共查询到20条相似文献,搜索用时 31 毫秒
1.
Vassiliki Kotoula Mattheos Bobos Zoi Alexopoulou Christos Papadimitriou Kyriaki Papadopoulou Elpida Charalambous Eleftheria Tsolaki Grigorios Xepapadakis Irene Nicolaou Irene Papaspirou Gerasimos Aravantinos Christos Christodoulou Ioannis Efstratiou Helen Gogas George Fountzilas 《PloS one》2014,9(8)
Background
HER2 and TOP2A gene status are assessed for diagnostic and research purposes in breast cancer with fluorescence in situ hybridization (FISH). However, FISH probes do not target only the annotated gene, while chromosome 17 (chr17) is among the most unstable chromosomes in breast cancer. Here we asked whether the status of specifically targeted genes on chr17 might help in refining prognosis of early high-risk breast cancer patients.Methods
Copy numbers (CN) for 14 genes on chr17, 4 of which were within and 10 outside the core HER2 amplicon (HER2- and non-HER2-genes, respectively) were assessed with qPCR in 485 paraffin-embedded tumor tissue samples from breast cancer patients treated with adjuvant chemotherapy in the frame of two randomized phase III trials.Principal Findings
HER2-genes CN strongly correlated to each other (Spearman’s rho >0.6) and were concordant with FISH HER2 status (Kappa 0.6697 for ERBB2 CN). TOP2A CN were not concordant with TOP2A FISH status (Kappa 0.1154). CN hierarchical clustering revealed distinct patterns of gains, losses and complex alterations in HER2- and non-HER2-genes associated with IHC4 breast cancer subtypes. Upon multivariate analysis, non-HER2-gene gains independently predicted for shorter disease-free survival (DFS) and overall survival (OS) in patients with triple-negative cancer, as compared to luminal and HER2-positive tumors (interaction p = 0.007 for DFS and p = 0.011 for OS). Similarly, non-HER2-gene gains were associated with worse prognosis in patients who had undergone breast-conserving surgery as compared to modified radical mastectomy (p = 0.004 for both DFS and OS). Non-HER2-gene losses were unfavorable prognosticators in patients with 1–3 metastatic nodes, as compared to those with 4 or more nodes (p = 0.017 for DFS and p = 0.001 for OS).Conclusions
TOP2A FISH and qPCR may not identify the same pathology on chr17q. Non-HER2 chr17 CN patterns may further predict outcome in breast cancer patients with known favorable and unfavorable prognosis. 相似文献2.
Monica M Reinholz Jeanette E Eckel-Passow S Keith Anderson Yan W Asmann Michael A Zschunke Ann L Oberg Ann E McCullough Amylou C Dueck Beiyun Chen Craig S April Eliza Wickham-Garcia Robert B Jenkins Julie M Cunningham Jin Jen Edith A Perez Jian-Bing Fan Wilma L Lingle 《BMC medical genomics》2010,3(1):1-16
Background
The c D NA-mediated A nnealing, extension, S election and L igation (DASL) assay has become a suitable gene expression profiling system for degraded RNA from paraffin-embedded tissue. We examined assay characteristics and the performance of the DASL 502-gene Cancer Panelv1 (1.5K) and 24,526-gene panel (24K) platforms at differentiating nine human epidermal growth factor receptor 2- positive (HER2+) and 11 HER2-negative (HER2-) paraffin-embedded breast tumors.Methods
Bland-Altman plots and Spearman correlations evaluated intra/inter-panel agreement of normalized expression values. Unequal-variance t -statistics tested for differences in expression levels between HER2 + and HER2 - tumors. Regulatory network analysis was performed using Metacore (GeneGo Inc., St. Joseph, MI).Results
Technical replicate correlations ranged between 0.815-0.956 and 0.986-0.997 for the 1.5K and 24K panels, respectively. Inter-panel correlations of expression values for the common 498 genes across the two panels ranged between 0.485-0.573. Inter-panel correlations of expression values of 17 probes with base-pair sequence matches between the 1.5K and 24K panels ranged between 0.652-0.899. In both panels, erythroblastic leukemia viral oncogene homolog 2 (ERBB2) was the most differentially expressed gene between the HER2 + and HER2 - tumors and seven additional genes had p-values < 0.05 and log2 -fold changes > |0.5| in expression between HER2 + and HER2 - tumors: topoisomerase II alpha (TOP2A), cyclin a2 (CCNA2), v-fos fbj murine osteosarcoma viral oncogene homolog (FOS), wingless-type mmtv integration site family, member 5a (WNT5A), growth factor receptor-bound protein 7 (GRB7), cell division cycle 2 (CDC2), and baculoviral iap repeat-containing protein 5 (BIRC5). The top 52 discriminating probes from the 24K panel are enriched with genes belonging to the regulatory networks centered around v-myc avian myelocytomatosis viral oncogene homolog (MYC), tumor protein p53 (TP53), and estrogen receptor α (ESR1). Network analysis with a two-step extension also showed that the eight discriminating genes common to the 1.5K and 24K panels are functionally linked together through MYC, TP53, and ESR1.Conclusions
The relative RNA abundance obtained from two highly differing density gene panels are correlated with eight common genes differentiating HER2 + and HER2 - breast tumors. Network analyses demonstrated biological consistency between the 1.5K and 24K gene panels. 相似文献3.
Erika Feltrin Stefano Campanaro Alexander D Diehl Elisabeth Ehler Georgine Faulkner Jennifer Fordham Chiara Gardin Midori Harris David Hill Ralph Knoell Paolo Laveder Lorenza Mittempergher Alessandra Nori Carlo Reggiani Vincenzo Sorrentino Pompeo Volpe Ivano Zara Giorgio Valle Jennifer Deegan née Clark 《BMC medical genomics》2009,2(1):1-8
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HER2 gene amplification is observed in about 15% of breast cancers. The subgroup of HER2-positive breast cancers appears to be heterogeneous and presents complex patterns of gene amplification at the locus on chromosome 17q12-21. The molecular variations within the chromosome 17q amplicon and their clinical implications remain largely unknown. Besides the well-known TOP2A gene encoding Topoisomerase IIA, other genes might also be amplified and could play functional roles in breast cancer development and progression. This review will focus on the current knowledge concerning the HER2 amplicon heterogeneity, its clinical and biological impact and the pitfalls associated with the evaluation of gene amplifications at this locus, with particular attention to TOP2A and the link between TOP2A and anthracycline benefit. In addition it will discuss the clinical and biological implications of the amplification of ten other genes at this locus (MED1, STARD3, GRB7, THRA, RARA, IGFPB4, CCR7, KRT20, KRT19 and GAST) in breast cancer. 相似文献
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Faxiang Wan Yu Pan Jinghua Li Xiangfu Chen Yanglu Pan Yongqing Wang Shibing Tian Xingguo Zhang 《Plant cell reports》2014,33(12):1951-1961
Key message
Our study shows that the expression of AtCBF3 and AtCOR15A improved the chilling tolerance in transgenic eggplant.Abstract
In an attempt to improve chilling tolerance of eggplant (Solanum melongena L) plants, Arabidopsis C-repeat binding factor 3 (AtCBF3) and cold-regulated 15A (AtCOR15A) genes both driven by an Arabidopsis RESPONSIVE TO DESSICATION 29A promoter (AtRD29A) were transferred into the plants of eggplant cultivar Sanyueqie. Two independent homozygous transgenic lines were tested for their cold tolerance. The leaves of the transgenic plants in both lines withered much slower and slighter than the wild-type plants after exposure to cold stress treatment at 2 ± 1 °C. The gene expression of AtCBF3 and AtCOR15A was significantly increased as well as the proline content and the levels of catalase and peroxidase activities, while the relative electrical conductivity and the malondialdehyde content were remarkably decreased in the transgenic plants compared with the wild type at 4 ± 0.5 °C. The results showed that the expression of the exogenous AtCBF3 and AtCOR15A could promote the cold adaptation process to protect eggplant plants from chilling stress. 相似文献6.
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Toko Tanikawa Masako Dannoura Keitarou Yamase Hidetoshi Ikeno Yasuhiro Hirano 《Plant and Soil》2014,380(1-2):445-450
Introduction
We showed that root orientation affected a parameter of ground penetrating radar (GPR), amplitude area (A) (Tanikawa et al. Plant Soil 373:317–327, 2013). The aims of this reply to Wu et al. (2014) are (i) to correct the two inaccuracies in Tanikawa et al. (2013) and (ii) to improve our method of estimating A(90°) using A(x) of root angle x.Methods
Measured A values of Tanikawa et al. (2013) were analyzed with the modified equations.Results
The first inaccuracy was the use of incorrect units for the coefficient b (the phase shift) in the sinusoidal waveform of A(x). The units should have been radians instead of degrees. The second inaccuracy was the mis-derivation of A(x) into A(x?+?90°). In the modified method, A(90°) was estimated by A(x) from two orthogonally intersecting transect lines and a transect line at a diagonal to them.Conclusions
The two inaccuracies did not affect the previous main conclusions that the parameter T was suitable for estimating root diameter and that grid transects are likely to identify clear hyperbolas reflecting roots in radar profiles (Tanikawa et al. 2013). By the improved method, we could accurately estimate root diameter by scanning using three transect lines intersecting at angles of x, x?+?45°, and x?+?90°. 相似文献10.
John E. Major Alex Mossler Debby C. Barsi Moira Campbell John Malcolm 《Trees - Structure and Function》2014,28(2):329-344
Key message
After 3 years of CO 2 treatments, A stimulation from ambient to elevated CO 2 was strongly related to the total dry mass change (%), supporting the sink demand A hypothesis.Abstract
Adaptations related to gas exchange are important fitness traits in plants and have significant growth and ecological implications. Assimilation (A) and assimilation to internal CO2 (AC i ) response curve parameters were quantified from a red spruce (RS) (Picea rubens Sarg.)—black spruce (BS) [P. mariana (Mill.) B.S.P.] controlled-cross hybrid complex grown under ambient and elevated CO2 conditions. Under ambient conditions, maximum A (A max), maximum rate of carboxylation by rubisco (V cmax), maximum rate of electron transport (J max), and carboxylation efficiency (CE) generally increased with increasing BS content; however, under elevated CO2 conditions, hybrid index 50 (hybrid index number is the percentage of RS, balance BS) often had greater values than the other indices. There were significant hybrid index, CO2, and hybrid index × CO2 effects for A growth at 360 ppm (A 360) and 720 ppm (A 720). The net A stimulation (A stim), from ambient to elevated CO2 treatment after 3 years was 10.8, 57.8, 74.1, 69.8, and 58.7 %, for hybrid indices 0 (BS), 25, 50, 75, and 100 (RS), respectively. Why does BS have the least A stim, hybrid index 50 the most, and RS a moderate level? There was a significant relationship between A 360 and ambient total biomass among indices (P = 0.096), but none was found between A 720 and elevated total biomass. However, A stim (%) was strongly related to the change in total dry mass (%) in response to elevated CO2 (R 2 = 0.931, P = 0.008), supporting the hypothesis that sink demand drives A. Traits A max, V cmax and J max were correlated to total chlorophyll concentration. Moreover, A max V cmax and J max also showed a significant underlying male effect, particularly under ambient conditions consistent with the paternal inheritance of the chloroplast genome. 相似文献11.
Spatial and temporal variation in malaria transmission in a low endemicity area in northern Tanzania
MJAM Oesterholt JT Bousema OK Mwerinde C Harris P Lushino A Masokoto H Mwerinde FW Mosha CJ Drakeley 《Malaria journal》2006,5(1):1-7
Background
Current detection or screening for malaria infection necessitates drawing blood by fingerprick or venipuncture, which poses risks and limitations for repeated measurement. This study presents PCR detection of Plasmodium falciparum in human urine and saliva samples, and illustrates this potential application in genotyping malaria infections.Methods
Urine and saliva were obtained from 47 thick film positive and 4 negative individuals one day after collection of blood slides and filter paper blood spots. P. falciparum DNA was extracted from blood, urine and saliva, in separate groups, using the Chelex method or Qiagen DNEasy® kit (urine and saliva only). Blood, urine and saliva extracts were subjected to PCR in separate batches. Amplicons from the various sample types were examined for MSP2 polymorphisms and restriction fragment patterns on DHFR amino acid codon 59.Results and discussion
Malaria infections exhibited primarily low-grade parasite densities, with a geometric mean of 775 asexual parasites/μl. Regularly matching polymorphic MSP2 genotypes were found between the corresponding urine, saliva and peripheral blood amplicons of each individual, with different inter-individual polymorphic genotypes. Amplicon yields were significantly dependent on DNA extraction method, parasite density and primer set (p < 0.001). A Qiagen® kit extraction had more than 2× higher amplicon yield than the Chelex method, for both urine and saliva. Amplicon yields were 1.6 fold higher from saliva than urine. For each unit increase in log parasite density, the probability of amplicon enhanced 1.8 fold. Highest amplicon yields were obtained from the primer set with the shortest PCR product.Conclusion
P. falciparum infection is detectable by PCR on human urine and saliva samples. Subject to further refinement of extraction technique and amplicon yields, large-scale malaria parasite screening and epidemiological surveys could be possible without the need to collect blood and use of needles or sharps. 相似文献12.
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Lisha Chen Xiaoyan Liu Xinying Zhang Shanshan Liu Jing Wei Gang Xu 《Plant and Soil》2013,368(1-2):355-363
Aims
Responses of typical wetland plant Acorus tatarinowii to diesel stress were investigated to provide basis of ecological monitoring system and phytoremediation for diesel-contaminated wetland.Methods
Greenhouse experiments were established to determine the germinability of seedlings, hydrogen peroxide in leaves, and DNA damage in roots exposed to a range of potentially phytotoxic diesel.Results
The presence of diesel did not benefit the growth of A. tatarinowii. The germination ratio and germination rate decreased with the increase of diesel concentration, both the lowest value appeared when the concentration of diesel was 10,000 mg?kg?1. The lowest diesel concentration (2,000 mg?kg?1) in the soil significantly reduced the length, average diameter, and projected area of root, especially on the stress of the higher diesel concentration (4,000, 8,000, and 10,000 mg?kg?1). Furthermore, H2O2 concentration in leaves rose with the increasing concentration of diesel. However, no DNA oxidative damage to root was observed in our experiment.Conclusions
Diesel exposure significantly inhabited the seed germination, root elongation, and seedlings growth of A. tatarinowii. Diesel stress caused the accumulation of H2O2 in the leaves of A. tatarinowii. 相似文献16.
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David Hersi Smith Ib Jarle Christensen Niels Frank Jensen Bo Markussen Maria Unni R?mer Sune Boris Nyg?rd Sven Müller Hans J?rgen Nielsen Nils Brünner Kirsten Vang Nielsen 《PloS one》2013,8(4)
Background
Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III CRC and how these can be detected by fluorescent in situ hybridization (FISH).Methods
Nine CRC cell line metaphase spreads were analyzed by FISH with a TOP1 probe in combination with a reference probe covering either the centromeric region of chromosome 20 (CEN-20) or chromosome 2 (CEN-2). Tissue sections from 154 chemonaive stage III CRC patients, previously studied with TOP1/CEN-20, were analyzed with TOP1/CEN-2. Relationships between biomarker status and overall survival (OS), time to recurrence (TTR) in CRC and time to local recurrence (LR; rectal cancer only) were determined.Results
TOP1 aberrations were observed in four cell line metaphases. In all cell lines CEN-2 was found to reflect chromosomal ploidy levels and therefore the TOP1/CEN-2 probe combination was selected to identify TOP1 gene gains (TOP1/CEN-2≥1.5). One hundred and three patients (68.2%) had TOP1 gain, of which 15 patients (14.6%) harbored an amplification (TOP1/CEN-20≥2.0). TOP1 gene gain did not have any association with clinical endpoints, whereas TOP1 amplification showed a non-significant trend towards longer TTR (multivariate HR: 0.50, p = 0.08). Once amplified cases were segregated from other cases of gene gain, non-amplified gene increases (TOP1/CEN-2≥1.5 and TOP1/CEN-20<2.0) showed a trend towards shorter TTR (univariate HR: 1.57, p = 0.07).Conclusions
TOP1 gene copy number increase occurs frequently in stage III CRC in a mechanism that often includes CEN-20. Using CEN-2 as a measurement for tumor ploidy levels, we were able to discriminate between different mechanisms of gene gain, which appeared to differ in prognostic impact. TOP1 FISH guidelines have been updated. 相似文献18.
Toko Tanikawa Yasuhiro Hirano Masako Dannoura Keitarou Yamase Kenji Aono Masahiro Ishii Tetsurou Igarashi Hidetoshi Ikeno Yoichi Kanazawa 《Plant and Soil》2013,373(1-2):317-327
Aim
Ground-penetrating radar (GPR) has been applied to detect coarse tree roots. The horizontal angle of a root crossing a scanning line is a factor that affects both root detection and waveform parameter values. The purpose of this study was to quantitatively evaluate the influence of root orientation (x, degree) on two major waveform parameters, amplitude area (A, dB × ns) and time interval between zero crossings (T, ns).Methods
We scanned four diameter classes of dowels in a sandy bed as simulated roots using a 900 MHz antenna from multiple angles to clarify the relationships between the parameters and x.Results
Angle x strongly affected reflection images and A values. The variation in A(x) fitted a sinusoidal waveform, whereas T was independent of x. The value of A scanning at 90° was estimated by A values of arbitrary x in two orthogonal transects. The sum of T in all reflected waveforms showed a significant linear correlation with dowel diameter.Conclusions
We clarified that root orientation dramatically affected root detection and A values. The sum of T of all reflected waveforms was a suitable parameter for estimating root diameter. Applying grid transects can overcome the effects of root orientation. 相似文献19.
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