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To develop a multi-functional edible bread with significant adjuvant therapeutic effect, a functional bread (FB) with anti-oxidative and hypoglycaemic functional ingredients from sericulture waste, mulberry branch bark powder (MBBP) and silk sericin powder (SSP), was investigated. Trial settings of low, medium and high doses of sample powder (5, 10, 15% MBBP and 0.3, 0.6, 1.0% SSP) are three FB diet groups LBB, MBB, and HBB, respectively. After four weeks of oral administration, HFB had a hypoglycaemic rate of 36.54% and significantly alleviated the symptoms of hyperglycaemia. TG and LDL-C levels in serum were evidently reduced while HDL-C, T-SOD, and CAT levels increased significantly. MDA and 8-OHdG levels were evidently decreased (P < 0.05, P < 0.001); abnormal glucose tolerance and insulin resistance were significantly alleviated; abnormally increased glycated serum protein (GSP) levels and serum liver function enzyme activity (AST and ALT) were also significantly reduced. Liver glycogen content also increased significantly. These results demonstrate that the addition of FB to a diet can significantly reduce the blood glucose level of T2D mice, enhance antioxidant capacity, improve insulin resistance, and improve the ability of glycogen to regulate blood sugar, thus offering new possibilities for developing multi-functional healthy bread products.

A large number of Ginkgo biloba L. seed (GBS) has not been widely consumed as functional foods due to its doubtful biological activity. After GBS is thermally detoxified in a microwave oven for 2 min, anti-hyperglycemic effect of GBS ingestion on type 2 diabetic (T2D) mice and possible mechanism are investigated in details. Oral administration of the detoxified GBS for 4 weeks can reduce fasting blood glucose and serum insulin levels, improve glucose tolerance and insulin tolerance, and significantly increase antioxidative capacity of liver tissue in T2D mice. The pathological damage to liver tissue, pancreatic β-cells and the kidney was ameliorated. GBS ingestion may ameliorate glucose level in T2D mice, regulate glucose and lipid metabolism, and improve insulin resistance by enhancing anti-oxidative and anti-inflammatory activities in the body. Therefore, GBS has the potential to be developed as a novel functional food.

Nutrients in runoff degrade water quality. The development of schemes to mitigate such degradation requires a characterization of the underlying dynamic processes of nutrient loss. The drinking-water source protection area in the Lake Hongfeng watershed of Guiyang City, the capital of Guizhou Province, China, has been delimited for effective conservation. However, no systematic observations have provided data on nutrient losses from these areas that could support optimal management. We selected one typical watershed in the area. Automatic gauges were installed to record the water levels and calculate runoff rates during 2010 and 2011. A total of 1523 runoff samples were collected at an interval of 3 h during a day; total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) were tested. The results indicated that surface runoff rates were primarily less than 15 L/s but rapidly increased 1-30 times 15 L/s when it rained. TN, TP, and COD concentrations primarily fluctuated between 0.06 and 18.79 mg/L, between 0.01 and 1.57 mg/L, and between 0.01 and 160 mg/L, respectively. TN and COD concentrations in 98.98% and 52.04% of the runoff samples, respectively, exceeded the upper limit required by the Environmental Quality Standards for Surface Water (EQSSW) in China. Conversely, 94.29% of the runoff samples had lower concentrations than the upper limit of TP concentration. Surface runoff has been seriously polluted by nitrogen and organic pollutants. The occurrence frequency of different runoff rates and TP and COD concentrations showed different distributions, but TN concentrations had a normal distribution. There was a significant relationship between runoff rates and TP concentration and TN, TP, or COD loss. TN, TP, and COD loss primarily occurred on vegetable lands, rice fields, and residential sites. Effectively controlling nitrogen fertilizer that is applied on vegetable lands and paddy fields and managing wastewater and solid waste are urgent. The results reported here will also provide references for many other regions facing similar problems.

The sericin protein from silk-processing waste added to the normal diet at 0.8% (g%) level was administered orally to type 2 diabetic (T2D) mice to investigate its hypoglycaemic effects and mechanism. The oral protein is in the form of silk sericin hydrolysate, obtained from a boiling treatment of 0.025% calcium hydroxide solution. The protein significantly decreased fasting blood glucose, fasting plasma insulin, and glycosylated serum protein levels; improved oral glucose tolerance and insulin tolerance, and enhanced antioxidative activities. The protein could ameliorate the pathological damage in pancreatic β-cells and the liver tissue. It enhanced the expression of key proteins and enzymes, including insulin receptor, insulin receptor substrate, PI3K, phosphorylated-AKT, hepatic kinase, GLUT4, glycogen synthase, GSK3β, GLK, PFK1, PKM2, and AMPKα, which are related to insulin metabolism and glycolysis. The protein also reduced the expression of G6Pase, PCK, and ACC, which are related to gluconeogenesis and lipid metabolism in the liver, and decreased the expression of TNF-α, IL-6, P65, and IKKβ related to inflammation. In general, sericin could maintain normal glucose levels and regulate insulin secretion, insulin and lipid metabolism, and inhibition of inflammation. Therefore, sericin protein could be developed into a novel functional health food with significantly hypoglycaemic effect.

The aluminum joints were prepared by overcasting liquid aluminum A356 onto 6101 aluminum extrusion bars. The microstructure, element distribution, hardness and tensile strength of the joint interface area were investigated, the mechanism of interface formation and fracture behavior were analyzed. The results show that good metallurgical bonding was formed in the joints by electro-plating the solid 6101 aluminum alloy with a layer of zinc coating and carefully controlling the overcasting process. There is a transition zone between the two bonded aluminum alloys, and the fine equiaxed grained structure in the transition zone is due to the high undercooling during solidification. The tensile strength of the joint interface is higher than that of the as-cast A356 aluminum alloy (about 145 MPa) and the final fracture is always located in the as-cast A356 material.

The present study aimed to examine the inhibitory effects of morusin on the human lung cancer cell line A549. Various doses of morusin were applied to A549 cells and the effects were assessed by wound‑healing and MTT assays, flow cytometry analysis of apoptosis, a mitochondrial membrane potential assay and RT‑PCR. The results indicated that the concentrations of 10 and 30 µg/ml morusin significantly inhibited A549 cells and signs of apoptosis were observed. In addition, the wound‑healing assay results revealed that morusin inhibited cell migration. Flow cytometry analysis demonstrated that the rates of apoptosis were 16.46, 55.80 and 70.80% following treatment with 1, 10 and 30 µg/ml of morusin, respectively, and that the mitochondrial membrane potentials also decreased with the increase of morusin. Furthermore, morusin increased the antioxidant activities of the A549 cells. RT‑PCR analysis revealed that the expression levels of COX‑2 and VEGF were downregulated following morusin treatment. In conclusion, morusin significantly inhibited the proliferation of the lung cancer cell line A549, and may have affected the invasion and migration of the cells by downregulating the expression of tumor angiogenesis‑related genes.

This experiment, based on the previous study on R. mori, introduces whole mulberry branch powder into the diet to treat diabetic mice. Mulberry branch bark powder (MBBP) was administered orally to streptozotocin (STZ)-induced type II diabetic (T2D) mice to investigate hypoglycemic effects. After a 4-week period of diet consumption containing 5%, 10% and 20% MBBP, the fasting blood glucose, body weight and the related western blotting were measured, pathologic and immunohistochemical were observed. The 20% MBBP group showed a significant reduction in hyperglycemia and hyperinsulinemia; fasting blood glucose and insulin decreased from 25.0 to 14.8 mmol/L and 26.5 to 16.0 mU/L, respectively. Pathologic and immunohistochemical observation showed that MBBP administration lead to the repair of pancreas cells and restoration of insulin secretion. Dietary MBBP was associated with the decrease in the contents of 3, 4-methylenedioxeamphetamine, 8-OHdG, aspartate aminotransferase, and alanine aminotransferase, and the increase in antioxidative ability and glucose tolerance. Western blotting (WB) analysis suggested that MBBP decreased the TNF-α levels, thus relieving inflammation and improving liver function. It also led to the downregulation of apoptosis factor expression. WB also confirmed that MBBP enhanced the gene expression of the key enzymes: insulin receptor, insulin receptor substrate, p-AKT, GSK3β, glycogen synthase, G6Pase and phosphoenolpyruvate carboxykinase, which are related to glucose metabolism in the liver, and increase the expression of the genes PDX-1, GLUT2, MafA, and glucokinase, related to insulin secretion. Thus, oral administration of MBBP regulated insulin secretion and effectively maintained normal levels of glucose metabolism in mice, which may be done by improving the antioxidant capacity and activating insulin signaling with T2D..

Bi-level coupling algorithm which is based on the improved genetic algorithm was proposed in this paper. Its upper-level module was designed to solve the load optimal distributing problem among the cascade hydropower plants and its lower-level module was designed to solve the generator group optimal-uniting problem among the generators in a hydropower system. This algorithm has advantages in getting the optimal operation schemes of the load distribution, as well as the generator group unitization at the same time. By using a practical basin cascade plants as an example, the results show that the software can carry on rational and optimal decision to the producing operation schemes. The Bi-level coupling algorithm has higher practical value in hydropower system management.

Natural polymers are playing an increasingly important role in formulations and some have become important core ingredients for cosmetic products. In this chapter we will discuss the various natural polymers used in a personal care product. We will focus primarily on protein-based natural polymers, study their production and compare the various chemical and physical properties of these proteins and how they can affect personal care applications.

A novel compact, multilayer wideband bandpass filter (BPF) with lumped elements is presented in this paper. It is realized by cascading a high pass filter (HPF) and a low pass filter (LPF). Two finite transmission zeros are added to achieve a sharp out-of-band roll-off skirts. Quasi-lumped elements and the multilayer structure are employed to miniaturize the filter's size. The filter is analyzed by using equivalent circuit model and full-wave electromagnetic simulation first. Good agreement between equivalent circuit model, full-wave simulated and measured responses of proposed filter is demonstrated. and validated its operation principle. Then, its performance is experimentally verified and a wide 3dB bandwidth from 1.1-2.7GHz and a 15dB-rejection stopband can be obtained.

Few studies have been conducted to investigate the genomic survey of oncogene amplification in medulloblastoma. Low frequency of N-myc, C-myc, and epidermal grow factor receptor (EGFR) gene amplification (10%) has been reported in medulloblastoma. Previous comparative genomic hybridization (CGH) study of primary medulloblastomas has revealed chromosomal amplification on 2p21, 3p, 5p15.3, 7q, 8q24, 11q22.3, and 17q. The aim of this study was to detect common oncogenes involved in medulloblastoma tumorigenesis.The authors studied a series of 14 samples by performing CGH and array-based CGH. The CGH analysis detected nonrandom losses on 8p, 17p, 16q, 8q, and 1p, whereas gains were found on 17q, 12q, 7q, and 1p. Array-based CGH was conducted to investigate amplification of 58 oncogenes throughout the genome of these samples. Gene amplifications identified for the first time included PGY1 at 7q21.1, MDM2 at 12q14.3-q15, and ERBB2 at 17q21.2. The highest frequencies of oncogene gain were detected in D17S1670 (61.5%), PIK3CA (46.2%), PGY1 (38.5%), MET (38.5%), ERBB2 (38.5%), and CSE1L (38.5%). The gain in gene copy numbers was confirmed in 34 additional archival medulloblastoma cases by using fluorescence in situ hybridization analysis.This is the first genome-wide survey of multiple oncogene amplifications involved in the development of medulloblastoma. Gains of several candidate oncogenes such as D17S1670, ERBB2, PIK3CA, PGY1, MET, and CSE1L were frequently detected. These genes may be used as molecular markers and therapeutic targets of medulloblastomas.

Ganglioglioma is a mixed neuronal and glial tumor first described by Perkin in 1926. Because of its rare occurrence in the central nervous system, the pathogenesis of this neoplasm is still largely unknown. Previous studies of ganglioglioma mainly focused on histologic features, immunohistochemical analysis, clinical treatment, and patient outcome. Very few cytogenetic and molecular genetic studies have been reported on this neoplasm. To better understand the mechanism underlying the development of ganglioglioma, we performed comparative genomic hybridization analysis to investigate chromosomal imbalances across the entire genome in five cases of gangliogliomas. Loss of genetic material on the short arm of chromosome 9 was a common genetic alteration found in three of five cases. Overrepresentation of partial or the whole chromosome 7 was another recurrent chromosomal imbalance, confirmed by fluorescence in situ hybridization. Immunohistochemical analysis was performed; all five cases revealed no reaction or low expression for epidermal growth factor receptor antibody. Our study highlights chromosomal regions for further fine mapping and investigation of candidate tumor suppressor genes involved in the pathogenesis of ganglioglioma.

To identify critical tumor suppressor loci that are associated with the development of medulloblastoma, we performed a comprehensive genome-wide allelotype analysis in a series of 12 medulloblastomas. Non-random allelic imbalances were identified on chromosomes 7q (58.3%), 8p (66.7%), 16q (58.3%), 17p (58.3%) and 17q (66.7%). Comparative genomic hybridization analysis confirmed that allelic imbalances on 8p, 16q and 17p were due to loss of genetic materials. Finer deletion mapping in an expanded series of 23 medulloblastomas localized the common deletion region on 8p to an interval of 18.14 cM on 8p22-23.2. We then searched within the region of loss on 8p for loci that might contain homozygous deletion using comparative duplex PCR. An overlapping homozygous deletion region was identified in a 1.8 cM interval on 8p22-23.1, between markers D8S520 and D8S1130, in two medulloblastomas. This region of homozygous deletion also encompasses the 1.4 cM minimal deletion region detected on 8p in ductal carcinoma in situ of breast. In conclusion, we reported for the first time a detailed deletion mapping on 8p in medulloblastoma and have identified a region of homozygous deletion on 8p22-23.1 that is likely to contain a critical tumor suppressor gene involved in the development of medulloblastoma.

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytic tumor found in the central nervous system. Histologically, the tumor is characterized by markedly pleomorphic and lipidized cells. Although most of the patients have a favorable prognosis, a small number of cases undergoing recurrence or progression to anaplastic astrocytoma were reported. Very few genetic studies have been performed on PXA because of its rarity and the pathogenesis of this neoplasm is largely unknown. In order to provide an overview of genetic alterations in PXA, we performed comparative genomic hybridization to identify chromosomal imbalances (DNA gains and losses) in three cases of PXA. Genetic imbalance was detected on at least one chromosome for each case. One case, which revealed multiple genetic alterations, showed a poor prognosis. DNA gain on chromosome 7 and loss on 8p were demonstrated in two of three cases, suggesting that the candidate gene(s) located on these regions may play a role in the development of PXA. Further studies are needed to identify the residing candidate genes that are involved in the tumorigenesis of PXA. In addition, the histopathological features and previous genetic studies on PXA are reviewed.

Purpose Our aim was to determine whether abundance of epidermal growth factor receptor (EGFR) mutations in tumors predicts benefit from treatment with EGFR–tyrosine kinase inhibitors (TKIs) for advanced non–small-cell lung cancer (NSCLC). Patients and Methods We detected EGFR mutations in 100 lung cancer samples using direct DNA sequencing and amplification refractory mutation system (ARMS). Mutation-positive tumors by both methods carried high abundance of EGFR mutations. Tumors that were mutation positive by ARMS but mutation negative by direct DNA sequencing harbored low abundance of EGFR mutations. Mutation-negative tumors by both methods carried wild-type EGFR. All patients received gefitinib treatment. The correlation between EGFR mutation abundance and clinical benefit from gefitinib treatment was analyzed. Results Of 100 samples, 51 and 18 harbored high and low abundances of EGFR mutations, respectively; 31 carried wild-type EGFR. Median progression-free survival (PFS) was 11.3 (95% CI, 7.4 to 15.2) and 6.9 months (95% CI, 5.5 to 8.4) in patients with high and low abundances of EGFR mutations, respectively (P = .014). Median PFS of patients with low abundance of EGFR mutations was significantly longer than that of those with wild-type tumors (2.1 months; 95% CI, 1.0 to 3.2; P = .010). Objective response rates (ORRs) were 62.7%, 44.4%, and 16.1%, and overall survival (OS) rates were 15.9 (95% CI, 13.4 to 18.3), 10.9 (95% CI, 2.7 to 19.1), and 8.7 months (95% CI, 4.6 to 12.7) for patients with high abundance of EGFR mutations, low abundance of EGFR mutations, and wild-type EGFR, respectively. The difference between patients with high and low abundances of EGFR mutations was not significant regarding ORR and OS. Conclusion The relative EGFR mutation abundance could predict benefit from EGFR-TKI treatment for advanced NSCLC.

Osteopontin (OPN) has close relationship with metastasis in hepatocellular carcinoma but its downstream signal pathways have not been well defined in hepatocellular carcinoma. The object of this study is to identify the associated signal pathways in human HCC tissues. The expressions of OPN, intergrin aV, CD44v6, P-FAK, FAK, P-Src, Src, P-ERK and P-AKT were assayed using TMA analysis. The relationship of OPN with P-ERK, P-Src and P-AKT were explored and the role in HCC metastasis was analysed. The expression levels of OPN, intergrin aV, CD44v6, P-FAK, P-Src, Src, P-ERK and P-AKT in HCC tissue were significantly higher than that in normal tissue (P value is less than 0.05). No significant difference was found between the expression levels of FAK in HCC tissue and normal tissue (P value is more than 0.05). OPN expression was significantly associated with Integrin av (P value is less than 0.01), CD44V6 (P value is less than 0.01) and P-ERK (P value is less than 0.05) but not with P-Src, P-FAK and P-AKT (P value is more than 0.05). The expressions of P-FAK (P value is less than 0.05), P-Src (P value is less than 0.01) and P-AKT (P value is less than 0.05) were significantly associated with Integrin av and the P-FAK expression was also significantly associated with CD44V6 (P value is less than 0.01). OPN promotes HCC metastasis though Integrin av/CD44V6/MAPK pathway in human HCC.

To investigate the clinical pathological characteristics and prognosis of gastrointestinal stromal tumors (GISTs).One hundred and seven cases, admitted to our hospital from Apr. 1996 to Oct. 2005, were detected by Envision immunohistochemical method and diagnosed as GISTs. Their pathological features, immunohistochemical phenotypes, clinical manifestations and imaging findings were analyzed.Of the 107 GISTs, 107 cases were positive for vimentin (107/107, 100%), 107 cases were positive for CD117 (107/107, 100%), 89 cases were positive for CD34 (89/107, 83.2%), 14 cases were positive for SMA (14/107, 13.1%), 10 cases were positive for desmin (10/107, 9.3%), 22 cases were positive for S-100 (22/87, 20.6%) and 15 cases were positive for NSE (15/107, 14.0%). Among all the GISTs, 73 cases occurred in stomach (68.2%), 28 in small intestine (26.2%), 1 in colon (0.9%) and 5 occurred in other position including mesentery, omentum, and retroperitoneum (4.7%). Fifteen cases were diagnosed as very low grade (14.0%), 25 cases as low grade (23.4%), 33 cases as low malignancy (30.8%) and 34 cases as high malignancy (31.8%). The follow-up was obtained successfully in 89 cases (83.2%). Fourteen cases (13.1%) were confirmed to have recurrences or metastases by review and medical records.The diagnosis of GIST depends on pathological observation and immunohistochemical study. CD117 is a sensitive marker for the diagnosis of GIST. Surgical resection is the choice for treating GIST. Extended resection, even combined resection of involved organs, is required for malignant GIST.

Hypothermia has been demonstrated to protect the brain from ischemia or traumatic brain injury. Achieving profound hypothermia has relied on techniques requiring total body cooling, which may result in serious cardiovascular and pulmonary complications. A technique to selectively cool the brain could conceivably exert a marked protection on cerebral structures and provide a relatively bloodless operative surgical field without systemic complications. Accordingly, this approach was tried in 7 rhesus monkeys after induction of general anesthesia. The right internal carotid artery and both internal jugular veins were each occlusively cannulated and connected to a circulation pump. The left internal carotid artery, both external carotid arteries, and both external jugular veins were temporarily clamped to establish severe cerebral ischemia. Using a closed-circuit system, cooled Ringer's lactate liquid (4 degrees C) was infused through right internal carotid artery with outflow draining though both internal jugular veins. Cooled perfusate decreased cerebral temperature to the target temperature of 15 degrees C. Thereafter, pump flow was discontinued, and brains were rewarmed spontaneously, while the temporarily clamped carotid arteries and jugular veins were opened to resume normal cerebral blood circulation. Neurological functions were recorded daily and cerebral histology was examined at the conclusion of the experiment. Magnetic resonance (MR) scans were routinely taken before and 3 weeks after ischemia. In the normothermia control group of five rhesus monkeys, Ringer's solution at 37 degrees C was infused in the same manner as the cold solution with cerebral temperature maintained at 36.7 +/- 0.32 degrees C. Right cerebral temperature decreased from 36.5 +/- 0.49 to 15.5 +/- 2.29 degrees C, and simultaneously the left cerebral temperature decreased from 36.4 +/- 0.38 to 16.3 +/- 2.4 degrees C for 62.8 +/- 9.76 min during selective cerebral cooled Ringer's liquid perfusion. In contrast, rectal temperature was only reduced to 32.4 +/- 0.96 degrees C from a baseline of 37.2 +/- 0.76 degrees C. Internal jugular vein hematocrit was 38.2 +/- 0.31% before perfusion and 2.82 +/- 0.46% at the end of perfusion in profound hypothermia group; hematocrit was 39.7 +/- 0.62% before perfusion and 3.42 +/- 0.38% at the end of perfusion in the normothermia group. In the hypothermic group, neurological functions were normal during 6 months of follow-up, and microscopic examination of brain tissue did not show evidence of pathological changes in hippocampus or medulla. MR scans did not show any cerebral infarction. In contrast, none of the monkeys in normothermia group survived for more than several hours, and microscopic examination of the brain revealed extensive neuronal necrosis within the medulla. Selective cerebral profound hypothermia provides significant histologic and neurologic protection after severe cerebral ischemia. In addition, there were no major complications, and the operative field remained relatively bloodless in the profound hypothermic group.

To study the genetic alterations of ganglioglioma through the entire genome, and to investigate the pathogenesis of this neoplasm.Comparative genomic hybridization was used to provide an overview of genetic abnormalities in gangliogliomas.Five cases of gangliogliomas, including 3 males and 2 females, were studied genetically. Loss of genetic materials on the short arm of chromosome 9(9p) was a common genetic alteration found in 3 of 5 cases. Overrepresentation of chromosome 7 was another recurrent chromosomal imbalance, which was further confirmed by fluorescence in situ hybridization. Immunohistochemical analysis was performed on epidermal growth factor receptor (EGFR), which was located on 7p11-p13. All five cases revealed no abnormal expression of EGFR. On the other hand, genetic imbalances were also involved in multiple chromosomes including 2q33-q34, 8q12-q22, 14q21-qter, 15q26-qter and Y.Loss of genetic materials on chromosome 9p and gain on chromosome 7 may be associated with the pathogenesis of this neoplasm.

To investigate global genetic alterations in medulloblastoma, and to localize critical chromosomal loci with allelic imbalances associated with the development of medulloblastoma.A high-resolution genome-wide allelotype analysis, including 384 microsatellite markers, was performed in 12 medulloblastomas.An average of 238 (62.3%) allelic imbalances were detected on all 39 autosomal arms. Non-random allelic gains or losses were detected on chromosomes 7q (58.3%), 8p (66.7%), 16q (58.3%), 17p (58.3%) and 17q (66.7%). In addition, chromosomal arms with frequencies of allelic imbalances higher than the mean percentage were identified on 3p (33.3%), 3q (33.3%), 4q (41.7%), 7p (33.3%), 8q (41.7%), 10q (41.7%), 13q (33.3%), 14q (33.3%) and 20q (33.3%). No relationship was found between the frequency of allelic imbalances and the clinical outcome of the patients.A global view of the genetic alterations in medulloblastoma was provided. The allelic imbalances involving chromosomes 7q, 8p, 16q, 17p and 17q may play an important role in the pathogenesis of medulloblastoma.

Object. The loss of genetic material from specific chromosome loci is a common feature in the oncogenesis of tumors and is often indicative of the presence of important tumor suppressor genes at these loci. Recent molecular genetic analyses have demonstrated frequent loss of chromosomes 10q, 11, and 16 in medulloblastomas. The aim of this study was to localize the targeted deletion regions on the three aforementioned chromosomes in medulloblastomas. Methods. Loss of heterozygosity (LOH) was examined on chromosomes 10q, 11, and 16 in a series of 22 primary and two recurrent medulloblastomas by using polymerase chain reaction—based microsatellite analysis. The DNA extracted from the tumors and corresponding normal blood samples were amplified independently in the presence of radioactively labeled microsatellite primers, resolved by denaturing gel electrophoresis and processed for autoradiography. The DNA obtained from control blood samples that displayed allelic heterozygosity at a given microsatellite locus were considered informative. Loss of heterozygosity was inferred when the allelic signal intensity of the tumor sample was reduced by at least 40%, relative to that of the constitutional control. The LOH analysis demonstrated that deletions of chromosomes 10q, 11p, and 16q are recurrent genetic events in the development of medulloblastomas. Three subchromosomal regions of loss have been identified and are localized to the deleted in malignant brain tumors 1 [DMBT1] gene site on chromosomes 10q25, 11p13–11p15.1, and 16q24.1–24.3. Conclusions. These results indicate that DMBT1 is closely associated with the oncogenesis of medulloblastomas and highlight regions of loss on chromosomes 11p and 16q for further fine mapping and cloning of candidate tumor suppressor genes that are important for the genesis of medulloblastoma.

We have used a new method of genomic microarray to investigate amplification of oncogenes throughout the genome of glioblastoma multiforme (GBM). Array-based comparative genomic hybridization (array CGH) allows for simultaneous examination of 58 oncogenes/amplicons that are commonly amplified in various human cancers. Amplification of multiple oncogenes in human cancers can be rapidly determined in a single experiment. Tumor DNA and normal control DNA were labeled by nick translation with green- and red-tagged nucleotides, respectively. Instead of hybridizing to normal metaphase chromosomes in conventional comparative genomic hybridization (CGH), the probes of the mixed fluorescent labeled DNA were applied to genomic array templates comprised of P1, PAC, and BAC clones of 58 target oncogenes. The baseline for measuring deviations was established by performing a series of independent array CGH using test and reference DNA made from normal individuals. In the present study, we examined fourteen GBMs (seven cell lines and seven tumours) with CGH and array CGH to reveal the particular oncogenes associated with this cancer. High-level amplifications were identified on the oncogenes/amplicons CDK4, GLI, MYCN, MYC, MDM2, and PDGFRA. The highest frequencies of gains were detected on PIK3CA (64.3%), EGFR (57.1%), CSE1L (57.1%), NRAS (50%), MYCN (42.9%), FGR (35.7%), ESR (35.7%), PGY1 (35.7%), and D17S167 (35.7%). These genes are suggested to be involved in the GBM tumorigenesis.

Object. Central neurocytomas are rare neuronal tumors commonly found in the intraventricular regions. Little is known about the tumorigenesis of these neoplasms. The aim of this study was to provide an overview of genetic imbalances in central neurocytomas.Methods. In this study, comparative genomic hybridization was used to identify DNA sequence copy number changes (losses and gains) in a series of 10 central neurocytomas. Tumor DNA and normal reference DNA were differentially labeled and allowed to cohybridize to normal metaphase chromosomes. After hybridization and fluorescent staining of the bound DNA, regions of gain or of loss of DNA sequences were detected as changes in the tumor/normal fluorescence intensity ratio along the target metaphase chromosomes. A gain of DNA sequence was detected in chromosomes 2p, 10q, and 18q. A protooncogene, Bcl2, which maps to 18q21, was evaluated by immunohistochemical analysis to determine its role in the formation of central neurocytomas.Conclusions. In this study the authors identified recurrent genetic changes on chromosomes 2p, 10q, and 18q in central neurocytomas and highlighted chromosomal regions for additional mapping and cloning of candidate genes that are important in the development of central neurocytomas.

To investigate the expression deficiency of key molecular markers in the homologous recombination pathway.Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mutated (ATM), ATM-Rad3-related (ATR), mediator of DNA damage checkpoint protein 1 (MDC1) and meiotic recombination 11 (Mre11) were correlated with their clinicopathological parameters in gastric cancer (GC). One hundred and twenty treatment-naive GC samples were formalin-fixed and paraffin-embedded into tissue blocks. Two representative cores from each block were extracted and constructed into tissue microarrays. Expression levels of BRCA1, ATM, ATR, MDC1 and Mre11 were determined using immunohistochemical analysis, and correlated with clinical parameters, including age, gender, Lauren subtype, tumor grades, clinical stage and overall survival.Expression loss of BRCA1, ATM, ATR, MDC1, and Mre11 was found in 21.4%, 20.2%, 21.0%, 11.1% and 4.6%, respectively, of interpretable cases. BRCA1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 8.2% vs 31.7%, P = 0.001), higher tumor grade (I/II vs III, 10.7% vs 20.5; I/II vs IV, 10.7% vs 54.5%, P = 0.047) and advanced clinical stage (I/II vs III, 12.9% vs 16.9%; I/II vs IV, 12.9% vs 45.5%, P = 0.006). MDC1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 0% vs 19.7%, P = 0.001) and higher tumor grade (I/II vs III, 0% vs 12%; I/II vs IV, 0% vs 30.8%, P = 0.012). In addition, the survival time of the patients with expression loss of BRCA1 was significantly shorter than those with positive expression of BRCA1 (2-year survival rate, 32.4% vs 62.8%, P = 0.015). No correlations were found between clinicopathological parameters and expression loss of ATM, ATR and Mre11.Our results support the hypothesis that homologous recombination deficiency plays an important role in the progression of gastric carcinoma. Loss of expression of BRCA1 and MDC1 may serve as predictive factors in tumor development or progression in GC patients.