Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients.

BACKGROUND: RAS, BRAF, and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described. AIM: To analyze the clinicopathological features of KRAS, NRAS, BRAF, and PIK3CA mutations and the DNA MMR status in CRC. METHODS: We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression. RESULTS: The KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ, stage I, or stage II tumors. CONCLUSION: This study analyzed the molecular profiles of KRAS, NRAS, BRAF, PIK3CA, and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.

Anesthesia management in a pediatric patient with complicatedly difficult airway: A case report.

BACKGROUND: Reports on perioperative anesthesia management in pediatric patients with difficult airways are scarce. In addition to relatively more difficulties in the technique of endotracheal intubation, the time for manipulation is restricted compared to adults. Securing the airways safely and avoiding the occurrence of hypoxemia in these patients are of significance. CASE SUMMARY: A 9-year-old boy with spastic cerebral palsy, severe malnutrition, thoracic scoliosis, thoracic and airway malformation, laryngomalacia, pneumonia, and epilepsy faced the risk of anesthesia during palliative surgery. After a thorough preoperative evaluation, a detailed scheme for anesthesia and a series of intubation tools were prepared by a team of anesthesiologists. Awake fiberoptic intubation is the widely accepted strategy for patients with anticipated difficult airways. Given the age and medical condition of the patient, we kept him sedated with spontaneous breathing during endotracheal intubation. The endotracheal intubation was completed on the second attempt after the failure of the first effort. Fortunately, the surgery was successful without postoperative complications. CONCLUSION: Dealing with difficult airways in the pediatric population, proper sedation allows time to intubate without interrupting spontaneous breathing. The appropriate endotracheal intubation method based on the patient's unique characteristics is the key factor in successful management of these rare cases.

Long-term safety and absorption assessment of a novel bioresorbable nitrided iron scaffold in porcine coronary artery.

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 µm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products.

miR-296-5p suppresses stem cell potency of hepatocellular carcinoma cells via regulating Brg1/Sall4 axis.

Epithelial-mesenchymal transition (EMT), a pivotal event during cancer progression such as relapse and metastasis, is positively correlated with the stemness potency of tumor cells. Our previous study showed that miR-296-5p attenuated EMT program of hepatocellular carcinoma cells (HCC) through NRG1/ERBB2/ERBB3 signaling. In the present study, we uncovered that miR-296-5p was able to inhibit the stemness potency of HCC by decreasing the number and size of tumorspheres, downregulating the expression of CSC biomarkers and hampering the ability of tumorigenesis in NOD/SCID mice. Brahma-related gene-1 (Brg1), as the target protein of miR-296-5p detected by bioinformatics methods, activates a series of downstream cascades through directly binding to Sall4 promoter and enhancing Sall4 transcription. Importantly, the higher expressions of Brg1 and Sall4 in tumor tissues of HCC patients suggest poorer prognoses after surgical extraction. In conclusion, miR-296-5p exerts an inhibitory effect on stemness potency of HCC cells via Brg1/Sall4 axis.

[Progress on wheat A genome illustration and its evolutional analysis].

Wheat is one of the main food crops and widely grown in the world. It feeds more than 35% of the world's population. Obtaining high-quality genome sequences of wheat is important for its basic and breeding researches. However, the large and complex genome of wheat once led to its genome sequencing as an "impossible task". Recently, with the development of high-throughput sequencing and assembly technology, many wheat genome sequences have been released, and their sequencing and assembly quality is being improved continuously. In the last two years, five wheat reference genomes with different ploidy levels have been published, including two diploid ancestors Triticum urartu (AA) and Aegilops tauschii (DD), wild and cultivated tetraploid wheat T. turgidum ssp. dicoccoides (BBAA) and hexaploid wheat T. aestivum (BBAADD). Among them, the sequencing and analysis of the T. urartu genome, a donor of polyploid wheat A subgenome, was led by the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences. In this review, we summarize the research progress on structure and evolution analyses of the T. urartu genome to provide some valuable information for promoting the basic and applied researches of wheat.

Steroidal dimer by001 inhibits proliferation and migration of esophageal cancer cells via multiple mechanisms.

OBJECTIVE: To investigate the potential inhibitory effects of structurally novel steroidal dimer by001 in esophageal cancer in vitro. METHODS: The cytotoxicity of by001 on esophageal, gastric, neuroblastoma and prostate cancer cells was examined MTT assay and colony formation assay. By001 induced apoptosis and production of intracellular reactive oxygen species on esophageal cancer cells Ec109, TE-1 and human normal gastric epithelial cells GES-1 was detected by flow cytometry. The effect of by001 on mitochondrial membrane potential was detected by fluorescence microscope through JC-1 staining. The level of intracellular reactive oxygen species was measured by fluorescence microscope and flow cytometry via DCFH-DA staining. The effect of by001 on members of Bcl-2 family, Fas, LC3, PARP and caspases was determined by Western blot. The effect of by001 on migration was measured by transwell assay. RESULTS: By001 effectively inhibited proliferation of esophageal, gastric, neuroblastoma and prostate cancer cells in a time- and concentration-dependent manner in vitro. By001 reduced the number and the size of colonies at low micromolar concentrations, elevated cellular ROS levels and caused mitochondrial dysfunction in esophageal cancer cells. Molecular mechanistic studies showed that by001 triggered apoptosis through regulating members of Bcl-2 family and Fas. CONCLUSIONS: These findings suggested that by001 may inhibited proliferation of esophageal cancer cells through mitochondria and death receptor-mediated apoptotic pathways, autophagy induction, as well as suppressed migration of esophageal cancer cells.

Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer agents.

A series of new steroidal pyridines have been synthesized through the based-promoted three-component reaction and preliminarily evaluated for their antiproliferative activity against different types of cancer cell lines. SARs studies showed that the heterocyclic rings attached to the 4-position of the pyridine ring were preferred over the phenyl rings for the activity. Among these compounds, the most potent compound exhibited good growth inhibition against all the tested cancer cells, especially for PC-3 cells with an IC50 value of 1.55 µM. Further mechanistic studies revealed that the most potent compound inhibited colony formation, migration and evasion of PC-3 cells in a concentration-dependent manner as well as induced apoptosis of PC-3 cells possibly through the mitochondria-related apoptotic pathways. Caspase-3/-9 and PARP were activated, finally leading to the apoptosis of PC-3 cells. For the androgen-sensitive (AR+) prostate cancer cell line LNCaP, the most potent compound was less potent than abiraterone with the IC50 value of 8.48 and 3.29 µM, respectively. The most potent compound could be used as a starting point for the development of new steroidal heterocycles with improved anticancer potency and selectivity. The synthesized steroidal pyridines contain the functional -OEt and CN groups, which could be used for further modifications for the construction of the steroid library.

Efficacy of pEgr-1-endostatin combined with ionizing radiation on hypoxic conditions in nude mice bearing SKOV3 ovarian carcinoma.

Hypoxia occurs in a wide range of solid tumors, and is strongly associated with radio-resistance of malignant tumors. The aim of the present study was to investigate the effect of endostatin combined with ionizing radiation (IR) on hypoxic conditions. A total of 24 mice bearing SKOV3 ovarian carcinoma were divided into three groups. Following injection with pEgr-1-endostatin plasmid for 12 h, the mice in the endostatin-IR-treated group were exposed to 300 cGy/min X-ray for 48 h, and the IR-treated group was exposed to the same condition. Then, the expression of endostatin, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) was detected by reverse transcription-polymerase chain reaction, ELISA, immunohistochemistry and western blotting. In addition, the tumor microvessel density (MVD) was examined by immunohistochemistry analysis of cluster of differentiation 31-positive cells. The results revealed that pEgr-1-endostatin was successfully induced by IR. The level of endostatin messenger RNA in the endostatin-IR-treated group was significantly higher than that in the control and IR-treated groups (F=380.078, P<0.001). Statistical differences were also examined at the protein level by western blotting and ELISA. An obvious increase in MVD was observed in the IR-treated group compared with that in the control group (t=7.040, P<0.001), and a significant decrease in MVD was observed in the endostatin-IR-treated group compared with that in the control group (t=18.153, P<0.001). By comparing the morphology of the tumor vasculature in the three groups, it was noticed that the microvessels in the endostatin-IR-treated group were more regularly distributed and had fewer giant branches than those in the IR-treated group. Further investigation revealed that the expression levels of HIF-1α and VEGF in the endostatin-IR-treated group were lower compared with those in the control (t=5.339, P=0.001; and t=13.880, P<0.001, respectively) and the IR-treated groups (t=12.930, P<0.001; and t=14.050, P<0.001, respectively). Our findings suggested that endostatin decreased the number of microvessels via the HIF-1/VEGF signaling pathway, and that pEgr-1-endostatin combined with IR may improve hypoxic conditions and may be a novel approach for treating solid tumors.

Geridonin and paclitaxel act synergistically to inhibit the proliferation of gastric cancer cells through ROS-mediated regulation of the PTEN/PI3K/Akt pathway.

Paclitaxel, a taxane, is a cytotoxic chemotherapeutic agent that targets microtubules. It has become a front-line therapy for a broad range of malignancies, including lung, breast, gastric, esophageal, and bladder carcinomas. Although paclitaxel can inhibit tumor development and improve survival, poor solubility, myelotoxicity, allergic reactions, and drug resistance have restricted its clinical application. Paclitaxel is frequently combined with other chemotherapeutics to enhance the antitumor effects and reduce side effects. We synthesized geridonin, a derivative of oridonin, and demonstrate that geridonin and paclitaxel act synergistically to inhibit the growth of gastric cancer cells. Importantly, geridonin enhanced the antitumor effects of paclitaxel without increasing toxicity in vivo. Mechanistic analysis revealed that administration of geridonin in combination with paclitaxel up-regulated the tumor suppressor PTEN and inhibited phosphorylation of Akt and MDM2. This led to the accumulation of p53 and induced apoptosis though the mitochondrial pathway. Thus, geridonin in combination with paclitaxel is a new treatment strategy for gastric cancer.

[Myxoinflammatory fibroblastic sarcoma: a clinicopathologic study of 6 cases with review of literature].

OBJECTIVE: To study the clinicopathologic features, immunophenotypes and differential diagnosis of myxoinflammatory fibroblastic sarcoma (MIFS). METHODS: The clinical and pathologic features of 6 cases of MIFS were analyzed. Immunohistochemical study was performed using the standard EnVision method. RESULTS: There were altogether 2 adult males and 4 adult females (median age = 47 years and mean age = 50 years). Three cases were located in the lower extremities, 2 in the upper limbs and 1 in the axillary region. Common presentation included slowly growing mass or swelling in the extremities, accompanied by mild pain or tenderness. Grossly, the tumor appeared multinodular and ranged from 2.5 cm to 4.6 cm in diameter (mean = 3.4 cm). Microscopically, there was a dense inflammatory infiltrate merging with hyaline and myxoid zones in various proportions. Spindle-shaped tumor cells were seen admixed with large atypical cells which distributed singly or in small clusters, amongst an inflammatory, hyaline or a myxoid background. These atypical cells had large nuclei and prominent nucleoli, resembling virocytes, Reed-Sternberg cells or ganglion cells. Mitotic figures were rarely identified. Extracellular mucin associated with scattered monovacuolated or multivacuolated lipoblast-like cells was noted. Immunohistochemically, these bizarre cells were consistently positive for vimentin, but negative for a panel of antibodies including LCA, CD15, CD30, CD34, CD68, S-100, HMB45, AE1/AE3, smooth muscle actin and desmin. Follow-up result was available in 4 cases; and 2 of them showed local recurrence after an incomplete excision. There was no evidence of distant metastasis. CONCLUSIONS: MISF is a low-grade sarcoma of fibroblastic differentiation. Awareness of the clinical and pathologic characteristics is helpful in arriving at the correct diagnosis and distinction from benign inflammatory fibromyxoid lesions.

[Correlation analysis among characters of gas vesicle in Microcystis strains].

In order to explore the roles of gvpA copies and repeated sequences of gvpC, three Microcystis strains including M. aeruginosa FACHB910, M. aeruginosa FACHB930 and M. wesenbergii FACHB929 were used in this research. The length and diameter of gas vesicle, relative gas vesicle volume, appear pressure values, critical pressure values, cell turgor values were measured, and the correlations among these characters, gvpA copies, and repeated sequences of gvpC were analyzed. The results indicate that there are a significant positive linear correlation between gvpA copies and relative gas vesicle volume (r = 0.999); gvpA copies are negatively correlated with diameter of gas vesicle (r = -0.861). However, repeated sequences of gvpC have a significant positive correlation with diameter of gas vesicle (r = 0.911), and have significant negative correlations with relative gas vesicle volume, appear pressure values and critical pressure values, with the correlation coefficient of -0.851, - 0.999, - 0.928 respectively. So we presume that gvpA copies are probably the primary impact factor for relative gas vesicle volume. The diameter of gas vesicle is not only regulated by repeated sequences of gvpC, but also regulated by gvpA copies.

Assessing the combination effects of environmental estrogens in fish.

The method on combined effects of environmental estrogens and mixture environmental risk assessment was discussed. Batch tests were conducted to assess the in vivo potency of mixtures of estrogens using plasma vitellogenin concentrations in male crucian carp (Carassius carassius) as the endpoint. A nonlinear regression was determined on the concentration response relationship for the single chemical of 17ß-estradiol (E(2)), 17α-ethynylestradiol (EE(2)), 4-tert-octylphenol (OP), bisphenol A (BPA), and that of the mixed compounds at equipotent concentrations (E(2)-EE(2), E(2)-EE(2)-OP-BPA), the mixture was tested using a fixed-ratio design. On the basis of statistical selection criteria, the best-fit model is chosen individually for each set of data. Furthermore, the bootstrap methodology is applied for constructing confidence intervals for the estimated effect concentrations. The combined effects of the mixture can be predicted using biomathematical models based on the concentration and potency of the individual mixture components. The finding of non-monotonic dose-response relationship and the combined effects can be accurately predicted in whole range of exposure concentration by the reference models, whereas the outcome of simple effect summation with a great deal of indetermination. Results suggested that there can be a risk of mixture effects. The potential impact of components on mixture would depend predominantly on its concentration, the mixture ratio, and its relative potency. Existing environmental risk assessment procedures are limited in their ability to evaluate the combined effects of chemical mixtures, therefore further improvement is needed.

[Profile of chromosomal imbalances in 10 cases of primary alveolar rhabdomyosarcoma analyzed by comparative genomic hybridization].

OBJECTIVE: The aim of this study was to characterize the profile of chromosomal imbalances of alveolar rhabdomyosarcoma (ARMS). METHODS: One-step RT-PCR was used to detect the expression of PAX3-FKHR and PAX7-FKHR fusion transcripts in 10 cases of alveolar rhabdomyosarcoma and in an ARMS cell line. Comparative genomic hybridization (CGH) was used to investigate the genomic imbalances in these cases. It was analyzed according to the histological type, pathologic grading, clinical staging, gender and age, respectively. RESULTS: The 10 patients with alveolar rhabdomyosarcoma showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome. (1) The frequently gained chromosome arms of ARMS were 12q, 2p, 6p, 6q, 10q, 2q, 4q, 15q, 1p, 9q, 14q and 18q (> or = 30.0%), and the frequently lost chromosome arms of ARMS were 3p, 6p, 20q and 21q (> 30.0%). (2) The frequently gained chromosome arm translocation associated with ARMS were 12q, 10q, 2p, 2q, 6p, 6q, 1p, 4q, 8q, 11q, 14q and 15q (> 30.0%). The frequently lost chromosome arms were 3p, 5q, 6p, 1q, 8p, 11p, 20q and 21q (> 30.0%). (3) There were no correlation between chromosome changes and histological type, pathologic grade, clinical stage, gender and age, respectively. CONCLUSION: These observations suggest that: (1) 12q, 2p, 6p, 6q, 10q, 2q, 4q, 15q, 1p, 9q, 14q, 18q gain and 3p, 6p, 20q, 21q loss may correlated with ARMS-related carcinogenesis; (2) 12q gain may be correlated with translocation.

[Comparison between R-CHOP regimen and CHOP regimen in treating naive diffuse large B-cell lymphoma in China--a multi-center randomized trail].

BACKGROUND & OBJECTIVE: CHOP regimen is a standard treatment for patients with diffuse large B-cell non-Hodgkin's lymphoma (NHL), and its 5-year overall survival (OS) rate is 30%-40%. Rituximab is a chimeric monoclonal antibody (MoAb) directly against CD20-positive B cells, and has good effect on diffuse large B-cell NHL. Rituximab combined with standard chemotherapy has been approved for treating aggressive B-cell NHL in Europe and the US. This study was to determine efficacy and safety of the combination of Rituximab and CHOP regimen in treating Chinese patients with CD20-positive diffuse large B-cell NHL. METHODS: From Sep. 2003 to Nov. 2004, a total of 63 patients in 9 centers were enrolled. All the patients were randomized into 2 groups: 32 received CHOP regimen alone (CHOP group), and 31 received Rituximab and CHOP regimen (R-CHOP group). All patients signed informed consent. The complete response rates, overall response rates, and side events of the 2 groups were compared. RESULTS: The complete response rates were similar in R-CHOP and CHOP groups (41.9% vs. 37.5%, P=0.719); the overall response rates were slightly higher in R-CHOP group than in CHOP group (83.8% vs. 65.6%, P=0.096). Disease progression during treatment was reported for 7 (21.9%) patients in CHOP group and 1 (3.2%) patient in R-CHOP group (P=0.026). The occurrence rates of adverse events were similar in R-CHOP and CHOP groups (65.6% vs. 67.7%, P=0.859). The most common adverse event was leukopenia; fever and chills were rather common in R-CHOP group. Clinically relevant toxicity was similar in both groups. CONCLUSION: When compared with standard CHOP alone, the addition of Rituximab to standard CHOP regimen reduces the risk of treatment failure in patients with diffuse large B-cell NHL, and doesn't increase the occurrence of chemotherapy-related adverse events.