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Biomedical subjects

X Cheng

Publications and source records attributed to X Cheng.

At least 19 recordsLinked to original sources
PubMed2006

Proximal femoral density and geometry measurements by quantitative computed tomography: association with hip fracture.

INTRODUCTION: Bone mineral density and geometry measurements by volumetric quantitative computed tomography (vQCT) have been utilized in clinical research studies of aging, pharmacologic intervention and mechanical unloading, but there is relatively little information about the association of these measures with hip fracture. To address this issue, we have carried out a study comparing vQCT parameters in elderly Chinese women with hip fractures with measurements in age-matched controls. MATERIALS AND METHODS: Forty-five women (mean age 74.71+/-5.94) with hip fractures were compared to 66 age-matched control subjects (mean age 70.70+/-4.66). vQCT was employed to characterize the volumetric bone mineral density in cortical, trabecular, and integral volumes of interest in the proximal femur. In addition to the volume of interest measurements, we computed the cross-sectional areas of the femoral neck and intertrochanteric planes, the femoral neck axis length, indices of femoral neck bending and compressive strength, and measures of femoral neck cortical geometry. To determine if cortical geometry measures were associated with hip fracture independently of trabecular vBMD, we carried out multi-variate analyses including these parameters in a logistic regression model. RESULTS AND CONCLUSIONS: All vQCT measurements discriminated between fractured subjects and age-matched controls. There was no significant difference in predictive strength between volumetric and areal representations of BMD and trabecular and integral vBMD showed comparable discriminatory power, although both of these measures were more correlated to fracture status than cortical vBMD. We found that fractured subjects had larger femoral neck cross-sectional areas, consistent with adaptation to lower BMD in these osteoporotic subjects. The larger neck cross-sectional areas resulted in bending strength indices in the fractured subjects that were comparable or larger than those of the control subjects. In multi-variate analyses, reduced femoral neck cortical thickness and buckling ratio indices were associated with fracture status independently of trabecular vBMD.

Aged↗
PubMed2006

Alterations in transporter expression in liver, kidney, and duodenum after targeted disruption of the transcription factor HNF1alpha.

The transcription factor hepatocyte nuclear factor 1alpha (HNF1alpha) is involved in regulation of glucose metabolism and transport, and in the expression of several drug and bile acid metabolizing enzymes. Targeted disruption of the HNF1alpha gene results in decreased Cyp1a2, and Cyp2e1 expression, and increased Cyp4a1 and Cyp7a1 expression, suggesting these enzymes are HNF1alpha target genes. Since hepatic metabolism can be coordinately linked with drug and metabolite transport, this study aims to demonstrate whether HNF1alpha regulates expression of a variety of organic anion and cation transporters through utilization of an HNF1alpha-null mouse model. Expression of 32 transporters, including members of the Oat, Oatp, Oct, Mrp, Mdr, bile acid and sterolin families, was quantified in three different tissues: liver, kidney, and duodenum. The expression of 17 of 32 transporters was altered in liver, 21 of 32 in kidney, and 6 of 32 in duodenum of HNF1alpha-null mice. This includes many novel observations, including marked downregulation of Oats in kidney, as well as upregulation of many Mrp and Mdr family members in all three tissues. These data indicate that disruption of HNF1alpha causes a marked attenuation of several Oat and Oatp uptake transporters in liver and kidney, and increased expression of efflux transporters such as Mdrs and Mrps, thus suggesting that HNF1alpha is a central mediator in regulating hepatic, renal, and intestinal transporters.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Hormonal regulation of renal multidrug resistance-associated proteins 3 and 4 (Mrp3 and Mrp4) in mice.

Multidrug resistance-associated proteins 3 and 4 (Mrp3 and Mrp4) are expressed at much higher levels in female than male kidney. Sex steroids and sex-specific growth hormone (GH) secretion patterns often mediate gender-predominant gene expression. Thus, three models were used to investigate potential endocrine regulation of Mrp3 and Mrp4: (1) gonadectomized (GNX) mice with 17beta-estradiol (E2) or 5alpha-dihydroxytestosterone (DHT) replacement; (2) hypophysectomized (HPX) mice receiving E2, DHT, or simulated male-pattern (MP) or female-pattern (FP) GH secretion; (3) lit/lit mice, which have a spontaneous mutation in the growth-hormone releasing-hormone (GHRH) receptor, with simulated MP- or FP-GH secretion. GNX and HPX decreased Mrp3 mRNA levels compared with intact females. In both respective models E2 administration increased Mrp3 expression in GNX and HPX mice. DHT markedly repressed Mrp3 from GNX+placebo levels, however, this was not observed in the HPX model. In lit/lit mice, Mrp3 expression was lower than in wild-type controls, and MP-GH and FP-GH simulation slightly increased Mrp3 expression. Whereas GNX increased Mrp4 in males to female levels, HPX actually increased Mrp4 expression in both genders +375% and +66%, respectively. In both models DHT markedly repressed Mrp4. Furthermore, Mrp4 was higher in lit/lit than wild-type male mice, and simulation of MP-GH secretion suppressed female-predominant Mrp4 expression. In conclusion, these data indicate that E2 contributes to higher Mrp3 mRNA expression in females, yet a role for androgens in Mrp3 repression cannot be discounted. In contrast, Mrp4 mRNA is higher in females due to repression by both DHT and MP-GH secretion in males.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

Neutralizing IL-7 promotes long-term allograft survival induced by CD40/CD40L costimulatory blockade.

Memory T cells are somewhat resistant to immunosuppresion. They therefore pose a threat to inducing long-term allograft survival. IL-7 is essential for memory T-cell generation. Here, we investigated whether neutralizing IL-7 promotes allograft survival. We found that neutralizing IL-7 alone did not significantly prolong allograft survival. However, blocking both IL-7 and CD154 signaling synergistically prolonged allograft survival. In contrast, neutralizing IL-2 failed to further prolong allograft survival induced by CD40/CD154 costimulatory blockade. Allospecific memory CD8+ T-cell generation was severely impaired under the treatment of anti-IL-7 plus anti-CD154 Ab while administering recombinant IL-7 enhanced CD8+ memory generation even under donor-specific transfusion plus anti-CD154 Ab treatment. Neutralizing IL-7, but not IL-2, together with blocking CD154 synergistically suppressed the proliferation of naïve/effector CD8+ T cells infiltrating grafts. Nevertheless, neutralizing IL-7 did not alter regulatory T-cell generation while neutralizing IL-2 suppressed their generation. Hence, targeting IL-7 represents a new strategy to prolong allograft survival by acting on both naïve and memory T cells. Long-term allograft survival may be achieved by neutralizing IL-7 plus CD40/CD154 blockade, since CD40/CD154 costimulatory blockade prevents acute rejection while neutralizing IL-7 suppresses the generation of memory T cells that persist and mediate late or chronic rejection.

Animals↗
PubMed2005

Clinical and cytogenetic features of 508 Chinese patients with myelodysplastic syndrome and comparison with those in Western countries.

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by ineffective hematopoiesis and leukemia progression. Racial differences may exist on clinical pictures and the molecular events leading to MDS, which are heterogeneous. To better define the clinical and cytogenetic features in Chinese patients, a retrospective multicentric study was performed in 508 MDS cases. Compared with Western countries, Chinese patients showed younger age (median: 49 vs 65-73 years), lower percentages of RARS (2.8 vs 6.6-15.3%), and CMML (5.2 vs 11.7-30.6%). Cytogenetically, among 367 cases with evaluable data, abnormal karyotypes were found in 136 cases, including 56 numerical and 80 structural changes. Incidences of single chromosome 5 and 7 abnormalities were lower than those in Western countries (2.2 vs 17.8-42.5%). However, complex cytogenetic aberrations and chromosome translocations were frequently observed and related to poor prognosis. Both multiple chromosome deletions and translocations were detected in advanced subtypes (RAEB and RAEB-T). Analysis of 200 cases revealed a higher incidence of hepatitis-B-virus infection than that in non-MDS population (21.00 vs 9.75%). This study further confirmed: (1) different genetic/environmental backgrounds between Asian and Western MDS populations; (2) a strong predictive value of cytogenetic abnormalities on disease outcome and involvement of genomic instability in leukemia clone development.

Adolescent↗
PubMed2005

Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress induced activation of cultured rat hepatic stellate cells.

BACKGROUND: Oxidative stress, including the generation of reactive oxygen species (ROS), is involved in hepatofibrogenesis. The authors' previous studies have shown that oestradiol suppresses hepatic fibrosis in animal models and attenuates the activation of cultured rat hepatic stellate cells (HSCs), which possess oestrogen receptor subtype beta and are also activated by ROS. AIMS: To define the mechanisms by which female sex hormones play an antifibrogenic role in activated HSCs, the effects of oestradiol and progesterone on ROS generation processes and intracellular pathways, leading to the activation of HSCs undergoing oxidative stress, was examined. METHODS: HSCs, isolated from rats, were cultured for 7 days with oestradiol or progesterone for 24 hours as pretreatment, and oxidative stress was then induced by exposure to low doses of hydrogen peroxide for another 24 hours. RESULTS: Oestradiol inhibited ROS generation and antioxidant enzyme loss via the suppression of NADH/NADPH oxidase activity, and attenuated hydrogen peroxide induced transforming growth factor-beta1 (TGF-beta1) expression, HSC proliferation and transformation, and the activation of mitogen activated protein kinase (MAPK) pathways and transcription factors. Progesterone exerted a stimulatory effect through the progesterone receptor on the induction of ROS generation processes and intracellular pathways, resulting in TGF-beta1 expression and HSC activation, and fibrogenic effects were inhibited by oestradiol. CONCLUSION: These findings show for the first time that oestradiol inhibits the activation of transcription factors by suppressing ROS generation processes and the MAPK pathways, and inactivates the downstream transcription processes involved in TGF-beta1 expression and HSC activation, whereas progesterone acts in opposition to the favourable effects of oestradiol and its effects are blocked by oestradiol.

Animals↗
PubMed2003

Antibody like peptidomimetics as large scale immunodetection probes.

Antibodies are often used to study the molecular basis of physiologic processes. Despite the widespread applications of monoclonal antibodies (mAb) from basic science to successful therapeutics in clinical settings their use is limited. Production of mAb is often cumbersome and creating diverse and therapeutic amounts of useful mAb is difficult. We have developed a methodology to reduce an antibody into much smaller peptidomimetics and have engineered the mimetics for increased serum half life and affinity. The novel species are termed "antibody like binding peptidomimetics" (ABiP). We developed the Anti-Her2/neu peptidomimetic (AHNP) which is a mimic of Herceptin, a mAb used for advanced breast cancer therapy. The AHNP has been used as a defining tool to develop immunodetection probes that exemplify a general process application. AHNP has been expressed as an oligomeric fusion protein with streptavidin. These Herceptin like ABiPs were used to detect the Her2/neu antigen at extremely low concentrations using the immunodetection amplification technique (IDAT) which our laboratory has also developed. A fully developed highly diverse library of ABiPs represents an alternative for panels of monoclonal antibodies and may also be useful for target validation, antigen detection, therapeutics and as a platform for drug development.

Animals↗
PubMed2002

Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases.

Mechanism-based inhibitors of enzymes, which mimic reactive intermediates in the reaction pathway, have been deployed extensively in the analysis of metabolic pathways and as candidate drugs. The inhibition of cytosine-[C5]-specific DNA methyltransferases (C5 MTases) by oligodeoxynucleotides containing 5-azadeoxycytidine (AzadC) and 5-fluorodeoxycytidine (FdC) provides a well-documented example of mechanism-based inhibition of enzymes central to nucleic acid metabolism. Here, we describe the interaction between the C5 MTase from Haemophilus haemolyticus (M.HhaI) and an oligodeoxynucleotide duplex containing 2-H pyrimidinone, an analogue often referred to as zebularine and known to give rise to high-affinity complexes with MTases. X-ray crystallography has demonstrated the formation of a covalent bond between M.HhaI and the 2-H pyrimidinone-containing oligodeoxynucleotide. This observation enables a comparison between the mechanisms of action of 2-H pyrimidinone with other mechanism-based inhibitors such as FdC. This novel complex provides a molecular explanation for the mechanism of action of the anti-cancer drug zebularine.

Antineoplastic Agents↗
PubMed2002

Kashin-Beck disease in children: radiographic findings in the wrist.

OBJECTIVE: To characterize the features and prevalence of radiographic abnormalities of the wrist in children with Kashin-Beck disease (KBD) and to determine whether the presence of radiographic abnormalities in the wrist correlates with the severity of KBD. DESIGN AND PATIENTS: Two hundred and eight posteroanterior radiographs of the right hand (including wrist) in children with KBD, ranging in age from 4 to 11 years (mean age 7.7 years), from endemic areas of China were reviewed. Carpal bony margins were evaluated for blurring, thinning, irregularity with and without sclerosis, interruption, depression or destruction. The radiocarpal, intercarpal and carpometacarpal joints were assessed for widening or narrowing. The severity of the disease was graded using the hand criteria from the Chinese Radiographic Criteria of KBD Diagnosis, which classifies the following five types according to the location of the hand involved: I, metaphysis; II, diaphysis; III, I+II; IV, metaphysis and epiphysis; V, II+IV. RESULTS: Of the 208 children, 95 had abnormalities in the hand but not in the wrist; 108 had both hand and wrist abnormalities; only five had abnormal wrist findings without any hand abnormalities. Of the 108 cases with wrist abnormalities, all the carpal bones were involved in 33 cases, of which the hand types were either IV or V. However, any individual carpal bone, or combination of bones, may become involved. The carpal bones most likely to show abnormalities were the capitate and the hamate (93%), followed by the triquetrum (31%), the lunate (9%), the scaphoid (6%), and the trapezoid and the trapezium (5%). The pisiform bones were not evaluated because they cannot be seen on the overlapping posteroanterior radiographs. The most commonly involved carpal joint was the midcarpal joint (42%). CONCLUSIONS: Recognizing carpal abnormalities on radiographs is helpful for the diagnosis of KBD and the evaluation of the severity of the disease. The more severe the KBD, the more likely that the carpal bones will be involved. The capitate and hamate are frequently affected if the disease involves the carpal bones.

Bone Diseases, Developmental↗
PubMed2002

A molt-associated chitinase cDNA from the spruce budworm, Choristoneura fumiferana.

Chitinase (CfChitinase) cDNA from the spruce budworm, Choristoneura fumiferana, was cloned using reverse transcription PCR and cDNA library screening. The CfChitinase cDNA was determined to be 2856 nucleotides long with the longest open reading frame made up of 1671 nucleotides that encoded a protein that was 557 amino acid long with a predicted molecular mass of 62 kDa. The deduced amino acid sequence showed 76-79% identity with other lepidopteran chitinases. Northern blots revealed that transcripts of CfChitinase appeared prior to each molt and peaked on the day of ecdysis from the second instar to the pupal stage but disappeared immediately after the molt. No transcripts could be detected in the early first instar prior to the spinning of the hibernaculum or in the diapausing second instars or during the intermolt periods of the other instars. Western blot analysis revealed that the protein appeared 12 h prior to ecdysis and disappeared 12 h after ecdysis from the sixth instar to pupal stage. The 20-hydroxyecdysone analog, tebufenozide (RH5992), induced expression of CfChitinase in the early stage of the sixth instar and caused a precocious and incomplete molt into an extra larval stage. During the sixth instar to the pupal molt, transcripts could be detected only in the epidermis and fat bodies, but not in the midgut. Western blots showed that the protein was present in the epidermis and midgut, but not in the fat bodies. The recombinant protein expressed in Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) showed high levels of chitinolytic activity with an optimal pH range 6-9. Glycosylation appeared to be necessary for the chitinolytic activity and secretion of the recombinant protein.

Amino Acid Sequence↗
PubMed2002

Influence of region of interest and bone size on calcaneal BMD: implications for the accuracy of quantitative ultrasound assessments at the calcaneus.

There is considerable technological diversity among quantitative ultrasound (QUS) devices used to assess osteoporosis. Because the distance between the transducer and the footplate remains constant, the location of the calcaneus measured will vary with foot size. This study was designed to quantify the variation in bone mineral density (BMD) between a manufacturer's region of interest (ROI_M), which is fixed relative to the footplate, and an anatomical region of interest (ROI_A), which is defined as 20% of calcaneal length. The effect of foot length and width on QUS variables measured using two Food and Drug Administration cleared QUS devices, the Sahara (Hologic) and the Achilles+ (Lunar) was assessed. 26 healthy subjects (12 male and 14 female), aged 22-54 years (35.6+/-10 years) and with foot lengths of 21.5 cm to 29.7 cm (25.1+/-2.3 cm) were recruited. QUS assessments were performed at the right calcaneus. In addition, a Hologic 4500 densitometer was used to measure the BMD of the calcaneus in the ROI_M and ROI_A. The sizes of the ROIs were approximated to the sizes of the transducers of the Sahara and Achilles+ devices. The results showed a significant difference in BMD between the two ROI locations for the Sahara device (BMD 0.642+/-0.135 g cm(-2) vs 0.616+/-0.114 g cm(-2), p=0.014), but no significant difference was found in BMD between the two locations for the Achilles device (BMD 0.661+/-0.120 g cm(-2) vs 0.662+/-0.123 g cm(-2), p=0.818). At the ROI_A, there was a significant difference in BMD between the two QUS devices (p<0.001). The correlation between QUS variables and BMD was slightly higher for the ROI_M (r=0.68-0.79, since this is site-matched) than the ROI_A (r=0.59-0.70) for the Achilles device, while for the Sahara device the correlations were r=0.35-0.40 and r=0.51-0.54, respectively. The smaller ROI of the Sahara device resulted in more than 50% of the subjects having BMD differences of greater than 5% between the ROI_A and the ROI_M, compared with only 20% of the subjects on the Achilles device. ROIs containing cortical bone edge and other soft tissues were found in 58% of cases for the Achilles device and 46% of cases for the Sahara device. The greatest differences occurred in very small and very large feet. Calcaneal length correlated significantly with Sahara speed of sound (SOS), and heel width correlated significantly with Achilles SOS. Heel width also correlated significantly with Sahara broadband ultrasound attenuation (BUA) but not Achilles+ BUA. These results suggest that variation in ROI and bone size might affect the accuracy of QUS measurements, since the calcaneus is heterogeneous both in terms of its external geometry and its internal structure and density.

Adult↗
PubMed2001

[Survey of diagnosis and treatment of acute pulmonary embolism in 21 hospitals in China].

OBJECTIVE: To understand the diagnostic and therapeutic status of acute pulmonary embolism in China. METHODS: Clinical data of 297 patients with acute pulmonary embolism were registered in 21 hospitals in China that participated in the "multicenter clinical trial on the efficacy of thrombolytic therapy with urokinase and/ or anticoagulation with low molecular weight heparin (Fluxum) in patients with acute pulmonary embolism" from August 1997 to July 1999. RESULTS: 297 patients with acute pulmonary embolism were diagnosed and treated in the 21 hospitals during 2 years. The total effective rate of thrombolytic therapy was 80.8% (231/286), and the mortality rate was 9.8% (28/286). CONCLUSION: Acute pulmonary embolism is a common disease. In order to decrease the rate of misdiagnosis and missed diagnosis it is necessaryto raise the consciousness of diagnosis. Thrombolytic therapy is an effective first-aid meaure.

Adolescent↗
PubMed2001

[Risk factors of chronic obstructive pulmonary disease in patients with chronic bronchitis].

OBJECTIVE: To explore the risk factors of chronic obstructive pulmonary disease (COPD) in patients with chronic bronchitis in following-up 8 years. METHODS: The baseline survey of the study was carried out on 1,999 patients with chronic bronchitis screened out from 67,251(15 years or more) rural people in 1992. In 2000, 1,114 patients were reexamined by simple random sampling method. RESULTS: 869 (78.0% of 1,114) with complete data entered analysis of this study. Smoking, and family history of COPD were associated significantly positively with the decrement per capita yearly of FEV1(forced expiratory volume in the first second) and/or FEV1/FVC (forced vital capacity) ratio. Ex-smoking decreased the decrement of lung function in smokers. The accumulative incidence of COPD was associated positively with smoking and family history of COPD and negatively with baseline FEV1 and FEV1/FVC. The relative risk of COPD was not significantly different between non-smokers and ex-smokers. CONCLUSION: For Chinese rural patients with chronic bronchitis, aging, smoking, family history of COPD, lower pulmonary function are independent risk factors of COPD while sex is not one. Ex-smoking can almost decrease the relative risk of COPD to the approximative risk level of non-smoking.

Adult↗
PubMed2001

Subsite-specific incidence rate and stage of disease in colorectal cancer by race, gender, and age group in the United States, 1992-1997.

BACKGROUND: Subsite specific incidence rates of colorectal cancer vary considerably by age, gender, and race. This variation may be related not only to distinctions in exposure to genetic and environment factors but also to current strategies of early detection screening. Patterns of stage of disease in anatomic subsite may reflect the effect of screening. This study used the largest aggregation of cancer incidence data in the U.S. to examine subsite specific incidence rates of colorectal cancer and the relation of stage of disease to anatomic subsites by race, gender, and age group. METHODS: Data on the incidence of invasive colorectal cancer were obtained from 28 population-based central cancer registries. Age-specific and age-adjusted rates and stage distributions were analyzed by subsite, race, and gender. RESULTS: The impact of screening can be observed in the percentage of localized disease, which increased from 31.9% among cancers in the proximal colon to 37.0% in the descending colon to 41.5% in the distal colorectum. Within the same subsite, blacks were less likely than whites to receive a diagnosis of localized disease and more likely to receive a diagnosis of distant disease whereas stage distributions were approximately the same for males and females. Blacks were more likely than whites to receive a diagnosis of proximal colon cancer than distal colorectal cancer. The male-to-female rate ratios progressively increased from the proximal colon to the distal colorectum. The ratios of proximal-to-distal colorectal cancer gradually increased with advancing age. CONCLUSIONS: Differentials in stage of disease by subsites indicate a need for a targeted effort at early detection of cancer in the proximal colon. Risk factors and higher risk populations for colorectal cancers in each subsite need to be studied further to guide actions for improving the efficacy of screening.

Age Factors↗
PubMed2001

AdoMet-dependent methylation, DNA methyltransferases and base flipping.

Twenty AdoMet-dependent methyltransferases (MTases) have been characterized structurally by X-ray crystallography and NMR. These include seven DNA MTases, five RNA MTases, four protein MTases and four small molecule MTases acting on the carbon, oxygen or nitrogen atoms of their substrates. The MTases share a common core structure of a mixed seven-stranded beta-sheet (6 downward arrow 7 upward arrow 5 downward arrow 4 downward arrow 1 downward arrow 2 downward arrow 3 downward arrow) referred to as an 'AdoMet-dependent MTase fold', with the exception of a protein arginine MTase which contains a compact consensus fold lacking the antiparallel hairpin strands (6 downward arrow 7 upward arrow). The consensus fold is useful to identify hypothetical MTases during structural proteomics efforts on unannotated proteins. The same core structure works for very different classes of MTase including those that act on substrates differing in size from small molecules (catechol or glycine) to macromolecules (DNA, RNA and protein). DNA MTases use a 'base flipping' mechanism to deliver a specific base within a DNA molecule into a typically concave catalytic pocket. Base flipping involves rotation of backbone bonds in double-stranded DNA to expose an out-of-stack nucleotide, which can then be a substrate for an enzyme-catalyzed chemical reaction. The phenomenon is fully established for DNA MTases and for DNA base excision repair enzymes, and is likely to prove general for enzymes that require access to unpaired, mismatched or damaged nucleotides within base-paired regions in DNA and RNA. Several newly discovered MTase families in eukaryotes (DNA 5mC MTases and protein arginine and lysine MTases) offer new challenges in the MTase field.

Binding Sites↗
PubMed2001

Structures of yeast ARF2 and ARL1: distinct roles for the N terminus in the structure and function of ARF family GTPases.

Structures were determined by x-ray crystallography for two members of the ADP-ribosylation factor (ARF) family of regulatory GTPases, yeast ARF1 and ARL1, and were compared with previously determined structures of human ARF1 and ARF6. These analyses revealed an overall conserved fold but differences in primary sequence and length, particularly in an N-terminal loop, lead to differences in nucleotide and divalent metal binding. Packing of hydrophobic residues is central to the interplay between the N-terminal alpha-helix, switch I, and the interswitch region, which along with differences in surface electrostatics provide explanations for the different biophysical and biochemical properties of ARF and ARF-like proteins.

ADP-Ribosylation Factors↗
PubMed2001

Increased genetic damage in oral leukoplakia from high risk sites: potential impact on staging and clinical management.

BACKGROUND: Two staging systems for oral leukoplakias have been proposed to better predict prognosis. Although one system includes site as an independent determinant, its use is controversial. METHODS: Recent studies have shown that loss of heterozygosity (LOH) in oral premalignancies is associated with risk of progression. The authors analyzed 127 oral dysplasias for LOH on 3 chromosome arms (3p, 9p, and 17p). The lesions included 71 from the floor of mouth, ventrolateral tongue, and soft palate complex (designated high risk [HR] sites) and 56 from the rest of the oral cavity (low risk [LR] sites). RESULTS: Dysplasias from HR sites contained significantly higher LOH frequencies than LR sites (percentage with any loss, P = 0.0004; percentage with multiple losses, P = 0.0001; percentage loss on each of the arms, P < 0.05). Loss on 3p and/or 9p, a pattern associated with a 24-fold increased risk of progression (Rosin MP, Cheng X, Poh C, Lam WL, Huang Y, Lovas J, et al. Use of allelic loss to predict malignant risk for low-grade oral epithelial dysplasia. Clin Cancer Res 2000;6:357-62) was more frequent among HR lesions (P = 0.0005). Loss of heterozygosity frequencies were elevated at HR sites among both genders and among smokers and nonsmokers. For different histologic groups, LOH frequencies were elevated for HR sites in mild dysplasias (P < 0.05) and moderate dysplasias (marginal significance, P = 0.06), but not in severe dysplasias/carcinoma in situ. CONCLUSIONS: Anatomic location of mild and moderate oral dysplasias in Western populations may be an important diagnostic indicator because lesions at HR sites have a greater tendency to include genetic alterations associated with elevated risk of progression.

Adult↗