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Early career researchers (ECR) face a series of challenges related to the inherent difficulties of starting their careers. Microplastic (MP) research is a topical field attracting high numbers of ECRs with diverse backgrounds and expertise from a wealth of disciplines including environmental science, biology, chemistry and ecotoxicology. In this perspective the challenges that could hinder scientific, professional, or personal development are explored, as identified by an international network of ECRs, all employed in MP research, that was formed following a bilateral workshop for scientists based in the UK and China. Discussions amongst the network were grouped into four overarching themes of technical challenges: in the field, in the laboratory, in the post data collection phase, and miscellaneous. The three key areas of representativeness, access to appropriate resources, training, and clean labs, and the use of databases and comparability, as well as the overarching constraint of available time were identified as the source of the majority of challenges. A set of recommendations for pathways forward are proposed based on the principles of research openness, access to information and training, and widening collaborations. ECRs have great capacity to promote research excellence in the field of MPs and elsewhere, when provided with appropriate opportunities and suitable support.

Purpose: Airway remodeling is a significant pathological change of asthma. This study aimed to detect differentially expressed microRNAs in the serum of asthma patients and airway smooth muscle cells (ASMCs) of asthmatic mice, exploring their role in the airway remodeling of asthma.Methods: The differentially expressed microRNAs in the serum of mild and moderate-severe asthma patients compared to healthy subjects were revealed using the "limma" package. Gene Ontology (GO) analysis was used to annotate the functions of microRNA target genes. The relative expressions of miR-107 (miR-107-3p in mice sharing the same sequence) in the primary airway smooth muscle cells (ASMCs) of the asthma mice model were tested by RT-qPCR. Cyclin-dependent kinases 6 (Cdk6), a target gene of miR-107, was predicted by algorithms and validated by dual-luciferase reporter assay and Western blot. The roles of miR-107, Cdk6, and protein Retinoblastoma (Rb) in ASMCs were examined by transwell assay and EDU KIT in vitro.Results: The expression of miR-107 was down-regulated in both mild and moderate-severe asthma patients. Intriguingly, the level of miR-107 was also decreased in ASMCs of the asthma mice model. Up-regulating miR-107 suppressed ASMCs' proliferation by targeting Cdk6 and the phosphorylation level of Rb. Increasing the expression of Cdk6 or suppressing Rb activity abrogated the proliferation inhibition effect of ASMCs induced by miR-107. In addition, miR-107 also inhibits ASMC migration by targeting Cdk6.Conclusion: The expression of miR-107 is down-regulated in serums of asthma patients and ASMCs of asthmatic mice. It plays a critical role in the and of ASMCs via Cdk6.

Yi Xiong,1,2,* Yani Luo,2,* Ting Yuwen,2,* Jiana Li,2 Rongchang Chen,3 Fei Shi1 1Emergency Department, Shenzhen People’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong Province, People’s Republic of China; 3Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rongchang Chen, Email chenrc@vip.163.com Fei Shi, Email shi.fei@szhospital.comPurpose: Airway remodeling is a significant pathological change of asthma. This study aimed to detect differentially expressed microRNAs in the serum of asthma patients and airway smooth muscle cells (ASMCs) of asthmatic mice, exploring their role in the airway remodeling of asthma.Methods: The differentially expressed microRNAs in the serum of mild and moderate-severe asthma patients compared to healthy subjects were revealed using the “limma” package. Gene Ontology (GO) analysis was used to annotate the functions of microRNA target genes. The relative expressions of miR-107 (miR-107-3p in mice sharing the same sequence) in the primary airway smooth muscle cells (ASMCs) of the asthma mice model were tested by RT-qPCR. Cyclin-dependent kinases 6 (Cdk6), a target gene of miR-107, was predicted by algorithms and validated by dual-luciferase reporter assay and Western blot. The roles of miR-107, Cdk6, and protein Retinoblastoma (Rb) in ASMCs were examined by transwell assay and EDU KIT in vitro.Results: The expression of miR-107 was down-regulated in both mild and moderate-severe asthma patients. Intriguingly, the level of miR-107 was also decreased in ASMCs of the asthma mice model. Up-regulating miR-107 suppressed ASMCs’ proliferation by tar

The ubiquity and high bioavailability of microplastics have an unknown risk on the marine environment. Biomonitoring should be used to investigate biotic impacts of microplastic exposure. While many studies have used mussels as indicators for marine microplastic pollution, a robust and clear justification for their selection as indicator species is still lacking. Here, we review published literature from field investigations and laboratory experiments on microplastics in mussels and critically discuss the suitability and challenges of mussels as bioindicator for microplastic pollution. Mussels are suitable bioindicator for microplastic pollution because of their wide distribution, vital ecological niches, susceptibility to microplastic uptake and close connection with marine predators and human health. Field investigations highlight a wide occurrence of microplastics in mussels from all over the world, yet their abundance varies enormously. Problematically, these studies are not comparable due to the lack of a standardized approach, as well as temporal and spatial variability. Interestingly, microplastic abundance in field-collected mussels is closely related to human activity, and there is evidence for a positive and quantitative correlation between microplastics in mussels and surrounding waters. Laboratory studies collectively demonstrate that mussels may be good model organisms in revealing microplastic uptake, accumulation and toxicity. Consequently, we propose the use of mussels as target species to monitor microplastics and call for a uniform, efficient and economical approach that is suitable for a future large-scale monitoring program.

Brassica napus is one of the most important oil crops in the world, and stem rot caused by the fungus Sclerotinia sclerotiorum results in major losses in yield and quality. To elucidate resistance genes and pathogenesis-related genes, genome-wide association analysis of 347 accessions was performed using the Illumina 60K Brassica SNP (single nucleotide polymorphism) array. In addition, the detached stem inoculation assay was used to select five highly resistant (R) and susceptible (S) B. napus lines, 48 h postinoculation with S. sclerotiorum for transcriptome sequencing. We identified 17 significant associations for stem resistance on chromosomes A8 and C6, five of which were on A8 and 12 on C6. The SNPs identified on A8 were located in a 409-kb haplotype block, and those on C6 were consistent with previous QTL mapping efforts. Transcriptome analysis suggested that S. sclerotiorum infection activates the immune system, sulphur metabolism, especially glutathione (GSH) and glucosinolates in both R and S genotypes. Genes found to be specific to the R genotype related to the jasmonic acid pathway, lignin biosynthesis, defence response, signal transduction and encoding transcription factors. Twenty-four genes were identified in both the SNP-trait association and transcriptome sequencing analyses, including a tau class glutathione S-transferase (GSTU) gene cluster. This study provides useful insight into the molecular mechanisms underlying the plant's response to S. sclerotiorum.

Brassica napus is one of the most important oil crops in the world, and stem rot caused by the fungus Sclerotinia sclerotiorum results in major losses in yield and quality. To elucidate resistance genes and pathogenesis-related genes, genome-wide association analysis of 347 accessions was performed using the Illumina 60K Brassica SNP (single nucleotide polymorphism) array. In addition, the detached stem inoculation assay was used to select five highly resistant (R) and susceptible (S) B. napus lines, 48 h postinoculation with S. sclerotiorum for transcriptome sequencing. We identified 17 significant associations for stem resistance on chromosomes A8 and C6, five of which were on A8 and 12 on C6. The SNPs identified on A8 were located in a 409-kb haplotype block, and those on C6 were consistent with previous QTL mapping efforts. Transcriptome analysis suggested that S. sclerotiorum infection activates the immune system, sulphur metabolism, especially glutathione (GSH) and glucosinolates in both R and S genotypes. Genes found to be specific to the R genotype related to the jasmonic acid pathway, lignin biosynthesis, defence response, signal transduction and encoding transcription factors. Twenty-four genes were identified in both the SNP-trait association and transcriptome sequencing analyses, including a tau class glutathione S-transferase (GSTU) gene cluster. This study provides useful insight into the molecular mechanisms underlying the plant's response to S. sclerotiorum.

Brassica napus is one of the most important oil crops in the world, and stem rot caused by the fungus Sclerotinia sclerotiorum results in major losses in yield and quality. To elucidate resistance genes and pathogenesis-related genes, genome-wide association analysis of 347 accessions was performed using the Illumina 60K Brassica SNP (single nucleotide polymorphism) array. In addition, the detached stem inoculation assay was used to select five highly resistant (R) and susceptible (S) B. napus lines, 48 h postinoculation with S. sclerotiorum for transcriptome sequencing. We identified 17 significant associations for stem resistance on chromosomes A8 and C6, five of which were on A8 and 12 on C6. The SNPs identified on A8 were located in a 409-kb haplotype block, and those on C6 were consistent with previous QTL mapping efforts. Transcriptome analysis suggested that S. sclerotiorum infection activates the immune system, sulphur metabolism, especially glutathione (GSH) and glucosinolates in both R and S genotypes. Genes found to be specific to the R genotype related to the jasmonic acid pathway, lignin biosynthesis, defence response, signal transduction and encoding transcription factors. Twenty-four genes were identified in both the SNP-trait association and transcriptome sequencing analyses, including a tau class glutathione S-transferase (GSTU) gene cluster. This study provides useful insight into the molecular mechanisms underlying the plant's response to S. sclerotiorum.

Brassica napus is one of the most important oil crops in the world, and stem rot caused by the fungus Sclerotinia sclerotiorum results in major losses in yield and quality. To elucidate resistance genes and pathogenesis-related genes, genome-wide association analysis of 347 accessions was performed using the Illumina 60K Brassica SNP (single nucleotide polymorphism) array. In addition, the detached stem inoculation assay was used to select five highly resistant (R) and susceptible (S) B. napus lines, 48 h postinoculation with S. sclerotiorum for transcriptome sequencing. We identified 17 significant associations for stem resistance on chromosomes A8 and C6, five of which were on A8 and 12 on C6. The SNPs identified on A8 were located in a 409-kb haplotype block, and those on C6 were consistent with previous QTL mapping efforts. Transcriptome analysis suggested that S. sclerotiorum infection activates the immune system, sulphur metabolism, especially glutathione (GSH) and glucosinolates in both R and S genotypes. Genes found to be specific to the R genotype related to the jasmonic acid pathway, lignin biosynthesis, defence response, signal transduction and encoding transcription factors. Twenty-four genes were identified in both the SNP-trait association and transcriptome sequencing analyses, including a tau class glutathione S-transferase (GSTU) gene cluster. This study provides useful insight into the molecular mechanisms underlying the plant's response to S. sclerotiorum.

Brassica napus is one of the most important oil crops in the world, and stem rot caused by the fungus Sclerotinia sclerotiorum results in major losses in yield and quality. To elucidate resistance genes and pathogenesis-related genes, genome-wide association analysis of 347 accessions was performed using the Illumina 60K Brassica SNP (single nucleotide polymorphism) array. In addition, the detached stem inoculation assay was used to select five highly resistant (R) and susceptible (S) B. napus lines, 48 h postinoculation with S. sclerotiorum for transcriptome sequencing. We identified 17 significant associations for stem resistance on chromosomes A8 and C6, five of which were on A8 and 12 on C6. The SNPs identified on A8 were located in a 409-kb haplotype block, and those on C6 were consistent with previous QTL mapping efforts. Transcriptome analysis suggested that S. sclerotiorum infection activates the immune system, sulphur metabolism, especially glutathione (GSH) and glucosinolates in both R and S genotypes. Genes found to be specific to the R genotype related to the jasmonic acid pathway, lignin biosynthesis, defence response, signal transduction and encoding transcription factors. Twenty-four genes were identified in both the SNP-trait association and transcriptome sequencing analyses, including a tau class glutathione S-transferase (GSTU) gene cluster. This study provides useful insight into the molecular mechanisms underlying the plant's response to S. sclerotiorum.

Brassica napus is one of the most important oil crops in the world, and stem rot caused by the fungus Sclerotinia sclerotiorum results in major losses in yield and quality. To elucidate resistance genes and pathogenesis-related genes, genome-wide association analysis of 347 accessions was performed using the Illumina 60K Brassica SNP (single nucleotide polymorphism) array. In addition, the detached stem inoculation assay was used to select five highly resistant (R) and susceptible (S) B. napus lines, 48 h postinoculation with S. sclerotiorum for transcriptome sequencing. We identified 17 significant associations for stem resistance on chromosomes A8 and C6, five of which were on A8 and 12 on C6. The SNPs identified on A8 were located in a 409-kb haplotype block, and those on C6 were consistent with previous QTL mapping efforts. Transcriptome analysis suggested that S. sclerotiorum infection activates the immune system, sulphur metabolism, especially glutathione (GSH) and glucosinolates in both R and S genotypes. Genes found to be specific to the R genotype related to the jasmonic acid pathway, lignin biosynthesis, defence response, signal transduction and encoding transcription factors. Twenty-four genes were identified in both the SNP-trait association and transcriptome sequencing analyses, including a tau class glutathione S-transferase (GSTU) gene cluster. This study provides useful insight into the molecular mechanisms underlying the plant's response to S. sclerotiorum.

Background: Histamine is an established growth factor for gastrointestinal malignancies. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Histamine receptor H4 (HRH4), the newest member of the histamine receptor family, is positively expressed on the epithelium of the gastrointestinal tract, and its function remains to be elucidated. Previously, we reported the decreased expression of HRH4 in colorectal cancers and revealed its correlation with tumor proliferation. In the current study, we aimed to investigate the abnormalities of HRH4 gene in gastric carcinomas (GCs). Methodology/Principal Findings: We analyzed H4R expression in collected GC samples by quantitative PCR, Western blot analysis, and immunostaining. Our results showed that the protein and mRNA levels of HRH4 were reduced in some GC samples, especially in advanced GC samples. Copy number decrease of HRH4 gene was observed (17.6%, 23 out of 131), which was closely correlated with the attenuated expression of H4R. In vitro studies, using gastric cancer cell lines, showed that the alteration of HRH4 expression on gastric cancer cells influences tumor growth upon exposure to histamine. Conclusions/Significance: We show for the first time that deletion of HRH4 gene is present in GC cases and is closely correlated with attenuated gene expression. Down-regulation of HRH4 in gastric carcinomas plays a role in histamine-mediated growth control of GC cells.

The adenomatous polyposis coli (APC) gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It has been shown to be involved in genetic instability and to be down-regulated in several human carcinomas. The chromosome locus of APC, 5q21-22, is frequently deleted in gastric cancers (GCs). The functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of GC and adjacent normal epithelium (n=141) were included in this study. Quantitative PCR was carried out to examine the copy number as well as mRNA expression of APC gene in gastric malignancies. Our results showed that copy number deletions of APC were present in a relatively high percentage (25.9%, 34 out of 131) of gastric cancer samples. There was a correlation between APC deletion and tumor progression (p < 0.01) as well as gene expression (p < 0.05) in collected GC samples. On the other hand, mRNA levels of APC were also impaired in GC samples with unaltered copy numbers. Sporadic GCs exhibit different mechanisms of APC regulation.

Background: Histamine is an established growth factor for gastrointestinal malignancies. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Histamine receptor H4 (HRH4), the newest member of the histamine receptor family, is positively expressed on the epithelium of the gastrointestinal tract, and its function remains to be elucidated. Previously, we reported the decreased expression of HRH4 in colorectal cancers and revealed its correlation with tumor proliferation. In the current study, we aimed to investigate the abnormalities of HRH4 gene in gastric carcinomas (GCs). Methodology/Principal Findings: We analyzed H4R expression in collected GC samples by quantitative PCR, Western blot analysis, and immunostaining. Our results showed that the protein and mRNA levels of HRH4 were reduced in some GC samples, especially in advanced GC samples. Copy number decrease of HRH4 gene was observed (17.6%, 23 out of 131), which was closely correlated with the attenuated expression of H4R. In vitro studies, using gastric cancer cell lines, showed that the alteration of HRH4 expression on gastric cancer cells influences tumor growth upon exposure to histamine. Conclusions/Significance: We show for the first time that deletion of HRH4 gene is present in GC cases and is closely correlated with attenuated gene expression. Down-regulation of HRH4 in gastric carcinomas plays a role in histamine-mediated growth control of GC cells.

The adenomatous polyposis coli (APC) gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It has been shown to be involved in genetic instability and to be down-regulated in several human carcinomas. The chromosome locus of APC, 5q21-22, is frequently deleted in gastric cancers (GCs). The functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of GC and adjacent normal epithelium (n=141) were included in this study. Quantitative PCR was carried out to examine the copy number as well as mRNA expression of APC gene in gastric malignancies. Our results showed that copy number deletions of APC were present in a relatively high percentage (25.9%, 34 out of 131) of gastric cancer samples. There was a correlation between APC deletion and tumor progression (p < 0.01) as well as gene expression (p < 0.05) in collected GC samples. On the other hand, mRNA levels of APC were also impaired in GC samples with unaltered copy numbers. Sporadic GCs exhibit different mechanisms of APC regulation.

Background: Histamine is an established growth factor for gastrointestinal malignancies. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Histamine receptor H4 (HRH4), the newest member of the histamine receptor family, is positively expressed on the epithelium of the gastrointestinal tract, and its function remains to be elucidated. Previously, we reported the decreased expression of HRH4 in colorectal cancers and revealed its correlation with tumor proliferation. In the current study, we aimed to investigate the abnormalities of HRH4 gene in gastric carcinomas (GCs). Methodology/Principal Findings: We analyzed H4R expression in collected GC samples by quantitative PCR, Western blot analysis, and immunostaining. Our results showed that the protein and mRNA levels of HRH4 were reduced in some GC samples, especially in advanced GC samples. Copy number decrease of HRH4 gene was observed (17.6%, 23 out of 131), which was closely correlated with the attenuated expression of H4R. In vitro studies, using gastric cancer cell lines, showed that the alteration of HRH4 expression on gastric cancer cells influences tumor growth upon exposure to histamine. Conclusions/Significance: We show for the first time that deletion of HRH4 gene is present in GC cases and is closely correlated with attenuated gene expression. Down-regulation of HRH4 in gastric carcinomas plays a role in histamine-mediated growth control of GC cells.

The adenomatous polyposis coli (APC) gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It has been shown to be involved in genetic instability and to be down-regulated in several human carcinomas. The chromosome locus of APC, 5q21-22, is frequently deleted in gastric cancers (GCs). The functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of GC and adjacent normal epithelium (n=141) were included in this study. Quantitative PCR was carried out to examine the copy number as well as mRNA expression of APC gene in gastric malignancies. Our results showed that copy number deletions of APC were present in a relatively high percentage (25.9%, 34 out of 131) of gastric cancer samples. There was a correlation between APC deletion and tumor progression (p < 0.01) as well as gene expression (p < 0.05) in collected GC samples. On the other hand, mRNA levels of APC were also impaired in GC samples with unaltered copy numbers. Sporadic GCs exhibit different mechanisms of APC regulation.

The centrosome-associated kinase aurora A (AURKA) has been shown to be involved in genetic instability and to be over-expressed in several human carcinomas including gastric cancers (GCs). The chromosome locus of AURKA, 20q13, is frequently amplified in GCs, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of gastric carcinomas and adjacent normal epithelium (n = 141) were included in this study. Quantitative PCR was carried out to examine the copy number and mRNA expression of AURKA in GCs. Our results showed copy-number gains of AUKRA were detected in a relative high percentage of GC samples (30.5%, 43 out of 141). There was a positive correlation between copy-number increase of AURKA and tumor progression. And copy-number gains of AURKA also showed a positive correlation with mRNA over-expression in GCs. However, expression level of AURKA mRNA was also enhanced in the group of GC samples with unaltered copy numbers. These findings indicated that sporadic gastric cancers exhibit different mechanisms of AURKA regulation and that this may impact the efficacy of aurora-targeted therapies.

Background: Earlier studies have reported the production of histamine in colorectal cancers (CRCs). The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4) is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Methods: Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107) and adjacent normal tissues (ANTs). To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. Results: The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. Conclusion: The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs.

The adenomatous polyposis coli (APC) gene has been shown to be involved in genetic instability and to be downregluated in several human carcinomas. The chromosome locus of APC, 5q21-22, is frequently deleted in colorectal cancers (CRCs). The functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of CRC and adjacent normal epithelium (n = 134) were included in this study. Quantitative PCR was carried out to examine the copy number as well as mRNA expression of APC gene in colorectal malignancies. Our results showed that copy number deletions of APC were present in a relatively high percentage of colorectal cancer samples (26.1%, 35 out of 134). There was a positive correlation between copy number decrease of APC and tumor progression in CRCs. Furthermore, copy number loss of APC was correlated with decreased mRNA expression. However, mRNA levels of APC were also impaired in CRC samples with unaltered copy numbers, indicating that sporadic CRCs exhibit different mechanisms of APC regulation.

Background: Earlier studies have reported the production of histamine in colorectal cancers (CRCs). The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4) is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Methods: Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107) and adjacent normal tissues (ANTs). To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. Results: The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. Conclusion: The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs.

The adenomatous polyposis coli (APC) gene has been shown to be involved in genetic instability and to be downregluated in several human carcinomas. The chromosome locus of APC, 5q21-22, is frequently deleted in colorectal cancers (CRCs). The functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of CRC and adjacent normal epithelium (n = 134) were included in this study. Quantitative PCR was carried out to examine the copy number as well as mRNA expression of APC gene in colorectal malignancies. Our results showed that copy number deletions of APC were present in a relatively high percentage of colorectal cancer samples (26.1%, 35 out of 134). There was a positive correlation between copy number decrease of APC and tumor progression in CRCs. Furthermore, copy number loss of APC was correlated with decreased mRNA expression. However, mRNA levels of APC were also impaired in CRC samples with unaltered copy numbers, indicating that sporadic CRCs exhibit different mechanisms of APC regulation.

The adenomatous polyposis coli (APC) gene has been shown to be involved in genetic instability and to be downregluated in several human carcinomas. The chromosome locus of APC, 5q21-22, is frequently deleted in colorectal cancers (CRCs). The functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of CRC and adjacent normal epithelium (n = 134) were included in this study. Quantitative PCR was carried out to examine the copy number as well as mRNA expression of APC gene in colorectal malignancies. Our results showed that copy number deletions of APC were present in a relatively high percentage of colorectal cancer samples (26.1%, 35 out of 134). There was a positive correlation between copy number decrease of APC and tumor progression in CRCs. Furthermore, copy number loss of APC was correlated with decreased mRNA expression. However, mRNA levels of APC were also impaired in CRC samples with unaltered copy numbers, indicating that sporadic CRCs exhibit different mechanisms of APC regulation.

Background: Earlier studies have reported the production of histamine in colorectal cancers (CRCs). The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4) is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Methods: Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107) and adjacent normal tissues (ANTs). To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. Results: The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. Conclusion: The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs.

The centrosome-associated kinase aurora A (AURKA) has been shown to be involved in genetic instability and to be over-expressed in several human carcinomas including gastric cancers (GCs). The chromosome locus of AURKA, 20q13, is frequently amplified in GCs, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of gastric carcinomas and adjacent normal epithelium (n = 141) were included in this study. Quantitative PCR was carried out to examine the copy number and mRNA expression of AURKA in GCs. Our results showed copy-number gains of AUKRA were detected in a relative high percentage of GC samples (30.5%, 43 out of 141). There was a positive correlation between copy-number increase of AURKA and tumor progression. And copy-number gains of AURKA also showed a positive correlation with mRNA over-expression in GCs. However, expression level of AURKA mRNA was also enhanced in the group of GC samples with unaltered copy numbers. These findings indicated that sporadic gastric cancers exhibit different mechanisms of AURKA regulation and that this may impact the efficacy of aurora-targeted therapies.

Expression level of integrin alpha 5 in tumor cells has been indicated to be involved in cell proliferation and organ-specific metastasis We previously demonstrated that ITGA5 expression was downregulated in the high invasive MDA-MB-468 cells compared with other breast cancer cell lines. In this study, we found that the methylation status in the region around transcriptional start site of ITGA5 gene was increased in MDA-MB-468 cells Overexpression of integrin alpha 5 on MDA-MB-468 cells resulted in cell growth inhibition, which could be reversed by adhesion to fibronectin Cell adhesion and spreading to fibronectin was enhanced after ITGA5 was overexpressed in MDA-MB-468 cells, while cell migration was attenuated. Knockdown of ITGA5 in MCF-7 cells led to cell growth inhibition but had little influence on cell migration These findings indicated the diverse roles of ITGA5 expression in breast cancer cells J Cell Biochem 110 1130-1141, 2010 (C) 2010 Wiley-Liss. Inc

The centrosome-associated kinase aurora A (AURKA) is involved in genetic instability and is over-expressed in several human carcinomas including colorectal cancer (CRC). The choromosome locus of AURKA, 20q13, is frequently amplified in CRC, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of colorectal adenocarcinomas and adjacent normal epithelium (n= 134) were included in this study. Quantitative PCR was carried out to examine the copy number and mRNA level of AURKA in CRC. Our results showed that copy number gains of AUKRA were detected in a relative high percentage of CRC samples (32.4%, 43 of 134). There was a positive correlation between copy number increase of AURKA and tumor progression. And copy number gains of AURKA also showed a positive correlation with mRNA over-expression in CRC. However, the expression level of AURKA mRNA was also enhanced in the group of CRC samples with unaltered copy numbers. These findings indicated that sporadic colorectal cancers exhibit different mechanisms of aurora A regulation and this may impact the efficacy of aurora-targeted therapies.

Evidence suggests that the amplification of chromosome 20q13 is common in colorectal cancers (CRCs). Certain candidate oncogenes located in this region are reported to be associated with tumorigenesis of the gastrointestinal tract. The functional impact of such regions should be extensively investigated in a large number of clinical samples. In this study, 145 CRC samples with matched adjacent normal tissues were collected from a Chinese population for copy number variation (CNV) analysis. Our results showed that both the copy numbers of 25-hydroxy vitamin D3 24-hydroxylase (CYP24A1) and zinc-finger protein 217 (ZNF217) were amplified in a relatively high percentage of CRC samples (51.1 and 60%, respectively). The mRNA expression levels of both CYP24A1 and ZNF217 were found to have increased in the collected CRC samples as compared to the matched adjacent normal tissues. ZNF217, but not CYP24A1, showed a positive correlation between copy number increases and mRNA overexpression. These findings suggest the potential role of CNVs of certain oncogenes in CRCs.

Evidence suggests that the amplification of chromosome 20q13 is common in colorectal cancers (CRCs). Certain candidate oncogenes located in this region are reported to be associated with tumorigenesis of the gastrointestinal tract. The functional impact of such regions should be extensively investigated in a large number of clinical samples. In this study, 145 CRC samples with matched adjacent normal tissues were collected from a Chinese population for copy number variation (CNV) analysis. Our results showed that both the copy numbers of 25-hydroxy vitamin D3 24-hydroxylase (CYP24A1) and zinc-finger protein 217 (ZNF217) were amplified in a relatively high percentage of CRC samples (51.1 and 60%, respectively). The mRNA expression levels of both CYP24A1 and ZNF217 were found to have increased in the collected CRC samples as compared to the matched adjacent normal tissues. ZNF217, but not CYP24A1, showed a positive correlation between copy number increases and mRNA overexpression. These findings suggest the potential role of CNVs of certain oncogenes in CRCs.

The centrosome-associated kinase aurora A (AURKA) is involved in genetic instability and is over-expressed in several human carcinomas including colorectal cancer (CRC). The choromosome locus of AURKA, 20q13, is frequently amplified in CRC, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of colorectal adenocarcinomas and adjacent normal epithelium (n= 134) were included in this study. Quantitative PCR was carried out to examine the copy number and mRNA level of AURKA in CRC. Our results showed that copy number gains of AUKRA were detected in a relative high percentage of CRC samples (32.4%, 43 of 134). There was a positive correlation between copy number increase of AURKA and tumor progression. And copy number gains of AURKA also showed a positive correlation with mRNA over-expression in CRC. However, the expression level of AURKA mRNA was also enhanced in the group of CRC samples with unaltered copy numbers. These findings indicated that sporadic colorectal cancers exhibit different mechanisms of aurora A regulation and this may impact the efficacy of aurora-targeted therapies.

Expression level of integrin alpha 5 in tumor cells has been indicated to be involved in cell proliferation and organ-specific metastasis We previously demonstrated that ITGA5 expression was downregulated in the high invasive MDA-MB-468 cells compared with other breast cancer cell lines. In this study, we found that the methylation status in the region around transcriptional start site of ITGA5 gene was increased in MDA-MB-468 cells Overexpression of integrin alpha 5 on MDA-MB-468 cells resulted in cell growth inhibition, which could be reversed by adhesion to fibronectin Cell adhesion and spreading to fibronectin was enhanced after ITGA5 was overexpressed in MDA-MB-468 cells, while cell migration was attenuated. Knockdown of ITGA5 in MCF-7 cells led to cell growth inhibition but had little influence on cell migration These findings indicated the diverse roles of ITGA5 expression in breast cancer cells J Cell Biochem 110 1130-1141, 2010 (C) 2010 Wiley-Liss. Inc

The centrosome-associated kinase aurora A (AURKA) is involved in genetic instability and is over-expressed in several human carcinomas including colorectal cancer (CRC). The choromosome locus of AURKA, 20q13, is frequently amplified in CRC, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of colorectal adenocarcinomas and adjacent normal epithelium (n= 134) were included in this study. Quantitative PCR was carried out to examine the copy number and mRNA level of AURKA in CRC. Our results showed that copy number gains of AUKRA were detected in a relative high percentage of CRC samples (32.4%, 43 of 134). There was a positive correlation between copy number increase of AURKA and tumor progression. And copy number gains of AURKA also showed a positive correlation with mRNA over-expression in CRC. However, the expression level of AURKA mRNA was also enhanced in the group of CRC samples with unaltered copy numbers. These findings indicated that sporadic colorectal cancers exhibit different mechanisms of aurora A regulation and this may impact the efficacy of aurora-targeted therapies.

Evidence suggests that the amplification of chromosome 20q13 is common in colorectal cancers (CRCs). Certain candidate oncogenes located in this region are reported to be associated with tumorigenesis of the gastrointestinal tract. The functional impact of such regions should be extensively investigated in a large number of clinical samples. In this study, 145 CRC samples with matched adjacent normal tissues were collected from a Chinese population for copy number variation (CNV) analysis. Our results showed that both the copy numbers of 25-hydroxy vitamin D3 24-hydroxylase (CYP24A1) and zinc-finger protein 217 (ZNF217) were amplified in a relatively high percentage of CRC samples (51.1 and 60%, respectively). The mRNA expression levels of both CYP24A1 and ZNF217 were found to have increased in the collected CRC samples as compared to the matched adjacent normal tissues. ZNF217, but not CYP24A1, showed a positive correlation between copy number increases and mRNA overexpression. These findings suggest the potential role of CNVs of certain oncogenes in CRCs.