Abstract:
:Environmental health science research, with its focus on fundamental science and disease prevention, is important for the development of rational and cost-effective public health and regulatory policies related to environmental protection. Environmentally related diseases are preventable, yet they impose a major burden on society in terms of human suffering and costs related to health care. Similarly, the expenditure of hundreds of billions of dollars for regulatory compliance is a major economic concern. There is considerable debate regarding current regulatory risk assessment practices for environmental agents. Implicit in all risk assessment schemes is the need to extrapolate from high-exposure studies to low-exposure situations and from known risks in rodents to probable risks in people. Both extrapolations are fraught with uncertainties. These uncertainties are accommodated in risk-assessment schemes by the incorporation of arbitrary "safety factors" and other default approaches. Since these factors are not derived experimentally, they may overestimate or under estimate actual risks. Risk-assessment methodology, its relevance to the human condition, and its use in protecting human health will greatly improve when our expanding knowledge of the basic biology of environmental effects is incorporated into toxicological testing and risk-assessment schemes. Moreover, exciting opportunities now exist to advance our understanding of the environmental and genetic bases of many common diseases and to design effective prevention and intervention strategies to combat their development. This report discusses some of the current opportunities and challenges.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Olden K,Klein JLdoi
10.1002/mc.2940140103subject
Has Abstractpub_date
1995-09-01 00:00:00pages
2-9issue
1eissn
0899-1987issn
1098-2744journal_volume
14pub_type
杂志文章,评审abstract::Peptidylarginine deiminase type 4 (PAD4/PADI4) posttranslationally converts peptidylarginine to citrulline, in a process known as citrullination. Evidence suggests that PAD4 plays an essential role in pathogenesis of rheumatoid arthritis (RA). RA synovium has many features in common with tumor tissues, including abnor...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20169
更新日期:2006-03-01 00:00:00
abstract::Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cance...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20664
更新日期:2010-10-01 00:00:00
abstract::Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9763 prostate cancers in a tissue microar...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22670
更新日期:2017-09-01 00:00:00
abstract::Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rode...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22164
更新日期:2015-09-01 00:00:00
abstract::Estrogen is thought to be an important etiologic agent in endometrial and breast cancers. However, the mechanism or mechanisms by which estrogen acts as a hormonal carcinogen are not well understood. We hypothesize that in response to chronic exposure to estrogens, human endometrial stromal fibroblasts (ESF) produce f...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199812)23:4<217::aid-mc4>3
更新日期:1998-12-01 00:00:00
abstract::Increased epidermal growth factor receptor (EGFR) expression in triple-negative breast cancer (TNBC) is recognized as a promising therapeutic target, specifically through the use of selective EGFR inhibitors combined with chemotherapies. TNBC is characterized by genetic instability that leads to increased sensitivity ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22596
更新日期:2017-05-01 00:00:00
abstract::We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or prolonged exposure to low-dose H(2)O(2) or CdCl(2). Stable transformation was confirmed by an anchorage-independence assay. The JB6P+ transformants formed more colonies (approximately six folds) in soft agar as compared to their JB6P+ par...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20410
更新日期:2008-07-01 00:00:00
abstract::In human lung cancers, alterations of both a dominant oncogene (ras) and a tumor suppressor gene (p53) have been identified. Polymerase chain reaction (PCR) analysis of mRNA was used to amplify the c-Ki-ras-2 and p53 genes from Syrian golden hamsters. The PCR products were confirmed by predicted-size analysis, probing...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940060305
更新日期:1992-01-01 00:00:00
abstract::The WW domain-containing oxidoreductase (WWOX) gene is an identified tumor suppressor gene, of which several single nucleotide polymorphisms have been reported to contribute to cancer susceptibility. We hypothesized that genetic variations in WWOX are associated with lung cancer risk. In two independent case-control s...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21934
更新日期:2013-11-01 00:00:00
abstract::To determine if hemizygous transgenic mice carrying the human c-Ha-ras gene (CB6F1-Tg Hras2 mice (Hras2 mice)) are susceptible to the carcinogenic potential of known murine carcinogens, male and female Hras2 mice and their non-transgenic CB6F1 littermates (non-Tg mice) were each given a single intraperitoneal injectio...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199711)20:3<298::aid-mc6>3
更新日期:1997-11-01 00:00:00
abstract::Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late-onset colorectal cancer (CRC). Our understanding of early-onset sporadi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21976
更新日期:2014-02-01 00:00:00
abstract::There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these mole...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22503
更新日期:2017-02-01 00:00:00
abstract::We confirmed the expression of cathepsin K, the most abundant and specific cysteine protease found in osteoclasts, at the mRNA level in most of our cases of breast cancer, and even at the protein level in bone metastatic lesions. Therefore, we investigated the functions of cathepsin K in osteoclasts with special atten...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.1067
更新日期:2001-10-01 00:00:00
abstract::Inflammation plays a major role in colon carcinogenesis. Endogenously produced specialized proresolving lipid mediators (SPMs) play a central role in inflammation and tissue homeostasis, and have been implicated in carcinogenesis. We studied the associations of plasma levels of two SPMs [lipoxin A4 (LXA4 ) and resolvi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,随机对照试验
doi:10.1002/mc.22629
更新日期:2017-08-01 00:00:00
abstract::Transformation of cloned rat embryo fibroblast (CREF) cells with the wild-type 5 adenovirus (wtAd5) transforming genes E1A and E1B (which extend from 0 to 11.2 map units) results in morphologically transformed cells that exhibit an increased saturation density in monolayer culture and display an anchorage-independent ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050207
更新日期:1992-01-01 00:00:00
abstract::Rat neoplasms induced by methylating carcinogens frequently contain ras genes activated by a single point mutation. Rat prostatic tumors induced by a combination of a single injection of N-methyl-N-nitrosourea (MNU) and long-term treatment with testosterone were examined for the presence of such activating point mutat...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940040507
更新日期:1991-01-01 00:00:00
abstract::RhoBTB2 was isolated recently as a tumor suppressor gene from human chromosome 8p21.3. Although RhoBTB2 was found to be frequently lost in breast cancer lines, expression status of RhoBTB2 in sporadic breast cancer tissues and its clinical and prognostic value, however, remain unclear. Tissue samples from breast cance...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20598
更新日期:2010-03-01 00:00:00
abstract::Krüppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor with tumor suppressor activity in various cancer types. Cells that sustain double strand breaks (DSBs) in their DNA due to high levels of reactive oxygen species (ROS) can develop genomic instability, which can result in cancer formation. On...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22161
更新日期:2015-09-01 00:00:00
abstract::Environmental or occupational exposure to low doses of arsenic induces a series of health problems including cancer. The molecular events in arsenic-induced carcinogenicity remain to be defined. In the NuLi-1 immortalized human lung epithelial cell line with p53 and pRb deficiency, exposure to low doses of arsenic tri...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21989
更新日期:2014-05-01 00:00:00
abstract::Triptolide is an active component from a Chinese herb, Tripterygium wilfordii which has been applied for treating immune-related diseases over centuries. Recently, it was reported that a variety of cancer cell lines could be sensitized to DNA-damage based chemotherapy drugs in combination with Triptolide treatment. In...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22795
更新日期:2018-06-01 00:00:00
abstract::The E5 open reading frame (ORF) from bovine papillomavirus type 1 (BPV 1) as well as the E5 ORFs from human papillomaviruses (HPV) type 6 and type 16 have been reported to transform immortalized rodent cells. In an analysis of murine and human tumors for the presence of putative papillomavirus-related sequences, we cl...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940060204
更新日期:1992-01-01 00:00:00
abstract::Transforming growth factor beta (TGF-beta) exerts an important role in the late steps of carcinogenesis by cooperating with Ras to induce cell motility and tumor invasion. The transcription complex AP-1 has been implicated in the regulation of genes involved in motility and invasion, by mechanisms not yet delineated. ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20492
更新日期:2009-06-01 00:00:00
abstract::Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor in the gastrointestinal tract. Prostate cancer associated transcript 6 (PCAT6) is a long noncoding RNA (lncRNA) and plays a pivotal role in tumor formation. Present study was designed to explore the function of PCAT6 in GIST. Ki67 staining, colony for...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23199
更新日期:2020-06-01 00:00:00
abstract::Formation of G4 DNA may occur in the course of replication and transcription, and contribute to genomic instability. We have quantitated abundance of G4 motifs and potential for G4 DNA formation of the nontemplate strand of 5' exons and introns of transcripts of human genes. We find that, for all human genes, G4 motif...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20496
更新日期:2009-04-01 00:00:00
abstract::Reflux of acidic gastric contents and bile acids into the lower esophagus has been identified to have a central role in esophageal malignancy and is reported to upregulate caudal-related homologue 2 (CDX2), a regulatory gene involved in embryonic development and axial patterning of the alimentary tract. The aim of thi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20549
更新日期:2009-10-01 00:00:00
abstract::The human p53 gene, a putative tumor suppressor gene, has a polymorphism in amino acid residue 72. We recently developed a method of detecting codon 72 polymorphism in this gene by digestion of polymerase chain reaction-amplified DNA using an allele-specific restriction endonuclease. This polymorphism allows the ident...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940040104
更新日期:1991-01-01 00:00:00
abstract::Although there are extensive studies on the genetics of bladder cancer, several questions remain unanswered. One of the pathways which are altered in bladder cancer is the mTOR signaling pathway. In the present study, we analyzed the expression of Rheb gene and genetic alterations in the LKB1 gene which are the key co...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21902
更新日期:2013-08-01 00:00:00
abstract::To assess systematically whether potentially functional polymorphisms in DNA repair genes influence the clinical behavior of non-small-cell lung cancer (NSCLC), we examined the impact of a comprehensive panel of 218 signal nucleotide polymorphisms (SNP) in 50 candidate DNA repair genes on overall survival of NSCLC in ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20819
更新日期:2012-07-01 00:00:00
abstract::2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a food carcinogen formed in cooked meats, can induce gene mutation at the hprt locus of CHO-K1 cells in the presence of hepatic S9 mix. To elucidate the molecular nature of IQ-induced mutation, we characterized the entire coding region of the hypoxanthine phosphoribosyl-tr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940130209
更新日期:1995-06-01 00:00:00
abstract::Regions of genomic DNA containing repetitive nucleotide sequences can adopt a number of different structures in addition to the canonical B-DNA form: many of these non-B DNA structures are causative factors in genetic instability and human disease. Although chromosomal DNA replication through such repetitive sequences...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.20508
更新日期:2009-04-01 00:00:00