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PubMedDate not supplied

The effect of trastuzumab/docatexel combination on breast cancer angiogenesis: dichotomus effect predictable by the HIFI alpha/VEGF pre-treatment status?

In this study we describe and discuss the dichotomous effects of docetaxel trastuzumab (Herceptin)/docetaxel therapy on the angiogenic molecular profile in two patients with her-2 + chemo-resistant recurrent breast carcinoma. In the first case, an intensification of angiogenesis occurred following therapy, accompanied by an impressive increase of the cancer cell proliferation index. This tumor did not express HIF1 alpha and shared a HIF-independent VEGF overexpression, which remained unaffected by therapy. An intensified formation of thymidine phosphorylase (TP)-rich stroma, presumably a response to docetaxel, shows a TP-dependent angiogenic response. In the second patient, VEGF and HIF1 alpha were down-regulated in post-treatment biopsies and this was accompanied by a sharp reduction of the vascular density and of the cancer cell proliferation rate. In both cases, c-erbB-2 expression was abrogated by Herceptin. Taking into account that Herceptin down-regulates VEGF through reduction of HIF1 alpha synthesis, this clinical study provides evidence that an anti-angiogenic effect from Herceptin/Docetaxel therapy is expected only in tumors with HIF1 alpha-dependent VEGF overexpression. In contrast, HIF1 alpha-independent VEGF angiogenic activity cannot be abrogated by Herceptin. Docetaxel mediated up-regulation of TP in the tumoral stroma may, on the contrary, result in angiogenesis intersification and rapid tumor relapse. Such an effect should be of clinical importance since Herceptin/Docetaxel-based regimens are currently evaluated for the adjuvant therapy of her-2 + breast cancer patients. Studying the Herceptin-induced phenotypic changes of tumors could lead to the identification of specific molecular profiles that bring about diverging angiogenic responses. Adjustment of the chemotherapy regimen accordingly would prove of clinical importance.

Antibodies, Monoclonal↗
PubMed1992

The effect of fetal hypophysectomy with or without ACTH replacement on the molecular weight profile of enkephalin-containing peptides in the adrenal medulla of the fetal sheep.

We have investigated the possible role of the fetal pituitary and ACTH in the control of the synthesis and post-translational processing of the enkephalin precursor, proenkephalin A (proEnk A), in the fetal sheep adrenal gland in late gestation. Fetal hypophysectomy (n = 8) or sham operations (n = 4) were performed between 109 and 118 days of gestation. At 138-139 days, either ACTH(1-24) (10.5 micrograms/0.24 ml saline per h, n = 4) was infused intravenously for 72 h into hypophysectomized fetal sheep or 0.9% (w/v) NaCl alone (0.24 ml/h, n = 4) was infused for 72 h into hypophysectomized fetal sheep and sham-operated animals. At the end of the infusion the pregnant ewe was killed and left or right adrenal glands (n = 12) were collected from the fetal sheep that were intact and given saline (Intact + sal; n = 4), hypophysectomized and given saline (Hx + sal; n = 4) and hypophysectomized and given ACTH (Hx + ACTH; n = 4). Each adrenal was homogenized in acid (acetic acid (1 mol/l)/HCl (20 mmol/l)/2-mercaptoethanol (0.2%)). After centrifugation, the supernatant was loaded onto a Sephadex G-75 column (2.0 x 50 cm), eluted at 80 ml/24 h and fractions were collected (5 ml, n = 42). An aliquot of each fraction (2 ml) was dried down prior to enzymatic digestion (trypsin/carboxypeptidase B) and oxidation with H2O2, and assay for methionine-O-enkephalin (immunoreactive Met-O-Enk).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed2006

Human bocavirus infection in young children in the United States: molecular epidemiological profile and clinical characteristics of a newly emerging respiratory virus.

BACKGROUND: Human bocavirus (HBoV) is a newly identified human parvovirus that was originally identified in the respiratory secretions of children with respiratory tract disease. To further investigate the epidemiological profile and clinical characteristics of HBoV infection, we screened infants and children <2 years of age (hereafter referred to as "children") for HBoV. METHODS: Children for whom respiratory specimens submitted to a diagnostic laboratory tested negative for respiratory syncytial virus, parainfluenza viruses (types 1-3), influenza A and B viruses, and adenovirus, as well as asymptomatic children, underwent screening for HBoV by use of polymerase chain reaction (PCR). Respiratory specimens were obtained from the children from 1 January 2004 through 31 December 2004. RESULTS: Twenty-two (5.2%) of the 425 children who had a respiratory specimen submitted to the diagnostic laboratory and 0 of the 96 asymptomatic children were found to be positive for HBoV by PCR (P=.02). Fever, rhinorrhea, cough, and wheezing were observed in > or =50% of the HBoV-positive children. Of the 17 children who had chest radiography performed, 12 (70.6%) had abnormal findings. HBoV appeared to have a seasonal distribution. Nucleotide polymorphisms were detected in the viral capsid protein (VP) 1/VP2 genes. Two distinct HBoV genotypes circulated during the study period. CONCLUSIONS: HBoV is circulating in the United States and is associated with both upper and lower respiratory tract disease in infants and young children.

Bocavirus↗
PubMed2005

Expression profile and molecular genetic regulation of cyclin D1 expression in epithelioid sarcoma.

Epithelioid sarcoma is a distinctive, aggressive soft tissue tumor typically presenting as a subcutaneous or deep dermal mass in the distal extremities of young adults. Molecular genetic data of well-characterized cases of epithelioid sarcoma are sparse. A recent cytogenetic study of epithelioid sarcoma by conventional metaphase comparative genomic hybridization reported recurrent gains at chromosome 11q13, a region containing many genes, including the cyclin D1 gene. Cyclin D1 is a positive cell cycle regulator that is overexpressed in a variety of neoplasms, including mantle cell lymphoma and breast carcinoma. The objective of this study was to examine cyclin D1 expression in epithelioid sarcoma. Of 24 cases evaluated, 23 (96%) displayed cyclin D1 nuclear expression using immunohistochemical evaluation. Eight cases, which expressed cyclin D1 by immunohistochemistry, were evaluated by fluorescence in situ hybridization (FISH) and RNA in situ hybridization (RISH) for amplification of the cyclin D1 gene and messenger RNA (mRNA) expression, respectively. Seven of eight cases showed a typical eusomic state. One case showed pseudoamplification due to aneusomy/polysomy. There was no evidence of cyclin D1 gene amplification or messenger RNA overexpression detected by FISH or RNA in situ hybridization analyses, respectively. Our data clearly demonstrate that cyclin D1 protein is upregulated in epithelioid sarcoma, suggesting a role for this cell cycle regulator in the pathogenesis of epithelioid sarcoma. The high level of cyclin D1 protein expression in epithelioid sarcoma appears to be regulated by translational and/or post-translational mechanisms.

Cyclin D1↗
PubMed2005

Molecular epidemiological profile of rotavirus in South Korea, July 2002 through June 2003: emergence of G4P[6] and G9P[8] strains.

To determine the distribution of rotavirus strain genotypes in South Korea, rotavirus-positive stool specimens were collected from July 2002 through June 2003 at 8 hospitals in the Korean Rotavirus Strain Surveillance Network, and they were genotyped by means of reverse-transcription polymerase chain reaction. The globally uncommon G4P[6] type was the most prevalent type identified among strains (27% of strains), the newly emerging G9P[8] strain accounted for 11% of strains, and the globally common genotypes (i.e., G1P[8], G2P[4], G3P[8], and G4P[8]) constituted 55% of the strains characterized. Ninety percent of G4P[6] strains were detected in specimens obtained from neonates. Common genotypes were responsible for the rotavirus epidemic that began in January 2003 and ended in May 2003; however, an early peak in infections with the G4P[6] strain occurred from August through October 2002, and infections with this strain were detected throughout the remaining study period. G4P[6] strains were most commonly identified at 6 urban health care centers, but they were absent from 2 rural health care centers. The newly emerging strain G9P[8] represented a relatively greater proportion of strains identified at a hospital in the central region of Korea and at 2 hospitals in the southern region. The identification of novel rotavirus genotypes in this laboratory-based surveillance study underscores the importance to public health of continued strain surveillance among children for whom prevention of rotavirus infection by vaccination might be considered.

Child, Preschool↗
PubMed1982

Molecular-weight profiles of immunoreactive corticotropin in the hypothalamus of the aging rat.

Extracts of the medial basal hypothalamus (MBH), the preoptic anterior hypothalamus (POA), or the pituitary gland of young (4-month-old) and old (18-month-old) female rats were fractionated on columns of Sephadex G-75 superfine. Five forms of immunoreactive corticotropin (ACTHi) were found in the MBH or POA: greater than 40K, 30-40K, 20-30K, 5.7K, and 4.5K. In contrast, 4 forms of ACTHi were found in the pituitary gland: 30-40K, 20-30K, 5.7K, and 4.5K. Thus, hypothalamic tissue contains a large form of ACTH (greater than 40K ACTH) which is not present in the pituitary gland. We tentatively identified greater than 40K ACTH as a large form of pro-opiocortin, 30-40K ACTH as pro-opiocortin, 20-30K ACTH as ACTH biosynthetic intermediate, 5.7K ACTH as glycosylated ACTH 1-39, and 4.5K ACTH as ACTH 1-39. The content of ACTHi in the MBH and POA of old rats was lower than that of young rats. Nevertheless, regardless of the age of the animals, the fractional amount of 30-40K ACTHi was high in the MBH (a region that includes the presumed site of biosynthesis of pro-opiocortin) compared to that in the POA (a region that is distant to the site of biosynthesis of pro-opiocortin). Moreover, the reduced fractional amount of 30-40K ACTHi in the POA was associated with an increased fractional amount of greater than 40K, 20-30K, 5.7K, and 4.5K ACTHi. These findings are consistent with a precursor-product relationship between the 30-40K ACTHi and 20-30K ACTHi, 5.7K ACTHi, and 4.5K ACTHi.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1990

The molecular weight profile of enkephalin-containing peptides in the sheep adrenal gland changes during development.

We have measured the content of enkephalin-containing peptides (ENK-containing peptides) in adrenal gland extracts from fetal sheep between 68-142 days gestation and from adult sheep. We investigated whether there are changes in the post-translational processing of ENK-containing peptides in the fetal sheep adrenal gland with increasing gestational age. ENK-containing peptides in adrenal extracts from fetal sheep (68-142 days gestation) and adult sheep were separated using gel filtration chromatography and the ENK immunoreactivity (ENK-IR) was measured using RIAs for Met-enkephalin-Arg6,Phe7 immunoreactivity (MERF-IR) and Met-o-enk immunoreactivity (MET-O-ENK-IR). The MET-O-ENK-IR in fetal and adult sheep adrenal extracts was distributed in four main peaks, which corresponded to mol wt (MW) ranges of more than 12, 7-12, 3-7, and less than 3 kDa. There was a significant increase (P less than 0.05) in the total ENK-IR content of the fetal adrenal between 68-78 (42.4 +/- 19.2 ng/adrenal) and 100-121 (320.1 +/- 142.6 ng/adrenal) days gestation. There was also a significant increase in the proportion of MET-O-ENK-IR and MERF in the less than 3 kDa range between 68-78 (MET-O-ENK, 6.8 +/- 2.7%; MERF, 10.3 +/- 1.4%) and 100-121 (MET-O-ENK, 24.4 +/- 5.1%; MERF, 26.2 +/- 5.8%) days gestation, with an associated decrease in the ratio of ENK-containing peptides in the high MW form (i.e. greater than 3 kDa) compared to those in the low MW (less than 3 kDa) forms (10.4 +/- 2.5 at 68-78 days gestation; 4.2 +/- 1.1 at 100-121 days gestation). There was also a significant decrease in the percentage of MET-O-ENK in the 12 kDa range after 139 days gestation (125-135 days gestation, 20.4 +/- 2.2%; 139-142 days gestation, 4.0 +/- 2.1%). Therefore, there is an increase in the proportion of the low MW forms of ENK-containing peptides in the fetal sheep adrenal with advancing gestational age, which may reflect changes in the post-translational processing of the precursor proenkephalin-A during development.

Adrenal Glands↗
PubMed2004

Protein expression profiling identifies molecular targets of quercetin as a major dietary flavonoid in human colon cancer cells.

A high dietary intake of plant foods is thought to contribute to the prevention of colorectal cancers in humans and flavonoids as part of such a diet are considered to contribute to those protective effects. Quercetin is a major dietary flavonoid consumed with a diet rich in onions, tea, and apples. We used HT-29 human colon cancer cells and investigated the effects of quercetin on proliferation, apoptosis, and differentiation as processes shown to be disregulated during cancer development. To identify the cellular targets of quercetin action, two-dimensional gel electrophoresis was performed and proteins altered in expression level after quercetin exposure of cells were identified by mass spectrometry of peptide fragments generated by tryptic digestion. Quercetin inhibited the proliferation of HT-29 cells with an IC(50)-value of 81.2 +/- 6.6 microM. Cell differentiation based on surface expression of alkaline phosphatase was enhanced 4-fold and the activity of the pro-apoptotic effector caspase-3 increased 3-fold. Those effects were associated with the regulation of heat-shock proteins and annexins shown to both play a crucial role in the process of apoptosis. Cytoskeletal caspase substrates were found as regulated as well and various proteins involved in intermediary metabolism and in gene regulation showed altered steady-state expression levels upon quercetin treatment of cells. In conclusion, quercetin alters the levels of a variety of proteins involved in growth, differentiation, and apoptosis of colon cancer cells. Their identification as molecular targets of quercetin may explain the anti-cancer activities of this flavonoid.

Apoptosis↗
PubMed2006

Molecular cytogenetic profiling of complex karyotypes in primary myelodysplastic syndromes and acute myeloid leukemia.

Complex chromosomal aberrations are present in < or =30% of patients with primary myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) and are associated with a poor prognosis. Specific alterations in complex karyotypes are difficult to define by conventional cytogenetics alone. To obtain a more comprehensive view of the recurrent aberrations, we performed spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) with selected probes on bone marrow samples from 17 patients with primary MDS and 3 with primary AML. All cases had chromosome 5 alterations. Two different types of 5q loss were identified: unbalanced translocations and interstitial deletions, or del(5q), each occurring in 10 patients. The most frequent additional chromosome aberrations were -3/-3p/-3q, -7/7q-, +8, 13q-, -16, 17p-, -18/18p-, -20/20q-, and +21q, each occurring in 25%. In the five cases with gain of 21q, involvement of the AML1 gene was excluded. Unbalanced 5q translocations occurred more often in combination with monosomy 3 and 7 and with gain of 21q, whereas del(5q) was associated more often with -1p and trisomy 8. A detailed analysis of specific breakpoints and deletions revealed recurrent involvement of specific chromosomal bands harboring known tumor suppressor genes or oncogenes. Analysis of large numbers of MDS and AML cases in a similar detailed manner with SKY and FISH will reveal whether new subgroups can be identified according to their genetic alterations. Correlation with clinical parameters may reveal the prognostic significance of these genetic subgroups.

Acute Disease↗
PubMed1997

The serological profile and molecular basis of a new partial D phenotype, DHR.

BACKGROUND AND OBJECTIVES: The Rh D antigen comprises a mosaic of at least 30 epitopes expressed on a 30-kD non-glycosylated Rh D polypeptide. The equivalent Rh CeEe polypeptide expressing the Rh C/c and E/e antigens differs in only 36 of the 417 amino acid residues. Partial D individuals have been described who fail to express a number of D epitopes. MATERIALS AND METHODS: Serologic methods were applied with monoclonal anti-D to map epitopes on the red cells of a proposita aberrant D typing. Polymerase chain reaction (PCR) and DNA sequencing were also done. RESULTS: DNA sequence analysis derived by RT-PCR using total RNA isolated from peripheral blood of this person suggests two mechanisms for the genetic basis of this variants: one here gene conversion events result in the replacement of RHD gene exons with the equivalent RHCE exons; the second where point mutation in the RHD gene generates an amino acid substitution in the Rh D protein. CONCLUSIONS: We report here a new partial D, DHR, where a single point mutation (G to A at nucleotide 686) in exon 5 of the RHD gene results in a conservative amino acid substitution (Arg229Lys), in the predicted Rh D protein. This residue is localised on the fourth predicted exofacial loop of the Rh D polypeptide as determined by hydropathy analysis. This substitution results in the lack of epD 1, 2, 12 and 20 (30 epitope model) and indicates the involvement of loop 4, and in particular the requirement of Arg229, in the expression of these epitopes.

Amino Acid Substitution↗
PubMedDate not supplied

2'-Fluoro-4'-thio-2',3'-unsaturated nucleosides: anti-HIV activity, resistance profile, and molecular modeling studies.

Both D- and L-2'-fluoro-4'-thio-2',3'-unsaturated nucleosides were synthesized and their anti-HIV activity against the drug sensitive virus and lamivudine-resistant mutant (M184V) were evaluated. In vitro antiviral evaluation indicated that the L-isomers are more potent than the D-isomers, but unfortunately all were cross-resistant with 3TC. Molecular modeling studies revealed that the unnatural sugar moiety of the L-nucleosides as well as 4'-sulfur atom of the D-isomer has a steric conflict with the bulky side chain of valine 184, resulting in cross-resistance.

Anti-HIV Agents↗
PubMed2004

Pathogenic profiles and molecular signatures of antinuclear autoantibodies rescued from NZM2410 lupus mice.

Two outstanding questions concerning antinuclear antibodies (ANAs) in lupus involve their pathogenic potential and their molecular signatures. To address these questions, a panel of 56 antinuclear and 47 nonnuclear binding monoclonal antibodies was rescued from four seropositive NZM2410 lupus mice. The monoclonals varied in their reactivity to nucleosomes, ssDNA, dsDNA, and glomerular substrate. A large fraction of the antibodies demonstrated apparent polyreactivity (to DNA, histones, and glomerular antigens) due to bound, DNase-1 sensitive nuclear antigenic bridges. Although nephrophilic immunoglobulin (Ig) M and IgG antibodies were the most pathogenic, the dsDNA-binding antibodies were modestly so; in contrast, antinucleosome antibodies were clearly not pathogenic. Compared with the nonnuclear antigen-binding monoclonal antibodies rescued from the same mice, ANAs exhibited increased utilization of VH5/7183 genes and highly cationic heavy chain (HC) CDR3 regions. Most intriguingly, the CDR3 regions of the ANAs exhibited alternating arginine/lysine peaks at H96, H98, and H100, with neutral troughs at H95, H97, and H99. To summarize, glomerular-binding anti-dsDNA antibodies appear to be the most pathogenic variety of lupus autoantibodies. The presence of an alternating charge pattern in their HC CDR3 regions appears to be a prominent hallmark of ANAs.

Amino Acid Sequence↗
PubMed1986

Antibiotic resistance profiles and molecular epidemiology of Salmonella typhimurium and S. dublin, mainly from cattle.

Among 130 strains of Salmonella typhimurium and 191 strains of S. dublin, all isolated from cattle in the early 1980s, 80% and 63%, respectively, were resistant to one or more (up to three) antibiotics. Monoresistance to sulphonamides was most common. In 169 strains of the two serotypes from 1985 the antibiotic resistance load was of a similar size. The latter batch was not studied with respect to plasmids. In the strains from 1980 and 1981 the plasmid load was analysed by conjugation, transformation, extraction of plasmid DNA and subsequent electrophoresis in agarose gels. Plasmid DNA from 38 strains was further analysed by restriction with endonuclease EcoRI. On the basis of this the strains were classified into four groups: two of S. typhimurium, one of S. dublin and one group of both serotypes. This suggested that dissemination of strains and plasmids mainly occurred through clonal spread of strains.

Animals↗
PubMed2001

Molecular phylogenetic profiling of prokaryotic communities in guts of termites with different feeding habits.

Termites are an important group of terrestrial insects that harbor an abundant gut microbiota, many of which contribute to digestion, termite nutrition and gas (CH(4), CO(2) and H(2)) emission. With 2200 described species, termites also provide a good model to study relationships between host diet and gut microbial community structure and function. We examined the relationship between diet and gut prokaryotic community profiles in 24 taxonomically and nutritionally diverse species of termites by using nucleic acid probes targeting 16S-like ribosomal RNAs. The relative abundance of domain-specific 16S-like rRNAs recovered from gut extracts varied considerably (ranges: Archaea (0-3%); Bacteria (15-118%)). Although Bacteria were always detectable and the most abundant, differences in domain-level profiles were correlated with termite diet, as evidenced by higher relative abundances of Archaea in guts of soil-feeding termites, compared to those of wood-feeding species in the same family. The oligonucleotide probes also readily distinguished gut communities of wood-feeding taxa in the family Termitidae (higher termites) from those of other wood-feeding termite families (lower termites). The relative abundances of 16S-like archaeal rRNA in guts were positively correlated with rates of methane emission by live termites, and were consistent with previous work linking high relative rates of methanogenesis with the soil (humus)-feeding habit. Probes for methanogenic Archaea detected members of only two families (Methanobacteriaceae and Methanosarcinaceae) in termite guts, and these typically accounted for 60% of the all archaeal probe signal. In four species of termites, Methanosarcinaceae were dominant, a novel observation for animal gut microbial communities, but no clear relationship was apparent between methanogen family profiles and termite diet or taxonomy.

Journal Article↗
PubMed2000

Primary hyperaldosteronism in essential hypertensives: prevalence, biochemical profile, and molecular biology.

There is evidence that primary aldosteronism (PA) may be common in patients with essential hypertension (EH) when determinations of serum aldosterone (SA), plasma renin activity (PRA), and the SA/PRA ratio are used as screening. An inherited form of primary hyperaldosteronism is the glucocorticoid-remediable aldosteronism (GRA) caused by an unequal crossing over between the CYP11B1 and CYP11B2 genes that results in a chimeric gene, which has aldosterone synthase activity regulated by ACTH. The aim of this study was to evaluate the prevalence of PA and the GRA in 305 EH patients and 205 normotensive controls. We measured SA (1-16 ng/dL) and PRA (1-2.5 ng/mL x h) and calculated the SA/PRA ratio in all patients. A SA/PRA ratio level greater than 25 was defined as being elevated. PA was diagnosed in the presence of high SA levels (>16 ng/dL), low PRA levels (<0.5 ng/mL x h), and very high SA/PRA ratio (>50). Probable PA was diagnosed when the SA/PRA ratio was more than 25 but the other criteria were not present. A Fludrocortisone test was done to confirm the diagnosis. GRA was differentiated from other forms of PA by: the aldosterone suppression test with dexamethasone, the high levels of 18-hydroxycortisol, and the genetic detection of the chimeric gene. In EH patients, 29 of 305 (9.5%) had PA, 13 of 29 met all the criteria for PA, and 16 of 29 were initially diagnosed as having a probable PA and confirmed by the fludrocortisone test. Plasma potassium was normal in all patients. The dexamethasone suppression test was positive for GRA in 10 of 29 and 18-hydroxycortisol levels were high in 2 of 29 patients who had also a chimeric gene. In normotensive subjects, 3 of 205 (1.46%) had PA, and 1 of 205 had a GRA. In summary, we found a high frequency of normokalemic PA in EH patients. A high proportion of PA suppressed SA with dexamethasone, but only a few had a chimeric gene or high levels of 18-hydroxycortisol. These results emphasize the need to further investigate EH patients.

Aldosterone↗
PubMed2004

Tissue microarrays.

The identification of disease-related genes is a major focus of modern biomedical research. Recent techniques, including array-based platforms for molecular profiling of disease tissues such as DNA arrays for expression profiling or matrix comparative genomic hybridization, allow for the comprehensive screening of the whole genome in a single experiment. Consequently, thousands of candidate genes have already been identified that may be linked to disease development and progression, and the process of lead discovery continues unimpeded. The evaluation of the clinical value of such leads is challenging because thousands of well-characterized tissue specimens must be analyzed. Tissue microarray (TMA) technology enables high-throughput tissue analyses to keep pace with the rapid process of lead discovery. With this technique, up to 1000 minute tissue samples are brought into an array format and analyzed simultaneously. The TMA technology is a fast, cost-effective, and statistically powerful method that will substantially facilitate translational research.

Animals↗
PubMed2004

Molecular cytogentic profiles of hepatitis C infection in patients at Sharkia Governorate, Egypt.

It has become apparent that hepatitis C virus (HCV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC) worldwide. The precise mechanism by which HCV causes HCC is not known. Unlike the hepatitis B virus (HBV), HCV is not a DNA virus and does not become integrated within the genome of hepatocytes. It is more likely that HCC occurs against a background of inflammation and regeneration, associated with liver injury due to chronic hepatitis. In this study, 40 of paraffin blocks liver tissues from HCV-PCR positive patients (HBV seronegative) were examined using DNA image cytometry to evaluate its role in diagnosing HCC associated with HCV infection. Fluorescent in situ hybridization (FISH) technique using LSIZNF 217 chromosome 20q 13.2 probe was applied as well. The results showed high percentage of S-phase fraction in cases of G2S2 and G3S3 with DNA diploidy. Only two cases of G3S3 showed DNA aneuploidy with severe amplification of chromosome 20q 13.2. Consequently, DNA imaging cytometry is a good approach in differentiating dysplasia from well-differentiated HCC on top of HCV infection. In conclusion HCV has an acquired role in development of HCC through amplification of the aggressive tumor behavior oncogene LSIZNF 217 at chromosome 20q 13.2.

Adult↗