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Identification and structural analysis of human RBM8A and RBM8B: two highly conserved RNA-binding motif proteins that interact with OVCA1, a candidate tumor suppressor.

The OVCA1 gene is a candidate for the breast and ovarian tumor suppressor gene at chromosome 17p13.3. To help determine the function(s) of OVCA1, we used a yeast two-hybrid screening approach to identify OVCA1-associating proteins. One such protein, which we initially referred to as BOV-1 (binder of OVCA1-1) is 173 or 174 amino acids in length and appears to be a new member of a highly conserved RNA-binding motif (RBM) protein family that is highly conserved evolutionarily. Northern blot analysis revealed that BOV-1 is ubiquitously expressed and that three distinct messenger RNA species are expressed, 1-, 3.2-, and 5.8-kb transcripts. The 1-kb transcript is the most abundant and is expressed at high levels in the testis, heart, placenta, spleen, thymus, and lymphocytes. Using fluorescence in situ hybridization and the 5.8-kb complementary DNA probe, we determined that BOV-1 maps to both chromosome 5q13-q14 and chromosome 14q22-q23. Further sequence analysis determined that the gene coding the 1- and the 3.2-kb transcripts (HGMW-approved gene symbol RBM8A) maps to 14q22-q23, whereas a second highly related gene coding for the 5.8-kb transcript resides at chromosome 5q13-q14 (HGMW-approved gene symbol RBM8B). The predicted proteins encoded by RBM8A and RBM8B are identical except that RBM8B is 16 amino acids shorter at its N-terminus. Molecular modeling of the RNA-binding domain of RBM8A and RBM8B, based on homology to the sex-lethal protein of Drosophila, identifies conserved residues in the RBM8 protein family that are likely to contact RNA in a protein-RNA complex. The conservation of sequence and structure through such an evolutionarily divergent group of organisms suggests an important function for the RBM8 family of proteins.

Amino Acid Motifs↗

[Molecular-genetic analysis of expression features of the evolutionary-conservative neurogene Nc73EF of Drosophila melanogaster].

Molecular-genetic analysis of the Nc (neural conserved) genome sequence of Drosophila melanogaster located at the position 73EF of Drosophila melanogaster was performed. The Nc73EF sequence was shown to be expressed in the nervous system of Drosophila. We constructed the restriction map of this sequence and revealed the main RNA-coding fragment in the 5'-3' orientation. The RNA-dot analysis data demonstrated that expression of the Nc73EF transcripts took place mainly in the nervous system. Hybridization with the human brain poly(A)+RNA confirmed the basic RNA-coding fragment to be evolutionary conservative. Southern blot analysis showed this fragment to be unique in the Drosophila genome. Northern blots detected three transcripts of this DNA fragment.

Animals↗

Mammalian hexokinase 1: evolutionary conservation and structure to function analysis.

We have amplified and sequenced the complete coding region of bovine hexokinase isoenzyme 1 (HK1) from brain RNA with PCR primers selected for sequence conservation. The sequence information was analyzed to evaluate the evolutionary and structure-function relationships among the mammalian and yeast HK isoenzymes. Structure to function analysis identified an unduplicated, invariant N-terminal domain involved in HK1 outer mitochondrial membrane targeting, as well as putative carbohydrate and nucleotide-binding sites in the regulatory and catalytic halves of HK1 essential to enzyme function. The ATP-binding site in the catalytic half of the HK1 protein resembles nucleotide-binding regions from protein kinases, with the single amino acid replacement (lysine to glutamate) in the ATP-binding site of the amino half explaining the loss of HK1 catalytic function in the regulatory domain. Sequence comparisons suggest that the 50-kDa mammalian and yeast glucokinases arose separately in evolution. In addition to providing valuable phylogenetic and structure-function insights, this work provides an efficient strategy for rapid cloning and sequencing of the coding regions for other HKs and related proteins.

Amino Acid Sequence↗

Management of nodal metastases from head and neck melanoma.

Ninety-three patients with nodal metastases from melanoma (stage II) located in the head and neck underwent surgery at the National Cancer Institute of Milan. Different surgical techniques were employed, ranging from radical to conservative treatment. Analysis of the data shows no significant difference from an oncological standpoint between radical and conservative surgery when a radical dissection is performed. Elective nodal dissections for malignant melanoma of the head and neck region, like those at other sites of lymphatic drainage such as the groin and axilla, did not prove beneficial. We do recommend parotidectomy in cases where the primary tumor arises in the superior area of the head. The number of nodes involved and the type of disease spread constitute the major prognostic factors, as in the case of melanomas located in other sites. Our data further indicate that the incidence of distant and local recurrence is not influenced by the type of dissection performed.

Adult↗

Characterization of conservatively resected renal tumors using automated image analysis DNA cytometry.

The DNA histograms of 57 conservatively resected renal tumors were studied using automated image analysis DNA cytometry (Leytas II). Forty-nine of the analyzed tumors were renal cell carcinomas, six were oncocytomas, one was an angiomyolipoma, and one was a renal cell adenoma. On the basis of their DNA histograms, diploid, tetraploid, and aneuploid tumors could be distinguished. Aneuploid tumors could be subtyped further according to the DNA content of the stem cell line as hyperdiploid, hypertriploid, or hypertetraploid. Eight of the tumors were characterized by a combination of diploid and hypertriploid stem cell lines. During a mean follow-up of 5 years, only the two patients with a pure hypertriploid tumor died of distant metastases. These results indicate that automated DNA image analysis cytometry is able to differentiate among several types of renal tumors with obviously different prognoses.

Adenoma↗

[Conservative treatment of anal canal carcinoma with external radiotherapy and interstitial brachytherapy, with or without chemotherapy: long-term results].

PURPOSE: A retrospective analysis of conservative treatment of anal canal cancers with external radiation therapy and interstitial brachytherapy with or without chemotherapy. PATIENTS AND METHODS: From 1986 to 1996, 69 patients were treated with external radiotherapy (40 Gy/20 fractions) and interstitial brachytherapy (20 Gy) after a mean interval of six weeks for a localized epidermoid carcinoma of the anal canal. Patients who did not complete the whole therapeutic sequence were not included. Forty-five patients received additional 5-fluorouracil- and/or mitomycin C-based chemotherapy regimen. RESULTS: Acute toxicity was acceptable. Complete response rate was 81%. Actuarial local control rate was at two and five years, 65% and 59% respectively (median follow-up: eight years). At two, five and ten years, actuarial colostomy rate was 26%, 33% and 33% respectively, and colostomy-free survival rates 61%, 47% and 37%. Overall survival at two, five and ten years was 81%, 65% and 53% respectively. Distant metastases occurred in 11 patients (16%). Prognostic factors for overall survival were performance status (PS) (79% survival at five years for patients with PS 0 versus 50% for patients with PS 1-3, P = 0.04) and tumor stage (80% at five years for T1-T2 versus 53% for T3-T4, P = 0.03). Overall treatment time less than 12 weeks and time interval between external radiotherapy and brachytherapy inferior than six weeks were associated with a better local control (P = 0.05). In multivariate analysis, these prognostic factors were not significant. CONCLUSION: These results confirm the efficacy of external radiotherapy and brachytherapy in the treatment of small anal canal cancers, and point out the need for improving treatment outcome of larger tumors.

Adult↗

The significance of pneumatosis intestinalis or bowel perforation in patients with gynecologic malignancies.

OBJECTIVES: The objectives of this study were to evaluate the clinical significance and outcome of pneumatosis intestinalis or bowel perforation in patients with gynecologic malignancies. METHODS: A retrospective review of all gynecologic oncology patients at our institution from 1996 to the present was performed to identify computed tomography examinations showing pneumatosis, free air, or the presence of portal venous gas. Admission symptoms, laboratory testing, radiographic and operative findings, and overall survival were evaluated. At the discretion of the attending gynecologic oncologist, patients were managed either surgically or conservatively. Statistical analysis was performed with Fisher's exact test. RESULTS: Twenty-eight patients met study criteria. Thirteen patients were excluded as a result of radiographic free air immediately following surgery, thus leaving 15 patients for analysis. Sixty percent (n = 9) of patients were managed surgically while 40% (n = 6) were managed conservatively. Pain and tenderness at presentation prompted surgical intervention in a statistically significant number of patients (P = 0.04). No other sign or symptom was significant. Of the 6 patients managed conservatively, 3 (50%) died within 1 week of diagnosis. Survival for the others was 2, 4, and 6 months. Of the 9 patients managed surgically 6 (67%) patients died, 4 within 2 weeks of surgery and the remainder at 2 and 12 months postoperatively. The 3 patients who survived all had surgical intervention and none had radiographic or pathologic evidence of cancer at the time of presentation (P = 0.01). Overall mortality at 6 months was 73% (11/15). Surgical management was associated with prolonged ICU care, mechanical ventilation, and sepsis. CONCLUSIONS: Pneumatosis intestinalis and bowel perforation carry a grave prognosis for patients with gynecologic malignancies. These data suggest that patients explored for radiographic evidence of pneumatosis or perforation with preoperative evidence of active malignancy do not survive the immediate postoperative period. The balance between quality and quantity of life must be considered when weighing the options for the management of this condition.

Adult↗

Economic growth, biodiversity loss and conservation effort.

This paper investigates the relationship between economic growth, biodiversity loss and efforts to conserve biodiversity using a combination of panel and cross section data. If economic growth is a cause of biodiversity loss through habitat transformation and other means, then we would expect an inverse relationship. But if higher levels of income are associated with increasing real demand for biodiversity conservation, then investment to protect remaining diversity should grow and the rate of biodiversity loss should slow with growth. Initially, economic growth and biodiversity loss are examined within the framework of the environmental Kuznets hypothesis. Biodiversity is represented by predicted species richness, generated for tropical terrestrial biodiversity using a species-area relationship. The environmental Kuznets hypothesis is investigated with reference to comparison of fixed and random effects models to allow the relationship to vary for each country. It is concluded that an environmental Kuznets curve between income and rates of loss of habitat and species does not exist in this case. The role of conservation effort in addressing environmental problems is examined through state protection of land and the regulation of trade in endangered species, two important means of biodiversity conservation. This analysis shows that the extent of government environmental policy increases with economic development. We argue that, although the data are problematic, the implications of these models is that conservation effort can only ever result in a partial deceleration of biodiversity decline partly because protected areas serve multiple functions and are not necessarily designated to protect biodiversity. Nevertheless institutional and policy response components of the income biodiversity relationship are important but are not well captured through cross-country regression analysis.

Animals↗

Genetic diversity and differentiation of central European freshwater pearl mussel (Margaritifera margaritifera L.) populations: implications for conservation and management.

Despite the fact that mollusc species play an important role in many aquatic ecosystems, little is known about their biodiversity and conservation genetics. Freshwater pearl mussel (Margaritifera margaritifera L.) populations are seriously declining all over Europe and a variety of conservation programs are being established to support the remaining endangered central European populations. In order to provide guidelines for conservation strategies and management programs, we investigated the genetic structure of 24 freshwater pearl mussel populations originating from five major central European drainages including Elbe, Danube, Rhine, Maas and Weser, representing the last and most important populations in this area. We present a nondestructive sampling method of haemolymph for DNA analyses, which is applicable for endangered bivalves. The analyses of nine microsatellite loci with different levels of polymorphism revealed a high degree of fragmented population structure and very different levels of genetic diversity within populations. These patterns can be explained by historical and demographic effects and have been enforced by anthropogenic activities. Even within drainages, distinct conservation units were detected, as revealed from high F(ST) values, private alleles and genetic distance measures. Populations sampled close to contact zones between main drainage systems showed lowest levels of correct assignment to present-day drainage systems. Populations with high priority for conservation should not only be selected by means of census population size and geographical distance to other populations. Instead, detailed genetic analyses are mandatory for revealing differentiation and diversity parameters, which should be combined with ecological criteria for sustainable conservation and recovery programs.

Animals↗

Intronic alternative splicing regulators identified by comparative genomics in nematodes.

Many alternative splicing events are regulated by pentameric and hexameric intronic sequences that serve as binding sites for splicing regulatory factors. We hypothesized that intronic elements that regulate alternative splicing are under selective pressure for evolutionary conservation. Using a Wobble Aware Bulk Aligner genomic alignment of Caenorhabditis elegans and Caenorhabditis briggsae, we identified 147 alternatively spliced cassette exons that exhibit short regions of high nucleotide conservation in the introns flanking the alternative exon. In vivo experiments on the alternatively spliced let-2 gene confirm that these conserved regions can be important for alternative splicing regulation. Conserved intronic element sequences were collected into a dataset and the occurrence of each pentamer and hexamer motif was counted. We compared the frequency of pentamers and hexamers in the conserved intronic elements to a dataset of all C. elegans intron sequences in order to identify short intronic motifs that are more likely to be associated with alternative splicing. High-scoring motifs were examined for upstream or downstream preferences in introns surrounding alternative exons. Many of the high-scoring nematode pentamer and hexamer motifs correspond to known mammalian splicing regulatory sequences, such as (T)GCATG, indicating that the mechanism of alternative splicing regulation is well conserved in metazoans. A comparison of the analysis of the conserved intronic elements, and analysis of the entire introns flanking these same exons, reveals that focusing on intronic conservation can increase the sensitivity of detecting putative splicing regulatory motifs. This approach also identified novel sequences whose role in splicing is under investigation and has allowed us to take a step forward in defining a catalog of splicing regulatory elements for an organism. In vivo experiments confirm that one novel high-scoring sequence from our analysis, (T)CTATC, is important for alternative splicing regulation of the unc-52 gene.

Alternative Splicing↗

Structure, linkage mapping and expression of the heart-type fatty acid-binding protein gene (fabp3 ) from zebrafish (Danio rerio).

We have determined the cDNA nucleotide sequence, deduced the amino acid sequence and defined the gene structure for the cellular heart-type (H-FABP) or fatty acid-binding protein 3 (FABP3) from zebrafish. The zebrafish FABP3 exhibited the greatest amino acid sequence identity to fish and mammalian heart-type FABPs. 3' RACE and 5' RLM-RACE mapped two alternative polyadenylation sites and three transcription start sites, respectively. Southern blot and hybridization analysis indicated that a single fabp3 gene exists in the zebrafish genome. The zebrafish fabp3 gene consists of four exons interrupted by three introns with identical exon/intron structure and coding capacity with that of orthologous mammalian H-FABP genes. Radiation hybrid mapping assigned the zebrafish fabp3 gene to linkage group 19 of the zebrafish genome. Comparative genomic analysis revealed conserved syntenies of the zebrafish fabp3 gene and the orthologous human and mouse fabp3 genes. Northern blot analysis detected an mRNA transcript of 780 nucleotides. In situ hybridization of the zebrafish fabp3-specific oligonucleotide probe to tissue sections of adult zebrafish revealed that the fabp3 mRNA was localized in the ovary and liver, but not in the heart, muscle or brain as reported for the mammalian fabp3 gene transcript. RT-PCR, however, detected zebrafish fabp3 mRNA in all the tissues examined. Emulsion autoradiography further revealed that the zebrafish fabp3 mRNA was most abundant in primary growth stage (stage I) oocytes and decreased during the oocyte growth phase. The fabp3 mRNA levels were reduced and restricted to the ooplasm of cortical alveolus stage (stage II) oocytes, and nearly undetectable in stage III and matured oocytes. Inspection of the 5' upstream sequence of the zebrafish fabp3 gene revealed a number of cis elements that may be involved in the expression of the zebrafish fabp3 gene in oocytes and liver.

5' Flanking Region↗

Genome-wide characterization of NOD-like receptor genes links NLR repertoire evolution to spleen immune responses after Aeromonas hydrophila challenge in the Chinese spiny frog (Quasipaa spinosa).

NOD-like receptors (NLRs) are cytosolic pattern-recognition receptors that detect pathogen-associated and damage-associated molecular patterns and mediate innate immune signaling in vertebrates. However, the genomic repertoire, evolutionary diversification, and infection-associated expression of NLR genes remain poorly defined in non-model amphibians. In this study, 66 NLR genes were identified from the Chinese spiny frog (Quasipaa spinosa) genome and designated as QsNLR1-QsNLR66. These genes were unevenly distributed across chromosomes and were classified into three phylogenetic groups, with most members exhibiting conserved motif architectures. Gene duplication analysis indicated that dispersed duplication was the main contributor to QsNLR expansion. Synteny analysis detected five conserved orthologous gene pairs between Q. spinosa and Pelophylax nigromaculatus, suggesting partial conservation of NLR genomic organization between the two amphibians. Ka/Ks analysis showed that several duplicated gene pairs, including NLRC3-like/QsNLR36 and NLRC3-like/QsNLR50, exhibited Ka/Ks ratios greater than one, suggesting potential sequence divergence after duplication. Spleen RNA sequencing (RNA-seq) after Aeromonas hydrophila challenge revealed enrichment of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Weighted gene co-expression network analysis linked several QsNLRs to infection-associated modules, among which QsNLR57 was co-expressed with CYBB, ADAM17, SPI1, and HK2. RT-qPCR using time-matched phosphate-buffered saline (PBS) controls showed distinct temporal patterns, with stronger induction of QsNLR29, QsNLR57, and QsNLR66 and weaker or delayed responses of QsNLR50 and QsNLR56. These results characterize the NLR repertoire of Q. spinosa and identify infection-associated QsNLR candidates for future studies of antibacterial immunity in amphibians.

Animals↗

Mouse Brca1: localization sequence analysis and identification of evolutionarily conserved domains.

The human genes BRCA1, conferring susceptibility to early-onset breast and ovarian cancer, has recently been isolated. Here we describe isolation of cDNAs, sequence analysis, and genomic localization of the murine homolog, Brac1. The mouse cDNA sequence predicts a protein of 1812 amino acids; a number of small gaps account for the 51 fewer residues in the mouse protein relative to human BRCA1. While the predicted mouse and human proteins display on the whole a high level of homology (58% identity, 73% similarity), the regions of greatest homology are at the respective amino and carboxyl termini. Most reported disease-associated missense mutations in human BCRA1 occurred within these more highly conserved terminal regions. A predicted zinc-building RING finger domain near the amino terminus lies within a 50 amino acid stretch that is perfectly conserved in both species. The strong conservation during mammalian evolution argues for the importance of this domain, perhaps mediating a role for BRCA1 in DNA and/or protein binding. We have also identified a conserved highly acidic domain in the carboxyl terminal half of the BCRA1 protein resembling acidic transactivation domains of certain transcription factors. Using an interspecific backcross panel, Brca1 was mapped to a region of mouse chromosome 11 that exhibits conserved linkage with 17q21. The sequence and isolated cDNAs will provide useful reagents for studying the expression of Brca1 in the mouse, and for testing the importance of the evolutionarily conserved domains.

Amino Acid Sequence↗

Microsatellite variation within and among populations of Oryza officinalis (Poaceae), an endangered wild rice from China.

Oryza officinalis Wall. ex Watt. is an agriculturally important but seriously endangered species of wild rice. To obtain more accurate estimates of population structure for improved conservation planning of the species, genetic variability at 14 microsatellite DNA loci was examined in population samples covering most of the species' range in China. Considerable genetic variability (overall Na = 1.886, P = 62%, HO = 0.056, HE = 0.216, and HS = 0.277) was detected at the 14 loci in 442 individuals of the 18 natural populations. The evaluation of partitioning of genetic variability (FST = 0.442) suggested high genetic differentiation among the Chinese O. officinalis populations. An overall value of Nm = 0.316 suggested limited gene flow occurred among the sampled populations. Most of the populations showed heterozygote deficits in tests of Hardy-Weinberg equilibrium and significantly positive FIS values. This could be due to some inbreeding occurring in this predominantly outcrossing species. For effective in situ conservation and restoration genetics, maintenance of significant historical processes is particularly important, including high outbreeding, considerable gene flow, and large population effective sizes. The high FST values detected among populations in this study are instructive for adopting a conservation plan that includes representative populations with the greatest genetic variation for either in situ conservation management or germplasm collection expeditions.

China↗

Measurement and meaningfulness in conservation science.

Incomplete databases often require conservation scientists to estimate data either through expert judgment or other scoring, rating, and ranking procedures. At the same time, ecosystem complexity has led to the use of increasingly sophisticated algorithms and mathematical models to aid in conservation theorizing, planning, and decision making. Understanding the limitations imposed by the scales of measurement of conservation data is important for the development of sound conservation theory and policy. In particular, biodiversity valuation methods, systematic conservation planning algorithms, geographic information systems (GIS), and other conservation metrics and decision-support tools, when improperly applied to estimated data, may lead to conclusions based on numerical artifact rather than empirical evidence. The representational theory of measurement is described here, and the description includes definitions of the key concepts of scale, scale type, and meaningfulness. Representational measurement is the view that measurement entails the faithful assignment of numbers to empirical entities. These assignments form scales that are organized into a hierarchy of scale types. A statement involving scales is meaningful if its truth value is invariant under changes of scale within scale type. I apply these concepts to three examples of measurement practice in the conservation literature. The results of my analysis suggest that conservation scientists do not always investigate the scale type of estimated data and hence may derive results that are not meaningful. Recognizing the complexity of observation and measurement in conservation biology, and the constraints that measurement theory imposes, the examples are accompanied by suggestions for informal estimation of the scale type of conservation data and for conducting meaningful analysis and synthesis of this information.

Algorithms↗

Effects of study area size on geographic characterizations of health events: prostate cancer incidence in Southern New England, USA, 1994-1998.

BACKGROUND: We consider how representations of geographic variation in prostate cancer incidence across Southern New England, USA may be affected by selection of study area and/or properties of the statistical analysis. METHOD: A spatial scan statistic was used to monitor geographic variation among 35,167 incident prostate cancer cases diagnosed in Massachusetts, Connecticut and Rhode Island from 1994 to 1998, in relation to the 1990 populations of men 20+ years of age living in that region. Results from the combined-states analysis were compared to those from single-states. Impact of scanning procedures set to examine up to 50% or no more than 10% of at-risk populations also was evaluated. RESULTS: With scanning set to 50%, 5 locations in the combined-states analysis were identified with markedly distinct incidence rates. Fewer than expected cases were estimated for nearly all Connecticut, Rhode Island and West Central Massachusetts, whereas census tracts on and around Cape Cod, and areas of Southwestern Connecticut and adjacent to greater Boston were estimated to have yielded more than expected incidence. Results of single-state analyses exhibited several discrepancies from the combined-states analysis. More conservative scanning found many more locations with varying incidence, but discrepancies between the combined- and single-state analysis were fewer. CONCLUSION: It is important to acknowledge the conditional nature of spatial analyses and carefully consider whether a true cluster of events is identified or artifact stemming from selection of study area size and/or scanning properties.

Adult↗

Vibration analysis in the assessment of conservatively managed tibial fractures.

A simple and quantitative method for the assessment of fracture healing has been developed. this method depends on a technique of vibration analysis evolved from a study of 30 intact human tibiae and has been applied to the study of 22 tibial fractures. Real time vibration analysis will allow quantitative comparisons of different methods of non-operative fracture management, and, in addition to providing a uniquely powerful research tool, may have value in aiding clinical management decisions.

Biomedical Engineering↗

A gene encoding an apurinic/apyrimidinic endonuclease-like protein is up-regulated in human gastric cancer.

AIM: To identify the gene that may predispose to human gastric cancer and to analyze its expression in gastric cancer and non-tumorous gastric mucosa. METHODS: Cancer, para-tumor, and non-tumor gastric tissues were studied for gene expression profile using fluorescent differential display reverse transcription polymerase chain reaction (DDRT-PCR). The differentially expressed bands of interest were analyzed by cloning, Northern blotting, and sequencing. The sequencing results were compared with the GenBank database for homology and conserved domain analysis. In situ hybridization with DIG-labeled cRNA probes was used to detect the expression of gene in paraffin embedded gastric adenocarcinoma and non-cancerous tissues. RESULTS: A gene expressed higher in tumor and para-tumor tissues than in their non-tumor counterparts of all 7 tested gastric adenocarcinoma patients was identified by means of DDRT-PCR analysis. It was named GCRG213 (gastric cancer related gene 213). Northern blot confirmed the differential expression. GCRG213 (GenBank No. AY053451) consisted of 1094 base pairs with an open reading frame (ORF) which encoded 142 amino acids. The deduced amino acid sequence contained a putative conserved domain, apurinic/apyrimidinic endonuclease (APE). In situ hybridization analysis showed that GCRG213 was expressed higher in gastric cancer tissues than in their corresponding non-tumor ones. Precancerous leisions of gastric adenocarcinoma showed a high GCRG213 expression, too. No difference of the expression patterns was found between the early and advanced gastric cancer. CONCLUSION: A gene named GCRG213 was identified in human gastric adenocarcinoma. It encoded an APE-like protein which was probably a new member of the APE family. GCRG213 was over-expressed not only in gastric cancer, but also in its precancerous leisions. The role of GCRG213 expression in carcinogenesis needs further study.

Adult↗