Xiaofeng Zhou - Academia.edu (original) (raw)
Papers by Xiaofeng Zhou
Journal of Neuroscience Research, 2001
The Eph receptor ligands, the ephrins, are membrane-bound molecules that play important roles in ... more The Eph receptor ligands, the ephrins, are membrane-bound molecules that play important roles in establishing intercellular communication after neurogenesis by regulating cell migration, axon pathfinding, and topographic mapping. In diverse systems, such as embryonic day 17.5 (E17.5) hippocampal and cortical neurons, repulsive/inhibitory mechanisms underlie these cellular effects. However, although ligand/receptor expression occurs far earlier, during brain neurogenesis, little is known about potential ephrin functions in initial process outgrowth. We have examined ligand/receptor expression in E13.5 cortex in vivo and in culture, using alkaline phosphatase (AP)-conjugated reagents and RNase protection assay. B ephrins are highly expressed, including B1, B2, and B3, whereas A ephrins exhibit low expression levels. In contrast, the Eph receptors demonstrate an opposite pattern, exhibiting high levels of Eph A3, A4, and A5 mRNA transcripts and low levels of the B-class receptors. To examine effects on neurite outgrowth, soluble ephrins were incubated with antihuman IgG antibody, producing oligomeric agonist complexes, and dried onto culture dishes. Unexpectedly, both ephrin A and B complexes increased process outgrowth: Seventy to eighty percent of neuronal precursors exhibited long neurites on ephrins, whereas only 5–10% of cells had neurites on IgG control substrates, indicating that ephrins stimulated neuritogenesis by early cortical neurons. These observations suggest that ephrin ligand/receptor systems play ontogenetic roles not previously considered, activating mechanisms other than cellular repulsion. Ephrin systems may induce initial process elaboration by early cortical neurons that is restricted at later stages by well-characterized repulsive signaling mechanisms. J Neurosci. Res. 66:1054–1063, 2001. © 2001 Wiley-Liss, Inc.
Developmental Biology, 2000
The superior cervical ganglion (SCG) is a well-characterized model of neural development, in whic... more The superior cervical ganglion (SCG) is a well-characterized model of neural development, in which several regulatory signals have been identified. Vasoactive intestinal peptide (VIP) has been found to regulate diverse ontogenetic processes in sympathetics, though functional requirements for high peptide concentrations suggest that other ligands are involved. We now describe expression and functions of pituitary adenylate cyclase-activating polypeptide (PACAP) during SCG ontogeny, suggesting that the peptide plays critical roles in neurogenesis. PACAP and PACAP receptor (PAC(1)) mRNA's were detected at embryonic days 14.5 (E14.5) through E17.5 in vivo and virtually all precursors exhibited ligand and receptor, indicating that the system is expressed as neuroblasts proliferate. Exposure of cultured precursors to PACAP peptides, containing 27 or 38 residues, increased mitogenic activity 4-fold. Significantly, PACAP was 1000-fold more potent than VIP and a highly potent and selective antagonist entirely blocked effects of micromolar VIP, consistent with both peptides acting via PAC(1) receptors. Moreover, PACAP potently enhanced precursor survival more than 2-fold, suggesting that previously defined VIP effects were mediated via PAC(1) receptors and that PACAP is the more significant developmental signal. In addition to neurogenesis, PACAP promoted neuronal differentiation, increasing neurite outgrowth 4-fold and enhancing expression of neurotrophin receptors trkC and trkA. Since PACAP potently activated cAMP and PI pathways and increased intracellular Ca(2+), the peptide may interact with other developmental signals. PACAP stimulation of precursor mitosis, survival, and trk receptor expression suggests that the signaling system plays a critical autocrine role during sympathetic neurogenesis.
Journal of Neurochemistry, 2007
Normal brain development requires coordinated regulation of several processes including prolifera... more Normal brain development requires coordinated regulation of several processes including proliferation, differentiation, and cell death. Multiple factors from endogenous and exogenous sources interact to elicit positive as well as negative regulation of these processes. In particular, the perinatal rat brain is highly vulnerable to specific developmental insults that produce later cognitive abnormalities. We used this model to examine the developmental effects of an exogenous factor of great concern, methylmercury (MeHg). Seven-day-old rats received a single injection of MeHg (5 μg/gbw). MeHg inhibited DNA synthesis by 44% and reduced levels of cyclins D1, D3, and E at 24 h in the hippocampus, but not the cerebellum. Toxicity was associated acutely with caspase-dependent programmed cell death. MeHg exposure led to reductions in hippocampal size (21%) and cell numbers 2 weeks later, especially in the granule cell layer (16%) and hilus (50%) of the dentate gyrus defined stereologically, suggesting that neurons might be particularly vulnerable. Consistent with this, perinatal exposure led to profound deficits in juvenile hippocampal-dependent learning during training on a spatial navigation task. In aggregate, these studies indicate that exposure to one dose of MeHg during the perinatal period acutely induces apoptotic cell death, which results in later deficits in hippocampal structure and function.
Insect Biochemistry and Molecular Biology, 2000
The Israeli population of the cotton bollworm, Helicoverpa armigera (Hübner), undergoes a short-d... more The Israeli population of the cotton bollworm, Helicoverpa armigera (Hübner), undergoes a short-day, low-temperature pupal diapause and is also suspected of being a seasonal migrant in the eastern Mediterranean region. H. armigera were reared in the laboratory under several constant temperature and photoperiodic combinations which simulate average conditions encountered in the spring, summer, early-autumn and late-autumn in Israel. Juvenile hormone (JH) biosynthesis, the onset of calling behavior, sex pheromone production and ovarian development were examined in virgin female moths subsequent to eclosion. Allatal maturation, defined as acquisition of competence to synthesize JH, was significantly delayed in moths reared under simulated spring conditions. This was probably the cause for the observed delay in ovarian development and the onset of calling behavior, and to the reduction in sex pheromone biosynthesis. The delay in female sexual maturation, commonly associated with migratory flight, is consistent with presumptive pre-reproductive migration in H. armigera. : S 0 9 6 5 -17 48 ( 0 0 ) 0 0 05 9-X
Environmental Entomology, 2000
Heredity, 2000
The genetic structure of the cotton bollworm, Helicoverpa armigera (HuÈ bner) (Lepidoptera: Noctu... more The genetic structure of the cotton bollworm, Helicoverpa armigera (HuÈ bner) (Lepidoptera: Noctuidae), was studied in the eastern Mediterranean. Moths were sampled in six locations (®ve in Israel, and one in Turkey) and their genetic relationship was analysed using RAPD-PCR. Three 10-oligonucleotide primers revealed 84 presumptive polymorphic loci that were used to estimate population structure. Results reveal low level of genetic distances among Israeli and Turkish populations. The estimated values of F ST ST and h for the eastern Mediterranean populations were very low across all populations, indicating a high level of gene¯ow. Four distinct RAPD-product pro®le types were de®ned, and found in all Israeli and Turkish populations. Although no isolation by geographical distance was detected, topographical barriers may play a role in such isolation.
Human Genetics, 2004
Like most human cancers, oral squamous cell carcinoma (SCC) is characterized by genetic instabili... more Like most human cancers, oral squamous cell carcinoma (SCC) is characterized by genetic instabilities. In this study, a single platform (Affymetrix 10K SNP mapping array) was used to generate both loss of heterozygosity (LOH) and DNA copy number abnormality (CNA) read-outs for precise and high-resolution genetic alteration profiles. As a proof of principle, we performed this concordant analysis on a panel of deletion and trisomy cell lines with known chromosomal alterations and the precise LOH and CNA regions were detected as expected. Using a previously described oral SCC progression model system, we identified a set of genomic regions that may be associated with the malignancy progression, including chromosome regions 3pter–3p35.3, 3p14.1–3p13, 11p, 11q14.3–11q22.2, and 11q13.5–11q14.1. These data show that it is feasible to utilize high-density SNP arrays to generate concordant LOH and CNA profiles at high resolution.
Since morbidity and mortality rates due to oral cavity and oropharyngeal squamous cell carcinoma ... more Since morbidity and mortality rates due to oral cavity and oropharyngeal squamous cell carcinoma (OSCC) have improved little in the past 30 years, early detection or prevention of this disease is likely to be most effective. Using laser-capture microdissection, we have identified the expression of 2 cellular genes that are uniquely associated with OSCC: interleukin (IL) 6 and IL-8. These cytokines may contribute to the pathogenesis of this disease, and have been linked with increased tumor growth and metastasis.
BMC Genomics, 2008
The head and neck/oral squamous cell carcinoma (HNOSCC) is a diverse group of cancers, which deve... more The head and neck/oral squamous cell carcinoma (HNOSCC) is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC) is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC.
Neoplasia, 2006
Suppression of ovarian tumor growth by chromosome 3p was demonstrated in a previous study. Delete... more Suppression of ovarian tumor growth by chromosome 3p was demonstrated in a previous study. Deleted in Lung and Esophageal Cancer 1 (DLEC1) on 3p22.3 is a candidate tumor suppressor in lung, esophageal, and renal cancers. The potential involvement of DLEC1 in epithelial ovarian cancer remains unknown. In the present study, DLEC1 downregulation was found in ovarian cancer cell lines and primary ovarian tumors. Focus-expressed DLEC1 in two ovarian cancer cell lines resulted in 41% to 52% inhibition of colony formation. No chromosomal loss of chromosome 3p22.3 in any ovarian cancer cell line or tissue was found. Promoter hypermethylation of DLEC1 was detected in ovarian cancer cell lines with reduced DLEC1 transcripts, whereas methylation was not detected in normal ovarian epithelium and DLEC1-expressing ovarian cancer cell lines. Treatment with demethylating agent enhanced DLEC1 expression in 90% (9 of 10) of ovarian cancer cell lines. DLEC1 promoter methylation was examined in 13 high-grade ovarian tumor tissues with DLEC1 downregulation, in which 54% of the tumors showed DLEC1 methylation. In addition, 80% of ovarian cancer cell lines significantly upregulated DLEC1 transcripts after histone deacetylase inhibitor treatment. Therefore, our results suggested that DLEC1 suppressed the growth of ovarian cancer cells and that its downregulation was closely associated with promoter hypermethylation and histone hypoacetylation. Neoplasia (2006) 8, 268 -278
Neoplasia, 2006
Regional lymph node metastasis is a critical event in oral tongue squamous cell carcinoma (OTSCC)... more Regional lymph node metastasis is a critical event in oral tongue squamous cell carcinoma (OTSCC) progression. The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making for improved management of OTSCC patients. Global expressional profiles were obtained for 25 primary OTSCCs, where 11 cases showed lymph node metastasis (pN + ) histologically and 14 cases were nonmetastatic (pN À ). Seven of pN + cases also exhibited extracapsular spread (ECS) of metastatic nodes. Multiple expression indices were used to generate signature gene sets for pN +/À and ECS +/À cases. Selected genes from signature gene sets were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The classification powers of these genes were then evaluated using a logistic model, receiver operating characteristic curve analysis, and leave-oneout cross-validation. qRT-PCR validation data showed that differences at RNA levels are either statistically significant (P < .05) or suggestive (P < .1) for six of eight genes tested (BMP2, CTTN, EEF1A1, GTSE1, MMP9, and EGFR) for pN +/À cases, and for five of eight genes tested (BMP2, CTTN, EEF1A1, MMP9, and EGFR) for ECS +/À cases. Logistic models with specific combinations of genes (CTTN+MMP9+EGFR for pN and CTTN+EEF1A1+ MMP9 for ECS) achieved perfect specificity and sensitivity. Leave-one-out cross-validation showed overall accuracy rates of 85% for both pN and ECS prediction models. Our results demonstrated that the pN and the ECS of OTSCCs can be predicted by gene expression analyses of primary tumors. Neoplasia (2006) 8, 925-932
Molecular and Cellular Biology, 2006
The phytohormone abscisic acid (ABA) plays an important role in modulating plant growth, developm... more The phytohormone abscisic acid (ABA) plays an important role in modulating plant growth, development, and stress responses. In a genetic screen for mutants with altered drought stress responses, we identified an ABA-overly sensitive mutant, the abo1 mutant, which showed a drought-resistant phenotype. The abo1 mutation enhances ABA-induced stomatal closing and increases ABA sensitivity in inhibiting seedling growth. abo1 mutants are more resistant to oxidative stress than the wild type and show reduced levels of transcripts of several stress-or ABA-responsive genes. Interestingly, the mutation also differentially modulates the development and growth of adjacent guard cells. Map-based cloning identified ABO1 as a new allele of ELO2, which encodes a homolog of Saccharomyces cerevisiae Iki3/Elp1/Tot1 and human IB kinase-associated protein.
BMC Bioinformatics, 2007
Background: DNA copy number aberration (CNA) is one of the key characteristics of cancer cells. R... more Background: DNA copy number aberration (CNA) is one of the key characteristics of cancer cells. Recent studies demonstrated the feasibility of utilizing high density single nucleotide polymorphism (SNP) genotyping arrays to detect CNA. Compared with the two-color array-based comparative genomic hybridization (array-CGH), the SNP arrays offer much higher probe density and lower signal-to-noise ratio at the single SNP level. To accurately identify small segments of CNA from SNP array data, segmentation methods that are sensitive to CNA while resistant to noise are required.
Archives of Oral Biology, 2007
Oral fluid (saliva) meets the demands for a noninvasive and accessible diagnostic medium. Recent ... more Oral fluid (saliva) meets the demands for a noninvasive and accessible diagnostic medium. Recent reports by our group and others described the presence and use of human RNA in saliva as a diagnostic or forensic tool, including the use for oral cancer detection. To gain insights into the integrity of salivary RNA, we examined in detail the integrity of salivary RNA by generating a cDNA library from pooled supernatant saliva of 10 healthy donors. From a library with a primary library titer of 1.3 × 10 6 cfu/mL of which 95 % of the clones had inserts, we successfully sequenced 117 random colonies containing recombinant clones. BLAST search results indicated that all of these clones contained sequences of human origin. Most of the salivary RNAs appeared to be endonucleolytically cleaved at random positions as indicated by comparisons to respective full length parental RNAs from the Genbank. Twelve of the insert sequences matched to the normal salivary core transcriptome sequences, which are highly abundant mRNAs present in healthy individuals. This study provides an in-depth molecular analysis of the saliva transcriptome and should be a useful resource for future basic and translational studies of RNA in human saliva. In addition this paper presents unequivocal evidence for the presence of RNA in saliva as determined by the use of diverse techniques such as reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), in vitro translation, and the construction of a salivary cDNA library.
Cancer Genetics and Cytogenetics, 2005
Genetic aberrations, such as deletions and amplifications are among the major pathogenetic mechan... more Genetic aberrations, such as deletions and amplifications are among the major pathogenetic mechanisms underlying many medical disorders. Analysis of chromosomal aberrations is particularly important in cancer research, where amplifications of oncogenes and deletions of tumor suppressor genes are major steps in the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;multi-hit&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; process of tumorigenesis. Genome-wide molecular biological analyses, such as loss of heterozygosity (LOH) profiling and comparative genomic hybridization (CGH) have significantly enhanced our ability to detect chromosomal aberrations in cancer cells and assess their role in tumorigenesis. The recent introduction of high-density oligonucleotide arrays for measuring single nucleotide polymorphisms (SNP) has sparked a new wave of high-resolution genetic mapping studies, including LOH and CGH applications on various cancer types. This review highlights recent progress on concurrent LOH and CGH analyses utilizing high density SNP arrays and their application in cancer research.
Human Genetics, 2004
Gene copy-number abnormalities (CNAs) are characteristic of solid tumors and are found in associa... more Gene copy-number abnormalities (CNAs) are characteristic of solid tumors and are found in association with developmental abnormalities and/or mental retardation. The ultimate impact of CNAs is exerted by the altered expression of encoded genes. We have utilized high-density oligonucleotide arrays from Affymetrix to identify DNA CNAs via their impact on mRNA expression levels. In these studies, we have used three different trisomic cell lines (trisomy 9, trisomy 18, trisomy 21) as models of CNAs and have compared mRNA expression in those trisomic cells with that observed in diploid cell lines of matched tissue origin. Our data clearly show that genes from CNA chromosome regions are substantially over-represented (P<0.000001 by chi-square analysis) in the differentially expressed subset from comparisons of all three trisomic cell lines with normal matching cells. In addition, we have been able to detect the origin of the duplication by a statistical scan for over-expressed genes. These data show that microarray detection of differential mRNA expression can be used to identify significant DNA CNAs.
Journal of Neuroscience Research, 2001
The Eph receptor ligands, the ephrins, are membrane-bound molecules that play important roles in ... more The Eph receptor ligands, the ephrins, are membrane-bound molecules that play important roles in establishing intercellular communication after neurogenesis by regulating cell migration, axon pathfinding, and topographic mapping. In diverse systems, such as embryonic day 17.5 (E17.5) hippocampal and cortical neurons, repulsive/inhibitory mechanisms underlie these cellular effects. However, although ligand/receptor expression occurs far earlier, during brain neurogenesis, little is known about potential ephrin functions in initial process outgrowth. We have examined ligand/receptor expression in E13.5 cortex in vivo and in culture, using alkaline phosphatase (AP)-conjugated reagents and RNase protection assay. B ephrins are highly expressed, including B1, B2, and B3, whereas A ephrins exhibit low expression levels. In contrast, the Eph receptors demonstrate an opposite pattern, exhibiting high levels of Eph A3, A4, and A5 mRNA transcripts and low levels of the B-class receptors. To examine effects on neurite outgrowth, soluble ephrins were incubated with antihuman IgG antibody, producing oligomeric agonist complexes, and dried onto culture dishes. Unexpectedly, both ephrin A and B complexes increased process outgrowth: Seventy to eighty percent of neuronal precursors exhibited long neurites on ephrins, whereas only 5–10% of cells had neurites on IgG control substrates, indicating that ephrins stimulated neuritogenesis by early cortical neurons. These observations suggest that ephrin ligand/receptor systems play ontogenetic roles not previously considered, activating mechanisms other than cellular repulsion. Ephrin systems may induce initial process elaboration by early cortical neurons that is restricted at later stages by well-characterized repulsive signaling mechanisms. J Neurosci. Res. 66:1054–1063, 2001. © 2001 Wiley-Liss, Inc.
Developmental Biology, 2000
The superior cervical ganglion (SCG) is a well-characterized model of neural development, in whic... more The superior cervical ganglion (SCG) is a well-characterized model of neural development, in which several regulatory signals have been identified. Vasoactive intestinal peptide (VIP) has been found to regulate diverse ontogenetic processes in sympathetics, though functional requirements for high peptide concentrations suggest that other ligands are involved. We now describe expression and functions of pituitary adenylate cyclase-activating polypeptide (PACAP) during SCG ontogeny, suggesting that the peptide plays critical roles in neurogenesis. PACAP and PACAP receptor (PAC(1)) mRNA's were detected at embryonic days 14.5 (E14.5) through E17.5 in vivo and virtually all precursors exhibited ligand and receptor, indicating that the system is expressed as neuroblasts proliferate. Exposure of cultured precursors to PACAP peptides, containing 27 or 38 residues, increased mitogenic activity 4-fold. Significantly, PACAP was 1000-fold more potent than VIP and a highly potent and selective antagonist entirely blocked effects of micromolar VIP, consistent with both peptides acting via PAC(1) receptors. Moreover, PACAP potently enhanced precursor survival more than 2-fold, suggesting that previously defined VIP effects were mediated via PAC(1) receptors and that PACAP is the more significant developmental signal. In addition to neurogenesis, PACAP promoted neuronal differentiation, increasing neurite outgrowth 4-fold and enhancing expression of neurotrophin receptors trkC and trkA. Since PACAP potently activated cAMP and PI pathways and increased intracellular Ca(2+), the peptide may interact with other developmental signals. PACAP stimulation of precursor mitosis, survival, and trk receptor expression suggests that the signaling system plays a critical autocrine role during sympathetic neurogenesis.
Journal of Neurochemistry, 2007
Normal brain development requires coordinated regulation of several processes including prolifera... more Normal brain development requires coordinated regulation of several processes including proliferation, differentiation, and cell death. Multiple factors from endogenous and exogenous sources interact to elicit positive as well as negative regulation of these processes. In particular, the perinatal rat brain is highly vulnerable to specific developmental insults that produce later cognitive abnormalities. We used this model to examine the developmental effects of an exogenous factor of great concern, methylmercury (MeHg). Seven-day-old rats received a single injection of MeHg (5 μg/gbw). MeHg inhibited DNA synthesis by 44% and reduced levels of cyclins D1, D3, and E at 24 h in the hippocampus, but not the cerebellum. Toxicity was associated acutely with caspase-dependent programmed cell death. MeHg exposure led to reductions in hippocampal size (21%) and cell numbers 2 weeks later, especially in the granule cell layer (16%) and hilus (50%) of the dentate gyrus defined stereologically, suggesting that neurons might be particularly vulnerable. Consistent with this, perinatal exposure led to profound deficits in juvenile hippocampal-dependent learning during training on a spatial navigation task. In aggregate, these studies indicate that exposure to one dose of MeHg during the perinatal period acutely induces apoptotic cell death, which results in later deficits in hippocampal structure and function.
Insect Biochemistry and Molecular Biology, 2000
The Israeli population of the cotton bollworm, Helicoverpa armigera (Hübner), undergoes a short-d... more The Israeli population of the cotton bollworm, Helicoverpa armigera (Hübner), undergoes a short-day, low-temperature pupal diapause and is also suspected of being a seasonal migrant in the eastern Mediterranean region. H. armigera were reared in the laboratory under several constant temperature and photoperiodic combinations which simulate average conditions encountered in the spring, summer, early-autumn and late-autumn in Israel. Juvenile hormone (JH) biosynthesis, the onset of calling behavior, sex pheromone production and ovarian development were examined in virgin female moths subsequent to eclosion. Allatal maturation, defined as acquisition of competence to synthesize JH, was significantly delayed in moths reared under simulated spring conditions. This was probably the cause for the observed delay in ovarian development and the onset of calling behavior, and to the reduction in sex pheromone biosynthesis. The delay in female sexual maturation, commonly associated with migratory flight, is consistent with presumptive pre-reproductive migration in H. armigera. : S 0 9 6 5 -17 48 ( 0 0 ) 0 0 05 9-X
Environmental Entomology, 2000
Heredity, 2000
The genetic structure of the cotton bollworm, Helicoverpa armigera (HuÈ bner) (Lepidoptera: Noctu... more The genetic structure of the cotton bollworm, Helicoverpa armigera (HuÈ bner) (Lepidoptera: Noctuidae), was studied in the eastern Mediterranean. Moths were sampled in six locations (®ve in Israel, and one in Turkey) and their genetic relationship was analysed using RAPD-PCR. Three 10-oligonucleotide primers revealed 84 presumptive polymorphic loci that were used to estimate population structure. Results reveal low level of genetic distances among Israeli and Turkish populations. The estimated values of F ST ST and h for the eastern Mediterranean populations were very low across all populations, indicating a high level of gene¯ow. Four distinct RAPD-product pro®le types were de®ned, and found in all Israeli and Turkish populations. Although no isolation by geographical distance was detected, topographical barriers may play a role in such isolation.
Human Genetics, 2004
Like most human cancers, oral squamous cell carcinoma (SCC) is characterized by genetic instabili... more Like most human cancers, oral squamous cell carcinoma (SCC) is characterized by genetic instabilities. In this study, a single platform (Affymetrix 10K SNP mapping array) was used to generate both loss of heterozygosity (LOH) and DNA copy number abnormality (CNA) read-outs for precise and high-resolution genetic alteration profiles. As a proof of principle, we performed this concordant analysis on a panel of deletion and trisomy cell lines with known chromosomal alterations and the precise LOH and CNA regions were detected as expected. Using a previously described oral SCC progression model system, we identified a set of genomic regions that may be associated with the malignancy progression, including chromosome regions 3pter–3p35.3, 3p14.1–3p13, 11p, 11q14.3–11q22.2, and 11q13.5–11q14.1. These data show that it is feasible to utilize high-density SNP arrays to generate concordant LOH and CNA profiles at high resolution.
Since morbidity and mortality rates due to oral cavity and oropharyngeal squamous cell carcinoma ... more Since morbidity and mortality rates due to oral cavity and oropharyngeal squamous cell carcinoma (OSCC) have improved little in the past 30 years, early detection or prevention of this disease is likely to be most effective. Using laser-capture microdissection, we have identified the expression of 2 cellular genes that are uniquely associated with OSCC: interleukin (IL) 6 and IL-8. These cytokines may contribute to the pathogenesis of this disease, and have been linked with increased tumor growth and metastasis.
BMC Genomics, 2008
The head and neck/oral squamous cell carcinoma (HNOSCC) is a diverse group of cancers, which deve... more The head and neck/oral squamous cell carcinoma (HNOSCC) is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC) is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC.
Neoplasia, 2006
Suppression of ovarian tumor growth by chromosome 3p was demonstrated in a previous study. Delete... more Suppression of ovarian tumor growth by chromosome 3p was demonstrated in a previous study. Deleted in Lung and Esophageal Cancer 1 (DLEC1) on 3p22.3 is a candidate tumor suppressor in lung, esophageal, and renal cancers. The potential involvement of DLEC1 in epithelial ovarian cancer remains unknown. In the present study, DLEC1 downregulation was found in ovarian cancer cell lines and primary ovarian tumors. Focus-expressed DLEC1 in two ovarian cancer cell lines resulted in 41% to 52% inhibition of colony formation. No chromosomal loss of chromosome 3p22.3 in any ovarian cancer cell line or tissue was found. Promoter hypermethylation of DLEC1 was detected in ovarian cancer cell lines with reduced DLEC1 transcripts, whereas methylation was not detected in normal ovarian epithelium and DLEC1-expressing ovarian cancer cell lines. Treatment with demethylating agent enhanced DLEC1 expression in 90% (9 of 10) of ovarian cancer cell lines. DLEC1 promoter methylation was examined in 13 high-grade ovarian tumor tissues with DLEC1 downregulation, in which 54% of the tumors showed DLEC1 methylation. In addition, 80% of ovarian cancer cell lines significantly upregulated DLEC1 transcripts after histone deacetylase inhibitor treatment. Therefore, our results suggested that DLEC1 suppressed the growth of ovarian cancer cells and that its downregulation was closely associated with promoter hypermethylation and histone hypoacetylation. Neoplasia (2006) 8, 268 -278
Neoplasia, 2006
Regional lymph node metastasis is a critical event in oral tongue squamous cell carcinoma (OTSCC)... more Regional lymph node metastasis is a critical event in oral tongue squamous cell carcinoma (OTSCC) progression. The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making for improved management of OTSCC patients. Global expressional profiles were obtained for 25 primary OTSCCs, where 11 cases showed lymph node metastasis (pN + ) histologically and 14 cases were nonmetastatic (pN À ). Seven of pN + cases also exhibited extracapsular spread (ECS) of metastatic nodes. Multiple expression indices were used to generate signature gene sets for pN +/À and ECS +/À cases. Selected genes from signature gene sets were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The classification powers of these genes were then evaluated using a logistic model, receiver operating characteristic curve analysis, and leave-oneout cross-validation. qRT-PCR validation data showed that differences at RNA levels are either statistically significant (P < .05) or suggestive (P < .1) for six of eight genes tested (BMP2, CTTN, EEF1A1, GTSE1, MMP9, and EGFR) for pN +/À cases, and for five of eight genes tested (BMP2, CTTN, EEF1A1, MMP9, and EGFR) for ECS +/À cases. Logistic models with specific combinations of genes (CTTN+MMP9+EGFR for pN and CTTN+EEF1A1+ MMP9 for ECS) achieved perfect specificity and sensitivity. Leave-one-out cross-validation showed overall accuracy rates of 85% for both pN and ECS prediction models. Our results demonstrated that the pN and the ECS of OTSCCs can be predicted by gene expression analyses of primary tumors. Neoplasia (2006) 8, 925-932
Molecular and Cellular Biology, 2006
The phytohormone abscisic acid (ABA) plays an important role in modulating plant growth, developm... more The phytohormone abscisic acid (ABA) plays an important role in modulating plant growth, development, and stress responses. In a genetic screen for mutants with altered drought stress responses, we identified an ABA-overly sensitive mutant, the abo1 mutant, which showed a drought-resistant phenotype. The abo1 mutation enhances ABA-induced stomatal closing and increases ABA sensitivity in inhibiting seedling growth. abo1 mutants are more resistant to oxidative stress than the wild type and show reduced levels of transcripts of several stress-or ABA-responsive genes. Interestingly, the mutation also differentially modulates the development and growth of adjacent guard cells. Map-based cloning identified ABO1 as a new allele of ELO2, which encodes a homolog of Saccharomyces cerevisiae Iki3/Elp1/Tot1 and human IB kinase-associated protein.
BMC Bioinformatics, 2007
Background: DNA copy number aberration (CNA) is one of the key characteristics of cancer cells. R... more Background: DNA copy number aberration (CNA) is one of the key characteristics of cancer cells. Recent studies demonstrated the feasibility of utilizing high density single nucleotide polymorphism (SNP) genotyping arrays to detect CNA. Compared with the two-color array-based comparative genomic hybridization (array-CGH), the SNP arrays offer much higher probe density and lower signal-to-noise ratio at the single SNP level. To accurately identify small segments of CNA from SNP array data, segmentation methods that are sensitive to CNA while resistant to noise are required.
Archives of Oral Biology, 2007
Oral fluid (saliva) meets the demands for a noninvasive and accessible diagnostic medium. Recent ... more Oral fluid (saliva) meets the demands for a noninvasive and accessible diagnostic medium. Recent reports by our group and others described the presence and use of human RNA in saliva as a diagnostic or forensic tool, including the use for oral cancer detection. To gain insights into the integrity of salivary RNA, we examined in detail the integrity of salivary RNA by generating a cDNA library from pooled supernatant saliva of 10 healthy donors. From a library with a primary library titer of 1.3 × 10 6 cfu/mL of which 95 % of the clones had inserts, we successfully sequenced 117 random colonies containing recombinant clones. BLAST search results indicated that all of these clones contained sequences of human origin. Most of the salivary RNAs appeared to be endonucleolytically cleaved at random positions as indicated by comparisons to respective full length parental RNAs from the Genbank. Twelve of the insert sequences matched to the normal salivary core transcriptome sequences, which are highly abundant mRNAs present in healthy individuals. This study provides an in-depth molecular analysis of the saliva transcriptome and should be a useful resource for future basic and translational studies of RNA in human saliva. In addition this paper presents unequivocal evidence for the presence of RNA in saliva as determined by the use of diverse techniques such as reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), in vitro translation, and the construction of a salivary cDNA library.
Cancer Genetics and Cytogenetics, 2005
Genetic aberrations, such as deletions and amplifications are among the major pathogenetic mechan... more Genetic aberrations, such as deletions and amplifications are among the major pathogenetic mechanisms underlying many medical disorders. Analysis of chromosomal aberrations is particularly important in cancer research, where amplifications of oncogenes and deletions of tumor suppressor genes are major steps in the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;multi-hit&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; process of tumorigenesis. Genome-wide molecular biological analyses, such as loss of heterozygosity (LOH) profiling and comparative genomic hybridization (CGH) have significantly enhanced our ability to detect chromosomal aberrations in cancer cells and assess their role in tumorigenesis. The recent introduction of high-density oligonucleotide arrays for measuring single nucleotide polymorphisms (SNP) has sparked a new wave of high-resolution genetic mapping studies, including LOH and CGH applications on various cancer types. This review highlights recent progress on concurrent LOH and CGH analyses utilizing high density SNP arrays and their application in cancer research.
Human Genetics, 2004
Gene copy-number abnormalities (CNAs) are characteristic of solid tumors and are found in associa... more Gene copy-number abnormalities (CNAs) are characteristic of solid tumors and are found in association with developmental abnormalities and/or mental retardation. The ultimate impact of CNAs is exerted by the altered expression of encoded genes. We have utilized high-density oligonucleotide arrays from Affymetrix to identify DNA CNAs via their impact on mRNA expression levels. In these studies, we have used three different trisomic cell lines (trisomy 9, trisomy 18, trisomy 21) as models of CNAs and have compared mRNA expression in those trisomic cells with that observed in diploid cell lines of matched tissue origin. Our data clearly show that genes from CNA chromosome regions are substantially over-represented (P<0.000001 by chi-square analysis) in the differentially expressed subset from comparisons of all three trisomic cell lines with normal matching cells. In addition, we have been able to detect the origin of the duplication by a statistical scan for over-expressed genes. These data show that microarray detection of differential mRNA expression can be used to identify significant DNA CNAs.