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Biomedical subjects

P Aman

Publications and source records attributed to P Aman.

At least 19 recordsLinked to original sources
PubMed2000

Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice.

BACKGROUND: In this study, we investigated whether dietary intervention could inhibit tumor growth of an androgen-sensitive human prostatic cancer. METHODS: LNCaP cells were transplanted subcutaneously in nude-mice. The animals were then put on different diets and tumor take, tumor growth and prostate specific antigen (PSA) secretion were studied during 9 weeks. RESULTS: Palpable tumors developed in 75% of the tumor-cell injected sites in animals fed a control diet (corn starch, sucrose, etc.) whereas, for animals given rye bran (RB), ethyl acetate extraction from rye bran supplemented cellulose based diets (CCEE), palpable tumors were seen in only 30% and for soy protein based diets (SCC) 50% of the transplantation sites, respectively. The tumors that grew to palpable size in the rye (RB) and soy (SCC) groups were smaller and secreted less PSA than those in the control group. In the rye and soy groups tumor cell apoptosis was increased, but cell proliferation was unaffected. Addition of fat to the rye diet reduced its effect on prostate cancer growth. CONCLUSIONS: Factors in rye bran and soy protein may inhibit prostate cancer growth. The effect is more apparent for rye than for soy. Further studies are needed to identify the effective substances and to explore the mechanism of action.

Adenocarcinoma↗
PubMed1999

Fusion of the EWS-related gene TAF2N to TEC in extraskeletal myxoid chondrosarcoma.

Extraskeletal myxoid chondrosarcomas (EMCs) are characterized by a recurrent t(9;22)(q22;q12) translocation, resulting in the fusion of the EWS gene in 22q12 and the TEC gene in 9q22. Here we report that a third member of the EWS, TLS/FUS gene family, TAF2N, can replace EWS as a fusion partner to TEC in EMC. Two tumors, one with a novel t(9;17)(q22;q11) variant translocation and one with an apparently normal karyotype, expressed TAF2N-TEC fusion transcripts. In both cases, the chimeric transcripts were shown to contain exon 6 of TAF2N fused to the entire coding region of TEC. This transcript is structurally and functionally very similar to the EWS-TEC fusions. The exchange of the EWS NH2-terminal part with the TAF2N NH2-terminal part in EMC further underscores the oncogenic potential of these protein domains as partners in fusion genes.

Aged↗
PubMed1999

Identification of genes differentially expressed in TLS-CHOP carrying myxoid liposarcomas.

Myxoid liposarcomas (MLS) carry a t(12;16) or, more rarely, a t(12;22) resulting in fusion of the transcription factor gene CHOP on chromosome 12 with TLS/FUS on chromosome 16 or EWS on chromosome 22. The chimeric TLS-CHOP or EWS-CHOP proteins most probably function as abnormal transcription factors, causing transcriptional de-regulation of several target genes and relaxation of functions critical for growth and differentiation control. A PCR-based subtractive hybridization technique was used to identify genes that are differentially expressed in TLS-CHOP-carrying MLS but not in normal fat tissue. Six myxoid-liposarcoma-associated transcripts, MLAT, were isolated. The genes identified as MLAT can be divided into 2 groups. MLAT1, 2 and 6 show high similarity to glia-derived nexin, neuronatin and the RET oncogene, respectively, all normally involved in development of tissues of neural origin. MLAT3 to MLAT5 represent new genes.

CCAAT-Enhancer-Binding Proteins↗
PubMed1999

Characterization of TFG in mus musculus and Caenorhabditis elegans.

TFG was discovered as a fusion partner of NTRK1 in human papillary thyroid carcinoma. We assembled the mouse TFG cDNA from EST sequences and 5' end RACE product, identified full coding length TFG EST clones in pig (c17b07) and Schistosoma mansoni (SMNAS62), and analyzed the genomic structure of TFG in Caenorhabditis elegans (Y63D3A). The protein sequences of mouse, pig, and S. mansoni TFG are highly homologous to human TFG. The C. elegans sequence has diverged, but its predicted secondary structure is remarkably conserved. Human, mouse, and C. elegans TFG contain a putative trimeric N-terminal coiled-coil domain, glycosylation, myristylation, and phosphorylation sites, and SH2- and SH3-binding motifs. The SH2-binding motif is absent in C. elegans TFG. The expression of TFG does not vary among 7, 11, 15, and 19 day mouse embryonal stages. In situ hybridization with a TFG probe in 10, 5-day whole mouse embryos showed preferential staining of the limb buds, branchial arches, nasal processes, and brain, and weak staining of the primitive spinal cord and dorsal root ganglia.

Amino Acid Sequence↗
PubMed1999

Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: further definition of the HML-6 group.

Previously, we found a retroviral sequence, HML-6.2BC1, to be expressed at high levels in a multifocal ductal breast cancer from a 41-year-old woman who also developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28) selected by high-stringency hybridization with HML-6.2BC1 is reported here. It was 99% identical to HML-6.2BC1 and gave the same restriction fragments as total DNA. HML-6.28 is a 4.7-kb provirus with a 5'LTR, truncated in RT. Data from two similar genomic clones and sequences found in GenBank are also reported. Overlaps between them gave a rather complete picture of the HML-6.2BC1-like human endogenous retroviral elements. Work with somatic cell hybrids and FISH localized HML-6.28 to chromosome 6, band p21, close to the MHC region. The causal role of HML-6.28 in breast cancer remains unclear. Nevertheless, the ca. 20 Myr old HML-6 sequences enabled the definition of common and unique features of type A, B, and D (ABD) retroviruses. In Gag, HML-6 has no intervening sequences between matrix and capsid proteins, unlike extant exogenous ABD viruses, possibly an ancestral feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but gave a phylogenetic tree different from trees made from other ABD genes, indicating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the amino terminus of some ABD envelope genes suggested a conserved function.

Adult↗
PubMed1999

A novel PCR-based approach for the detection of the Huntington disease associated trinucleotide repeat expansion.

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder associated with expansions of an unstable CAG trinucleotide repeat in exon 1 of the IT15 gene. In normal individuals, IT15 contains up to 35 CAG repeats, while in affected the repeat length is >36. Polymerase chain reaction (PCR) is used to estimate the number of CAG repeats but may be inefficient in long repeats because of the high C+G content of the HD locus. We present a novel PCR approach for the diagnosis of HD, which permits direct visualization of the amplified products on agarose gel, using ethidium bromide. It is based on the methylation-sensitive conversion of C residues to U by bisulfite treatment of single-stranded DNA and subsequent amplification of the sense strand with specific primers. The bisulfite treatment dramatically reduces the C + G content of the region; thus, the high Tm and stable secondary structures are no longer obstacles to PCR. In both normal and affected individuals, UAG repeats (5'- CAG-3', before bisulfite treatment) in the sense strand can easily be amplified and visualized on a gel by ethidium bromide staining. The method has considerable advantages compared with other described PCR-based diagnostic tests for HD.

Base Sequence↗
PubMed1999

A methylation PCR approach for detection of fragile X syndrome.

Fragile X syndrome is associated with the expansion of the number of CGG trinucleotide tandem repeats at the 5' untranslated region of the FMR1 gene. The number of CGG trinucleotide repeats in normal individuals ranges between 5 and 50, in asymptomatic carrier individuals it ranges between 50 and 200, and in affected individuals it is more than 200 CGG repeats. In addition, in affected individuals the cytosine residues in the CGG repeats and the adjacent CpG island are methylated and the FMR1 gene is transcriptionally inactive. The most common diagnostic method for the detection of the syndrome is Southern blot analysis. Methods based on the polymerase chain reaction (PCR) could facilitate the rapid screening of large numbers of individuals by accurately determining the number of CGG repeats. Current PCR techniques for amplification of CGG repeats are, however, inefficient and unreliable because of their 100% C+G composition. Thus, most of the described PCR protocols require subsequent Southern blot analysis and autoradiography. We present a novel PCR approach for the diagnosis of fragile X syndrome based on the methylation-sensitive conversion of C residues to U by bisulfite on single-strand DNA and subsequent amplification of the antisense strand with specific primers. A PCR with primers for methylated C residues will amplify the CpG dinucleotide region upstream to CGG repeats exclusively in affected males. As a result of extensive mismatch between primers and bisulfite-treated DNA, no PCR fragments will be obtained in normal and transmitting males. Moreover, the bisulfite treatment dramatically reduces the C+G component of the region; thus, the high Tm and the strong secondary structures are no longer obstacles for PCR amplification. In normal and carrier individuals, UUG repeats (previously 3'-CCG-5') in the antisense strand can easily be amplified and visualized on a gel by ethidium bromide staining. We applied our method on 25 males previously diagnosed by Southern blot analysis. All the samples were easily and accurately diagnosed. The method has considerable advantages compared with other diagnostic tests for fragile X syndrome.

Base Sequence↗
PubMed1999

Fusion genes in solid tumors.

Tumor development in different cell types and tissue locations involves many pathways, distinct genes and exogenous factors. Tumor type-specific chromosome rearrangements resulting in fusion genes or promoter swapping are believed to be involved in the early development of many tumor types. They are present in almost all cases of a particular tumor type and cases have been described that carry only tumor type-specific translocations without any signs of other cytogenetic changes. The mechanisms behind chromosome rearrangements in solid tumors are largely unknown. Radiation is an important factor in thyroid carcinomas but no com-$bmon sequence motifs are made out in the break points of solid tumors. The fusion genes found in sarcomas are dominated by the transcription factor type of genes with the TLS/FUS and EWS series of fusion genes as the largest group. More than 50% of papillary thyroid carcinomas carry fusion proteins with tyrosine kinase activity. Rearrangements involving HMGIC, HMGIY, and PLAG1 are common in benign mesenchymal tumors and salivary gland adenomas. Many recurrent tumor translocations show a strict specificity for tumor type. This specificity can most likely be explained by the specific sets of target genes that are deregulated by the fusion gene products. Identification of the downstream target genes is currently the object of intense research and may provide us with information that will help design better diagnostic tools and eventually find a cure for these diseases.

Gene Expression Regulation, Neoplastic↗
PubMed1999

The human CILP gene: exon/intron organization and chromosomal mapping.

The human cDNA for cartilage intermediate layer protein (CILP) codes for a larger precursor protein that consists of CILP and a homologue to porcine Nucleotide pyrophosphohydrolase (NTPPHase) [Lorenzo et al. 1998a. J. Biol. Chem. 273, 23469-23475]. The human gene has now been isolated and characterized. Southern blot analysis indicated a single copy of the CILP gene in the human genome. The gene spans approximately 15.3 kbp of genomic DNA, and is organized in nine exons. The 5' flanking region contains a putative promoter region with a TATA-like box localized from -29 to -23 bp upstream of the transcription start site. Analysis of the putative promoter region revealed potentially cis-regulatory eukaryotic elements such as GATA-1, MyoD, MZF1, and CdxA. The protein coding region begins in exon 2 with the putative signal peptide. CILP is encoded from exon 3 to exon 9. In addition, exon 9 also codes for the entire NTPPHase homologue and contains the 3' untranslated region of the gene. All the introns follow the 'gt-ag' rule, except the last intron, intron 8, that belongs to the minor class of pre-mRNA introns that contain 'at-ac' at their 5' and 3' ends, respectively. The CILP gene was mapped to human chromosome 15q22.

Base Sequence↗
PubMed1999

Nucleotide sequences specific for nonnominal immunoglobulin allotypes in rheumatoid arthritis patients and in normal individuals and their expression in synovial tissue of rheumatoid arthritis patients.

The production of antibodies against nonnominal immunoglobulin allotypes in rheumatoid arthritis (RA) patients suggests that the immune system of these patients has been exposed to such foreign allotypes. The presence of nonnominal allotypes is, however, a genetic enigma. We searched for nucleotide sequences specific for nonnominal G3mg and G3mb copies in individuals homozygous for these alleles. Using a sensitive and specific nested polymerase chain reaction (PCR) method with genomic DNA from blood of 18 RA patients and 5 normal controls, we found G3mg sequences in 18 of 18 tested G3mb homozygous persons. The allele specificity of the PCR fragments was confirmed by sequencing and RFLP analysis. The PCR products contained genomic nonspliced parts of the nonnominal sequences. An analysis of cDNA from inflammatory tissue of 5 RA patients detected nonnominal G3mb sequences in 1 of 3 tested G3mg homozygotes and G3mg sequences in 2 of 2 tested G3mb homozygotes. The cDNA-derived PCR products contained sequences from normally spliced nonnominal Ig fragments. The results also showed that the nonnominal Ig sequences were present in very low copy numbers, lower than the Mendelian 1-2 copies per cell. The origin of such a low copy number of Ig gene fragments may be explained by a virus-mediated capture and transfer mechanism of Ig gene fragments generated by the normal Ig switch-associated gene excision process.

Arthritis, Rheumatoid↗
PubMed1998

Inhibitory effects of soy and rye diets on the development of Dunning R3327 prostate adenocarcinoma in rats.

METHODS: Dunning R3327 PAP prostate tumors were transplanted in 125 rats, the rats were divided into five groups, and tumor development was examined for 24 weeks during treatment with diets containing 33% of soy flour (SD), rye bran (RB), heat-treated rye bran (HRB), or rye endosperm (RE). RESULTS: In the SD, RB, and HRB groups, significantly fewer palpable tumors and lower tumor volume were detected 14 and 16 weeks after transplantation when compared with the control, fiber-free dietary (FF) group. The body weight was lower 16 weeks after tumor transplantation in the RB and HRB groups when compared with the control group (P < 0.05). Rats in the RB and the HRB groups had a significant lower energy intake than the FF group during the first metabolic observation period, 3-6 weeks after tumor transplantation (P < 0.05), whereas the energy intake was the same in all groups during the second metabolic observation period, 13-16 weeks after tumor transplantation. However, when the tumor volume was adjusted for the body weight of the animals, there were still significant lower tumor volumes in the SD, RB, and HRB groups compared with the FF group (P < 0.05). A significant increase in daily urinary excretion of the isoflavonoids, daidzein, O-desmethylangolensin, equol, and Genistein, was observed in the rats fed SD, and of the ligands enterolactone and enterodiol in the rats fed RB and HRB during both metabolic periods. There were no differences in testosterone levels between the groups. CONCLUSIONS: The present study shows that SD inhibits implanted prostate cancer growth. Although RB and HRB had a protective effect, further studies are needed to exclude the possibility that a low energy intake played a role in this respect. The results suggest that phytoestrogens (isoflavonoids and ligands), may be responsible for the delayed prostate tumor growth.

Adenocarcinoma↗
PubMed1998

Expression analysis and chromosomal mapping of a novel human gene, APRIL, encoding an acidic protein rich in leucines.

Clone 120041 was selected from the EST database for sequence similarity to DEK and SET proteins rearranged in leukemias. The ends of the cDNA were isolated by RACE technique. The assembled cDNA encodes an LRR-containing protein of 251 amino acids designated APRIL (acidic protein rich in leucines). APRIL has high similarity to human pp32, also named PHAPI (bovine I[PP2A]1), and to rat LANP, respectively. APRIL shows tissue-specific expression as shown by Northern blot analysis. It was localized to 15q25 by FISH.

Amino Acid Sequence↗
PubMed1997

The macrophage migration inhibitory factor MIF is a phenylpyruvate tautomerase.

A macrophage migration inhibitory factor (MIF), originally described as a product of activated lymphocytes, has been defined as a 12 kDa protein, expressed in a wide variety of tissues. Here MIF is identified as a phenylpyruvate tautomerase (EC 5.3.2.1) having p-hydroxyphenylpyruvate and phenylpyruvate as its natural substrates. The definition of MIF as an enzyme may yield insight into the mechanism of action of this proinflammatory and immunomodulating cytokine.

Amino Acids↗
PubMed1997

Characterization and chromosomal mapping of the human TFG gene involved in thyroid carcinoma.

Homology searches in the Expressed Sequence Tag Database were performed using SPYGQ-rich regions as query sequences to find genes encoding protein regions similar to the N-terminal parts of the sarcoma-associated EWS and FUS proteins. Clone 22911 (T74973), encoding a SPYGQ-rich region in its 5' end, and several other clones that overlapped 22911 were selected. The combined data made it possible to assemble a full-length cDNA sequence. This cDNA sequence is 1677 bp, containing an initiation codon ATG, an open reading frame of 400 amino acids, a poly(A) signal, and a poly(A) tail. We found 100% identity between the 5' part of the consensus sequence and the 598-bp-long sequence named TFG. The TFG sequence is fused to the 3' end of NTRK1, generating the TRK-T3 fusion transcript found in papillary thyroid carcinoma. The cDNA therefore represents the full-length transcript of the TFG gene. TFG was localized to 3q11-q12 by fluorescence in situ hybridization. The 3' and the 5' ends of the TFG cDNA probe hybridized to a 2.2-kb band on Northern blot filters in all tissues examined.

Amino Acid Sequence↗
PubMed1997

Additional evidence of a variant translocation t(12;22) with EWS/CHOP fusion in myxoid liposarcoma: clinicopathological features.

It is well established that the majority of myxoid/round cell liposarcomas (LPS) are characterized by a reciprocal translocation t(12;16)(q13;p11) which at the molecular level results infusion of the CHOP and FUS/TLS genes. It is assumed that functional characterization of these genes may provide insight into the molecular pathogenesis of this tumour type. This study describes two new cases of myxoid/round cell LPS having a t(12;22). By reverse transcription-polymerase chain reaction (RT-PCR) it has been shown that this leads to fusion between the CHOP and EWS genes, thus indicating involvement of the EWS gene, at least occasionally, in yet another sarcoma type. Combining these two cases with two others which were recently similarly characterized at the molecular level, their clinicopathological features have been compared with cases having the more usual t(12;16). It was not possible to identify any clinical or pathological differences between these molecular genetic subsets. The relevance or significance of these gene fusion products in myxoid/round cell LPS remains to be determined.

Adult↗
PubMed1997

Variable FHIT transcripts in non-neoplastic tissues.

We used nested reverse transcriptase PCR to investigate the expression of the FHIT gene, a presumptive tumor suppressor gene located in chromosomal band 3p 14.2, in non-neoplastic samples. Multiple transcripts of the FHIT gene were found in peripheral blood lymphocytes, skeletal muscle, and liver of healthy individuals, as well as in a cell line derived from isynovial tissue. The data indicate that variable splicing of the FHIT transcript, leading to deletions of exons and thus anomalous or absent FHIT protein production, occurs frequently in non-neoplastic tissues. Hence, the finding of multiple nonfunctional FHIT transcripts is not tumor-specific and cannot be used as a genetic marker of neoplasia.

Acid Anhydride Hydrolases↗
PubMed1997

Characteristic sequence motifs at the breakpoints of the hybrid genes FUS/CHOP, EWS/CHOP and FUS/ERG in myxoid liposarcoma and acute myeloid leukemia.

We have sequenced the breakpoint regions in one acute myeloid leukemia (AML) with t(16;21)(p11;q22) resulting in the formation of a FUS/ERG hybrid gene and in four myxoid liposarcomas (MLS), three of which had the translocation t(12;16) (q13;p11) and a FUS/CHOP fusion gene and one with t(12;22;20)(q13;q12;q11) and an EWS/CHOP hybrid gene. The breakpoints were localized to intron 7 of FUS, intron 1 of CHOP, an intronic sequence of ERG and intron 7 of EWS. In two MLS cases with t(12;16) and in the AML, the breaks in intron 7 of FUS had occurred close to each other, a few nucleotides downstream from a TG dinucleotide repeat region. The break in the two MLS had occurred in the same ATGGTG hexamer and in the AML 40 nucleotides upstream from the hexamer. The third case of t(12;16) MLS had a break upstream and near a TC-dinucleotide repeat region and a sequence similar to the chi bacterial recombination element was found to flank the breakpoint. In the MLS with the EWS/ CHOP hybrid gene, the break in intron 7 of EWS had occurred close to an Alu sequence. Similarly, in all 4 MLS, the breaks in intron 1 of CHOP were near an Alu sequence. No Alu or other repetitive sequences were found 250 bp upstream or downstream from the break in the ERG intron involved in the AML case. In the AML, the MLS with ESW/CHOP and in one MLS with FUS/CHOP there were one, two and six, respectively, nucleotide identity between the contributing germline sequences in the breakpoint. In the other two MLS cases, two and three extra nucleotides of unknown origin were inserted between the FUS and CHOP sequences. At the junction and/or in its close vicinity, identical oligomers, frequently containing a trinucleotide TGG, were found in both partner genes. Our data thus show that all four genes-FUS, EWS, CHOP and ERG-contain characteristic motifs in the breakpoint regions which may serve as specific recognition sites for DNA-binding proteins and have functional importance in the recombination events taking place between the chromosomes. Different sequence motifs may, however, play a role in each individual case.

Acute Disease↗