in tumor invasion and metastasis. Downregulation of miR­145 was reported to occur in various types of human cancer; however, the role of miR­145 in lung cancer metastasis and its potential mechanisms of action remain to be elucidated. The present study aimed to investigate the effects of miR­145 on metastasis and epithelial­mesenchymal transition (EMT) in A549 human lung adenocarcinoma cells. In addition, the underlying mechanisms by which miR­145 regulates EMT were examined. The miR­145 mimic was transfected into A549 cells; cell invasion and adhesion assays were then performed in order to investigate cell metastasis, and western blot analysis was used to examine the expression of EMT markers. In order to further examine the underlying mechanisms by which miR­145 regulates EMT, a luciferase reporter assay was performed to determine whether miR­145 targeted Oct4. In addition, the expression of Wnt3a and ß­catenin in A549 cells was measured following transfection with small hairpin RNA­Oct4. To the best of our knowledge, the results of the present study demonstrated for the first time, that miR­145 inhibited lung cancer cell metastasis and EMT via targeting the Oct4 mediated Wnt/ß­catenin signaling pathway.

[Preparation and property evaluation of graphene oxide based silver nanoparticles composite materials].

We prepared silver nanoparticles/polyethyleneimine-reduction graphene oxide (AgNP/rGO-PEI) composite materials, and evaluated their quality performance in our center. Firstly, we prepared AgNP/rGO-PEI, and then analysed its stability, antibacterial activity, and cellular toxicity by comparing the AgNP/rGO-PEI with the silver nanoparticles (PVP/AgNP) modified by polyvinylpyrrolidone. We found in the study that silver nanoparticles (AgNP) distributed relatively uniformly in AgNP/rGO-PEI surface, silver nanoparticles mass fraction was 4.5%, and particle size was 6-13 nm. In dark or in low illumination light intensity of 3 000 lx meter environment (lux) for 10 days, PVP/AgNP aggregation was more obvious, but the AgNP/rGO-PEI had good dispersibility and its aggregation was not obvious; AgNP/rGO-PEI had a more excellent antibacterial activity, biological compatibility and relatively low biological toxicity. It was concluded that AgNP/rGO-PEI composite materials had reliable quality and good performance, and would have broad application prospects in the future.

The in vitro biological properties of Mg-Zn-Sr alloy and superiority for preparation of biodegradable intestinal anastomosis rings.

BACKGROUND: Magnesium (Mg) alloy is a metal-based biodegradable material that has received increasing attention in the field of clinical surgery, but it is currently seldom used in intestinal anastomosis. This study was conducted to comprehensively assess a ternary magnesium (Mg)-zinc (Zn)-strontium (Sr) alloy's biological superiorities as a preparation material for intestinal anastomosis ring. MATERIAL AND METHODS: Mouse L-929 fibroblasts were cultured with Mg-Zn-Sr alloy extract and compared with both positive (0.64% phenol) and negative (original broth culture) controls. The cell morphology of different groups was examined using microscopy, and a cytotoxicity assessment was performed. Fresh anticoagulated human blood was mixed with Mg-Zn-Sr alloy extract and compared with both positive (distilled water) and negative (normal saline) controls. The absorbance of each sample at 570 nm was used to calculate the Mg-Zn-Sr alloy hemolysis ratio in order to test the Mg alloy's blood compatibility. Bacterial cultures of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were added to Mg-Zn-Sr alloy block samples and compared with positive (Ceftazidime), negative (316LSS stainless steel), and blank controls. The broth cultures were sampled to compare their bacterial colony counts so as to evaluate the antibacterial properties of the Mg-Zn-Sr alloy. The Mg-Zn-Sr alloy was surface-coated with a layer of poly(lactic-co-glycolic acid) carrying everolimus. The surface morphology and degradability of the coating were examined so as to demonstrate feasibility of coating, which can release the drug evenly. RESULTS: The experiments proved that Mg-Zn-Sr alloy has good biocompatible, antibacterial, and drug-loaded coating performances, which are lacking in existing intestinal anastomosis devices/materials. CONCLUSIONS: The Mg-Zn-Sr alloy increases biocompatibility, and yields a safer and better therapeutic effect; therefore, it is a novel biomaterial that is feasible for use when preparing biodegradable intestinal anastomosis rings.

Effect of Ku70 expression on radiosensitivity in renal carcinoma 786-O cells.

BACKGROUND: Radiotherapy plays an important role in cancer therapy. However, the radioresistance of some human cancers, particularly renal carcinoma, often results in radiotherapy failure. The Ku protein is essential for the repair of a majority of DNA double-strand breaks in mammalian cells, but effect of Ku70 expression on radiosensitivity in renal carcinoma is unclear. Here, we investigate the impact of Ku70 on radiosensitivity in renal carcinoma cells through regulating the expression of Ku70. METHODS: The stable overexpression of Ku70 or suppression of Ku70 in renal carcinoma cell line (786-O) was generated by retrovirus-mediated Ku70 cDNA or shRNA targeting Ku70. Ku70 expression was determined by RT-PCR and Western blot analysis, the apoptosis of the stable cells was assayed with flow cytometry and TUNEL assay and the effect of radiation on the livability of stable cells was assessed by MTT assay. RESULTS: Up-regulation of Ku70 expression of 786-O cells could inhibit cell apoptosis and reduce susceptibility to radiation. On the contrary, 786-O cells with suppression of Ku70 expression could induce cell apoptosis and significantly enhance the sensitivity to radiation. CONCLUSIONS: These findings indicated that Ku70 might play an important role in radioresistance of renal carcinoma, and inhibition of Ku70 can increase the radiosensitivity of 786-O cells by enhancing apoptosis, suggesting down-regulation of Ku70 expression combined with radiotherapy will be a potential strategy for renal cell carcinoma therapy.

The roles of miR-200c in colon cancer and associated molecular mechanisms.

The expression of miR-200c has been widely reported to be elevated in tumor tissues and sera of patients with colorectal cancer (CRC) and has been found to correlate with poor prognosis. However, how miR-200c regulates the apoptosis, survival, invasion, metastasis, and tumor growth in colon cancer cells remains to be fully elucidated. This study seeks to further investigate the role of miR-200c in colon cancer development. The expression of miR-200c in tumor and peritumoral tissues of 101 colon cancer patients was measured by real-time PCR. miR-200c expression in HCT-116 and HT-29 colon cancer cells was silenced by adenovirus-carried expression of antisense mRNA against miR-200c. The protein levels of PTEN, p53 Ser(15), PP1, and activated caspase-3 in HCT-116 and HT-29 cells were measured by Western blot. This study demonstrated that the expression of miR-200c was significantly higher in tumor tissues than in peritumoral tissues of colon cancer patients. The elevated miR-200c expression significantly correlated with the TNM stage, lymph node metastasis, and invasion of colon cancer. Silencing miR-200c expression significantly induced cell apoptosis, inhibited long-term survival, invasion, and metastasis, and delayed xenograft tumor growth. Importantly, silencing miR-200c expression sensitized the therapeutic effect of Ara-C (Cytarabine). The effects of silencing miR-200c expression were associated with upregulation of PTEN protein and p53 Ser(15) phosphorylation levels in HCT-116 cells and PTEN protein expression in HT-29 cells. In conclusion, miR-200c functions as an oncogene in colon cancer cells through regulating tumor cell apoptosis, survival, invasion, and metastasis as well as xenograft tumor growth through inhibition of PTEN expression and p53 phosphorylation.

Detection of cell apoptosis in pelvic lymph nodes of patients with cervical cancer after neoadjuvant chemotherapy.

OBJECTIVE: To investigate if the administration of neoadjuvant chemotherapy (NACT) reduces pelvic lymph node metastasis by inducing tumour cell apoptosis in patients with cervical cancer. METHODS: This study enrolled patients with stage Ib2-IIb cervical cancer who underwent surgery with (NACT group) or without (control group) prior cisplatin-based chemotherapy. Immunohistochemical staining of caspase-3 and an in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling assay were used to measure the levels of apoptosis in primary tumours and pelvic lymph nodes. RESULTS: A total of 185 patients participated in the study: 102 in the NACT group and 83 in the control group. Treatment was considered to be clinically effective in 69.6% (71/102) of the NACT group. The rate of metastasis in the NACT group (20.6%; 21/102) was significantly lower than the control group (42.2%; 35/83). The level of caspase-3 immunostaining and the rate of apoptosis in primary tumours and pelvic lymph nodes in the NACT group were significantly higher than in the control group. CONCLUSIONS: NACT appeared to limit pelvic node metastasis by inducing tumour cell apoptosis in patients with cervical cancer.

Predicting distant metastasis and chemoresistance using plasma miRNAs.

In the clinic, predicting metastasis and chemoresistance takes high priority, but has not been well established. This study seeks to investigate whether dynamically monitoring serum microRNAs (miRNAs) can help predict metastasis, chemoresistance, and prognosis of colorectal cancer. Serum miR-155, miR-200c, and miR-210 levels in 15 patients with colon cancer were measured by real-time PCR at different time points post surgery and chemotherapy for 3 years. Significant increases in miR-155, miR-200c, and miR-210 levels were observed in the serum and tumor tissues of colon cancer patients compared to that of healthy subjects. After surgery and chemotherapy, the serum levels of these miRNAs in patients with good prognosis returned to normal levels found in healthy controls during the 3-year follow-up. In patients with recurrence and distant metastasis, serum miR-155, miR-200c, and miR-210 levels remained at an elevated level or became elevated again after a short period of decline. In patients with good response to chemotherapy for metastatic tumors, re-elevation of miR-155 was not significant compared to miR-200c and miR-210. In contrast, miR-155 re-elevated more significantly in patients not sensitized to chemotherapy than miR-200c and miR-210. Our study suggests that re-elevation or sustained elevation of serum miR-155 level after surgery and chemotherapy is a sign of chemoresistance in colon cancer, while high and/or re-elevated miR-155, miR-200c, and miR-210 levels implicate local recurrence and distant metastasis as well as poor prognosis.

Wnt4 is overexpressed in human pituitary adenomas and is associated with tumor invasion.

The Wnt4 molecule is a secretory glycoprotein implicated in proliferation and differentiation of both normal and malignant cells. Despite extensive investigation of Wnt4 expression in various cancers, little is known about its expression pattern in different types of pituitary tumors. In this study, we examined the expression of Wnt4 and its downstream molecule ß-catenin in pituitary adenoma specimens. Pituitary adenoma tissues were collected from 43 patients and four normal pituitary tissue samples were obtained at autopsy. Quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blot were performed to detect the expression of Wnt4 and ß-catenin mRNA and protein, respectively. Tumor invasion grade (Knosp grade) was determined on MRI images and was correlated to ß-catenin expression. Immunohistochemistry demonstrated elevated Wnt4 expression in follicle-stimulating hormone-producing adenomas, growth hormone-producing adenomas, prolactin-producing adenomas, thyroid-stimulating hormone-producing adenomas and non-functioning adenomas, while adrenocorticotropic hormone-producing adenomas showed a low level of Wnt4 expression that was comparable to normal pituitary tissue. These results were confirmed by real-time RT-PCR and western blot analyses. The expression pattern of ß-catenin was similar to that of Wnt4 and was inversely correlated to the Knosp grade of tumor invasion. These data indicate that Wnt4 signaling is deregulated in most pituitary adenomas and its excessive activation may inhibit pituitary tumor invasion.

Study on optimisation of extraction process of tanshinone IIA and its mechanism of induction of gastric cancer SGC7901 cell apoptosis.

The objective of this paper was to investigate the extraction process of tanshinone IIA and its mechanism of induction of gastric cancer SGC7901 cell apoptosis. Extraction process of tanshinone IIA was optimised by orthogonal experimental method, and its effect on gastric cancer SGC7901 cell apoptosis was observed using MTT assay and electron microscopy. The optimum extraction process of tanshinone IIA was as follows: addition of a 10-fold amount of 80% ethanol, one-time extraction, and extraction time of 45 minutes. The study concluded that tanshinone IIA can induce apoptosis of gastric cancer SGC7901 cells.

Increased expression of microRNA-335 predicts a favorable prognosis in primary gallbladder carcinoma.

BACKGROUND: MicroRNAs (miRNAs) display aberrant expression patterns and functional abnormalities in many types of cancer. However, their roles in primary gallbladder carcinoma (PGC) have not been well documented. miR-335 has been demonstrated to be involved in tumorigenesis of several cancers in the digestive system. The aim of this study was to investigate the clinical significance of miR-335 in PGC. METHODS: miR-335 expression in 166 human PGC tissues and matched adjacent nondysplastic gallbladder epithelia was measured by real-time quantitative polymerase chain reaction (RT-PCR) assay. RESULTS: The expression level of miR-335 was significantly lower in PGC tissues than that in nondysplastic gallbladder epithelia (P<0.001). Of 166 PGC patients, 96 (57.83%) had reduced expression of miR-335. Additionally, the expression of miR-335 was significantly lower in PGC tissues with high histologic grade (P=0.02), advanced pathologic T stage (P=0.009) and clinical stage (P=0.008), and with positive lymph node metastasis (P=0.001). In univariate analysis by log-rank test, histologic grade (P=0.03), pathologic T stage (P=0.008), clinical stage (P=0.01), lymph node metastasis (P<0.001), and miR-335 expression (P<0.001) were significant prognostic factors for overall survival of PGC patients. Multivariate analysis further revealed that pathologic T stage (P=0.02), lymph node metastasis (P=0.008), and miR-335 expression (P=0.006) maintained independent prognostic influence on overall survival. CONCLUSION: This study offers convincing evidence for the first time that miR-335 was downregulated in a majority of PGC patients and may be associated with the aggressive tumor behaviors. Loss of miR-335 expression may be a useful marker for clinical outcome and a therapeutic target for PGC.

MicroRNA-22 expression in hepatocellular carcinoma and its correlation with ezrin protein.

OBJECTIVE: Expression of microRNA-22 (miR-22) and ezrin protein (a membrane-cytoskeleton linking protein) in hepatocellular carcinoma (HCC) was investigated. METHODS: Specimens of HCC and paracancerous tissue (control; ~5 cm away from tumour tissue) were collected from 192 patients. miR-22 expression was detected by real-time polymerase chain reaction; ezrin protein expression in tumour tissue was assessed immunohistochemically. Associations between miR-22 expression and clinicopathological features of HCC and ezrin expression were analysed. RESULTS: miR-22 expression was lower in HCC tissue than in paracancerous tissue samples (median relative expression 0.676 versus 1.000 for control tissue). Expression of miR-22 was significantly associated with histological differentiation (relative expression 0.431 for lower grades of differentiation versus 0.918 for higher grades), and was associated with lymphatic metastasis (relative expression 0.518 if metastasis was present, 0.919 if absent). Survival time was shorter in patients with low miR-22 expression than in those with high expression (31.0 ± 2.6 versus 52.2 ± 5.1 months). There was a significant negative correlation between the expression of miR-22 and that of ezrin. CONCLUSIONS: miR-22 is downregulated in HCC and its expression is associated with the differentiation, metastasis and prognosis of the carcinoma. Ezrin is a potential regulatory protein of miR-22.