BackgroundGenomics has substantially changed our approach to cancer research. Gene expression profiling, for example, has been utilized to delineate subtypes of cancer, and facilitated...Full Text Available
Cancers are highly heterogeneous and contain many passenger and driver mutations. To functionally identify tumor suppressor genes relevant to human cancer, we compiled pools of short harpin...Full Text Available
Defects in mismatch repair genes cause the genetic instability characteristic of hereditary nonpolyposis colorectal cancer and a subset of sporadic colon tumors. The newest member of the mismatch repair gene family, GTBP, has recently been identified as a partial cDNA. Here, we describe the isolation of its 5{prime} terminus, allowing definition of the entire coding region. Several polymorphisms within the 5{prime} end were identified and are presented. 13 refs., 1 fig.
DFNA5 was first identified as a gene causing autosomal dominant hearing loss (HL). Different mutations have been found, all exerting a highly specific gain-of-function effect, in which skipping of exon 8 causes the HL. Later reports revealed the involvement of the gene in different types of cancer. Epigenetic silencing of DFNA5 in a large percentage of gastric, colorectal and breast tumors and p53-dependent transcriptional activity have been reported, concluding that DFNA5 acts as a tumor suppressor gene in different frequent types of cancer. Despite these data, the molecular function of DFNA5 has not been investigated properly. Previous transfection studies with mutant DFNA5 in yeast and in mammalian cells showed a toxic effect of the mutant protein, which was not seen after transfection ...
Cervical cancer is emerging as a leading cause of morbidity and mortality in women worldwide. Toll-like Receptor (TLR) gene polymorphisms may contribute to subsequent inter-individual variability in cancer susceptibility. The present study aimed to identify the role of TLR 3 (c.1377C/T) [rs3775290] and TLR 9 (G2848A) [rs352140] gene polymorphisms in the risk of developing cervical cancer in North India. Peripheral blood samples were collected from 200 histopathologically confirmed cervical cancer patients from North India and 200 unrelated, cancer-free, age-matched healthy female controls of similar ethnicity. Genomic DNA was extracted using the salting-out method, and genotyped for TLR 3 and TLR 9 using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). O...
Purpose : To detect differentially expressed genes in the patients with uterine cervical cancer during the radiation therapy. Materials and Methods : In patients with biopsy proven uterine cervical cancer, we took a tumor tissue just before radiation therapy and at 40 minutes after external irradiation of 1.8 Gy. Total RNAs isolated from non-irradiated and irradiated tumor tissue samples were analyzed using the differential-display reverse transcription-polymerase chain reaction (DDRT-PCR). Complementary DNA (cDNA) fragments corresponding to differentially expressed messenger RNAs(mRNAs) were eluted, and cloned. The differential expression of the corresponding mRNAs was confirmed by reverse northern blot. Differentially expressed cDNA bands were sequenced. Nucleotide sequence data were analyzed in the Gene Bank and EMBL databases via the BLAST network server to identify homologies ...
BackgroundThe orphan nuclear receptor estrogen-related receptor α (ERRα) is a member of the nuclear receptor superfamily. It was identified through a search for genes...Full Text Available
Using a syngeneic p53-null mouse mammary gland tumor model that closely mimics human breast cancer, we have identified, by limiting dilution transplantation and in vitro mammosphere assay, a Lin(-)CD29(H)CD24(H) subpopulation of tumor-initiating cells. Upon subsequent transplantation, this subpopulation generated heterogeneous tumors that displayed properties similar to the primary tumor. Analysis of biomarkers suggests the Lin(-)CD29(H)CD24(H) subpopulation may have arisen from a bipotent mammary progenitor. Differentially expressed genes in the Lin(-)CD29(H)CD24(H) mouse mammary gland tumor-initiating cell population include those involved in DNA damage response and repair, as well as genes involved in epigenetic regulation previously shown to be critical for stem cell self-renewal. These studies provide in vitro and in vivo data that support the cancer stem cell (CSC) hypothesis. ...
The use of Sleeping Beauty transposons as somatic mutagens to discover cancergenes in hematopoietic tumors and sarcomas has been documented. Here, we discuss the future of Sleeping...Full Text Available
Multiple discrete regions at 8q24 were recently shown to contain alleles that predispose to many cancers including prostate, breast, and colon. These regions are far from any annotated gene and their...Full Text Available
Erythroid differentiation regulator (Erdr1) was first discovered in mouse leukemia cell lines and functions as a stress-related survival factor. This study investigated whether Erdr1 regulates murine melanoma progression, as well as the mechanism involved in Erdr1-regulated metastasis. The expression of Erdr1 is negatively correlated with IL-18 expression, which has a pro-cancer effect in melanoma. To study the role of Erdr1 as an anti-cancer factor, cell migration, invasion, and proliferation were measured. Erdr1 overexpression markedly inhibited the level of cell migration, invasion, and proliferation in B16F10 cells in vitro. In addition, Erdr1 overexpression significantly suppressed melanoma lung colonization, metastasis, and tumor growth in vivo. To identify the factors involved in Er...
Large-scale cancer genome projects will soon be able to sequence many cancer genomes to comprehensively identify genetic changes in human cancer. Genome-wide association studies have also identified...Full Text Available
BackgroundThe zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are...Full Text Available
BackgroundDifferent microarray studies have compiled gene lists for predicting outcomes of a range of treatments and diseases. These have produced gene lists that have little overlap,...Full Text Available
The ability to achieve tumor selective expression of therapeutic genes is an area that needs improvement for cancergene therapy to be successful. One approach to address this is through the...Full Text Available
Previous studies have been conducted in gene expression profiling to identify groups of genes that characterize the colorectal carcinoma disease. Despite the success of previous attempts to identify...Full Text Available
Recessive mutations of the early phase change (epc) gene in maize affect several aspects of plant development. These mutations were identified initially because of...Full Text Available
Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this...Full Text Available
IL-4-induced Stat6 signaling is active in a variety of cell types and plays a role in cell proliferation/growth and resistance to apoptosis. Using EMSA, we identified differential IL-4/Stat6 activities in colorectal cancer cell lines, HT-29 being active Stat6"h"i"g"h phenotype and Caco-2 being defective Stat6"n"u"l"l phenotype, respectively. Active Stat6"h"i"g"h HT-29 cells exhibited resistance to apoptosis by flowcytometry and aggressive metastasis by Transwell assay compared with defective Stat6"n"u"l"l Caco-2 cells. Comparing one another using RT-PCR, Stat6"h"i"g"h HT-29 cells expressed more mRNA of anti-apoptotic and pro-metastatic genes Survivin, MDM2, and TMPRSS4, while Stat6"n"u"l"l Caco-2 cells expressed more mRNA of pro-apoptotic and anti-metastatic genes BAX, CAV1, and P53, respectively. This is the first study describing correlations of IL-4/Stat6 activities with apoptosis and metastasis in ...
Unlike the well-characterized nuclear function of the Notch intracellular domain, it has been difficult to identify a nuclear role for the ligands of Notch. Here we provide evidence for the nuclear function of the Notch ligand Delta-like 1 in colon cancer (CC) cells exposed to butyrate. We demonstrate that the intracellular domain of Delta-like 1 (Dll1icd) augments the activity of Wnt signaling-dependent reporters and that of the promoter of the connective tissue growth factor (CTGF) gene. Data suggest that Dll1icd upregulates CTGF promoter activity through both direct and indirect mechanisms. The direct mechanism is supported by co-immunoprecipitation of endogenous Smad2/3 proteins and Dll1 and by chromatin immunoprecipitation analyses that revealed the occupancy of Dll1icd on CTGF promot...
To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), including...Full Text Available
Significant emphasis has recently been placed on the characterization of the human cancer genome. This effort has been assisted by the development of new DNA sequencing technologies that allow...Full Text Available
SummaryEpigenetic drugs have been shown to enhance gene expression and drug sensitivity in ovarian cancer cell lines and animal models. Based on promising pre-clinical studies,...Full Text Available
BackgroundIn cancer research, the association between a gene and clinical outcome suggests the underlying etiology of the disease and consequently can motivate further studies. The...Full Text Available
BackgroundPolymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung...Full Text Available
BackgroundModern approaches to treating genetic disorders, cancers and even epidemics rely on a detailed understanding of the underlying gene signaling network. Previous work has...Full Text Available
The National Cancer Institute Laboratory of Human Carcinogenesis is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize a gene signature for prognosis of hepatocellular carcinoma in patients.
Gene expression profiling has played an important role in cancer risk classification and has shown promising results. Since gene expression profiling often involves determination of a set of...Full Text Available
Although the roots of Ras sprouted from the rich history of retrovirus research, it was the discovery of mutationally activated RAS genes in human cancer in 1982 that stimulated an...Full Text Available
AbstractThe elucidation of the human and mouse genome sequence and developments in high-throughput genome analysis, and in computational tools, have made it possible to profile entire...Full Text Available
Despite the recent success of genome-wide association studies (GWASs) in identifying loci consistently associated with coronary artery disease (CAD), a large proportion of the genetic components of...Full Text Available
Thyroid cancer is the most frequently diagnosed endocrine cancer and causes more deaths than all other endocrine cancers combined. Research findings support the concept that a subpopulation of thyroid cancer cells displays properties characteristic of stem cells. These putative cancer-forming entities drive tumorigenesis as a result of their dual ability to undergo self-renewal and to differentiate into various types of cancer cells; they also mediate metastasis and are resistant to the effects of chemotherapy and radiation therapy. This Review discusses the cellular origin of thyroid cancer and the properties of the thyroid cancer stem cell niche. The article critically evaluates the methods used to identify molecular markers expressed by thyroid-cancer-initiating cells and ...
Receptor protein tyrosine phosphatase T (PTPRT/PTPρ) is frequently mutated in human cancers including colon, lung, gastric and skin cancers. More than half of the identified tumor-derived...Full Text Available
AbstractStudies performed to identify early events of ovarian cancer and to establish molecular markers to support early detection and development of chemopreventive regimens have been...Full Text Available
AIM: To isolate and identify the biological characteristics of human colon cancer stem cells (SW1116 cells) and further study their proteome.METHODS: SW1116 cells were isolated and cultured with...Full Text Available
OBJECTIVE--To determine whether the seeming excess of childhood leukaemia and lymphoma identified in Seascale, Cumbria, UK, remains unusual when put into a wider context. DESIGN--Analysis of cancer...Full Text Available
Epidermal growth factor receptor (EGFR) gene alterations have been found in human lung cancers. However, there is no information on the factors inducing EGFR mutations. In rodents, K-ras mutations are frequently found in many lung carcinogenesis models, but hitherto, Egfr mutations have not been reported. Their presence was therefore investigated in representative lung carcinogenesis models with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N-nitrosobis(2-hydroxypropyl)amine (BHP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) and ethyl carbamate (urethane), as well as X-ray irradiation. With the chemical carcinogenesis models, no mutations were detected in Egfr, which is in clear contrast to the high rates observed in either codon 12 or 61 of K-ras (21/23 of the lung tumors induced with NNK, 4/5 with MelQx, 1/4 with urethane and 7/18 with BHP). However, in the X-ray-induced lung tumors, Egfr mutations with amino acid ...
The development of leukemia and thyroid cancer is characterized by activation of the abl oncogene and ret oncogene, respectively. In order to clarify the relationship between these gene aberrations and radiation, the pro-myelogenous leukemia-derived cell line HL60 and the thyroid cancer-derived cell line 8505C, were irradiated in vitro with 100Gy of X-rays. RNA was then extracted from 10"8 cells of the respective cell lines and examined by the reverse transcription PCR method for rearrangements of abl and ret genes. Five kinds of positive bands were observed in the HL-60 cells irradiated with 100Gy of X-ray. Similarly, six positive bands were also observed in the 8505C cells irradiated with 100Gy. In vitro X-irradiation activation of oncogenes found in radiation induced cancers imply that gene rearrangement by X-rays is involved in the development of malignant ...
There is a need for earlier and more accurate cancer diagnostics as well as new targets for cancer immunotherapy. To this end, it is important to identify sets of tumour antigens specific for different cancer forms. Several methods that identify potential tumour antigens in an arrayed and high-throughput format have been developed during the last years of SEREX (serological identification of antigens by recombinant expression cloning) related research. Such techniques may hold the potential to describe the complete immunogenic part of the cancer proteome, also called the cancer immunoproteome.We have developed a powerful platform for automated serological high-throughput filter screening of tumour cDNA libraries. The screening format of this method is 18,000 single cDNAs clones, which is s...
BackgroundMicroarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide a limited selection...Full Text Available
Extending genome wide association analysis by the inclusion of gene expression data may assist in the dissection of complex traits. We examined piebald, a pigmentation phenotype in both human and Merino...Full Text Available
Noncoding RNAs play important roles in various aspects of gene regulation. We have identified 7SK RNA to be enriched in nuclear speckles or interchromatin granule clusters (IGCs), a subnuclear domain...Full Text Available
BackgroundGene regulation is a key mechanism in higher eukaryotic cellular processes. One of the major challenges in gene regulation studies is to identify regulators affecting the...Full Text Available
Comparative sociogenomics has the potential to provide important insights into how social behaviour evolved. We examined brain gene expression profiles of the primitively eusocial wasp Polistes...Full Text Available
From Toki-shakuyaku-san, an herbal formulation for “cleansing stagnated blood,” a key gene regulatory compound was purified and identified through a screening based on DNA microarray...Full Text Available
Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, na...
Colorectal cancer is the third most common malignant tumor and the fourth-leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. 392 single nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized ...
A substantial proportion of lymph node-negative patients who receive adjuvant chemotherapy do not derive any benefit from this aggressive and potentially toxic treatment. However, standard histopathological...Full Text Available
The 37/67-kd laminin receptor, LAMR, is a multifunctional protein that associates with the 40S ribosomal subunit and also localizes to the cell membrane to interact with the extracellular matrix. LAMR...Full Text Available
A method has been developed to predict the effects of mutations in the p53 cancer suppressor gene. The new method uses novel parameters combined with previously established parameters. The most important...Full Text Available
Exosomes are small membrane vesicles secreted from various types of cells. Tumor-derived exosomes contain MHC class I molecules and tumor-specific antigens, receiving attention as a potential cancer...Full Text Available
BackgroundRecent data show aberrant and altered expression of regulatory noncoding micro (mi) RNAs in prostate cancer (PCa). A large number of miRNAs are encoded in organized intronic...Full Text Available
Decitabine, an epigenetic modifier that reactivates genes otherwise suppressed by DNA promoter methylation, is effective for some, but not all cancer patients, especially those with solid tumors. It...Full Text Available
As the result of genetic alterations and tumor hypoxia, many cancer cells avidly take up glucose and generate lactate through lactate dehydrogenase A (LDHA), which is encoded by a target gene of c-Myc...Full Text Available
Telomerase, a ribonucleoprotein enzyme that maintains telomere length, is crucial for cellular immortalization and cancer progression. Telomerase activity is attributed primarily to the expression of...Full Text Available
Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive....Full Text Available
It is widely accepted that specific human papillomavirus (HPV) types are the central etiologic agent of cervical carcinogenesis. However, a number of infected women do not develop invasive lesions,...Full Text Available
Werner Syndrome (WS) is an inherited disease characterized by premature onset of aging, increased cancer incidence, and genomic instability. The WS gene encodes a 1,432-amino acid polypeptide (WRN)...Full Text Available
Microarray data has a high dimension of variables but available datasets usually have only a small number of samples, thereby making the study of such datasets interesting and challenging. In the task...Full Text Available
Mutational inactivation of the RB1 tumor suppressor gene initiates retinoblastoma and other human cancers. RB1 protein (pRb) restrains cell proliferation by binding...Full Text Available
BackgroundIn cancer research, most clinical variables have already been investigated and are now well established. The use of transcriptomic variables has raised two problems: restricting...Full Text Available
Over the past few years, tissue microarray (TMA) technology has been established as a standard method for assessing the expression of proteins or genes across large sets of tissue specimens....Full Text Available
The carcinogenicity database used for this paper originated in the late 1960s by the National Cancer Institute (NCI) and since 1978 has been continued and made more comprehensive by the National Toxicology...Full Text Available
Motivation: The identification of gene regulatory modules is an important yet challenging problem in computational biology. While many computational methods have been proposed to identify...Full Text Available
While genomic alterations identified in human tumors using techniques such as comparative genomic hybridisation (CGH) may be recurrent, they frequently encompass large regions, in some cases...Full Text Available
A hallmark of several human cancers is loss of heterozygosity (LOH) of chromosome 17p13. The same chromosomal region is also frequently hypermethylated in cancer. Although loss of 17p13 has been often...Full Text Available
AIM: To evaluate the biological and clinical characteristics of miR-622 in gastric cancer.METHODS: We analyzed the expression of miR-622 in 57 pair matched gastric neoplastic and adjacent non-neoplastic...Full Text Available
LIMD1 is a tumour suppressor gene (TSG) down regulated in ∼80% of lung cancers with loss also demonstrated in breast and head and neck squamous cell carcinomas. LIMD1 is also a candidate TSG...Full Text Available
Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS)...Full Text Available
We have identified two novel, very closely related genes, SAS1 and SAS2, from Dictyostelium discoideum. These encode small, approximately 20-kilodaton proteins with amino acid sequences thought to be...Full Text Available
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancergene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosi...
To gain insight into the changes in the transcriptome of soybean roots during soybean cyst nematode (SCN) infection, we conducted genome-wide gene expression profiling using serial analysis of gene expression (SAGE) combined with Solexa sequencing. More than 3 million tags were generated from the SCN-infected and uninfected roots, and 366941 and 314591 clean UniTags were obtained from SCN-infected and uninfected samples, respectively. In the SCN-infected sample, 48249 UniTags represented 18114 reference genes. In the uninfected control, 46290 UniTags represented 19323 reference genes. Comparison of tag frequencies identified 1405 genes that were expressed at greater levels in SCN-infected roots than in uninfected roots, and 1191 genes that were expressed at lower levels. Quantitative real-...
AbstractBACKGROUND: The authors chose to examine the association between body mass index (BMI) and incident colorectal cancer across the spectrum of BMI, including underweight persons, because detailed prospective cohort data on this topic in Asians is scarce, as is data on underweight persons (BMI, <18.5 kg/m2) in any population. METHODS: Analysis of the Singapore Chinese Health Study included 51,251 men and women aged 45-74 years enrolled in 1993-1998 and followed through 2007. Incident cancer cases and deaths among cohort members were identified through record linkage, and 980 cases were identified. Cox regression models were used to investigate the association of baseline BMI with risk of incident colorectal cancer during a mean of 11.5 years of follow-up. RESULTS: A significant, U-sha...
Abstract Background: G proteins are ubiquitously expressed signal transduction proteins playing a key role in multiple signal transduction pathways. The Gas subunit has been considered as an apoptosis factor. In this study the role of GNAS T393C genotypes of the GNAS gene encoding Gas was analyzed for its influence on the development and progression of prostate cancer. Methods: Genotyping of the GNAS T393C polymorphism in 196 prostate cancer patients and 200 healthy controls was performed by DNA extraction followed by PCR and restriction analysis. Results: We observed no evidence of effects related to GNAS T393C genotype as demonstrated by a comparison of the genotype distribution in prostate cancer patients and healthy controls, the genotype distribution dependent on grade of the primary ...
The DNA sequence motif ATTTGCAT (octamer) or its inverse complement has been identified as an evolutionarily conserved element in the promoter region of immunoglobulin genes. Two major DNA-binding proteins that bind in a sequence-specific manner to the octamer DNA sequence have been identified in mammalian species--a ubiquitously expressed protein (Oct-1) and a lymphoid-specific protein (Oct-2). During characterization of the promoter region of the chicken immunoglobulin light chain gene, the authors identified two homologous octamer-binding proteins in chicken B cells. when the cloning of the human gene for Oct-2 revealed it to be a member of a distinct family of homeobox genes, they sought to determine if the human Oct-2 cDNA could be used to identify homologous chicken homeobox genes. Using a ...
Mutations or multiplications in a-synuclein gene cause familial forms of Parkinson disease or dementia with Lewy bodies (LB), and the deposition of wild-type a-synuclein as LB occurs as a hallmark lesion of these disorders, collectively referred to as synucleinopathies, implicating a-synuclein in the pathogenesis of synucleinopathy. To identify modifier genes of a-synuclein-induced neurotoxicity, we conducted an RNAi screen in transgenic C. elegans (Tg worms) that overexpress human a-synuclein in a pan-neuronal manner. To enhance the RNAi effect in neurons, we crossed a-synuclein Tg worms with an RNAi-enhanced mutant eri-1 strain. We tested RNAi of 1673 genes related to nervous system or synaptic functions, and identified 10 genes that, upon knockdown, caused severe growth/motor abnormalit...
Cancer immunotherapies can be guided by cellular imaging techniques, which can identify the presence or absence of immune-cell accumulation in the tumor tissue in-vivo and in real time. This...Full Text Available
Mouse models have dramatically improved our understanding of cancer development and tumor biology. However, these models have shown limited efficacy as tractable systems for unbiased genetic...Full Text Available
ObjectiveThis study was conducted to provide a nationwide analysis on barriers to cervical cancer screening in Korea.MethodsData used for this study...Full Text Available
The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome...Full Text Available
Cancer stem cells (CSCs) have been identified in a number of solid tumors, but not yet in rhabdomyosarcoma (RMS), the most frequently occurring soft tissue tumor in childhood. Hence, the aim of this...Full Text Available
AbstractBackground: A defective innate immune response may contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Employing a global gene expression analysis, this study was aimed at identifying specifically regulated genes within the epithelial compartment in inflammatory bowel disease (IBD). Methods: The epithelial fraction of human ileal mucosa samples from surgical specimens was obtained by laser microdissection. Gene expression was examined by global expression profiling (n = 18, Affymetrix), quantitative reverse-transcription polymerase chain reaction (RT-PCR) (n = 35), immunoblot analysis (n = 9), and immunohistochemistry (n = 25). Results: Global expression profiling revealed a pronounced downregulation of the retinoic acid-inducible gene I (RIG-I) with...
Background: A possible association between the polymorphic CAG repeat in the DNA polymerase gamma (POLG) gene and the risk of testicular germ-cell tumours (TGCT) was investigated in this study. The hypothesis was prompted by an earlier preliminary study proposing an association of the absence of the common 10-CAG-long POLG allele with testicular cancer as well as previously reported in some European populations' association with male subfertility, which is a condition carrying an increased risk of TGCT. Patients and methods: The number of CAG repeats in both POLG alleles was established in 243 patients with TGCT and in 869 controls by the analysis of the genomic DNA fragment. Results: A significantly higher proportion of men homozygous allele of other than the common 10 CAG repeats was fou...
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17b-estradiol (E2), although glycyrrhizin di...
The product of the human GRO gene is a cytokine with inflammatory and growth-regulatory properties; GRO is also called MGSA for melanoma growth-stimulatory activity. The authors have identified two additional genes, GRO#beta# and GRO#gamma#, that share 90% and 86% identity at the deduced amino acid level with the original GRO#alpha# isolate. One amino acid substitution of proline in GRO#alpha# by leucine in GRO#beta# and GRO#gamma# leads to a large predicted change in protein conformation. Significant differences also exist in the 3' untranslated region, including different numbers of ATTTA repeats associated with mRNA instability. A 122-base-pair region in the 3' region is conserved among the three GRO genes, and a part of it is also conserved in the Chinese hamster genome, suggesting a role in regulation. DNA hybridization with oligonucleotide probes and partial sequence analysis of the genomic clones ...
Somite boundary formation is crucial for segmentation of vertebrate somites and vertebrae and skeletal muscle morphogenesis. Previously, we developed a Tol2 transposon-mediated...Full Text Available
Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disease that is caused by defective complement regulation in over 50% of cases. Mutations have been identified in genes encoding both complement...Full Text Available
The Arabidopsis ref2 mutant was identified in a screen for plants having altered fluorescence under UV light. Characterization of the ref2 mutants showed that they...Full Text Available
BackgroundTwenty-eight genes putatively encoding cytosolic glutathione transferases have been identified in the Anopheles gambiae genome. We manually annotated these...Full Text Available
Sensory neurons in aging mammals undergo changes in anatomy, physiology and gene expression that correlate with reduced sensory perception. In this study we compared young and aged mice to identify...Full Text Available
The Salmonella PmrA-PmrB system controls the expression of genes necessary for polymyxin B resistance. Four loci were previously identified as part of the regulon, and interaction of...Full Text Available
In an earlier report, we used differential cloning to identifygenes that might be critical in controlling arterial neointima formation (Giachelli, C., N. Bae, D. Lombardi, M. Majesky, and S. Schwartz....Full Text Available
BackgroundOil palm (Elaeis guineensis Jacq.) is one of the most important oil bearing crops in the world. However, genetic improvement of oil palm through conventional...Full Text Available
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. We have recently identified a new gene (EYS) encoding...Full Text Available
Two bacteriolytic enzymes secreted by Achromobacter lyticus M497-1 were purified and identified as being very similar (considering their amino acid composition and N-terminal sequence) to alpha- and...Full Text Available
Using a genetic screen we have identified two chromosomal genes, cusRS (ylcA ybcZ), from Escherichia coli K-12 that encode a two-component, signal...Full Text Available
BackgroundThe long-term goal of the GKDZI (Genetics of Kidney Disease in Zuni Indians) Study is to identifygenes, environmental factors, and genetic-environmental...Full Text Available
The ETS proteins are a family of transcription factors (TFs) that regulate a variety of biological processes. We made genome-wide analyses to explore the classification of the ETS gene family. We identified...Full Text Available
CDC7 is an essential gene required for DNA replication in Saccharomyces cerevisiae. Cdc7p homologs have recently been identified in vertebrates, but their role in DNA...Full Text Available
BackgroundIt is often desirable to separate effects of different regulators on gene expression, or to identify effects of the same regulator across several systems. Here, we focus...Full Text Available
BackgroundHistone post-translational modifications are critical for gene expression and cell viability. A broad spectrum of histone lysine residues have been identified in yeast...Full Text Available
PurposeTo detail the highly variable ocular phenotypes of a French family affected with an autosomal dominantly inherited vitreoretinopathy and to identify the disease gene.MethodsSixteen...Full Text Available
Schizophrenia and bipolar disorder are leading causes of morbidity across all populations, with heritability estimates of ∼80% indicating a substantial genetic component. Population genetics...Full Text Available
We report the existence of a sixth replication arrest site, TerF, that is located within the coding sequences of the rcsC gene, a negative regulator of capsule biosynthesis. The TerF site is oriented...Full Text Available
Targeted genome capture combined with next-generation sequencing was used to analyze 2.9 Mb of the DFNB79 interval on chromosome 9q34.3, which includes 108 candidate genes. Genomic...Full Text Available
Peculiar DNA sequences made up by the tandem repetition of a 5 bp unit have been identified within or upstream from three avian protein-coding genes. One sequence is located within an intron of the...Full Text Available
BackgroundCoiled-coil domain containing 115 (Ccdc115) or coiled coil protein-1 (ccp1) was previously identified as a downstream gene of Fibroblast Growth Factor 2 (FGF2) highly expressed...Full Text Available
BackgroundAvian β-defensins (AvBDs) represent a group of innate immune genes with broad antimicrobial activity. Within the chicken genome, previous work identified 14 AvBDs...Full Text Available
DNA from 48 hr germinated rice embryos was cut with restriction endonuclease Bam H1 and cloned to the Bam H1 site on plasmid pBR 322. The clones containing recombinant DNA were selected by their sensitivity to tetracycline and resistance to ampicillin. Using /sup 32/P-labelled rice embryos tRNA as a probe two clones were identified to contain tRNA genes by colony hybridization.
A series of translocation break points found in a subset of human acute leukemias have one of the breaks on human chromosome 11q23. This region has recently been cloned and a large gene, ALL-1, with...Full Text Available
Lung cancer is still difficult to treat by current chemotherapeutic procedures. We recently found that MVL, an anti-HIV lectin from blue-green algae Microcystis viridis, also has antitumor activity. The objective of this study was to investigate apoptosis-inducing activity of recombinant MVL (R-MVL) and proteomic changes in A549 cells, and to identify the molecular pathways responsible for the anti-cancer action of R-MVL. We found that R-MVL induces A549 cells apoptosis in a dose-dependent manner by using MTT assay, fluorescent microscope (FM) and flow cytometry (FCM), and the IC50 was calculated to be 24.12??g/ml. Subsequently, 7 altered proteins in R-MVL-treated A549 cells were identified, including upregulated aldehyde dehydrogenase 1 and ?-actin, and five downregulated proteins: heat s...
A prospective comparative study with pathology was performed to assess the clinical value of Computed Tomography (CT) and endoscopic ultrasound (EUS) for nodal staging in lung cancer. A total of 329 nodal stations were dissected or sampled and 755 lymph nodes were examined at histology. On a pre-station basis, CT had greater sensitivity (74%) than EUS (56%), but EUS was more specific (83% versus 93%). The accuracy rates of the two techniques were similar. In conclusion, endoscopic ultrasound should be part of a routine preoperative diagnostic approach to non-small-cell lung cancer., because of its high specificity. Results can be improved when EUS and CT are combined., which suggests that these imaging modalities should be used together in selected patients for the noninvasive staging of non-small-cell lung cancer to identify local lymphatic spread.
Purpose The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC). Although PITX2 is reportedly involved in various functions, including tissue development by controlling cell growth, its significance in CRC remains unclear. We report our findings regarding abnormal PITX2 expression in human CRC. Methods PITX2 expression was evaluated in 5 human CRC cell lines and 92 primary CRC samples. Cell growth was evaluated after inhibition of PITX2 expression or after exogenous introduction of PITX2. Results PITX2 expression was seen in all the five CRC cell lines. The study of tissue samples indicated that PITX2 expression was significantly higher in cancer...
The human zinc finger protein genes (ZFX/Y) were identified as a result of a systematic search for the testis-determining factor gene on the human Y chromosome. Although they play no direct role in sex determination, they are of particular interest because they are highly conserved among mammals, birds, and amphibians and because, in eutherian mammals at least, they have active alleles on both the X and the Y chromosomes outside the pseudoautosomal region. We used in situ hybridization to localize the homologues of the zinc finger protein gene to chromosome 1 of the Australian echidna and to an equivalent position on chromosomes 1 and 2 of the playtpus. The localization to platypus chromosome 1 was confirmed by Southern analysis of a Chinese hamster [times] platypus cell hybrid retaining most of platypus chromosome 1. This localization is consistent with the cytological homology of chromosome 1 between ...
Objectives: The purpose of this work was to study the genetic determinants responsible for extended-spectrum beta-lactamase (ESBL) resistance of Salmonella isolated from Dutch poultry, poultry meat and hospitalized humans. Methods: Thirty-four ESBL-resistant Salmonella isolates from The Netherlands were tested towards 21 antimicrobial agents. PCR and sequencing were used to determine the underlying genetic determinants responsible for the ESBL phenotypes. The transferability of the ESBL phenotypes was tested by conjugation to a susceptible Salmonella enterica serovar Dublin and plasmid purification, restriction fragment length polymorphism (RFLP) and pulsed-field gel electrophoresis (PFGE) were employed to further characterize a subset of the isolates. Results: A great genetic diversity was seen among the isolates. The bla(TEM-52) gene was most predominant and was found among Salmonella enterica serovars Blockley, Thomson, London, Enteritidis phage type 14b, ...
Normal human foreskin keratinocytes cotransfected with the neomycin resistance gene and recombinant human papillomavirus (HPV) DNAs (types 16, 18, 31, and 33) that have a high or moderate association with cervical malignancy acquired immortality and contained integrated and transcriptionally active viral genomes. Only transcripts from the intact E6 and E7 genes were detected in at least one cell line, suggesting that one or both of these genes are responsible for immortalization. Recombinant HPV DNAs with low or no oncogenic potential for cervical cancer (HPV1a, -5, -6b, and -11) induced small G418-resistant colonies that senesced as did the nontransfected cells. These colonies contained only episomal virus DNA; therefore, integration of HPV sequences is important for immortalization of keratinocytes. This study suggests that the virus-encoded immortalization function contributes to the pathogenesis of ...
BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) are transcription factors (TFs) that mediate estrogen signaling and define the hormone-responsive phenotype...Full Text Available
Australia?s nationally consistent framework for gene technology regulation is underpinned by the Gene Technology Act 2000, administered by an independent decision-maker, the Gene Technology Regulator. The object of the Act is ?to protect the health and safety of people, and to protect the environment, by identifying risks posed by or as a result of gene technology, and by managing those risks through regulating certain dealings with genetically modified organisms?. Marketing and trade impacts are outside the scope of assessments required by the Act. Since 2001, seven licences have been issued for the commercial cultivation of genetically modified (GM) cotton with insect resistance and/or herbicide tolerance. Licences have also been issued for 32 GM cotton field trials with a broader range ...
Abstract Gelatinization temperature (GT) is an important parameter in evaluating the cooking and eating quality of rice. Indeed, the phenotype, biochemistry and inheritance of GT have been widely studied in recent times. Previous map-based cloning revealed that GT was controlled by ALK gene, which encodes a putative soluble starch synthase II-3. Complementation vector and RNAi vector were constructed and transformed into Nipponbare mediated by Agrobacterium. Phenotypic and molecular analyses of transgenic lines provided direct evidence for ALK as a key gene for GT. Meanwhile, amylose content, gel consistency and pasting properties were also affected in transgenic lines. Two of four nonsynonymous single nucleotide polymorphisms in coding sequence of ALK were identified as essential for GT. ...
Rice is a very important food staple that feeds more than half the world's population. Two major Asian cultivated rice (Oryza sativa L.) subspecies, japonica and indica, show significant phenotypic variation in their stress responses. However, the molecular mechanisms underlying this phenotypic variation are still largely unknown. A common link among different stresses is that they produce an oxidative burst and result in an increase of reactive oxygen species (ROS). In this study, methyl viologen (MV) as a ROS agent was applied to investigate the rice oxidative stress response. We observed that 93-11 (indica) seedlings exhibited leaf senescence with severe lesions under MV treatment compared to Nipponbare (japonica). Whole-genome microarray experiments were conducted, and 1,062 probe sets were identified with gene expression level polymorphisms between the two rice cultivars in addition to differential expression under MV treatment, which were ...
Expressed sequence tags (ESTs) of the maxillary galea of the silkworm were analyzed to identify proteins involved in food selection systems. From the 1251 redundant genes of the ESTs, we identified 7 odorant-binding protein-like genes (bmObpL), 6 takeout-like genes (bmToL), and 6 chemosensory protein genes (bmCsp). Quantitative RT-PCR analysis indicated that bmObpL1, bmObpL2, bmObpL3, bmObpL5, bmToL1, bmToL3, and bmorCsp15 were predominantly expressed in the larval oral appendages, such as the maxilla, labrum, labium and antenna. Immunocytochemical analysis indicated that the proteins of bmObpL1, bmObpL3, and bmToL1 were localized in the gustatory chemosensilla on the maxillary galea and olfactory sensilla in the antenna. The proteins encoded by bmObpL1 and bmObpL3 were detected in the gus...
Two overlapping cDNA clones encoding human DNA topoisomerase II were identified by two independent methods. In one, a human cDNA library in phage {lambda} was screened by hybridization with a mixed oligonucleotide probe encoding a stretch of seven amino acids found in yeast and Drosophila DNA topoisomerase II; in the other, a different human cDNA library in a {lambda}gt11 expression vector was screened for the expression of antigenic determinants that are recognized by rabbit antibodies specific to human DNA topoisomerase II. The entire coding sequences of the human DNA topoisomerase II gene were determined from these and several additional clones, identified through the use of the cloned human TOP2 gene sequences as probes. Hybridization between the cloned sequences and mRNA and genomic DNA indicates that the human enzyme is encoded by a single-copy gene. The location of the ...
Functional activation of {beta}-catenin/Tcf signaling plays an important role in early events in carcinogenesis. We examined the effect of naringenin against {beta}-catenin/Tcf signaling in gastric cancer cells. Reporter gene assay showed that naringenin inhibited {beta}-catenin/Tcf signaling efficiently. In addition, the inhibition of {beta}-catenin/Tcf signaling by naringenin in HEK293 cells transiently transfected with constitutively mutant {beta}-catenin gene, whose product is not phosphorylated by GSK3{beta}, indicates that its inhibitory mechanism was related to {beta}-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that the {beta}-catenin distribution and the levels of nuclear {beta}-catenin and Tcf-4 proteins were unchanged after naringenin treatment. Moreover, the binding activities of ...
Mutations in the mouse formin (Fmn) gene, formerly known as the limb deformity (ld) gene, give rise to recessively inherited limb deformities and renal malformations or aplasia. The Fmn gene encodes many differentially processed transcripts that are expressed in both adult and embryonic tissues. To study the genomic organization of the Fmn locus, we have used Fmn probes to isolate and characterize genomic clones spanning 500 kb. Our analysis of these clones shows that the Fmn gene is composed of at least 24 exons and spans 400 kb. We have identified two novel exons that are expressed in the developing embryonic limb bud as well as adult tissues such as brain and kidney. We have also used a microsatellite polymorphism from within the Fmn gene to map it genetically to a 2.2-cM interval between D2Mit58 and D2Mit103. 36 refs., 6 figs., 1 tab.
African bovine trypanosomiasis caused by Trypanosoma sp., is a major constraint on cattle productivity in sub-Saharan Africa. Some African Bos taurus breeds are highly tolerant of infection, but the potentially more productive Bos indicus zebu breeds are much more susceptible. Zebu cattle are well adapted for plowing and haulage, and increasing their tolerance of trypanosomiasis could have a major impact on crop cultivation as well as dairy and beef production. We used three strategies to obtain short lists of candidate genes within QTL that were previously shown to regulate response to infection. We analyzed the transcriptomes of trypanotolerant N'Dama and susceptible Boran cattle after infection with Trypanosoma congolense. We sequenced EST libraries from these two breeds to identify polymorphisms that might underlie previously identified quantitative trait loci (QTL), and we assessed QTL regions and candidate loci for ...
To illustrate the implementation of a bottom-up approach to the study of culture in health disparities, this article describes the development of a cultural cancer screening scale (CCSS) using mixed methodologies. The aim was to identify cultural factors relevant to breast and cervical cancer screening, develop an instrument to assess them and examine its preliminary psychometric properties among Latin American (Latino) and non-Latino White (Anglo) women in Southern California. Seventy-eight Latino and Anglo women participated in semi-structured interviews, which were content coded based on Triandis' methods for the analysis of subjective culture. Based on the emerging cultural elements, items relevant to cancer screening were developed and pilot tested with 161 participants. After the instrument was refined, 314 Latino and Anglo women from various socioeconomic backgrounds completed the CCSS and data ...
Glycyrrhiza glabra root is one of the common traditional Chinese medicines and used as flavoring and sweetening agents for tobaccos, chewing gums, candies, toothpaste and beverages. While glycyrrhizin is one of the main components in the extract of G. glabra root and has been characterized, the other components have not been well characterized. The mechanism of growth activation of breast cancer MCF-7 cells, including the activation of Erk1/2 and Akt, and the transcriptional regulation of estrogen-responsive genes, was examined by means of sulforhodamine B, luciferase reporter gene, real-time RT-PCR and Western blotting assays after the induction of the cells with the extract of G. glabra root. The extract has similar activity to that induced by 17beta-estradiol (E(2)), although glycyrrhizin did not show such an activity. Moreover, the estrogen receptor alpha-dependent neurite outgrowth induced by the extract was similar to ...
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancergene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosis, infiltration of polymorphonuclear neutrophils and reduced microvessel density in the tumor samples. To study the molecular mechanism ...
Introduction: Tumor-derived heat shock protein (HSP)-peptide complexes (HSPPCs) induced immunity against malignancies in preclinical trials, working across tumor types and bypassing the need to identify single immunogenic peptides. These results paved the way for the use of human gp96 obtained from autologous tumor samples as an anti-cancer vaccine. Areas covered: Autologous tumor-derived HSP gp96 peptide complex (HSPPC-96) vaccine is emerging as a tumor- and patient-specific cancer vaccine, with confirmed activity in several malignancies. It has been tested in Phase III clinical trials in advanced melanoma and kidney cancer with evidence for efficacy in patients with earlier stage disease. HSPPC-96-based vaccine demonstrated an excellent safety profile, thus emerging as a novel therapeuti...
Purpose To evaluate disease failure patterns and overall survival (OS) of women with triple-negative (TN) breast cancer who underwent breast-conserving therapy (BCT) and to understand the relationship of TN tumors with other prognostic factors. Patients and Methods The Surveillance, Epidemiology, and End Results (SEER) registry identified 562 women diagnosed and/or treated with unilateral invasive breast cancer during 2003?2004 at three Emory hospitals. After medical record review, 193 eligible women, with all tumor types, received BCT. Primary endpoints (local, regional, and distant recurrences) and secondary endpoint (OS) were evaluated using chi-square tests and Cox proportional hazards models. Results Of the 193 women, 33 (17.1%) had TN tumors and 160 (82.9%) had non-TN tumors. Patient...
Childhood cancer survivors at highest risk of developing a secondary malignancy are those with hereditary retinoblastoma. The majority of such secondary cancers will be sarcomas, most commonly of bone. One-third of these occur outside a typical radiation field, commonly in an extremity. Bone sarcoma is also the most commonly reported secondary cancer to develop among survivors of Ewing's sarcoma. In this group, radiation doses greater than 60 Gy as well as alkylating agent chemotherapy have been identified as contributors to the increased risk. The prognosis for patients with a secondary sarcoma has been poor, with few cures reported to date. However, an aggressive, combined modality approach, including radical resection, postoperative radiation, and adjuvant chemotherapy, may improve the survival rate.
The PMS2 gene encodes a protein that is involved in DNA mismatch repair and is mutated in a subset of patients with hereditary nonpolyposis colon cancer (HNPCC). The previously published PMS2 cDNA sequence lack an upstream in-frame stop codon preceding the presumptive initiating methionine. To evaluate the 5` terminus of the PMS2 coding region further, we isolated additional cDNA clones, RT-PCR products, and the corresponding 5` genomic segment of the PMS2 locus. The PMS2 gene transcripts were found to have heterogeneous but colinear 5` termini, one of which contained an in-frame termination codon preceding the initiating methionine. In addition, a novel gene encoding a 34.5-kDa polypeptide was found to initiate transcriptionally within PMS2 from the opposite strand. 23 refs., 5 figs., 2 tabs.
A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n=18) from six experimental stages were collected from the resistant hepatocyte (RH) rat model of liver cancer and analyzed by 2D DIGE. The study included triplicates of regenerating liver, control "sham-operated" liver, three distinct premalignant stages and hepatomas. Out of 81 identified proteins two-thirds were differentially abundant in rat hepatomas compared to control rat liver and, secondly, the majority of proteins were also changed in precursor stages. This underscores the importance of adequate control samples in explorative cancer biomarker research. We confirm several proteomic changes previously identified in human ...
The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. ...
The human CDC25 tyrosine phosphatases trigger activation of CDC2 by removing inhibitory phosphates; thus the genes encoding these phosphatases may be suspected as potential oncogenes due to their role in promoting cell division. To date, three human CDC25 genes have been identified: CDC25A, B, and C. This communication describes the mapping of CDC25A to chromosome 3p21 and CDC25B to chromosome 20p13 by fluorescence in situ hybridization with confirmation by the polymerase chain reaction of hamster-human somatic cell hybrid DNA. 3p21 is near an area frequently involved in karyotypic abnormalities in renal carcinomas, small cell carcinomas of the lung, and benign tumors of the salivary gland. 20p13 does not seem to be a common area for karyotypic alteration in tumors. Mapping of these genes to their chromosomal loci may help identify tumors with abnormal regulation of CDC25 ...
Abstract The Hippo pathway is an evolutionally conserved protein kinase cascade involved in regulating organ size in vivo and cell contact inhibition in vitro by governing cell proliferation and apoptosis. Deregulation of the Hippo pathway is linked to cancer development. Its first core kinase Warts was identified in Drosophila more than 15 years ago, but it gained much attention when other core components of the pathway were identified 8 years later. Major discoveries of the pathway were made during past several years. The core kinase components Hippo, Salvador, Warts, and Mats in the fly and Mst1/2, WW45, Lats1/2, and Mob1 in mammals phosphorylate and inactivate downstream transcriptional co-activators Yorkie in the fly, Yes-associated protein (YAP) and transcriptional co-activator with ...
Abstract Many solute carrier transporters that interact with anticancer agents and contribute to their pharmacokinetics have been shown to be differentially upregulated in cancer cells as a result of adaptive response to altered nutritional requirements. This review focuses on pathophysiological function of membrane transporters responsible for the influx of physiological substances including oligopeptides, amino acids, and organic cations and anions, and summarizes the recent knowledge regarding mechanisms in their gene expressions. Broad substrate specificity of enhanced oligopeptide H+/peptide cotransporter 1 activity in cancer cells is useful for tumor tissue-specific delivery of chemotherapeutic agents and positron emission tomography diagnostic probes. Amino acid transporters such as...
Recent improvements in cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TIC). This discovery has led to the -cancer stem cell hierarchy- concept, which holds that tumors are organized as a hierarchy of malignant tissues sustained by such TIC. However, this concept remains controversial. In this review, we examine recent advances in cancer stem cell research that have been generated from studies of Philadelphia (Ph) chromosome-positive leukemia. The abnormal Ph chromosome, which arises from a translocation creating the BCR-ABL1 fusion gene, is most commonly associated with chronic myelogenous leukemia (CML) and precursor B cell acute lymphoblastic leukemia (B-ALL). Examination of the pathophysiology ...
DNA methylation is considered as a potential cause of aberrations in regulation of gene expression during carcinogenesis. Therefore, changes in DNA methylation patterns may be targets for chemoprevention. In the present study, we investigated effects of all-trans retinoic acid (ATRA), vitamin D3, and resveratrol alone and in combination with adenosine analogues: 2-chloro-2'-deoxyadenosine (2CdA) and 9-beta-d-arabinosyl-2-fluoroadenine (F-ara-A), on methylation and expression of retinoic acid receptor beta 2 (RARbeta2) in MCF-7 and MDA-MB-231 breast cancer cell lines. Alterations in methylation and expression levels after treatment of cells with the tested compounds were evaluated by methylation-sensitive restriction analysis (MSRA) and real-time PCR, respectively. RARbeta2 promoter in the ...
BACKGROUND Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Tumor suppressor genes retinoic acid receptor beta (RARb) and PDLIM4 are hypermethylated and silenced in prostate cancer (PCa) tissues and PCa cell lines compared to normal prostate cells. METHODS In this study, a benign prostate epithelial cell line RWPE1 was used as a model to study the epigenetic regulation of Myc on the RARb and PDLIM4 promoters. Forced Myc overexpression inhibited the RARb and PDLIM4 expression. RESULTS Pyrosequencing study showed that Myc overexpression increased methylation in several CpG sites of both promoters. A DNA methylation inhibitor 5-aza-2prime-deoxycytidine reversed the epigenetic alteration effect of Myc on both RARb and PDLIM4. CONCLUSION The epigenetic r...
Tissue factor pathway inhibitor (TFPI), a protease inhibitor that circulates in association with plasma lipoproteins (VLDL, LDL and HDL), helps to regulate the extrinsic blood coagulation cascade. The authors have cloned a 125-kb genomic region containing the entire human TFPI gene on six overlapping cosmids and prepared a restriction map of this contig to clarify gene structure. More than half (45 kb) of the 85-kb gene is occupied with 5[prime] noncoding elements: coding begins at exon 3. A HindIII RFLP identified with one cosmid was genotyped in the CEPH panel of 559 reference families. Linkage analysis using markers on human chromosome 2 located the TFPI gene on 2q, 36 cM proximal to D2S43(pYNZ15) and 13 cM distal to the crystalline [gamma]-polypeptide locus CRYGP1(p5G1). 31 refs., 3 figs., 3 tabs.
Summary CAG trinucleotide repeat length in the nuclear polymerase gamma gene (POLg) has been shown to be associated with men with reduced fertility. The present study investigated the frequency of CAG repeat length genotypes and three exonuclease motifs of the POLg in relation to the frequency of mitochondrial nucleotide substitutions. DNA from semen samples of 93 normozoospermic men and 192 non-normozoospermic men was isolated and the specific regions of the genes were amplified by polymerase chain reactions (PCR) and sequenced to identify mutations. The genotypic frequencies of pooled POLg CAG repeat lengths, =10/!=10 heterozygotes and !=10/!=10 homozygotes, were significantly different between normozoospermic and non-normozoospermic men (p p POLg genotype. Of the 17 men with non-synonym...
Background In chordates, retinoid metabolism is an important target of short-chain dehydrogenases/reductases (SDRs). It is not known whether SDRs play a role in retinoid metabolism of protostomes, such as Drosophila melanogaster. Methods Drosophila genome was searched for genes encoding proteins with ?50% identity to human retinol dehydrogenase 12 (RDH12). The corresponding proteins were expressed in Sf9 cells and biochemically characterized. Their phylogenetic relationships were analyzed using PHYLIP software. Results A total of six Drosophila SDR genes were identified. Five of these genes are clustered on chromosome 2 and one is located on chromosome X. The deduced proteins are 300 to 406 amino acids long and are associated with microsomal membranes. They recognize all-trans-retinaldehyd...
Polycyclic aromatic hydrocarbons (PAHs) are ubiquious in the environment both as natural products and as environmental contaminants. Among PAHs, phenanthrene (PH) that is ubiquitously distributed throughout the environment was subjected in this study. Although environmental distribution and metabolism of PH have been well reported, there are only a few studies examined the expression of mRNA and their functions on PH-induced toxicity. A new paradigm in toxicity screening, toxicogenomic technology represents a useful approach for evaluating the toxic properties of environmental pollutants. In this respect, we elicited the genes which were changed more than 2-fold by analysis of gene expression profiles in human hepatocellular carcinoma (HepG2) cells, exposed to PH by using human oligonucleo...
The full length cDNA of the Brn1 was first cloned, and then expression of the Brn1 was analyzed and the function was identified by silencing technology. Results show that the full length cDNA of the C. lunata Brn1 gene contains 1001 base pairs and an 801?bp open reading frame encoding 267 amino acids. Semi-quantitative PCR analysis shows that the expression of Brn1 at 96?h is significantly higher than at 24 and 72?h (p?Brn1-silenced transformants were light brown in culture filtrate, and have significantly reduced toxin production relative to the wild-type. These results imply that Brn1 gene in C. lunata is not only involved in 1,8-dihydroxynaphthalene melanin synthesis, but is also relatively associated with toxin biosynthesis of the pathogen.
The authors have identified a protein present only in erythroid cells that binds to two adjacent sites within an enhancer region of the chicken {beta}-globin locus. Mutation of the sites, so that binding by the factor can no longer be detected in vitro, leads to a loss of enhancing ability, assayed by transient expression in primary erythrocytes. Binding sites for the erythroid-specific factor (Eryf1) are found within regulatory regions for all chicken globin genes. A strong Eryf1 binding site is also present within the enhancer of at least one human globin gene, and proteins from human erythroid cells (but not HeLa cells) bind to both the chicken and the human sites.
Abstract in english Functional properties of soy proteins for food are closely related to the composition of their storage protein subunits. Using base excision sequence scanning (BESS), we show that the absence of the A4 peptide in the G4 glycinin subunit of the soybean (Glycine max L.) cultivar Enrei was caused by the same point mutation in the Gy4 gene as previously reported in the soybean cultivar Raiden. Although the genetic relationship between Raiden and Enrei is not known, the same p (more) oint mutation in their Gy4 genes may indicate that they probably share a related origin. The application of BESS to identify single nucleotide polymorphisms (SNPs) as co-dominant markers for marker-assisted selection (MAS) of a recessive null allele is also discussed.
Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1?year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study, we have combined the analysis of a murine model and human samples of HCC to identifygenes differentially expressed early in the process of hepatocarcinogenesis, using a microarray-based approach. Expression of 190 genes was impaired in murine ...
The human mitochondrial DNA (mtDNA) is a closed circular, 16,569-bp double-stranded DNA, encoding 13 genes whose protein products are subunits of the oxidative phosphorylation system required for synthesis of most of the ATP consumed by eukaryotic cells. Point mutations of the mtDNA that cause multi-tissue, loss-of-energy syndromes, called mitochondrial encephalomyopathies (e.g., MERRF and MELAS), have been identified. In addition, large-scale deletions of the human mtDNA have been identified and are the molecular bases for the neonatal and adolescent onset loss-of-energy syndromes Pearson and Kearns-Sayer, respectively. 5 refs., 1 fig.
The low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancergene therapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 x 108 plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 x 1011?v.g.), and complete tumor regression w...
The liver is a primary target of growth hormone (GH). GH signals are mediated by the transcription factor signal transducer and activator of transcription 5 (STAT5). Here, we focus on recent discoveries about the role of GH-STAT5 signaling in hepatic physiology and pathophysiology. We discuss roles of the GH-STAT5 axis in body growth, lipid metabolism, and the cell cycle pertaining to hepatosteatosis, fibrosis, and hepatocellular carcinoma. Finally, we discuss recent discoveries about the role of GH-STAT5 in sex-specific gene expression and bile acid, steroid, and drug metabolism.
Background. Through PSA screening the rate of prostate cancers detected at an early stage has increased significantly; thus a decrease in mortality can be expected in the near future. Despite all scientific efforts, however, the molecular mechanisms underlying the development and progression of prostate cancer remain poorly understood. Prostate cancer is a disease of aging men and epidemiological evidence supports a major contribution to its development through diet, lifestyle and environmental factors. Genetic instability is the basic phenomenon of tissue cell cancerisation. This instability can be hereditary or due to mutations and other chromosomal aberrations acquired during life. In recent years a large number of interesting data have been collected which show the relationships between focal atrophy and genetic instability of the prostate epithelia. Atrophy can be the result of prostatitis, ischemia as well as of ...
The low in vivo transduction efficiency of recombinant adeno-associated virus (rAAV) and the undesirably strong immunogenicity of adenovirus (rAdv) have limited their clinical utilization in cancergene therapy. We have previously demonstrated that intratumoral injection of rAAV expressing a C-terminal polypeptide of human telomerase reverse transcriptase (rAAV-hTERTC27) effectively inhibits the growth of glioblastoma xenografts in nude mice. To further improve its efficacy, we combined rAAV-hTERTC27 with rAdv and investigated the efficiency of the cocktail vectors in vivo. At a nontherapeutic dose (1 x 10(8) plaque-forming units (PFUs)), rAdv-null and rAdv-hTERTC27 were equipotent in enhancing the therapeutic efficacy of rAAV-hTERTC27 (1.5 x 10(11) v.g.), and complete tumor regression was achieved in 25% of the treated animals. Importantly, the combination of rAAV-hTERTC27 and a therapeutic dose (2.5 x 10(9) PFU) of rAdv-hTERTC27 significantly ...
We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms...Full Text Available
Background The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved. Methods We investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731 441 participants followed for up to 6-20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided. Results Compared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, Ptrend = ...
BackgroundBiodiesel or ethanol derived from lipids or starch produced by microalgae may overcome many of the sustainability challenges previously ascribed to petroleum-based fuels and first generation plant-based biofuels. The paucity of microalgae genome sequences, however, limits gene-based biofuel feedstock optimization studies. Here we describe the sequencing and de novo transcriptome assembly for the non-model microalgae species, Dunaliella tertiolecta, and identify pathways and genes of importance related to biofuel production.ResultsNext generation DNA pyrosequencing technology applied to D. tertiolecta transcripts produced 1,363,336 high quality reads with an average length of 400 bases. Following quality and size trimming, ~ 45% of the high quality reads were assembled into 33,307 isotigs with a 31-fold coverage and 376,482 singletons. Assembled sequences and singletons were subjected to BLAST similarity searches ...
The Myc oncoprotein is a potent inducer of cell growth, cell cycle progression, and apoptosis. While many direct Myc target genes have been identified, the molecular determinants of Myc’s transcriptional...Full Text Available
DescriptionThe recent sequencing of the complete genomes of several streptomycete species revealed the presence of a large number of cryptic' secondary metabolic gene clusters, and led to the realisation that these organisms have the ability to produce many more natural products than had previously been recognised. One of the aims of our work is to identify the physiological signals and regulatory mechanisms responsible for the activation of these 'cryptic' pathways, thus unleashing the full biosynthetic p [continued...
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations caused by mutations in at least 45 genes. Using homozygosity mapping, we identified a ∼4 Mb homozygous region...Full Text Available
A two-step polymerase chain reaction (PCR) procedure with two nested pairs of primers specific for the yadA gene of Yersinia enterocolitica was developed. The PCR assay identified all common pathogenic...Full Text Available
Genome sequences are essential tools for comparative and mutational analyses. Here we present the short read sequence of mouse chromosome 17 from the Mus musculus domesticus derived...Full Text Available
A multiple comparison approach using whole genome transcriptional arrays was used to identifygenes and pathways involved in calorie restriction/dietary restriction (DR) life span extension in Drosophila....Full Text Available
PurposeTo identify those metallothionein and α-crystallin/small heat-shock genes induced by toxic metals in human lens cells and to evaluate...Full Text Available
Case-parent trios were used in a genome wide association study of cleft lip with/without cleft palate (CL/P). SNPs near two genes not previously associated with CL/P [MAFB:...Full Text Available
Aim of this study was to evaluate the sensitivity of virtual colonoscopy (CT colonography) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality, as well as indications to the examination. It was examined prospectively 62 symptomatic patients aged 36 to 82 years (28 women and 34 men). All patients underwent both conventional and virtual colonoscopy on the same day; the conventional examination allowed exploration of the entire colon. Conventional colonoscopy identified 89 lesions 3-50 mm in diameter, namely 84 benign and 5 malignant lesions. No lesions were identified in 12 patients. CT colonography identified 52 of the 89 lesions, with 57.1% diagnostic accuracy. They were 11 false positives (82.5% positive predictive value and 52.2% specificity) and 37 false negatives (24.5% negative predictive value and 58.4% sensitivity). Sensitivity was ...
Cytoplasmic male sterility (CMS) is a maternally inherited trait that fails to produce functional pollen grains. The CMS system is widely employed to facilitate the utilization of heterosis in major crops. However, little is known about the CMS associated genes in Upland cotton (Gossypium hirsutum). The objective of this study was to compare CMS cotton (CMS-D2) with the cytoplasm from G. harknessii and its isogenic maintainer line with the normal fertile Upland cotton cytoplasm to identify CMS-D2 specific gene(s) and to develop CMS-specific sequence characterized amplified region (SCAR) markers. Based on Southern blot analysis using 10 mitochondrial gene-specific probes (cob, cox2, atp6, atp9, nad3, cox3, atpA, cox1, nad6 and nad9), three probes (cox3, atpA, and nad6) revealed restriction ...
[alpha]-Melanocyte stimulating hormone ([alpha]-MSH), a hormone originally named for its ability to regulate pigmentation of melanocytes, is a 13-amino-acid post-translational product of the pro-opiomelanocortin (POMC) gene. [alpha]-MSH and the other products of POMC processing, which share the core heptapeptide amino acid sequence Met-Glu (Gly)-His-Phe-Arg-Trp-Gly (Asp), the adrenocorticotropic hormone (ACTH), [beta]-MSH, and [gamma]-MSH, are collectively referred to as melanocortins. While best known for their effects on the melanocyte (pigmentation) and adrenal cortical cells (steroidogenesis), melanocortins have been postulated to function in diverse activities, including enhancement of learning and memory, control of the cardiovascular system, analgesia, thermoregulation, immunomodulation, parturition, and neurotrophism. To identify the chromosomal band encoding the human melanocortin-1 receptor gene, 1 [mu]g of an ...
Scientists have just taken a big step toward understanding the cause of Lou Gehrig's disease, one of the most devastating nerve degenerative diseases. A large team of researchers, led by Robert Brown Jr. of Harvards's Massachusetts General Hospital and Robert Horvitz, a Howard Hughes Medical Institute investigator at the Massachusetts Institute of Technology, report in the 4 March Nature that they've identified the gene that causes a hereditary form of the condition, which also goes by the name amyothophic lateral sclerosis (ALS). While most ALS cases - approximately 90% - are apparently sporadic' and not caused by an inherited gene defect, all the patients have such similar symptons that researchers are hopeful that what they learn about hereditary ALS will also apply to the sporadic form, possibly leading to new therapeutic strategies that will help both. It's a very important ...
Measuring gene expression using microarrays is relevant to many areas of biology and medicine, such as follow up of developmental stages and diseases onset, and treatment study. Since there can be tens of thousands of distinct probes on an array, each micro array experiment can accomplish the equivalent number of genetic tests in parallel. Arrays have therefore dramatically accelerated many types of investigations. For example, microarrays can be used to identify stress response genes by comparing gene expression in challenged versus normal cells. In the Molecular and Cellular Biology lab (MCB), the micro array experiments are performed within the Genomic Platform, fully equipped to analyse either the behaviour of bacteria during long space flight, the effect of low dose ionising radiation on the developing organism in mice, or the human individual radiation sensitivity. For the low dose effect, two ...
The recently described retinoid X receptors (RXRs) respond to the novel retinoid 9-cis-retinoic acid and also serve as heterodimeric partners for the vitamin D, thyroid hormone, and retinoic acid receptors (VDR, TR, and RAR, respectively). In this work, the authors report high-resolution localization of the human RXR genes within cytogenetic bands and also within a standard reference map of cosmid DNA markers on human chromosomes. They have determined the location of the human RXR genes by pairwise hybridization of the RXR cosmids and reference markers, using fluorescence in situ hybridization. They localized (i) RXR[alpha] (RXRA) to chromosome 9 band q34.3; (ii) RXR[beta] (RXRB) to chromosome 6 band 21.3; and (iii) RXR[gamma] (RXRG) to chromosome 1 band q22-q23. Six retinoid-responsive transcription factors have been identified so far, including three retinoic acid receptors in addition to the three RXRs. Interestingly, ...
Poaching of wildlife animals for subsistence and commercial purposes has lead to population declines in Africa. In forensic cases, a need exists to identify the species of origin of carcasses, meat or blood. In the study presented here, the mitochondrial COI gene was sequenced to determine the species of unknown samples in three suspect South African forensic wildlife cases. In two cases the unknown samples were identified as originating from domestic cattle (Bos taurus) and in the third case the sample was identified as common reedbuck (Redunca arundinum). This is the first report of the COI sequence of common reedbuck. The study highlights the need for accurate wildlife reference material from each country in order to convict wildlife cases.
Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal alpha7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC(50) approximately 1muM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis ...
Receptor interacting protein 140 (RIP140) is a coregulator for numerous nuclear receptors and transcription factors and primarily exerts gene-repressive activities on various target genes. We previously identified a spectrum of posttranslational modifications on RIP140 that augment its property and biological activity. In T(3)-triggered biphasic regulation of cellular retinoic acid binding protein 1 (Crabp1) gene along the course of fibroblast-adipocyte differentiation, we found TRAP220(MED1) critical for T(3)-activated chromatin remodeling whereas RIP140 essential for T(3)-repressive chromatin remodeling of this gene promoter. In this current study, we aim to examine whether and how RIP140 replaces TRAP220(MED1) on the CrabpI promoter in differentiating adipocyte cultures. We find increasing recruitment of RIP140 to this promoter, with corresponding reduction in TRAP220(MED1) ...
Purpose: Patients with ataxia-telangiectasia (A-T) show greatly increased radiation sensitivity and cancer predisposition. Family studies imply that the otherwise clinically silent heterozygotes of this autosomal recessive disease run a 3.5 to 3.8 higher risk of developing cancer. In vitro studies suggest moderately increased cellular radiation sensitivity of A-T carriers. They may also show elevated clinical radiosensitivity. We retrospectively examined patients who presented with severe adverse reactions during or after standard radiation treatment for mutations in the gene responsible for A-T, ATM, considering a potential means of future identification of radiosensitive individuals prospectively to adjust dosage schedules. Material and Methods: We selected 20 cancer patients (breast, 11; rectum, 2; ENT, 2; bladder, 1; prostate, 1; anus, 1; astrocytoma, 1; Hodgkins lymphoma, 1) with Grade 3 to 4 ...
Objectives: Intra-operative cisplatin-based intra-peritoneal chemotherapy (IPC) may alter renal function in patients with advanced ovarian cancer. The aim of this study was to describe postoperative alteration of renal function after cisplatin-based IPC and to identify risk factors for moderate to severe acute renal failure. Study design: This prospective observational study was carried out on 77 consecutive patients who underwent cisplatin-based IPC procedures, with (n=23) or without (n=54) intra-peritoneal epinephrine, for advanced ovarian cancer. Postoperative renal function was assessed using serial serum creatinine measurements and was based on serum creatinine changes from pre-operative values, according to the risk, injury, failure, loss, end-stage kidney disease (RIFLE) classificat...
Aim To better define the indications for adrenalectomy for adrenal metastasis we have analysed factors predicting survival in our institutional series. Methods A consecutive series of 30 patients undergoing adrenalectomy for metastasis (1996-2007), excluding patients with simultaneous ipsilateral renal cell carcinoma (RCC), was studied. Metastases were regarded as synchronous (6 mo), depending on the interval after primary surgery. Survival was calculated from time of adrenalectomy and factors influencing survival were identified. Results The tumour diagnoses were RCC n = 9, malignant melanoma n = 5, non-small-cell lung cancer n = 5, colorectal carcinoma n = 4, foregut carcinoid n = 2, adrenocortical carcinoma, breast cancer, hepatocellular carcinoma, urothelial c...
The potential association between xenotropic murine leukaemia virus-related gammaretrovirus (XMRV) and prostate cancer (PCa) has been documented since 2006. It is important for furthering our understanding of the biological mechanisms of PCa to ascertain whether this association is causal. To summarize the available information on the epidemiological and laboratory findings of the association, we conducted a literature search of the PubMed electronic database (from March 2006 to February 2011) to identify relevant published studies that examined the association between XMRV and PCa. Although several studies showed the positive association between XMRV and PCa, more recent studies did not support this conclusion. The positive findings might be due to contamination of human samples. Further ...
IntroductionBreast cancer is the most diagnosed and second leading cause of cancer deaths in the U.S. female population. An estimated 5 to 10 percent of all breast cancers are inherited, caused by mutations in the breast cancer susceptibility genes (BRCA1/2). As many as 90% of all mutations are nonsense mutations, causing a truncated polypeptide product. A popular and low cost method of mutation detection has been the protein truncation test (PTT), where target regions of BRCA1/2 are PCR amplified, transcribed/translated in a cell-free protein synthesis system and analyzed for truncated polypeptides by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography. We previously reported a novel High Throughput Solid-Phase PTT (HTS-PTT) based on an enzyme-linked immunosorbent assay (ELISA) format that eliminates the need for radioactivity, SDS-PAGE and ...
In neurodegenerative conditions such as Alzheimer's and prion disease it has been shown that host genetic background can have a significant effect on susceptibility. Indeed, human genome-wide association studies (GWAS) have implicated several candidate genes. Understanding such genetic susceptibility is relevant to risks of developing variant CJD (vCJD) in populations exposed to bovine spongiform encephalopathy (BSE) and understanding mechanisms of neurodegeneration. In mice, aspects of prion disease susceptibility can be modelled by examining the incubation period following experimental inoculation. Quantitative trait linkage studies have already identified multiple candidate genes; however, it is also possible to take an individual candidate gene approach. Rarb and Stmn2 were selected as candidates based on the known association with vCJD. Because of the increasing overlap described between prion and ...
Nineteen fungal strains having an ability to oxidize elemental sulfur in mineral salts medium were isolated from deteriorated sandstones of Angkor monuments. These fungi formed clearing zone on agar medium supplemented with powder sulfur due to the dissolution of sulfur. Representative of the isolates, strain THIF01, was identified as Fusarium solani on the basis of morphological characteristics and phylogenetic analyses. PCR amplification targeting 16S rRNA gene and analyses of full 16S rRNA gene sequence indicated strain THIF01 harbors an endobacterium Bradyrhizobium sp.; however, involvement of the bacterium in the sulfur oxidation is still unclear. Strain THIF01 oxidized elemental sulfur to thiosulfate and then sulfate. Germination of the spores of strain THIF01 was observed in a liqui...
The authors used a near full-length human ornithine [delta]-aminotransferase cDNA, huOAT6, as a probe under low stringency hybridization conditions to identify a new autosomal ornithine [delta]-aminotransferase-related sequence (OATL3). Cloning and characterization of this sequence reveal it to be a partial nonprocessed pseudogene corresponding to exon 3 and flanking intronic sequences of the ornithine [delta]-aminotransferase structural gene. Using somatic cell hybrids and fluorescence in situ hybridization, they mapped OATL3 to 10q26, adjacent to the ornithine [delta]-aminotransferase structural gene locus. 13 refs., 3 figs.
The gene encoding the human type I pituitary adenylate cyclase activating polypeptide receptor (ADCYAP1R1) was mapped to chromosome 7 by PCR analysis of genomic DNA from a human/rodent somatic cell hybrid mapping panel. This assignment was confirmed and the gene localized to chromosome band 7p14 by fluorescence in situ hybridization. A yeast artificial chromosome containing ADCYAP1R1 was identified in the CEPH {open_quotes}B{close_quotes} Mega-YAC library. This YAC includes two highly polymorphic dinucleotide repeat sequences that will facilitate genetic studies of the contribution of ADCYAP1R1 in disease states of the central nervous and neuroendocrine systems. 13 refs., 1 fig.
Abstract Hereditary primary hyperparathyroidism (HPT) may develop as a solitary endocrinopathy (FIHP) or as part of multiple endocrine neoplasia Type 1, multiple endocrine neoplasia Type 2A, or hereditary HPT-jaw tumor syndrome. Inactivating germline mutations of the tumor suppressor gene CDC73 account for 14 and 50% of all FIHP and HPT-JT patients, respectively, and have also been found in almost 20% of apparently sporadic parathyroid carcinoma patients. Although more than 60 independent germline mutations have been described, to date no rearrangement affecting the CDC73 locus has been identified. By means of multiplex-PCR we found a large germline deletion affecting the whole gene in a two-generation HPT-JT family. Subsequently array-CGH and specific PCR analysis determined that the muta...
Maps transformed so as to have constant density of residential population were used to analyze the spatial distribution of disease in three specific areas. Each area had received recent attention because of suspected environmental pollution. The area adjacent to the Rocky Flats Facility (CO) was examined to identify any association between possible plutonium releases and increases in lung cancer or leukemia incidence. The industrial area of northern Contra Costa County (CA) was studied to explore a relationship between petrochemical industrial emissions and histologic-specific lung cancers. Finally, a suspected increase in the risk of congenital cardiac defects possibly related to pollution of the Santa Clara County (CA) water supply was investigated. No evidence of elevated risk of disease was found to be associated with either the Rocky Flats Facility or the polluted water of Santa Clara County. An increase in lung ...
The large aggregating proteoglycan aggrecan is a major structural component of the extracellular matrix of articular cartilage. Recent cDNA cloning of the human aggrecan gene (AGC1) reveals a core protein of at least 2316 amino acids characterized by several distinct structural domains. Two globular domains, termed G1 and G2, are present at the amino terminus of the molecule and a third, termed G3, is present at the carboxy terminus. The G1 domain is homologous in structure to the cartilage link protein and accounts for the aggregating potential of aggrecan through its ability to interact with hyaluronic acid. The aggrecan gene is known to consist of 15 exons, with each exon encoding a distinct functional region of the mature protein. However, while the link protein gene is known to reside on chromosome 5 in the human, the location of the aggrecan gene is currently undetermined in any species. The probe ...
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Constitutive activation of the oncogenic transcription factor STAT3 frequently occurs in various human malignancies. STAT3 activation involves dimerization via intermolecular pTyr-SH2 interaction. Thus, antagonizing this interaction is a feasible approach to inhibit STAT3 activation for cancer therapy. In order to identify selective STAT3 inhibitors, we developed a biochemical HTS system based on AlphaScreen technology, which measures the abilities of test compounds to antagonize pTyr-SH2 interactions. We screened our chemical libraries using this system and identified 5,15-diphenylporphyrin (5,15-DPP) as a selective STAT3-SH2 antagonist. Selective inhibition of STAT3 nuclear translocation and DNA biding activity was observed in cells treated with 5,15-DPP. IL-6-dependent dimerization of STAT3, c-myc promoter binding and c-myc protein expression were all suppressed by 5,15-DPP, whereas no decrement in either expression or ...
This paper describes the chemical constituents isolated from aerial parts of the plant Galianthe brasiliensis. From a methanol extract, the iridoid glycosides asperuloside, deacetylasperuloside, mixture of Z- and E-6-O-p-coumaroylscandoside methyl ester, the triterpene ursolic acid and the steroids stigmasterol, campesterol, b-sitosterol and 3-O-b-glucopyranosyl sitosterol were isolated. The structures of the natural products were identified on the basis of spectral data, including 2D NMR experiments. The antiproliferative properties of the crude methanolic extract were investigated against a series of nine human cancer cell lines. (author)
B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC ...
Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. ...
We present changes in the p53 gene in a group of 70 thyroid tumours and 40 blood samples obtained from children from Belarus. Three thyroid tumours show a polymorphism in exon 6 (codon 213) and 5 tumours show a polymorphism in intron 6, 37 bp upstream to the 5'-end of exon 7. Only one patient has a mutation in exon 7 (codon 258) resulting in an amino acid substitution in the protein p53. The distribution of polymorphisms in the 40 blood samples was as follows: three patients had a polymorphism in exon 6 and two persons had a polymorphism in intron 6. One polymorphism in intron 6 was also found in the group of 30 healthy children from Belarus. The fact that the differences in the sequence in p53 found in the tumours was also seen in the blood of these patients demonstrates that they are polymorphisms not induced by radiation exposure. It is difficult to conclude, if the polymorphisms found by us could be associated with the predisposition to radiation-induced ...
Aims: Serotonin (5-hydroxytryptamine 3; 5-HT3) receptors are involved in chemotherapy-induced nausea and vomiting (CINV), and 5-HT3 antagonists are part of the `gold standard' antiemetic treatment during chemotherapy. We investigated the correlation of common variants in 5-HT3 receptor subunit genes with the occurrence of CINV. Materials & methods: A total of 110 previously characterized chemotherapy-naive women with primary breast cancer treated with anthracycline-containing chemotherapy served as a study group for mutational analysis by direct sequencing. Eight common SNPs in the 5-HT3 receptor genes, HTR3A, HTR3B, HTR3D and HTR3E, were selected for association analysis. Results: A nonsynonymous variant in HTR3D, p.G36A (rs6443930), was found to be over-represented in nonresponders, assu...
The work scope of 'Biological Research for the Radiation Protection' had contained the research about ornithine decarboxylase and its controlling proteins, thioredoxin, peroxiredoxin, S-adenosymethionine decarboxylase, and glutamate decarboxylase 67KD effect on the cell death triggered ionizing radiation and H_2O_2(toxic agents). In this study, to elucidate the role of these proteins in the ionizing radiation (or H_2O_2)-induced apoptotic cell death, we utilized sensesed (or antisensed) cells, which overexpress (or down-regulate) RNAs associated with these proteins biosynthesis, and investigated the effects of these genes on the cytotoxicity caused by ionizing radiation and H_2O_2(or paraquat). We also investigated whether genisteine(or thiamine) may enhance the cytotoxic efficacy of tumor cells caused by ionizing radiation (may enhance the preventing effect radiation or paraquat-induced damage) because such compounds are able to potentiate the cell-killing or cell ...
A non-invasive diagnostic tool that could identify malignancy in situ and in real time would have a major impact on the detection and treatment of cancer. We have developed and are testing early prototypes of an optical biopsy system (OBS) for detection of cancer and other tissue pathologies. The OBS invokes a unique approach to optical diagnosis of tissue pathologies based on the elastic scattering properties, over a wide range of wavelengths, of the microscopic structure of the tissue. The use of elastic scattering as the key to optical tissue diagnostics in the OBS is based on the fact that many tissue pathologies, including a majority of cancer forms, manifest significant architectural changes at the cellular and sub-cellular level. Since the cellular components that cause elastic scattering have dimensions typically on the order of visible to near-IR wavelengths, the elastic (Mie) scattering ...
In a previous study, to identifygenes of importance for hepatocellular carcinogenesis, and especially for processes involved in malignant transformation, the authors investigated differences in gene expression between adenomas and carcinomas by DNA microarray. In the present study, the authors investigated AW434047, one of the sequences that was upregulated in carcinomas. The investigation led to the identification of a novel gene, which the authors named hepatocyte malignant transforming factor (HMTF), of unknown function whose expression was increased in hepatocellular carcinomas. Northern blot and in situ hybridization also demonstrated high levels of HMTF in rat hepatocellular carcinoma (HCC) cell lines, lymphocytes in the spleen, colon mucosal epithelia, spermatocytes, and granule cells of the hippocampus. Reduction of HMTF by RNA interference (RNAi) in N1 cells, an HCC cell line, caused ...
Fetal nucleated cells within maternal blood represent a potential source of fetal genes obtainable by venipuncture. The authors used monoclonal antibody against the transferrin receptor (TIR) to identify nucleated erythrocytes in the peripheral blood of pregnant women. Candidate fetal cells from 19 pregnancies were isolated by flow sorting at 12 1/2-17 weeks gestation. The DNA in these cells was amplified for a 222-base-pair (bp) sequence present on the short arm of the Y chromosome as proof that the cells were derived from the fetus. The amplified DNA was compared with standardized DNA concentrations. In the case of the female fetus, DNA prepared from samples at 32 weeks of gestation and cord blood at delivery also showed the presence of the Y chromosomal sequence, suggesting Y sequence mosaicism or translocation. In 10/12 cases where the 222-bp band was absent, the fetuses were female. Thus, they were successful in detecting the Y chromosomal ...
Background Identifying susceptibility genes for endophenotypes by studying analogous behaviors across species is an important strategy for understanding the pathophysiology underlying psychiatric disorders. This approach provides novel biological pathways plus validated animal models critical for selective drug development. One such endophenotype is avoidance behavior. Methods In the present study, novel automated registration methods for longitudinal behavioral assessment in home cages are used to screen a panel of recently generated mouse chromosome substitution strains that are very powerful in quantitative trait loci (QTL) detection of complex traits. In this way, we identified chromosomes regulating avoidance behavior (increased sheltering preference) independent of motor activity lev...
Prepulse inhibition (PPI) is a measure of sensorimotor gating, a pre-attentional inhibitory brain mechanism that filters extraneous stimuli. Prepulse inhibition is correlated with measures of cognition and executive functioning, and is considered an endophenotype of schizophrenia and other psychiatric illnesses in which patients show PPI impairments. As a first step toward identifyinggenes that regulate PPI, we performed a quantitative trait locus (QTL) screen of PPI phenotypes in a panel of mouse chromosome substitution strains (CSSs). We identified five CSSs with altered PPI compared with the host C57BL/6J strain: CSS-4 exhibited decreased PPI, whereas CSS-10, -11, -16 and -Y exhibited higher PPI compared with C57BL/6J. These data indicate that A/J chromosomes 4, 10, 11, 16 and Y harbor...
The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and ?-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two ...
Background The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. Results We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayed embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated ...
The chromosomal region 17q12-q21 contains a gene (BRCA1) conferring susceptibility to early-onset familial breast and ovarian cancer. An 8000-rad radiation-reduced hybrid (RH) panel was constructed to provide a resource for long-range mapping of this region. A large fraction of the hybrids ([approximately]90%) retained detectable human chromosome 17 sequences. The complete panel of 76 hybrids was scored for the presence or absence of 22 markers from this chromosomal region, including 14 cloned genes, seven microsatellite repeats, and one anonymous DNA segment. Statistical analysis of the marker retention data employing multipoint methods provided both comprehensive and framework maps of this chromosomal region, including distance estimates between adjacent markers. The comprehensive RH map includes 17 loci and spans 179 cRays[sub (8000)]. Likelihood ratios of at least 1000:1 support the 10-locus framework order: ...
A 36-year-old woman underwent amniocentesis for advanced maternal age. The fetal karyotype had an extra dark staining G band on the long arm of chromosome 11 with no other identifiable abnormalities. FISH studies using a chromosome 11 paint probe confirmed the origin of the extra band. The abnormality was identified as a partial duplication of 11q: 46,XX dir dup (11)(q13.5q21) or (q21q23.1). The specific duplicated band could not be identified with certainty. Detailed fetal sonograms were normal. Family studies revealed the identical duplication in the mother but normal karyotypes in both maternal grandparents. The mother had strabismus and a short tongue frenulum which required surgical correction. Menses occurred late in adolescence and complete development of secondary sexual characteristics was delayed until adulthood. An infertility evaluation revealed duplication of the uterus, cervix, and vagina. An evaluation for ...
Synthetic gene networks can be used to control gene expression and cellular phenotypes in a variety of applications. In many instances, however, such networks can behave unreliably due to gene expression...Full Text Available
A gene designated BRCA1, implicated in the susceptibility to early-onset familial breast cancer, has recently been localized to chromosome 17q12-q21. To date, the order of DNA markers mapped within this region has been based on genetic linkage analysis. The authors report the use of multicolor fluorescence in situ hybridization to establish a physically based map of five polymorphic DNA markers and 10 cloned genes spanning this region. Three cosmid clones and Alu-PCR-Generated products derived from 12 yeast artificial chromosome clones representing each of these markers were used in two-color mapping experiments to determine an initial proximity of markers relative to each other on metaphase chromosomes. Interphase mapping was then employed to determine the order and orientation of closely spaced loci by direct visualization of fluorescent signals following hybridization of three probes, each detected in a different color. ...
PNAS-4, a novel pro-apoptotic gene activated during the early response to DNA damage, can inhibit proliferation via apoptosis when overexpressed in some tumor cells. Recent studies have indicated that honokiol can induce apoptosis, inhibit angiogenesis, and suppress tumor growth. In the present study, we investigated whether mouse PNAS-4 (mPNAS-4) could augment the apoptosis of tumor cells induced by honokiol in vitro, and whether the antiangiogenic activity of honokiol and induction of apoptosis by mPNAS-4 could work cooperatively to improve the antitumor efficacy in vivo. In vitro, mPNAS-4 inhibited proliferation of murine colorectal carcinoma CT26 and Lewis lung carcinoma LL2 cells through induction of apoptosis, and significantly augmented the apoptosis of CT26 and LL2 cells induced by honokiol. Compared with treatment with mPNAS-4 or honokiol alone, in vivo systemic administration of an expression plasmid encoding mPNAS-4 and low-dose honokiol significantly ...
pT181 is a naturally-occurring 4437 basepair (bp) plasmid isolated from Staphylococcus aureus which encodes inducible resistance to tetracycline (Tc). The DNA sequence data has identified three open reading frames (ORFs). The largest ORF B, has been found to be responsible for the Tc resistance phenotype of pT181. Since most Tc resistance systems appear to be regulated by an effector protein and a repressor protein, several Bal 31 deletion mutants of pT181 were constructed and analyzed in an effort to identify the elements involved in Tc resistance. Two transcomplementing groups of mutants were identified within the tet gene. The mechanism of Tc resistance was studied by assaying the accumulation of (7-/sup 3/H) Tc by Tc sensitive cells, and uninduced and induced pT181-containing cells. A sharp decrease in accumulation of the drug after an initial increase was observed in Tc induced pT181-containing ...
Abstract Common single nucleotide polymorphisms (SNPs) in SMAD7 (18q21) have been linked to colorectal cancer (CRC) risk in genome-wide association studies, but little is known about their effects on survival. SMAD7 regulates gastrointestinal inflammation by inhibiting transforming growth factor- (TGFB), which can act as both a tumor suppressor and a promoter of metastasis. Regular use of cyclooxygenase-2 (COX2) inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), reduces the risk of developing CRC. Because COX2 overexpression reduces the growth suppressing effects of TGFB, we hypothesized that survival may depend on both SMAD7 genotype and prediagnostic NSAID use. Postmenopausal women, ages 50-74, diagnosed with incident invasive CRC from 1997 to 2002 were identified using t...
Recent Reviews in Carcinogenesis is a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists. It contains abstracts ...
Despite the existence of effective analgesic drugs, many cancer patients live and die with ineffective pain control. The control of cancer pain is largely achievable with the appropriate use of available...Full Text Available
BackgroundAdnexal masses are not uncommon in patients with breast cancer. Breast cancer and ovarian malignancies are known to be associated. In patients with breast cancer and co-existing...Full Text Available
Laron syndrome (LS) is an autosomal recessively inherited condition characterized by insensitivity to endogenous and exogenous GH. Affected individuals have severe episodes and other characteristic features. GH receptor gene mutations are present in all affected individuals in whom molecular studies have been reported. The GH receptor is a plasma membrane-spanning protein in which the extracellular domain binds circulating GH and the intracellular domain interacts with the JAK-2 kinase and possibly other intracellular signaling molecules. GH receptor dimerization occurs on GH binding and is thought to be required for normal signal transduction. We have studied the GH receptor genes of four unrelated individuals affected with LS from the United States, Italy, Saudi Arabia, and India. We have identified four different missense mutations that alter consecutive amino acids 152 to 155 in or near the dimerization domain of the GH ...
Homology analyses of the protein sequences of chicken liver and rat mammary gland fatty acid synthases were carried out. The amino acid sequences of the chicken and rat enzymes are 67% identical. If conservative substitutions are allowed, 78% of the amino acids are matched. A region of low homologies exists between the functional domains, in particular around amino acid residues 1059-1264 of the chicken enzyme. Homologies between the active sites of chicken and rat and of chicken and yeast enzymes have been analyzed by an alignment method. A high degree of homology exists between the active sites of the chicken and rat enzymes. However, the chicken and yeast enzymes show a lower degree of homology. The DADPH-binding dinucleotide folds of the {beta}-ketoacyl reductase and the enoyl reductase sites were identified by comparison with a known consensus sequence for the DADP- and FAD-binding dinucleotide folds. The active sites of all of the enzymes are primarily in ...
We present our initial experience with a new biodegradable (BD) esophageal stent in two patients, one for a therapy-resistant benign esophageal stricture, and the other as a temporary measure during curative radiotherapy for oesophageal carcinoma. The BD stents need to be loaded into a conventional pull-back delivery system but are then placed in a standard fashion. Pre-dilatation should be avoided to reduce the risk of migration, however if migration occurs the stents can be left to dissolve in the stomach. The stents are radiolucent but easily identified on CT with minimal artefact and thus might even aid with radiotherapy planning. BD stents offer an exciting new strategy for therapy-resistant benign strictures as well as a supportive measure for oesophageal cancer undergoing non-surgical treatment. (orig.)
Twenty-four long-term survivors of Ewing's sarcoma were identified as being at risk for a second primary tumor. Among this group of patients followed from 3 to 22 y, 4 new bone tumors were observed, whereas 1.2 x 10"-"3 were expected. All new tumors arose in heavily irradiated areas. The risk associated with radiation after 3 years was 7.2 cases/million person-years per rad. The cumulative cancer risk over 10 years for irradiated patients was 35% (SE, 15.1%). Intensive chemotherapy (cyclophosphamide and vincristine administered in five or more courses) seemed to exert an enhancing effect, increasing the rate of development of new tumors.
The point at which the common final pathway for induction of cancer by chemical carcinogens and ionizing radiation has not been identified. Although common molecular targets are suggested by recent findings about the role of oncogenes, the mechanism by which the deposition of radiation energy and the formation of adducts or other DNA lesions induced by chemicals affects the changes in the relevant targets may be quite different. The damage to DNA that plays no part in the transformation events, but that influences the stability of the genome, and therefore, the probability of subsequent changes that influence tumorigenesis may be more readily induced by some agents than others. Similarly, the degree of cytotoxic effects that disrupt tissue integrity and increase the probability of expression of initiated cells may be dependent on the type of carcinogen. Also, evidence was presented that repair of the initial lesions could be demonstrated after ...
In Europe, the use of anti-EGFR monoclonal antibodies is restricted to Kirsten RAS (KRAS) wild-type colorectal tumors. Information on the KRAS status of the patients tumor is thus key for clinical practice; however, there is little guidance or definition on which KRAS mutations to assess and how to assess them. To ensure the consistency and the quality of KRAS test results in Europe, an interlaboratory control network needs to be set up. This pilot study aimed to identify the variables that need to be assessed in a quality control scheme and to provide a first assessment in a selected set of laboratories. Fourteen different tumor cases were circulated between 13 laboratories by a central laboratory acting as the referent for the mutation status determination. This study illustrated that of...
BackgroundPeritoneal metastasis occurs in up to 30% of patients with gastric cancer. The aim of this experimental study is to develop and validate a novel ex vivo model of the human peritoneum to better identify factors involved in the development of peritoneal metastasis in order to improve its management and prognosis. MethodsPeritoneal discs harvested from hernia sacs obtained at inguinal hernia surgery were suspended in media using Teflon rings. Viability of the tissue was investigated using MTS assay, light and scanning electron microscopy (LM and SEM) over 72 h. To assess validity of the model, phenotypic changes in tumor cells were investigated. Changes in matrix metalloproteinases (MMP)-2 and -9 activities in HGC and AGS gastric adenocarcinoma cells after co-culture were investigat...
Objective To report the clinical response to image-guided percutaneous cryotherapy (IPC) for the palliative management of localized metastases in patients with gynecologic malignancies. Methods Institutional review board approval and patient consent were obtained. Gynecologic oncology patients were identified from our institution's cryotherapy database from August 2003 to August 2007. Cryotherapy was performed with 2.4?mm diameter probes (Endocare, Irvine, CA) with ultrasound or computerized tomography (CT) guidance under conscious sedation and local anesthesia. Follow-up was conducted by imaging studies and clinical encounters, using Response Evaluation Criteria in Solid Tumors (RECIST criteria). Results Twenty-eight ablation sessions were performed for 41 metastatic foci in 15 patients w...
The paper describes the chemical constituents isolated from aerial parts of the plant Galianthe brasiliensis. From a methanol extract, the iridoid glycosides asperuloside, deacetylasperuloside, mixture of Z- and E-6-O-p-coumaroylscandoside methyl ester, the triterpene ursolic acid and the steroids stigmasterol, campesterol, b-sitosterol and 3-O-b-glucopyranosyl sitosterol were isolated. The structures of the natural products were identified on the basis of spectral data, including 2D NMR experiments. The antiproliferative properties of the crude methanolic extract were investigated against a series of nine human cancer cell lines. (author)
Breast cancer is a leading cause of female deaths worldwide. In Malaysia, it is the most common form of female cancer while Infiltrating ductal carcinoma (IDC) is the most common form of breast cancer....Full Text Available
Prostate biopsy is the current gold-standard procedure for prostate cancer diagnosis. Existing prostate biopsy procedures have been mostly focusing on detecting cancer presence. However, they...Full Text Available
Early detection of precancerous tissue has significantly improved survival of most cancers including colorectal cancer (CRC). Animal models designed to study the early stages of cancer are valuable...Full Text Available
Purpose: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. Methods: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice received a single intraprostatic ...
What genes are related to AEC syndrome? AEC syndrome is caused by mutations in the TP63 gene. This gene provides instructions for making a protein known as p63, which plays an...
Cocoon sericin plays an important role in the reeling of silk and serves as a valuable biomaterial in the field of biomedicine, skincare, and food industries; however, knowledge about cocoon sericin proteins has been limited. For a comprehensive study on sericin, cocoons of eight varieties of silkworm of different geographic origin and with varied cocoon color were analyzed utilizing proteomics and bioinformatics approaches. The electrophoresis pattern demonstrated some common protein bands for all silkworm varieties and distinctive protein bands for some of those examined in the present study. The Ser2 protein, a new Ser3 protein, and four other novel sericin proteins were identified in cocoons for the first time. Products of both Ser1 and Ser3 genes appear to be ubiquitous in the cocoon ...
The green fluorescent protein (GFP) asFP499 from Anemonia sulcata is a distant homologue of the GFP from Aequorea victoria. We cloned the asFP499 gene into a mammalian expression vector and showed that this protein was expressed in the human lymphoblast cell line Ramos RA1 and in the embryonic kidney 293T cell line (HEK 293T). In HEK 293T cells, asFP499 was localized mainly in the cytoplasm, suggesting that the protein was excluded from the nucleus. We identified _1_9_4LRMEKLNI_2_0_1 as a candidate nuclear export signal in asFP499 and mutated the isoleucine at position 201 to an alanine. Unlike the wildtype form, the mutant protein was distributed throughout the cytoplasm and nucleus. This is First report of a GFP that contains a functional NES.
Spindle cell sarcomas consist of tumors with different biological features, of which distant metastasis is the most ominous sign for a poor prognosis. However, metastasis is difficult to predict on the basis of current histopathological analyses. We have identified actin filament-associated protein 1-like 1 (AFAP1L1) as a candidate for a metastasis-predicting marker from the gene expression profiles of 65 spindle cell sarcomas. A multivariate analysis determined that AFAP1L1 was an independent factor for predicting the occurrence of distant metastasis (P=0.0001), which was further confirmed in another set of 41 tumors by a quantitative mRNA expression analysis. Immunohistochemical staining using paraffin-embedded tumor tissues revealed that the metastasis-free rate was significantly better...
Histone deacetylase (HDAC) inhibitors have been actively exploited as potential anticancer agents. To identifygene targets of HDAC inhibitors, we found that HDAC inhibitors such as sodium butyrate, scriptaid, apicidin and oxamflatin induced the expression of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a potential cyclooxygenase-2 (COX-2) antagonist and tumor suppressor, in a time and concentration dependent manner in A549 and H1435 lung adenocarcinoma cells. Detailed analyses indicated that HDAC inhibitors activated the 15-PGDH promoter-luciferase reporter construct in transfected A549 cells. A representative HDAC inhibitor, scriptaid, and its negative structural analog control, nullscript, were further evaluated at the chromatin level. Scriptaid but not nullscript induced a signific...
Meningococcal disease is an infection caused by Neisseria meningitidis. Genetic factors contribute to host susceptibility and progression to disease, but the genes responsible for disease development are largely unknown. We report here a genome-wide association study for host susceptibility to meningococcal disease using 475 individuals with meningococcal disease (cases) and 4,703 population controls from the UK. We performed, in Western European and South European cohorts (consisting of 968 cases and 1,376 controls), two replication studies for the most significant SNPs. A cluster of complement factor SNPs replicated independently in both cohorts, including SNPs within complement factor H (CFH) (rs1065489 (p.936D
The formation of a through-gut was a key innovation in the evolution of metazoans. There is still controversy regarding the origin of the anus and how it may have been either gained or lost during evolution in different bilaterian taxa. Thus, the study of groups with a blind gut is of great importance for understanding the evolution of this organ system. Here, we describe the morphogenesis and molecular patterning of the blind gut in the sexual triclad Schmidtea polychroa. We identify and analyze the expression of goosecoid, commonly associated with the foregut, and the GATA, ParaHox and T-box genes, members of which commonly are associated with gut regionalization. We show that GATA456a is expressed in the blind gut of triclads, while GATA456b is localized in dorsal parenchymal cells. Goo...
Mammary glands are special tissue characterized by proliferation of the epithelium, during puberty and pregnancy and by programmed cell death, during involution. In this study, apoptosis was identified by TUNEL staining and then related to cell proliferation, as determined by Ki-67 staining. The apoptotic index was at its highest at 8 days of involution, whereas the proliferation index was at its highest during lactation. Caspase-3 was immunolocalised only in mast cells and along the basal membrane in the mammary tissue at -10 days from lambing, 150 days of lactation and at 8 days of involution. This finding could indicate that caspase-3 is not involved in sheep mammary gland apoptosis, but that other proteins - such as apoptosis inducing factor (AIF) - can trigger apoptosis, through the m...
Acanthamoeba castellanii is a free-living amoeba found in soil, freshwater, and marine environments and an important predator of bacteria. Acanthamoeba castellanii is also an opportunistic pathogen of clinical interest, responsible for several distinct diseases in humans. In order to provide a genomic platform for the study of this ubiquitous and important protist, we generated a sequence survey of approximately 0.5 x coverage of the genome. The data predict that A. castellanii exhibits a greater biosynthetic capacity than the free-living Dictyostelium discoideum and the parasite Entamoeba histolytica, providing an explanation for the ability of A. castellanii to inhabit adversity of environments. Alginate lyase may provide access to bacteria within biofilms by breaking down the biofilm matrix, and polyhydroxybutyrate depolymerase may facilitate utilization of the bacterial storage compound polyhydroxybutyrate as a food source. Enzymes for the synthesis and breakdown of cellulose were ...
The sodium- and potassium-dependent adenosine triphosphatase (Na+,K(+)-ATPase) maintains the transmembrane Na+ gradient to which is coupled all active cellular transport systems. The R and S alleles of the gene encoding the Na+,K(+)-ATPase alpha 1 subunit isoform were identified in Dahl salt-resistant (DR) and Dahl salt-sensitive (DS) rats, respectively. Characterization of the S allele-specific Na+,K(+)-ATPase alpha 1 complementary DNA identified a leucine substitution of glutamine at position 276. This mutation alters the hydropathy profile of a region in proximity to T3(Na), the trypsin-sensitive site that is only detected in the presence of Na+. This mutation causes a decrease in the rubidium-86 influx of S allele-specific sodium pumps, thus marking a domain in the Na+,K(+)-ATPase alpha subunit important for K+ transport, and supporting the hypothesis of a putative role of these pumps in hypertension.
The rice blast resistance (R) gene Pi-ta mediates gene-for-gene resistance against strains of the fungus Magnaporthe grisea that express avirulent...Full Text Available
BackgroundInferring regulatory interactions between genes from transcriptomics time-resolved data, yielding reverse engineered gene regulatory networks, is of paramount importance...Full Text Available
The "ovalbumin Y" gene, one of three which constitute the ovalbumin gene family in chicken has been completely sequenced. The exact location of exons can be derived from the comparison with the ovalbumin...Full Text Available
BackgroundGene duplication is the primary force of new gene evolution. Deciphering whether a pair of duplicated genes has evolved divergent functions is often challenging. The zebrafish...Full Text Available
BackgroundMicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either...Full Text Available
The functional gene and three intronless pseudogenes for human triosephosphate isomerase were isolated from a recombinant DNA library and characterized in detail. The functional gene spans 3.5 kilobase...Full Text Available
Molecular analysis of the amo gene cluster in Nitrosococcus oceani revealed that it consists of five genes, instead of the three known genes, amoCAB....Full Text Available
We develop a statistical framework to study the relationship between chromatin features and gene expression. This can be used to predict gene expression of protein coding genes, as well as microRNAs....Full Text Available
We proposed a faster pedigree-based generalized multifactor dimensionality reduction algorithm, called PedG-MDR II (PII), to detect gene-gene interactions underlying complex traits. Inherited...Full Text Available
There are very different views on the health hazards of DU munitions. Most of the concerns of veterans and their advisors focus on the radiological effects of DU and consequently these are the focus of this editorial. Effects on the kidney and environmental consequences are, however, considered in the second of the Royal Society reports and the main conclusions of both of the reports are outlined in the summary document published in this issue of the journal. The main radiological concerns focus on the irradiation of lung tissues from inhaled DU particles and irradiation resulting from the translocation of inhaled particles to the thoracic lymph nodes.The overwhelming scientific view, presented in the two Royal Society reports and in other independent reviews, is that the main risks of exposure to DU aerosols are an increase in lung cancer and (from chemical toxicity) damage to the kidney, although these are likely to be evident only following substantial intakes. ...
Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not simply as a consequence of overcoming senescence, but as a result of a newly discovered step in the process of immortal ...
A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including ...
The epidermal compartment is complex and organized into several strata composed of keratinocytes (KCs), including basal, spinous, granular, and cornified layers. The continuous process of self-renewal and barrier formation is dependent on a homeostatic balance achieved amongst KCs involving proliferation, differentiation, and cell death. To determine genes responsible for initiating and maintaining a cornified epidermis, organotypic cultures comprised entirely of stratified KCs creating epidermal equivalents (EE) were raised from a submerged state to an air/liquid (A/L) interface. Compared to the array profile of submerged cultures containing KCs predominantly in a proliferative (relatively undifferentiated) state, EEs raised to an A/L interface displayed a remarkably consistent and distinct profile of mRNAs. Cultures lifted to an A/L interface triggered the induction of gene groups that regulate proliferation, differentiation, and cell death. ...
Attention-deficit hyperactivity disorder (ADHD) has been shown to be familial and heritable, in previous studies. As with most psychiatric disorders, examination of pedigrees has not revealed a consistent Mendelian mode of transmission. The response of ADHD patients to medications that inhibit the dopamine transporter, including methylphenidate, amphetamine, pemoline, and bupropion, led us to consider the dopamine transporter as a primary candidate gene for ADHD. To avoid effects of population stratification and to avoid the problem of classification of relatives with other psychiatric disorders as affected or unaffected, we used the haplotype-based haplotype relative risk (HHRR) method to test for association between a VNTR polymorphism at the dopamine transporter locus (DAT1) and DSM-III-R-diagnosed ADHD (N = 49) and undifferentiated attention-deficit disorder (UADD) (N = 8) in trios composed of father, mother, and affected offspring. HHRR analysis revealed ...
Mutations in the FGD1 gene have been shown to cause Aarskog-Scott syndrome (AAS), or facio-digito-genital dysplasia (OMIM#305400), an X-linked disorder characterized by distinctive genital and skeletal developmental abnormalities with a broad spectrum of clinical phenotypes. To date, 20 distinct mutations have been reported, but little phenotypic data are available on patients with molecularly confirmed AAS. In the present study, we report on our experience of screening for mutations in the FGD1 gene in a cohort of 60 European patients with a clinically suspected diagnosis of AAS. We identified nine novel mutations in 11 patients (detection rate of 18.33%), including three missense mutations (p.R402Q; p.S558W; p.K748E), four truncating mutations (p.Y530X; p.R656X; c.806delC; c.1620delC), one in-frame deletion (c.2020_2022delGAG) and the first reported splice site mutation (c.1935+3A>C). A recurrent mutation (p.R656X) was ...
Cockayne syndrome (CS) is a rare autosomal recessive disease, which shows diverse clinical symptoms such as photosensitivity, severe mental retardation and developmental defects. CS cells are hypersensitive to killing by ultraviolet (UV)-irradiation and defective in transcription-coupled repair. Two genetic complementation groups in CS (CS-A and CS-B) have been identified. We analyzed mutations of the CSA gene in 5 CS-A patients and identified 3 types of mutations. Four unrelated CS-A patients (CS2OS, CS2AW, Nps2 and CS2SE) had a deletion including exon 4, suggesting that there is a founder effect on the CSA mutation in Japanese CS-A patients. Patient CS2SE was a compound heterozygote for this deletion and an amino acid substitution at the 106th glutamine to proline (Q106P) in the WD-40 repeat motif of the CSA protein, which resulted in a defective nucleotide excision repair. Patient Mps1 had a large deletion in the ...
We present the draft genome sequence and its analysis for Fusobacterium nucleatum sub spp. vincentii (FNV), and compare that genome with F. nucleatum ATCC 25586 (FN). A total of 441 FNV open reading frames (ORFs) with no orthologs in FN have been identified. Of these, 118 ORFs have no known function and are unique to FNV, whereas 323 ORFs have functional orthologs in other organisms. In addition to the excretion of butyrate, H2S and ammonia-like FN, FNV has the additional capability to excrete lactate and aminobutyrate. Unlike FN, FNV is likely to incorporate galactopyranose, galacturonate, and sialic acid into its O-antigen. It appears to transport ferrous iron by an anaerobic ferrous transporter. Genes for eukaryotic type serine/threonine kinase and phosphatase, transpeptidase E-transglycosylase Pbp1A are found in FNV but not in FN. Unique ABC transporters, cryptic phages, and three types of restriction-modification systems have been ...
The structural organization of the genes encoding Bungarus multicinctus protease inhibitor-like proteins (PILPs), PILP-1, PILP-2 and PILP-3, are reported in this study. Unlike PILP-2 and PILP-3, recombinant PILP-1 exhibited inhibitory activity on trypsin. PILP genes and B chain genes shared identical organization with three exons interrupted by two introns in similar positions. On the contrary, intron 1 of these genes had a similar size, a notable variation with the size of intron 2 was observed. It was found that two regions at the second intron of B1 chain and B2 chain genes were absent in that of PILP genes. Noticeably, intronic insertion in the second intron of B chain genes appeared in the promoter region of PILP-1 gene, but not in that of PILP-2 and PILP-3 genes. Comparative analyses of PILP ...
Colorectal cancer is the second most common cause of cancer death in the world and about half of the patients with colorectal cancer require adjuvant therapy after surgical resection. Therefore, the eradication of cancer cells via chemotherapy constitutes a viable approach to treating patients with colorectal cancer. In this study, the effects of bufalin isolated from a traditional Chinese medicine were evaluated and characterized in HT-29 and Caco-2 human colon cancer cells. Contrary to its well-documented apoptosis-promoting activity in other cancer cells, bufalin did not cause caspase-dependent cell death in colon cancer cells, as indicated by the absence of significant early apoptosis as well as poly(ADP-ribose) polymerase and caspase-3 cleavage. Instead, bufalin activated an autophagy...
AbstractThere is an urgent need for innovative therapies against ovarian cancer, one of the leading causes of death from gynecological cancers in the United States. Immunotherapy employing...Full Text Available
BackgroundThe evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer...Full Text Available
BackgroundHeterogeneous results for research investigating health-related quality of life (HRQL) in patients undergoing sphincter-ablating procedures for rectal cancer...Full Text Available
Testicular neoplasm accounts for about 1% of all cancers in men. Over the last 40 years, the incidence of testicular cancer has increased in northern European male populations for unknown reasons. When...Full Text Available
While most cancer survivors are at risk for being lost in the transition from treatment to survivorship, rural breast cancer survivors face special challenges that might place them at particular...Full Text Available
BackgroundOral cancer is as prevalent as cervical and testicular cancer in the United Kingdom. Nursing staff provide the oral health care for the patient population in hospital....Full Text Available
Laparoscopic colon surgery for select cancers is slowly evolving as the standard of care but minimally invasive approaches for rectal cancer have been viewed with significant skepticism. This procedure...Full Text Available
NSCLC (non-small cell lung cancer) comprises about 80% of all lung cancer cases worldwide. Surgery is most effective treatment for patients with early-stage disease. However, 30%–55% of these...Full Text Available
Background and ObjectiveCervical cancer is one of the leading causes of morbidity and mortality amongst the gynecological cancers worldwide, especially in developing countries. It...Full Text Available
The virtual lack of well-characterized metastatic pancreatic cancer tissues for study has limited systematic studies of the metastatic process of this deadly disease. To address this important...Full Text Available
AIMS: To examine the frequency of intraocular metastases in patients who had died of cancer, in an eye bank and necropsy population sample. METHODS: The first group included 302 cancer cases received...Full Text Available
IntroductionColorectal cancer (CRC) is the second leading cause of cancer-related deaths, but currently available non-invasive screening programs have achieved only...Full Text Available
Patients experiencing several cancers can be a challenge, as optimal treatment options for the different cancers might interfere with each other. In this case report, we present a woman diagnosed with...Full Text Available
Epidemiologic research concerning electric and magnetic fields in relation to cancer has focused on the potential etiologic roles of residential exposure on childhood cancer and occupational exposure...Full Text Available
Lung cancer is the leading cause of cancer deaths worldwide. Standard chemotherapy has been shown to improve quality of life and has a modest influence on overall survival. This modest improvement in...Full Text Available
The use of spatially referenced data in cancer studies is gaining in prominence, fueled by the development and availability of spatial analytic tools and the broadening recognition of the linkages between...Full Text Available
The purpose of the meeting reported here was to develop a set of national evidence-based standards for assessing and managing patients with potentially resectable rectal cancer. This report represents...Full Text Available
IntroductionApproximately 25–30% of breast cancers are assumed to be HER-2/neu positive. It is well known that HER-2/neu-positive cancers after treatment with trastuzumab...Full Text Available
BackgroundCancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or...Full Text Available
Despite numerous investigations, the correlation between alcohol consumption and prostate cancer risk remains uncertain. This report investigated the association between alcohol use and prostate cancer...Full Text Available
A potent link to dairy seems to exist for three hormone-responsive glands. Acne, breast cancer and prostate cancer have all been linked epidemiologically to dairy intake. Although mechanisms postulated...Full Text Available
... York, 7/15/2008) Cancers Adrenal Gland Cancer Laparoscopic Adrenalectomy (Shawnee Mission Medical Center, Shawnee Mission, KS, ... MN, 1/24/2007) Colorectal Cancer Advances in Laparoscopic Colorectal Surgery (Charles E. Schmidt College of Biomedical ...
With advances in treatment, colorectal cancer is being transformed from a deadly disease to an illness that is increasingly curable. With this transformation has come increased interest in the...Full Text Available
This paper focuses on the Internet as a tool for enhancing behavior and lifestyle changes to reduce the burden of cancer at a population level. The premise of this paper is that the Internet...Full Text Available
Background/Aim:To assess the prognostic indicators preoperatively presenting and influencing the mortality rate following esophagectomy for esophageal cancer.Full Text Available
HypothesisBiomarkers, commonly expressed in breast cancer cells, may be correlated with their expression in breast skin of the same subjects.MethodsThe...Full Text Available
At present time, there is evidence from randomized controlled studies of the success of laparoscopic resection for the treatment of colon cancer with reported smaller incisions, lower morbidity rate...Full Text Available
Microcalcifications are an important diagnostic marker for breast cancer on mammograms, yet the mechanism of their formation is poorly understood. Indeed, there is presently no short-latency,...Full Text Available
PurposeTo determine the dosimetric impact of inter-fraction anatomical movements in prostate cancer patients receiving proton therapy.Full Text Available
ObjectiveTo determine whether accounting for the time dynamics of diabetes exposure will change the risk estimates for colorectal cancer.Full Text Available
Objectives:The efficacy of user-defined subject tagging and software-generated subject tagging for describing and organizing cancer blog contents was explored.Methods:The...Full Text Available
Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which...Full Text Available
Background Increasing numbers of cancer patients are using the Internet, but little is known about their attitudes toward online health care.Full Text Available
Malignancies Breast Malignancies Bladder, Prostate, and Testicular Malignancies Uses of Cancer Registry Data Brain Tumor Reporting Training Materials Overview Presentation and...
Malignancies Breast Malignancies Bladder, Prostate, and Testicular Malignancies Uses of Cancer Registry Data Brain Tumor Reporting Training Materials Overview Presentation and...
Malignancies Breast Malignancies Bladder, Prostate, and Testicular Malignancies Uses of Cancer Registry Data Brain Tumor Reporting Training Materials Overview Presentation and...
Breast cancer in the elderly has attracted considerable interest in recent years for three main reasons. Firstly, information concerning the profile (clinical and biological) of the disease in the geriatric...Full Text Available
Previous research with individuals undergoing surgery or diagnostic procedures provided a conceptual framework for analysis of radiation therapy, a common form of cancer treatment. The present...Full Text Available
The challenges of lung cancer radiotherapy are intra/inter-fraction tumor/organ anatomy/motion changes and the need to spare surrounding critical structures. Evolving radiotherapy technologies, such...Full Text Available
Adaptive radiation therapy for liver cancer has the potential to reduce normal tissue complications and enable dose escalation, allowing the potential for tumor control in this challenging site....Full Text Available
Several scientists have proposed that DNA repair deficiencies and the induction of a mutator phenotype are responsible for the generation of multiple mutagenic alterations in cancer cells. I propose...Full Text Available
IntroductionThe development of novel diagnostic agents for the detection of breast cancer microcalcifications requires a reliable animal model. Based on previous...Full Text Available
Purpose of this work is to investigate the role of Helical CT and the usefulness of three-dimensional (3D) imaging for pre-operative planning and follow-up of reconstructive maxillofacial surgery with alloplastic material in neoplastic disease involving this region. From 1996 to 1999 eleven patients were examined with Helical CT and 3D images for planning of maxillofacial plastic and reconstructive surgery for advanced cancer of this anatomically complex region. A 3D-modulated titanium mesh (100%) or micro nets was used to rebuild the anterior surface of maxillary bone and the orbital floor. The mesh was cut to the appropriate size and shape and curved where necessary. Within the residual sinusal cavity a siliconed filling was used surmounting an acrylic prosthesis with dental arch to rebuild the palate. A rehydrated bovine pericardium was affixed and moduled on the borders in two cases only. Three-dimensionally reconstructed CT images were obtained preoperatively ...
BackgroundMetastases to the stomach from an extra-gastric neoplasm are an unusual event, identified in less than 2% of cancer patients at autopsy. The stomach may be involved by hematogenous spread from a distant primary (most commonly breast, melanoma or lung), or by contiguous spread from an adjacent malignancy, such as the pancreas, esophagus and gallbladder. These latter sites may also involve the stomach via lymphatic or haematogenous spread. We present three cases of secondary gastric malignancy.Methods/ResultsThe first is a 19-year-old male who received a diagnosis of testicular choriocarcinoma in September 2004. Metastatic malignancy was demonstrated in the stomach after partial gastrectomy was performed to control gastric hemorrhage.The second is a 75-year-old male, generally well, who was diagnosed with adenocarcinoma of the lung in September 2005. Poorly differentiated adenocarcinoma of the lung was demonstrated in a subsequent ...
Purpose To analyze the clinical profile, management and outcome of non-hematological tumors in head and neck region in children less than 18?years of age. Patients and methods Medical records of patients (0?18?years) presenting with non-hematological tumors of head and neck region from 2000 to 2010 were reviewed. Result Out of the 78 patients identified, 50 were males with median age of 14?years (3?months to 18?years). Histologically, 58 out of the 78 patients had malignant tumors and 20 were metastatic at presentation. Common site of tumor origin was noted as thyroid (23/78), salivary glands (21/78) and nasopharynx (13/78). Out of 78 patients, 44 patients were treated by surgery, 26 patients received radiation and 13 patients received chemotherapy, while 9 patients received radio-iodine (...
Presently no one knows whether electromagnetic fields (EMFs) play a role in human cancer or other ailments, though epidemiological studies over the years have suggested that possibility. A study by the Electric Power Research Institute attempted to quantify everything it could about the magnetic environment of a home, identifying not only major sources of magnetic fields, but also their frequencies, strengths, and how they fall off with distance. Sources of a homes magnetic environment include appliances, overhead powerlines, and grounding connections to metallic water pipes. Fields will vary over time, depending on how much current is passing through the electrically conductive sources. Additional contributors to a home's magnetic background may include unusual wiring in the walls, underground power lines, and near-by high voltage transmission lines. This paper summarizes the study results, indicating weak, persistant EMFs may dominate, but ...
The authors have previously identified a small-cell lung cancer cell line (NCI-H209) that expresses an aberrant, underphosphorylated form of the retinoblastoma protein RB1. Molecular analysis of RB1 mRNA from this cell line revealed a single point mutation within exon 21 that resulted in a nonconservative amino acid substitution (cysteine to phenylalanine) at codon 706. Stable expression of this mutant RB1 cDNA in a human cell line lacking endogenous RB1 demonstrated that this amino acid change was sufficient to inhibit phosphorylation. In addition, this cysteine-to-phenylalanine substitution also resulted in loss of RB1 binding to the simian virus 40 large tumor and adenovirus E1A transforming proteins. These results confirm the importance of exon 21 coding sequences and suggest that the cysteine residue at codon 706 may play a role in achieving a specific protein conformation essential for protein-protein interactions.
Transposons are promising systems for somatic gene integration because they can not only integrate exogenous genes efficiently, but also be delivered to a variety of organs using a range of transfection...Full Text Available
The genome sequence of the Mamavirus, a new Acanthamoeba polyphaga mimivirus strain, is reported. With 1,191,693 nt in length and 1,023 predicted protein-coding genes, the Mamavirus...Full Text Available
BackgroundVariation of gene number among species indicates that there is a general process of new gene origination. One of the major mechanism providing raw materials for the origin...Full Text Available
The gram-positive pathogen Streptococcus pyogenes was recently reported to possess a homologue of the luxS gene that is responsible for the production of autoinducer...Full Text Available
Activation-induced deaminase (AID) initiates somatic hypermutation, gene conversion and class switch recombination by deaminating variable and switch region DNA cytidines to uridines. AID is predominantly...Full Text Available
The technology of gene targeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large...Full Text Available
Reverse engineering of gene regulatory networks has been an intensively studied topic in bioinformatics since it constitutes an intermediate step from explorative to causative gene expression...Full Text Available
Variant alleles of the mannose binding lectin (MBL) gene are associated with increased susceptibility to infection and polymorphisms of tumour necrosis factor and lymphotoxin alpha genes (TNF, LTA)...Full Text Available
URA5 genes encode orotidine-5′-monophosphate pyrophosphorylase (OMPpase), an enzyme involved in pyrimidine biosynthesis. We cloned the Histoplasma capsulatum URA5...Full Text Available
We have examined the expression and structure of several genes belonging to two classes of vegetative specific genes of the simple eukaryote, Dictyostelium discoideum. In amebae grown on bacteria, deactivation...Full Text Available
OBJECTIVE—Identification of arterial genes and pathways altered in obesity and diabetes.RESEARCH DESIGN AND METHODS—Aortic gene expression profiles of...Full Text Available
A plasmid carrying the bacteriophage lambda lysis genes under lac control was subjected to hydroxylamine mutagenesis, and mutations eliminating the host lethality of the S gene were selected. DNA sequence...Full Text Available
BackgroundMicroarray data are often used for patient classification and gene selection. An appropriate tool for end users and biomedical researchers should combine user friendliness...Full Text Available
Most human diseases are related in some way to the loss or gain in gene functions. Regulation of gene expression is a complex process. In addition to genetic mechanisms, epigenetic causes are...Full Text Available
Optimal sample handling techniques for tissue preparation and storage, RNA extraction and quantification, and target gene detection are crucial for reliable gene expression analysis. Methods...Full Text Available
The Japanese medaka fish Oryzias latipes has an XX/XY sex-determination system. The Y-linked sex-determination gene DMY is a duplicate of the autosomal gene DMRT1, which encodes a DM-domain-containing...Full Text Available
BackgroundCells dynamically adapt their gene expression patterns in response to various stimuli. This response is orchestrated into a number of gene expression modules consisting...Full Text Available
We have isolated a second gene (MLS1), which in addition to DAL7, encodes malate synthase from S. cerevisiae. Expression of the two genes is specific for their physiological roles in carbon and nitrogen...Full Text Available
The protein kinase CK2 (formerly casein kinase II) is thought to be involved in light-regulated gene expression in plants because...Full Text Available
BmpA, BmpB, BmpC, and BmpD are homologous Borrelia burgdorferi lipoproteins of unknown functions, encoded by the bmp genes of paralogous chromosomal gene family 36....Full Text Available
In filamentous fungi, RNA silencing is an attractive alternative to disruption experiments for the functional analysis of genes. We adapted the gene encoding the autofluorescent DsRed protein as a reporter...Full Text Available
The levels of General Transcription Factor (TF) IIA were examined during mammalian brain development and in rat embryo fibroblasts and transformed cell lines. The large TFIIA subunit paralogues ab and t are largely produced in unsynchronized cell lines, yet only TFIIA ab is observed in a number of differentiated tissue extracts. Steady-state protein levels of the TFIIA t, ab, and g subunits were significantly reduced when human embryonal (ec) and hepatic carcinoma cell lines were stimulated to differentiate with either all-trans-retinoic acid (ATRA) or sodium butyrate. ATRA-treated NT2-ec cells required replating to induce a neuronal phenotype and loss of detectable TFIIA t and g proteins. High levels of TFIIA t, ab, and g and Sp factors were identified in extracts from human fetal and rat...
Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression ...
Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression ...
High surface ozone concentration is increasingly being recognized as a factor that negatively affects crop yields in Asia. However, little progress has been made in developing ozone-tolerant genotypes of rice-Asias major staple crop. This study aimed to identify possible tolerance mechanisms by characterizing two quantitative trait loci (QTLs) that were previously shown to influence visible leaf symptoms under ozone exposure (120 nl l-1, 7 h d-1, 13 d). Two chromosome segment substitution lines (SL15 and SL41) that carried introgressions of the QTLs OzT3 and OzT9, respectively, were exposed to ozone at 120 nl l-1 along with their parent Nipponbare. In accordance with the expected QTL effect, SL15 showed stronger visible symptoms of ozone damage than Nipponbare, whereas SL41 had fewer sympt...
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...
The chicken extracellular matrix glycoprotein ES/130 is necessary for epithelial-mesenchymal transformation in the developing hear and is also expressed in noncardiac chicken tissues such as limb and notochord. We have identified hES, the human homology of chicken ES/130. Fluorescence in situ hybridization analysis (FISH) localizes hES to human chromosome 20p11.2-p12. FISH analyses of individuals with 20p12 deletions and affected by Alagille syndrome exclude hES as a candidate gene for this disorder. Reverse transcriptase-polymerase chain reaction studies reveal that hES is expressed in both fetal and adult human tissues and that hES expression in the left ventricle is increased in the failing adult heart. Further studies will evaluate how hES mutations may relate to congenital human cardiac and skeletal anomalies as well as cardiac remodeling in the adult. 16 refs., 2 figs.
The Drosophila melanogaster tissue-specific transcription factor NTF-1 was originally identified in vitro as a protein that could bind to and activate transcription from the Dopa decarboxylase (Ddc) gene. A structure-function analysis of NTF-1 led to the identification of a discrete amino-terminal activation domain. Here, we report that an NTF-1 mutant lacking the activation domain acts as a trans-dominant inhibitor of NTF-1 activation in tissue culture cells by forming inactive heterodimers with the full-length protein. Ectopically expressing this dominant-negative protein or the full-length protein in developing Drosophila embryos leads to dire developmental consequences. Overexpressing the trans-dominant NTF-1 leads to lethality, while overexpressing full-length NTF-1 results in both lethality and morphogenetic defects. Our results suggest that both the activity and the regulation of NTF-1 are critical for viability and proper development of ...
A new method is being developed to quickly screen for the human exposure potential to polycyclic aromatic hydrocarbons (PAHs) and organochlorines (OCs). The development involves two key elements: identifying suitable signals that represent intracellular changes that are specific to PAH and OC exposure, and constructing a device to guide the biological cell growth so that signals from individual cells are consistent and reproducible. We are completing the identification of suitable signals by using synchrotron radiation-based (SR) Fourier-transform infrared (FTIR) spectromicroscopy in the mid-infrared region (4000-400 cm-1). Distinct changes have been observed in the IR spectra after treatment of human cells in culture medium with PAHs and OCs. The potential use of this method for detecting exposure to PAHs and OCs has been tested and compared to a reverse transcription polymerase chain reaction (RT-PCR) assay that quantifies increased expression of the CYP1A1 ...
The subjects covered in this Symposium range through almost every clinical medical specialty. From an average of one paper in each of the past three Symposiums, the explosive interest in cerebral amyloidosis has led to the presentation of 12 papers on this subject in the present volume. The genetically predisposed familial amyloidotic processes, such as the polyneuropathies and familial Mediterranean fever have also stimulated extensive and intriguing investigations which have revealed the striking effect of a single amino acid substitution in transforming a normal protein into a lethal ''amyloidogenic'' one. This Symposium clearly depicts the advances since the first amyloid fibril protein was definitively identified and defined 14 years ago. Since all amyloid fibril proteins so far described are variants of normal proteins, attention to gene abnormalities now becomes a significant focus as well as the pathogenic sequences which lead in these ...
The identification of genes influencing sensitivity to stimulants and opioids is important for determining their mechanism of action and may provide fundamental insights into the genetics of drug abuse. We used a panel of C57BL/6J (B6; recipient)x A/J (donor) chromosome substitution strains (CSSs) to identify quantitative trait loci (QTL) for both open field activity and sensitivity to the locomotor stimulant response to methamphetamine (MA). Mice were injected with saline (days 1 and 2) and MA (day 3; 2 mg/kg i.p.). We analyzed the total distance traveled in the open field for 30 min following each injection. CSS-8, -11 and -16 showed reduced MA-induced locomotor activity relative to B6, whereas CSS-10 and -12 showed increased MA-induced locomotor activity. Further analysis focused on CSS...
It is becoming clear that simple sequence repeats (SSRs) play a significant role in fungal genome organization, and they are a large source of genetic markers for population genetics and meiotic maps. We identified SSRs in the Laccaria bicolor genome by in silico survey and analyzed their distribution in the different genomic regions. We also compared the abundance and distribution of SSRs in L. bicolor with those of the following fungal genomes: Phanerochaete chrysosporium, Coprinopsis cinerea, Ustilago maydis, Cryptococcus neoformans, Aspergillus nidulans, Magnaporthe grisea, Neurospora crassa and Saccharomyces cerevisiae. Using the MISA computer program, we detected 277,062 SSRs in the L. bicolor genome representing 8% of the assembled genomic sequence. Among the analyzed basidiomycetes, L. bicolor exhibited the highest SSR density although no correlation between relative abundance and the genome sizes was observed. In most genomes the short motifs (mono- to ...
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, M_r 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind "1"2"5I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold within 8 hr in FRTL-5 thyroid cells; ...
We previously reported the identification of a new family of plant methyltransferases (MTs), named the SABATH family, that use S-adenosyl-l-methionine (SAM) to methylate a carboxyl moiety or a nitrogen-containing functional group on a diverse array of plant compounds. The Arabidopsis genome alone contains 24 distinct SABATH genes. To identify the catalytic specificities of members of this protein family in Arabidopsis, we screened recombinantly expressed and purified enzymes with a large number of potential substrates. Here, we report that the Arabidopsis thaliana gene At3g44860 encodes a protein with high catalytic specificity towards farnesoic acid (FA). Under steady-state conditions, this farnesoic acid carboxyl methyltransferase (FAMT) exhibits K{sub M} values of 41 and 71 {mu}M for FA and SAM, respectively. A three-dimensional model of FAMT constructed based upon similarity to the experimentally determined structure of ...
Seed dormancy is an adaptive mechanism and an important agronomic trait. Temperature during seed development strongly affects seed dormancy in wheat (Triticum aestivum) with lower temperatures producing higher levels of seed dormancy. To identifygenes important for seed dormancy, we used a wheat microarray to analyze gene expression in embryos from mature seeds grown at lower and higher temperatures. We found that a wheat homolog of MOTHER OF FT AND TFL1 (MFT) was upregulated after physiological maturity in dormant seeds grown at the lower temperature. In situ hybridization analysis indicated that MFT was exclusively expressed in the scutellum and coleorhiza. Mapping analysis showed that MFT on chromosome 3A (MFT-3A) colocalized with the seed dormancy quantitative trait locus (QTL) QPhs.ocs-3A.1. MFT-3A expression levels in a dormant cultivar used for the detection of the QTL were higher after physiological maturity; this ...
We report the identification and characterization of a new Drosophila clock-regulated gene, takeout (to). to is a member of a novel...Full Text Available
Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to significant cell-to-cell variations in mRNA and protein levels. This variation...Full Text Available
The ras oncogenes function by indirectly controlling expression of a subset of yet-undefined genes that are crucial for cell growth and differentiation. In a differential display strategy, numerous...Full Text Available
These proceedings collect papers on the subject of lymphokines. Topics include: DNA-cloning of mouse and human lymphokine genes, inteferons, interleukins, gene expression, tumor necrosis factors, and recombinant DNA.
PASTICCINO (PAS) genes are required for coordinated cell division and differentiation during plant development. In loss-of-function pas mutants,...Full Text Available
In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences...Full Text Available
The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding...Full Text Available
Mutations in the Drosophila gene drop-dead (drd) result in early adult lethality and neurodegeneration, but the molecular identity of the drd...Full Text Available
Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant...Full Text Available
BackgroundDue to improvements in cancer survival the number of people of working age living with cancer across Europe is likely to increase. UK governments have made commitments...Full Text Available
New ELISA assays were developed to measure immunoreactivity for XMRV. Antibody titers were measured in a cohort of prostate cancer cases and cancer free controls from the central United States. No statistically significant differences were observed in immunoreactivity between cases and controls for either the XMRV-env or the XMRV-gag antigen.
One hundred and thirty-seven lung cancer patients (123 non-small-cell lung cancers (NSCLC), 10 small-cell lung cancers (SCLC) and four carcinoid tumours) who underwent surgery in an attempt at complete...Full Text Available
Introduction: Academic research has made a significant advancement in understanding the viral causes of cervical cancer and generating the technology for prevention, both at the primary and secondary levels. Human papillomaviruses (HPVs) have been recognized as the first necessary cause of cervical cancer, the second most common cancer in women worldwide. Areas covered: This paper reviews the epidemiological evidence of the causality of HPV in relation to cervical cancer, other genital tract cancers and some cancers of the oral cavity and oropharynx. The review also covers HPV DNA testing as a screening tool. DNA probes of high-risk HPV types in different formats have been fully validated as primary screening tests, as secondary triage tests and as a prognostic marker following treatment o...
Populations living close to high-voltage transmission lines often have residential magnetic field exposures in excess of 1 [mu]T, and sometimes over 2 [mu]T. Yet, populations studied in most epidemiologic investigations of the association between residential magnetic field exposure and cancer typically have exposures below 1 [mu]T and frequently below 0.5 [mu]T. To improve statistical power and precision, it would be useful to compare high exposure populations with low exposure population. Toward this end, we have developed an automated method for identifying populations living near high-voltage transmissions lines. These populations likely have more highly exposed individuals that the population at large. The method uses a geographic information system (GIS) to superimpose digitized transmission line locations on U.S. Census block location data and then extract relevant demographic data. Analysis of data from a pilot study of the population ...
...CanCom Dermatology Image Bank Dermatology Online Atlas Introduction to Skin Cancer Malignant Melanoma Skin Cancer (Not Melanoma) Comments: bubl@bubl.ac.... Covers anatomy, melanoma, infections, and dermatological disorders in AIDS. Author: University of Utah ...994 Resource type: document Malignant Melanoma This leaflet on malignant melanoma covers early detection, causes, clinical signs and symptoms, and provides ...9 Resource type: document Skin Cancer (Not Melanoma) Information on basal cell and squamous cell skin cancers. Author: ...
Aim of this study was to evaluate the sensitivity of virtual colonoscopy (CT colonography) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality, as well as indications to the examination. It was examined prospectively 62 symptomatic patients aged 36 to 82 years (28 women and 34 men). All patients underwent both conventional and virtual colonoscopy on the same day; the conventional examination allowed exploration of the entire colon. Conventional colonoscopy identified 89 lesions 3-50 mm in diameter, namely 84 benign and 5 malignant lesions. No lesions were identified in 12 patients. CT colonography identified 52 of the 89 lesions, with 57.1% diagnostic accuracy. They were 11 false positives (82.5% positive predictive value and 52.2% specificity) and 37 false negatives (24.5% negative predictive value and 58.4% sensitivity). Sensitivity was ...
We have observed significant differences in the response to ionizing radiation of two closely related human cell lines, and now compare the effects on these lines of both low and intermediate LET radiation. Compared to TK6, WTK1 has an enhanced X-ray survival, and is also more resistant to cell killing by {alpha}-particles. The hprt locus is more mutable in WTK1 than in TK6 by both X-rays and {alpha}-particles. WTK1 is also more mutable by {alpha}-particles than by X-rays at the hprt locus. X-ray-induced mutation at the heterozygous tk locus in WTK1 is about 25 fold higher than in TK6, while {alpha}-particle-induced mutation is nearly 50 fold higher at this locus. Also, the slowly growing tk- mutants, which comprise the majority of spontaneous and X-ray-induced tk- mutants of TK6, were not induced significantly by {alpha}-particles. Previously, we showed that TK6 has a reduced capacity for recombination compared with WTK1, and therefore, these results indicate that recombinational ...
The detection of rare mutations has many important applications, including risk assessment of drugs and chemicals, measuring environmental exposures to genotoxins, and cancer cell detection. A sensitive genotypic selection method has been developed that combines two different mutant allele selection techniques, MutEx enrichment and allele-specific competitive blocker PCR (ACB-PCR). This method was developed and evaluated for the detection of a CAA --> AAA mutation at codon 61 of the mouse H-ras gene. The MutEx enrichment is based on MutS binding to a mismatched basepair in heteroduplex DNA. The bound MutS protects the mutant allele from degradation during subsequent exonuclease treatment. ACB-PCR preferentially amplifies a mutant allele in a PCR reaction using a primer that has more mismatches to the wild-type allele than the mutant allele. By combining these two approaches, the codon 61 mutation was detected at mutant fractions as low as 1 ...
A {lambda}gt11 cDNA library was constructed from poly(U)-Spharose-selected Entamoeba histolytica trophozoite RNA in order to clone and identify surface antigens. The library was screened with rabbit polyclonal anti-E. histolytica serum. A 700-base-pair cDNA insert was isolated and the nucleotide sequence was determined. The deduced amino acid sequence of the cDNA revealed a cysteine-rich protein. DNA hybridizations showed that the gene was specific to E. histolytica since the cDNA probe reacted with DNA from four axenic strains of E. histolytica but did not react with DNA from Entamoeba invadens, Acanthamoeba castellanii, or Trichomonas vaginalis. The insert was subcloned into the expression vector pGEX-1 and the protein was expressed as a fusion with the C terminus of glutathione S-transferase. Purified fusion protein was used to generate 22 monoclonal antibodies (mAbs) and a mouse polyclonal antiserum specific for the E. histolytica portion ...
A #lambda#gt11 cDNA library was constructed from poly(U)-Spharose-selected Entamoeba histolytica trophozoite RNA in order to clone and identify surface antigens. The library was screened with rabbit polyclonal anti-E. histolytica serum. A 700-base-pair cDNA insert was isolated and the nucleotide sequence was determined. The deduced amino acid sequence of the cDNA revealed a cysteine-rich protein. DNA hybridizations showed that the gene was specific to E. histolytica since the cDNA probe reacted with DNA from four axenic strains of E. histolytica but did not react with DNA from Entamoeba invadens, Acanthamoeba castellanii, or Trichomonas vaginalis. The insert was subcloned into the expression vector pGEX-1 and the protein was expressed as a fusion with the C terminus of glutathione S-transferase. Purified fusion protein was used to generate 22 monoclonal antibodies (mAbs) and a mouse polyclonal antiserum specific for the E. histolytica portion ...
With the aim of an experimental check on the validity of the theory of molecular recognition, the authors have carried out the chemical-enzymatic synthesis and cloning of the gene of human calcitonin and also of the genes of antisense polypeptides to human calcitonin and miniproinsulin. It has been shown that recombinant plasmids obtained on the basis of these synthetic genes are capable of ensuring the biosynthesis of the given polypeptides in E. coli cells as hybrid proteins with the IgG-binding domain of staphylococcal protein A.
A 13.1-kb DNA fragment carrying Pseudomonas denitrificans cob genes has been sequenced. The nucleotide sequence and genetic analysis revealed that this fragment contained five different cob genes named...Full Text Available
Procedures are described for the use of synthetic oligonucleotides for Southern blot experiments and gene bank screening, and the effect of various mismatches on the efficiency of hybridization is demonstrated. The following topics are discussed: sensitivity vs. specificity, hybridization of a 12-mer to the lambda endolysin gene; hybridization of oligonucleotide probes to the E. coli lac operator; hybridization of synthetic probes to the CYC1 gene of yeast; and cloning eucaryotic genes. (HLW)
Gene silencing is a useful technique for elucidating biological function of genes by knocking down their expression. A recently developed artificial microRNAs (amiRNAs) exploits an endogenous...Full Text Available
We have isolated the human prointerleukin 1 (proIL-1) beta gene from leukocyte and fetal liver libraries. The nucleotide sequence and its gene organization reveals that the proIL-1 beta gene is composed...Full Text Available
Today you will learn about the parts of DNA and what DNA, genes and chromosomes are. Today you will learn what DNA, genes and chromosomes are and the parts of the DNA molecule. Look at all of the websites, take whatever notes you need to. At the end of the assignment, be able to describle DNA, the parts of DNA, genes and chromosomes. Covers Biology Core Curriculum, ...
The loss of #alpha#-globin gene transcriptional activity rarely occurs as an acquired abnormality during the evolution of myeloproliferative disease or preleukemia. To test whether the mutation responsible for the loss of #alpha#-globin gene expression (hemoglobin H disease) in these patients is linked with the #alpha#-globin genes on chromosome 16, the authors transferred chromosome 16 from preleukemic patients with acquired hemoglobin H disease to mouse erythroleukemia cells and measured the transcriptional activity of the human #alpha#-globin genes. After transfer to mouse erythroleukemia cells, the expression of human #alpha#-globin genes from the peripheral blood or marrow cells of preleukemic patients with acquired hemoglobin H disease was similar to that of human #alpha#-globin genes transferred to mouse erythroleukemia cells from normal donors. These ...
ObjectivesTo assess the influence of epigallocatechin-3-gallate (EGCG) on the efficacy of ionizing radiation on prostate cancer cells because of the increased use of dietary interventions, especially by patients with prostate cancer. Radiotherapy is used to treat localized prostate cancer. Some people consume green tea (EGCG) as a chemopreventive agent against prostate cancer. Green tea can act as an antioxidant and induce superoxide dismutase enzymes, which could scavenge the free oxygen radicals generated by radiotherapy. MethodsProstate cancer cell line DU145 cells were treated with EGCG or radiotherapy, or both. Cell death was assessed using trypan blue cell counting, and apoptosis was confirmed by assessing poly (adenosine phosphate ribose) polymerase cleavage. The antioxidant potenti...
Extensive epidemiological studies have been carried out in recent years to examine the possible effects of exposure to extremely low frequency electromagnetic fields on the development of cancer. In some studies, both residential and occupational, a number of cancers, in particular leukaemia and brain cancer, have occurred at an increased incidence at higher levels of exposure. In general, however, no consistent and coherent pattern of results has been obtained and no clear evidence of a cancer risk has been demonstrated. A better understanding of any effect of electromagnetic fields on the development of cancer must await the results of more informative epidemiological studies and an improved understanding of the mechanisms by which these fields may interact with the body and their likely consequences. (author)
Background Despite potentially relevant chemical differences between filtered and boiled coffee, this study is the first to investigate consumption in relation to the risk of incident cancer. Methods Subjects were from the V?sterbotten Intervention Project (64,603 participants, including 3,034 cases), with up to 15?years of follow-up. Hazard ratios (HR) were calculated by multivariate Cox regression. Results No associations were found for all cancer sites combined, or for prostate or colorectal cancer. For breast cancer, boiled coffee ?4 versus <1 occasions/day was associated with a reduced risk (HR?=?0.52, CI?=?0.30?0.88, p trend?=?0.247). An increased risk of premenopausal and a reduced risk of postmenopausal breast cancer were found for both total (HRpremenopausal?=?1.69, CI?=?0.96?2.98...
This investigation of a brain cancer cluster in Missouri used two approaches to investigate associations with potential risk factors. In a case-control study in a rural town, we interviewed surrogates of cases and controls about potential risk factors. We found a statistically significant positive association of brain cancer with reported exposure to dental x-rays. Occupation was not associated with the cluster in the rural town. In a standardized proportional mortality study for the state of Missouri, we calculated the observed and expected proportion of brain cancers by occupation and industry in Missouri decedents. We found that motor vehicle manufacturers, beauty shop workers, managers and administrators, elementary school teachers, and hairdressers and cosmetologists had significantly elevated proportions of brain cancer. Brain tumors are inconsistently associated with occupation in the literature. ...
Pancreatitis-associated protein (PAP) is a secretory pancreatic protein present in small amounts in normal pancreas and overexpressed during the acute phase of pancreatitis. In this paper, the authors describe the cloning, characterization, and chromosomal mapping of the human PAP gene. The gene spans 2748 bp and contains six exons interrupted by five introns. The gene has a typical promoter containing the sequences TATAAA and CCAAT 28 and 52 bp upstream of the cap site, respectively. They found striking similarities in genomic organization as well as in the promoter sequences between the human and rat PAP genes. The human PAP gene was mapped to chromosome 2p12 using rodent-human hybrid cells and in situ chromosomal hybridization. This localization coincides with that of the reg/lithostathine gene, which encodes a pancreatic secretory protein structurally ...
... be able to watch the many intricate steps Dr. Richard Alexander must accomplish to remove the cancer. ... door to informed medical care. Now let's join Dr. Richard Alexander at the University of Maryland Medical ...
PurposeWe evaluated the effects of surgery for rectal cancer on postoperative voiding and sexual function over the course of time.Materials and MethodsData...Full Text Available
The primary objective of our study is to describe urinary symptoms in women treated for endometrial cancer. We performed a cross-sectional survey of women who had undergone surgical treatment...Full Text Available
Materials and MethodsThe genomic effects of tumor-endothelial interactions in cancer are not yet well characterized. To study this interaction in breast...Full Text Available
BackgroundThymoquinone (TQ) is a compound extracted from Black Caraway seeds of Nigella Sativa and is active against various cancers. Cisplatin (CDDP) is the most...Full Text Available
Most breast cancers are multicentric in origin. They drain into two primary lymphatic depots—the axilla and internal mammary chain of nodes. The incidence of metastasis to the internal mammary...Full Text Available
This book examines the occupational health hazards imposed by neoplasms. Topics considered include: cancer as an occupational hazard; an overview; epidemiological evidence; and interaction of host and lifestyle factors with occupational chemicals in cancer causation.
Objective. Cervical cancer patients who had an abandoned radical hysterectomy were evaluated for preoperative clinical predictors, complication rates, and outcomes. Study...Full Text Available
Recent studies suggest that TJ-41, a herbal drug, possesses chemotherapeutic effects. Accordingly, this study was undertaken to investigate the anticarcinogenic effects of TJ-41 on human breast cancer...Full Text Available
Epidermal growth factor receptor (EGFR)-specific monoclonal antibodies predominantly inhibit colorectal cancer (CRC) growth by interfering with receptor signaling. Recent analyses have shown that patients...Full Text Available
To assess the merits of currently available treatment options in the management of patients with low rectal cancer, a review of the medical literature pertaining to the operative and non-operative management...Full Text Available
Background:Smoking cessation is an important strategy for reducing the harmful effects of tobacco, particularly in the prevention of lung cancer; however, prospective data on the...Full Text Available
Sirtuin 1 acts in various cell processes, deacetylating both chromatin and non-histone proteins, and its role in cancer and aging has long been studied and debated. Here we discuss another aspect of...Full Text Available
Human epidermal growth factor receptor 2 (HER2) is one of the most important prognostic and predictive factors for breast cancer patients. Recently, serum HER2...Full Text Available
This review presents a summary of existing knowledge regarding the impact of testicular cancer along four broad domains, including romantic and sexual relationships, body image, and fertility....Full Text Available
PurposeIn our previous studies we showed that upregulating claudin-6 (CLDN6) expression may contribute to preventing breast cancer, and that 17β-estradiol induces a concentration-...Full Text Available
Background:Parity has been linked to gallbladder cancer and gallstones, but the effects of other reproductive factors are less clear.Methods:We examined...Full Text Available
Epidermal growth factor receptor (EGFR) kinase domain mutations hyperactivate the kinase and confer kinase addiction of the non-small-cell lung cancer (NSCLC) tumor...Full Text Available
BackgroundThe optimal treatment for locally recurrent rectal cancer (LRRC) is still a matter of debate. This study assessed the outcome of LRRC patients treated with multimodality...Full Text Available
OBJECTIVE: The aim was to assess the psychosocial effects on the quality of life (QOL) of adults with head and neck cancer (HNC) and any gender variations with predictive factors that may influence...Full Text Available
Incidence of esophageal cancer (EC) is rising more rapidly in the Western world than that of any other cancer. Despite advances in therapy, more than 50% of patients have incurable disease at the time...Full Text Available
Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation....Full Text Available
BackgroundLung cancer diagnosis in tissue material with commonly used histological techniques is sometimes inconvenient and in a number of cases leads to ambiguous conclusions. Frequently...Full Text Available
BackgroundTissue microarray (TMA) data are commonly used to validate the prognostic accuracy of tumor markers. For example, breast cancer TMA data have led to the identification...Full Text Available
Cervical cancer is known to metastasize primarily by the lymphatic system. Dissemination through lymphatic vessels represents an early step in regional tumor progression, and the presence of lymphatic...Full Text Available
BackgroundIdentification of urinary biomarkers for detection of bladder cancer recurrence would be beneficial to minimize the frequency of cystoscopy. Our objective was to determine...Full Text Available
Because many diseases of the Western Hemisphere are hormone-dependent cancers, we have postulated that the Western diet, compared to a vegetarian or semivegetarian diet, may alter hormone production,...Full Text Available
During the past decade elevated phospholipase D (PLD) activity has been reported in virtually all cancers where it has been examined. PLD catalyzes the hydrolysis of phosphatidylcholine to generate...Full Text Available
Patients with pancreatic cancer normally present with advanced disease that is lethal and notoriously difficult to treat. Survival has not improved dramatically, despite routine use of chemotherapy...Full Text Available
Background:The non-surgical management of non-melanoma skin cancers is an area requiring clinical investigation. Radiotherapy has a role in treatment for a defined subset...Full Text Available
Development of mouse models representing human spontaneous ovarian cancer has been hampered by the lack of understanding of the etiology of this very complex disease. Mouse models representing the different...Full Text Available
Cancer cells constantly adapt to oxidative phosphorylation (OXPHOS) suppression resulting from hypoxia or mitochondria defects. Under the OXPHOS suppression, AMP-activated protein kinase (AMPK) regulates...Full Text Available
BackgroundStem cell characteristics are an important feature of human cancer cells and play a major role in the therapy resistance of tumours. Strategies to target cancer stem cells...Full Text Available
Aims: To study the expression of nuclear β catenin in patients with colorectal cancer, colorectal adenoma, and colorectal polyps to elucidate its role in carcinogenesis, and its...Full Text Available
A 63-year-old man was admitted to our hospital with a complaint of right lateroabdominal pain. He was diagnosed with metastatic colon cancer, and then developed multiple brain embolic infarctions 7...Full Text Available
The treatment of locally advanced rectal cancer including timing and dosage of radiotherapy, degree of sphincter preservation with neoadjuvant radiotherapy, and short and long term effects of radiotherapy...Full Text Available
Chemoprevention, especially through the use of naturally occurring phytochemicals capable of impeding the process of carcinogenesis at one or more steps, is an ideal approach for cancer management....Full Text Available
An evaluation of totally implanted venous access systems inserted in 163 consecutive children with cancer is reported. From 1988 to 1994, 180 subcutaneous ports were inserted in children more than 1...Full Text Available
BackgroundCD26 (dipeptidyl peptidase IV, DPPIV) is a 110 kDa surface glycoprotein expressed in most normal tissues, and is a potential novel therapeutic target for selected cancers....Full Text Available
Heart disease, cancer, and cerebrovascular disease together cause more than two out of three deaths in the United States annually. These three diseases are largely a result of widespread risk factors...Full Text Available
BackgroundSome breast cancer patients receiving anti-angiogenic treatment show increased metastases, possibly as a result of induced hypoxia. The effect of hypoxia on tumor cell...Full Text Available
ObjectiveThis report describes initial activities of the Cancer Patient-Reported Outcomes Measurement Information System (PROMIS) Sexual Function domain group (CaPS-SF),...Full Text Available
The use of dendritic cells (DCs) as a cellular adjuvant is a promising approach to the immunotherapy of cancer. It has previously been demonstrated that DCs pulsed ex vivo with Toxoplasma gondii...Full Text Available
Hyperglycemia and hyperinsulinemia accelerate both aging and cancer. Antidiabetic biguanides such as metformin decrease glucose, insulin and IGF-1 level. Metformin increases lifespan and prevents cancer...Full Text Available
Epigenetic remodeling is a hallmark of cancer, with the frequent acquisition of de novo DNA methylation in CpG islands. However, the functional relevance of de novo...Full Text Available
PurposeIntestinal stomas can pose significant challenges for long-term (≥ 5 years) rectal cancer (RC) survivors. Specifying common challenges and sociodemographic or clinical...Full Text Available
Every year nearly 200,000 men in the United States are diagnosed with prostate cancer (PCa), and another 29,000 men succumb to the disease. Within certain regions of the world population based...Full Text Available
Recently, there has been significant progress in the development of genetically-engineered mouse (GEM) models. By introducing genetic alterations and/or signaling alterations of human pancreatic cancer...Full Text Available
Available in vitro and animal studies have shown cancer protective effects of tea polyphenols. Recent study suggests a greater protective effect of green tea intake on breast cancer...Full Text Available
The heterogeneity of metastatic breast cancer mandates the need to select therapies taking into account tumor and patient characteristics. Chemotherapy is indicated in the palliative setting especially...Full Text Available
Colorectal cancer (CRC) survivors with ostomies can face complex concerns regarding sexuality. We used an anthropological perspective to examine the experiences of 30 female CRC survivors with...Full Text Available
BackgroundNon-small cell lung cancer (NSCLC) is the foremost cause of cancer-related death in Western countries, which is due partly to the propensity of NSCLC cells to metastasize....Full Text Available
BackgroundAt least some forms of breast cancer are increasingly being viewed as a chronic illness, where an emphasis is placed on meeting the various ongoing needs of people living...Full Text Available
OBJECTIVES: To appraise epidemiological evidence of the purported association between residential exposure to power frequency magnetic fields and adult cancers. METHODS: Literature review and epidemiological...Full Text Available
BackgroundCompared to healthy controls, cancer patients have a higher risk of unemployment, which has negative social and economic impacts on the patients and on society at large....Full Text Available
Hemoptysis in patients with lung cancer is not uncommon and sometimes have dangerous consequences. Hemoptysis has been managed with various treatment options other than surgery and medicine, such as...Full Text Available
Between 1943 and 1982, 5,140 new cases of testicular cancer were diagnosed in Denmark. The age-standardized incidence rate more than doubled in the period. Striking variations is seen in the age-relationship...Full Text Available
ObjectiveThe aim of this study was to ascertain whether all cervical cancer patients who received adjuvant concurrent chemoradiation (CCRT) for high risk of treatment failure after...Full Text Available
The risk of lung cancer associated with diesel exhaust has been calculated from 14 case-control or cohort studies. We evaluated the findings from these studies to determine whether there is sufficient...Full Text Available
Attention has shifted from the treatment of colorectal cancer (CRC) to chemoprevention using aspirin and folic acid as agents capable of preventing the onset of colon cancer. However, no sensitive...Full Text Available
The search for cancer treatment continues to be a global effort. As part of this global effort, many natural products have been tested against cancer cell lines, mostly from tropically located plants....Full Text Available
The results of clinical trials conducted in Europe and North America have been incorporated into treatment strategies for breast cancer in Japan. Despite the use of similar treatment regimens, why has...Full Text Available
While many lessons have been learned from the spatial analysis of cancer, there are several caveats that apply to many, if not all such analyses. As "flies in the ointment", these can substantially...Full Text Available
Urothelial carcinoma of the upper urinary tract represents only 5% of all urothelial cancers. The 5-year cancer-specific survival in the United States is roughly 75% with grade and stage being the most...Full Text Available
Colorectal cancer (CRC) is the third-ranked neoplasm in order of incidence and mortality, worldwide, and the second cause of cancer death in industrialized countries. One of the most important environmental...Full Text Available
The purpose of this study was to determine the clinical significance of nodal micrometastasis detected by immunohistochemistry in patients that had undergone curative surgery for pancreatic cancer....Full Text Available
We explored the association between groundwater radon levels and childhood cancer mortality in North Carolina. Using data from two state-wide surveys of public drinking water supplies, counties were...Full Text Available
A case-control study has been carried out to examine the occurrence of childhood cancer in relation to the proximity of overhead power lines to a child's home address at birth and to the calculated...Full Text Available
BackgroundPreclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib,...Full Text Available
Social support is a critical, yet underutilized resource when undergoing cancer care. Underutilization occurs in two conditions: (a) when patients fail to seek out information, material assistance,...Full Text Available
Carcinoma in situ in the contralateral testis was diagnosed in 27 of 500 patients (5.4%) with unilateral testicular germ cell cancer. Eight of the 27 patients received intensive chemotherapy for spread...Full Text Available
tumors make up two-thirds of all adult brain tumors and one-third of childhood brain tumors. Cancer Among Men, 2003-2007 Incidence rates decreased for lung, colorectal,...
OBJECTIVE: To test the hypothesis that perioperative transfusion of allogeneic and autologous red blood cells (RBCs) stored for a prolonged period speeds biochemical recurrence of prostate cancer...Full Text Available
ContextWhile opioids are increasingly used for chronic non-cancer pain (CNCP), we know little about opioid dosing patterns among individuals with CNCP in usual care...Full Text Available
The increased risk of thrombosis in patients with active cancer has multiple causes. Acute thrombosis of the aorta is an exceedingly rare but potentially devastating complication in patients with cancer...Full Text Available
IntroductionVarious multigene predictors of breast cancer clinical outcome have been commercialized, but proved to be prognostic only for hormone receptor (HR) subsets overexpressing...Full Text Available
BackgroundClassification systems may be useful to direct more aggressive treatment to cancer patients with a relatively poor prognosis. The definition of 'poor prognosis' often lacks...Full Text Available
ObjectivesThis feasibility study developed and pilot tested an intervention to: (1) increase knowledge about prostate cancer (CaP) screening; and (2) promote self-efficacy...Full Text Available