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1.
Cytopathology ; 33(3): 344-349, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34957617

RESUMEN

INTRODUCTION: Molecular testing for genetic alterations in thyroid neoplasms, including BRAF V600E (BRAF) mutation, are often applied to thyroid aspirates falling into the Bethesda System for Reporting Thyroid Cytopathology indeterminate categories. Current methods typically use dedicated aspirated material, without morphological determination of containing the cells of interest and may be of elevated cost. We describe our experience with BRAF mutation analysis on material obtained from Papanicolaou (PAP)-stained ThinPrep® (TP) slides. METHODS: Eighty-three cases collected between 2012 and 2019 with more than 100 cells were selected. An electronic record of a whole slide scan was made for each case before testing. The coverslips were removed, and DNA was extracted from material scraped from each slide using the Qiagen QIAamp DNA FFPE Tissue Kit. BRAF testing was performed using a highly sensitive mutation detection assay, either COLD-PCR, castPCR, or droplet digital PCR. RESULTS: Fourteen out of 83 cases had a BRAF mutation. Of these, 8 were classified as atypia of undetermined significance or suspicious for malignancy in which follow-up showed conventional papillary thyroid carcinoma in 5 out of 6 cases. The specificity and positive predictive value were 97% and 91%, respectively. CONCLUSIONS: BRAF mutation analysis can be performed on material obtained from routine clinical PAP-stained TP slides. As a first step, this unconventional effective approach may reduce costs related to the molecular evaluation of thyroid nodule aspirates and provides the opportunity for cytomorphological confirmation that the cells of interest are present in material submitted for BRAF mutation analysis.


Asunto(s)
Neoplasias de la Tiroides , Nódulo Tiroideo , Análisis Mutacional de ADN , Humanos , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/patología
2.
Emerg Infect Dis ; 21(1): 103-6, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25531075

RESUMEN

We detected WU polyomavirus (WUPyV) in a bronchoalveolar lavage sample from lungs transplanted into a recipient with Job syndrome by using immunoassays specific for the WUPyV viral protein 1. Co-staining for an epithelial cell marker identified most WUPyV viral protein 1-positive cells as respiratory epithelial cells.


Asunto(s)
Síndrome de Job/virología , Infecciones por Polyomavirus/diagnóstico , Mucosa Respiratoria/virología , Adulto , Femenino , Células HEK293 , Humanos , Síndrome de Job/cirugía , Trasplante de Pulmón , Poliomavirus/genética , Poliomavirus/aislamiento & purificación , Infecciones por Polyomavirus/virología
3.
BMC Cancer ; 13: 578, 2013 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-24308314

RESUMEN

BACKGROUND: Esophageal cancer is the sixth leading cause of cancer death worldwide; current early detection screening tests are inadequate. Esophageal balloon cytology successfully retrieves exfoliated and scraped superficial esophageal epithelial cells, but cytologic reading of these cells has poor sensitivity and specificity for detecting esophageal squamous dysplasia (ESD), the precursor lesion of esophageal squamous cell carcinoma (ESCC). Measuring telomere length, a marker for chromosomal instability, may improve the utility of balloon cytology for detecting ESD and early ESCC. METHODS: We examined balloon cytology specimens from 89 asymptomatic cases of ESD (37 low-grade and 52 high-grade) and 92 age- and sex-matched normal controls from an esophageal cancer early detection screening study. All subjects also underwent endoscopy and biopsy, and ESD was diagnosed histopathologically. DNA was extracted from the balloon cytology cells, and telomere length was measured by quantitative PCR. A receiver operating characteristic (ROC) curve was plotted for telomere length as a diagnostic marker for high-grade dysplasia. RESULTS: Telomere lengths were comparable among the low- and high-grade dysplasia cases and controls, with means of 0.96, 0.96, and 0.92, respectively. The area under the ROC curve was 0.55 for telomere length as a diagnostic marker for high-grade dysplasia. Further adjustment for subject characteristics, including sex, age, smoking, drinking, hypertension, and body mass index did not improve the use of telomere length as a marker for ESD. CONCLUSIONS: Telomere length of esophageal balloon cytology cells was not associated with ESCC precursor lesions. Therefore, telomere length shows little promise as an early detection marker for ESCC in esophageal balloon samples.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/diagnóstico , Detección Precoz del Cáncer , Neoplasias Esofágicas/diagnóstico , Telómero/genética , Área Bajo la Curva , Carcinoma de Células Escamosas/genética , Estudios de Casos y Controles , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Homeostasis del Telómero
5.
Diagn Cytopathol ; 49(1): E31-E35, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32770824

RESUMEN

BACKGROUND: Adenoid cystic carcinoma (AdCC) is an uncommon malignancy of the salivary gland characterized by slow growth, increased risk of recurrence and poor prognosis. The annual incidence in the United States is approximately 1200 cases per year and rarely involves the body cavities. CASE PRESENTATION: We present a case of a 48-year-old male diagnosed with AdCC of the left submandibular gland. He received his last chemotherapy in 2006 and presented with pleural metastasis. After undergoing pleurectomy and decortication procedure, pericardial fluid and biopsies from the chest wall, sixth rib, diaphragm, pleural cavity and pericardium were sent for pathologic evaluation. A diagnosis of metastatic adenoid cystic carcinoma was confirmed, including in the pericardium, pericardial fluid and diaphragm. CONCLUSION: AdCC of the submandibular gland is a malignant tumor with a high mortality rate. It is very rare for AdCC to metastasize to the pericardium and diaphragm. Metastasis to uncommon sites such as seen in our case with metastases to the pericardium and diaphragm shows the aggressive and unpredictable nature of this tumor, requiring close follow up, and indicating the need for molecular profile analysis and biomarker-stratified clinical trials.


Asunto(s)
Carcinoma Adenoide Quístico/patología , Metástasis de la Neoplasia/patología , Neoplasias de la Glándula Submandibular/patología , Biopsia , Diafragma/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pericardio/patología , Glándulas Salivales/patología
6.
Int J Cancer ; 127(1): 93-100, 2010 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-19918949

RESUMEN

Certain regions of China have high rates of esophageal squamous cell carcinoma (ESCC). Previous studies of human papillomavirus (HPV), a proposed causal factor, have produced highly variable results. We attempted to evaluate HPV and ESCC more definitively using extreme care to prevent DNA contamination. We collected tissue and serum in China from 272 histopathologically-confirmed ESCC cases with rigorous attention to good molecular biology technique. We tested for HPV DNA in fresh-frozen tumor tissue using PCR with PGMY L1 consensus primers and HPV16 and 18 type-specific E6 and E7 primers, and in formalin-fixed paraffin-embedded tumor tissue using SPF(10) L1 primers. In HPV-positive cases, we evaluated p16(INK4a) overexpression and HPV E6/E7 seropositivity as evidence of carcinogenic HPV activity. beta-globin, and thus DNA, was adequate in 98.2% of the frozen tumor tissues (267/272). Of these, 99.6% (95% confidence interval (CI) = 97.9-100.0%) were negative for HPV DNA by PGMY, and 100% (95% CI = 98.6-100%) were negative by HPV16/18 E6/E7 PCR. In the corresponding formalin-fixed paraffin-embedded tumor specimens, 99.3% (95% CI = 97.3-99.9%) were HPV negative by SPF(10). By PGMY, 1 case tested weakly positive for HPV89, a noncancer causing HPV type. By SPF(10), 2 cases tested weakly positive: 1 for HPV16 and 1 for HPV31. No HPV DNA-positive case had evidence of HPV oncogene activity as measured by p16(INK4a) overexpression or E6/E7 seropositivity. This study provides the most definitive evidence to date that HPV is not involved in ESCC carcinogenesis in China. HPV DNA contamination cannot be ruled out as an explanation for high HPV prevalence in ESCC tissue studies with less stringent tissue procurement and processing protocols.


Asunto(s)
Carcinoma de Células Escamosas/virología , Neoplasias Esofágicas/virología , Papillomaviridae/patogenicidad , Anciano , Carcinoma de Células Escamosas/patología , China , ADN Viral/genética , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Papillomaviridae/genética
7.
J Transl Med ; 8: 91, 2010 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-20920372

RESUMEN

BACKGROUND: Esophageal squamous cell carcinomas (ESCC) are usually asymptomatic and go undetected until they are incurable. Cytological screening is one strategy to detect ESCC at an early stage and has shown promise in previous studies, although improvement in sensitivity and specificity are needed. Proteases modulate cancer progression by facilitating tumor invasion and metastasis. In the current study, matrix metalloproteinases (MMPs) were studied in a search for new early detection markers for ESCC. METHODS: Protein expression levels of MMPs were measured using zymography in 24 cases of paired normal esophagus and ESCC, and in the tumor-associated stroma and tumor epithelium in one sample after laser capture microdissection (LCM). MMP-3 and MMP-10 transcripts in both the epithelium and stroma in five cases were further analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: Gelatin zymography showed bands corresponding in size to MMP-2, MMP-3, MMP-9, and MMP-10 enzymes in each of the 24 cancer cases. MMP levels tended to be higher in tumors than paired normal tissue; however, only the 45 kDa band that corresponds to the activated form of MMP-3 and MMP-10 was strongly expressed in all 24 tumors with little or no expression in the paired normal foci. LCM-based analysis showed the 45 kDA band to be present in both the stromal and epithelial components of the tumor microenvironment, and that MMP-3 and MMP-10 mRNA levels were higher in tumors than paired normal tissues for each compartment. CONCLUSIONS: Increased levels of MMPs occur in ESCC suggesting their up-regulation is important in esophageal tumorigenesis. The up-regulated gene products have the potential to serve as early detection markers in the clinic.


Asunto(s)
Carcinoma de Células Escamosas/enzimología , Neoplasias Esofágicas/enzimología , Metaloproteinasas de la Matriz/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/patología , Activación Enzimática , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa
8.
Int J Cancer ; 124(2): 456-60, 2009 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-18844222

RESUMEN

Pepsinogens are a class of endopeptidases that are secreted by the gastric epithelium and released into the circulation. Low serum pepsinogen I (PGI) and low serum pepsinogen I/pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy, and have recently been shown to be associated with increased risk of esophageal squamous cell carcinoma (ESCC). We conducted the current study to test whether these markers are also associated with esophageal squamous dysplasia (ESD), the precursor lesion of ESCC. We measured serum PGI and PGII, using enzyme-linked immunosorbent assays, in 125 case subjects (patients with moderate or severe ESD) and 250 sex-matched control subjects (no ESD) selected from an endoscopic screening study in Linxian, China. We used conditional logistic regression models adjusted for age, smoking and place of residence to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). Serum PGI showed no statistically significant association with ESD, whether analyzed as a dichotomous, ordinal (quartiles) or continuous variable. Lower serum PGI/II ratio, however, showed a dose-response association with increased risk of ESD, with an adjusted OR (95% CI) of 2.12 (1.08-4.18), comparing the lowest versus the highest quartile. The association between the lower serum PGI/II ratio and log OR of ESD was nearly linear, and the p-value for the continuous association was 0.03. Lower serum PGI/II ratio was linearly associated with higher risk of ESD. This result is consistent with recent findings that gastric atrophy may increase the risk of ESCC.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Pepsinógeno A/sangre , Pepsinógeno C/sangre , Enfermedades de la Piel/diagnóstico , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/epidemiología , Estudios de Casos y Controles , China , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/epidemiología , Femenino , Mucosa Gástrica/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Lesiones Precancerosas , Riesgo , Enfermedades de la Piel/sangre , Enfermedades de la Piel/epidemiología
9.
Cancer Epidemiol Biomarkers Prev ; 28(12): 2022-2029, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31501152

RESUMEN

BACKGROUND: Autoimmune gastritis is understudied and possibly associated with gastric noncardia adenocarcinoma (GNCA) and esophageal squamous cell carcinoma (ESCC) in Western populations when it presents as pernicious anemia. METHODS: A nested case-control study within a Chinese cohort included 100 ESCC, 200 gastric cardia adenocarcinoma (GCA), and 200 GNCA cases diagnosed between 1986 and 2001 and 400 controls. Serostatus of antiparietal cell antibodies (APCA), Helicobacter pylori antibodies, and pepsinogens were measured using commercial kits and serum collected at baseline. We used logistic regression to calculate odds ratios (OR) and 95% confidence interval (CI) for associations between serologic biomarkers and cancer risk adjusted for numerous potential confounders. RESULTS: There was an average interval of 8 years between baseline blood draw and cancer diagnosis. The baseline prevalence of APCA seropositivity was 10.0% and 14.5% in subjects who developed GCA and GNCA, respectively. APCA seropositivity was inversely associated with later development of GCA (OR = 0.42; 95% CI, 0.24-0.75), but not significantly associated with later development of GNCA (OR = 0.82; 95% CI, 0.50-1.36) or ESCC (OR = 1.05; 95% CI, 0.58-1.88). APCA seropositivity was significantly associated with low pepsinogen I/II ratios (OR = 3.69; 95% CI, 1.66-8.21), and individuals with low pepsinogen I/II ratios who were seronegative for APCA had the highest risk of both GCA and GNCA. CONCLUSIONS: APCA seropositivity measured years prior to diagnosis was associated with prevalent atrophic gastritis but inversely associated with incident GCA in this Chinese population. IMPACT: APCA may contribute to a growing list of serologic markers that can improve risk stratification for gastric cancer.


Asunto(s)
Autoanticuerpos/sangre , Neoplasias Esofágicas/etiología , Carcinoma de Células Escamosas de Esófago/etiología , Neoplasias Gastrointestinales/etiología , Infecciones por Helicobacter/complicaciones , Células Parietales Gástricas/inmunología , Pepsinógenos/sangre , Adulto , Anciano , Estudios de Casos y Controles , China , Estudios de Cohortes , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/sangre , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Estudios de Seguimiento , Neoplasias Gastrointestinales/sangre , Neoplasias Gastrointestinales/patología , Infecciones por Helicobacter/virología , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
10.
Cancer Epidemiol Biomarkers Prev ; 17(6): 1424-35, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18559558

RESUMEN

Molecular events associated with the initiation and progression of esophageal squamous cell carcinoma (ESCC) remain poorly understood but likely hold the key to effective early detection approaches for this almost invariably fatal cancer. CDC25B and LAMC2 are two promising early detection candidates emerging from new molecular studies of ESCC. To further elucidate the role of these two genes in esophageal carcinogenesis, we did a series of studies to (a) confirm RNA overexpression, (b) establish the prevalence of protein overexpression, (c) relate protein overexpression to survival, and (d) explore their potential as early detection biomarkers. Results of these studies indicated that CDC25B mRNA was overexpressed (>/=2-fold overexpression in tumor compared with normal) in 64% of the 73 ESCC cases evaluated, whereas LAMC2 mRNA was overexpressed in 89% of cases. CDC25B protein expression was categorized as positive in 59% (144 of 243) of ESCC cases on a tumor tissue microarray, and nonnegative LAMC2 patterns of protein expression were observed in 82% (225 of 275) of cases. Multivariate-adjusted proportional hazard regression models showed no association between CDC25B protein expression score and risk of death [hazard ratio (HR) for each unit increase in expression score, 1.00; P = 0.90]; however, several of the LAMC2 protein expression patterns strongly predicted survival. Using the cytoplasmic pattern as the reference (the pattern with the lowest mortality), cases with a diffuse pattern had a 254% increased risk of death (HR, 3.52; P = 0.007), cases with no LAMC2 expression had a 169% increased risk of death (HR, 2.69; P = 0.009), and cases with a peripheral pattern had a 130% greater risk of death (HR, 2.30; P = 0.02). CDC25B protein expression scores in subjects with esophageal biopsies diagnosed as normal (n = 35), dysplastic (n = 23), or ESCC (n = 32) increased significantly with morphologic progression. For LAMC2, all normal and dysplastic patients had a continuous pattern of protein expression, whereas all ESCCs showed alternative, noncontinuous patterns. This series of studies showed that both CDC25B and LAMC2 overexpress RNA and protein in a significant majority of ESCC cases. The strong relation of LAMC2 pattern of protein expression to survival suggests a role in prognosis, whereas the association of CDC25B with morphologic progression indicates a potential role as an early detection marker.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Laminina/genética , Lesiones Precancerosas/genética , ARN Mensajero/metabolismo , Fosfatasas cdc25/genética , China/epidemiología , Femenino , Perfilación de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Modelos Lineales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Análisis por Matrices de Proteínas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
11.
Acta Cytol ; 52(1): 14-23, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18323271

RESUMEN

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is associated with very high regional mortality rates in several countries. Our initial test of esophageal cytology screening devices found them not sensitive enough for an early detection program. The current study tested a newly designed "mechanical" balloon and a traditional Chinese inflatable balloon, followed by liquid-based cytology, to detect biopsy-proven squamous dysplasia and early cancer. STUDY DESIGN: Participants were randomized to a cytologic sampler, followed by endoscopy with iodine staining. For each patient, the cytologic diagnosis (test) was compared with the worst endoscopic biopsy diagnosis (truth). RESULTS: Seven hundred forty subjects completed both examinations. Approximately 30% showed atypical squamous cells of undetermined significance (ASCUS), and 10% showed squamous intraepithelial lesions. Seven hundred twenty-five subjects (98%) had satisfactory biopsies, and 32% had low grade dysplasia or worse disease. Defining > ASCUS, favor neoplastic, as a positive screening test, the sensitivities/specificities of the mechanical and inflatable balloons were 39%/85% and 46%/84%, respectively, for detecting any squamous dysplasia or cancer. CONCLUSION: These esophageal cell samplers performed equivalently, but the accuracy was still too low for a primary screening test. These results highlight the need to develop new cytologic criteria or molecular markers that can better detect early squamous esophageal disease [corrected]


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Lesiones Precancerosas/diagnóstico , Adulto , Anciano , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , China/epidemiología , Técnicas Citológicas , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/patología , Esofagoscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/patología
12.
Cancer Epidemiol Biomarkers Prev ; 16(9): 1889-93, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17855710

RESUMEN

BACKGROUND: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma, and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures for vitamin D exposure have reached different conclusions about the association between vitamin D and the risk of developing esophageal cancer. METHODS: We measured serum 25-hydroxyvitamin D [25(OH)D] concentrations in a cross-sectional analysis of 720 subjects from Linxian, China, a population at high risk for developing esophageal squamous cell carcinoma. All subjects underwent endoscopy and biopsy and were categorized by the presence or absence of histologic squamous dysplasia. We used crude and multivariate-adjusted generalized linear models to estimate the relative risks (RR) and 95% confidence intervals (95% CI) for the association between squamous dysplasia and sex-specific quartiles of serum 25(OH)D concentration. RESULTS: Two-hundred and thirty of 720 subjects (32%) had squamous dysplasia. Subjects with dysplasia had significantly higher median serum 25(OH)D concentrations than subjects without dysplasia, 36.5 and 31.5 nmol/L, respectively (Wilcoxon two-sample test, P = 0.0004). In multivariate-adjusted models, subjects in the highest compared with the lowest quartiles were at a significantly increased risk of squamous dysplasia (RR, 1.86; 95% CI, 1.35-2.62). Increased risks were similar when examined in men and women separately: men (RR, 1.74; 95% CI, 1.08-2.93); women (RR, 1.96; 95% CI, 1.28-3.18). CONCLUSIONS: Higher serum 25(OH)D concentrations were associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Esofágicas/etiología , Lesiones Precancerosas/etiología , Vitamina D/análogos & derivados , Adulto , Factores de Edad , Neoplasias Esofágicas/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lesiones Precancerosas/sangre , Riesgo , Factores de Riesgo , Factores Sexuales , Vitamina D/sangre
13.
BMC Oral Health ; 7: 10, 2007 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-17640341

RESUMEN

BACKGROUND: The oral health status of rural residents in the People's Republic of China has not been extensively studied and the relationship between poor oral health and esophageal cancer (EC) is unclear. We aim to report the oral health status of adults participating in an EC screening study conducted in a rural high-risk EC area of China and to explore the relationship between oral health and esophageal dysplasia. METHODS: National Health and Nutrition Examination Survey (NHANES) oral health examination procedures and the Modified Gingival Index (MGI) were used in a clinical study designed to examine risk factors for esophageal cancer and to test a new esophageal cytology sampling device. This study was conducted in three rural villages in China with high rates of EC in 2002 and was a collaborative effort involving investigators from the National Institutes of Health and the Cancer Institute of the Chinese Academy of Medical Sciences. RESULTS: Nearly 17% of the study participants aged 40-67 years old were edentulous. Overall, the mean number of adjusted missing teeth (including third molars and retained dental roots) was 13.8 and 35% had 7 contacts or less. Women were more likely to experience greater tooth loss than men. The average age at the time of first tooth loss for those with no posterior functional contacts was approximately 41 years for men and 36 years for women. The mean DMFT (decayed, missing, and filled teeth) score for the study population was 8.5. Older persons, females, and individuals having lower educational attainment had higher DMFT scores. The prevalence of periodontal disease (defined as at least one site with 3 mm of attachment loss and 4 mm of pocket depth) was 44.7%, and 36.7% of the study participants had at least one site with 6 mm or more of attachment loss. Results from a parsimonious multivariate model indicate that participants with poor oral health wemore likely to have esophageal dysplasia (OR = 1.59; 95% CI 1.06, 2.39). CONCLUSION: This report describes the first use of NHANES oral health protocols employed in a clinical study conducted outside of the United States. The extent and severity of poor oral health in this Chinese study group may be an important health problem and contributing factor to the prevalence of EC.

14.
BMC Cancer ; 6: 139, 2006 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-16729889

RESUMEN

BACKGROUND: The highest rates of esophageal squamous cell carcinoma (ESCC) in Brazil occur in Rio Grande do Sul, the most southern state, which has incidence rates of 20.4/100,000/year for men and 6.5/100,000/year for women. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) through tobacco smoke and other sources may increase the risk of ESCC. The aims of the current study were to investigate the degree and sources of PAH exposure of the inhabitants of this region of southern Brazil. METHODS: Two hundred healthy adults (half smokers, half non smokers, half male and half female) were recruited, given a standardized questionnaire, and asked to provide a urine sample for measurement of 1-hydroxypyrene glucuronide (1-OHPG), a PAH metabolite). Urine 1-OHPG concentrations were measured using immunoaffinity chromatography and synchronous fluorescence spectroscopy and urine cotinine was measured using a dipstick test. We examined factors associated with 1-OHPG concentration using Wilcoxon tests and multiple linear regression. RESULTS: Urine 1-hydroxypyrene glucuronide (1-OHPG) was successfully measured on 199 subjects. The median (interquartile range) of urine 1-OHPG in the 199 participants was 2.09 pmol/mL (0.51, 5.84). Tobacco smoke exposure and maté drinking were statistically significantly associated with higher urine 1-OHPG concentrations in the multivariate linear regression model. CONCLUSION: Tobacco smoke and maté both contribute to high levels of benzo[a]pyrene exposure in the people of southern Brazil. This high PAH exposure may contribute to the high rates of ESCC observed in this population. The increased urine 1-OHPG concentrations associated with maté suggest that contaminants, not just thermal injury, may help explain the increased risk of ESCC previously reported for maté consumption.


Asunto(s)
Benzo(a)pireno/farmacocinética , Bebidas/efectos adversos , Carcinógenos Ambientales/farmacocinética , Culinaria/estadística & datos numéricos , Glucuronatos/orina , Ilex paraguariensis/efectos adversos , Hidrocarburos Policíclicos Aromáticos/farmacocinética , Humo/efectos adversos , Fumar/efectos adversos , Contaminación por Humo de Tabaco/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Benzo(a)pireno/efectos adversos , Biomarcadores , Biotransformación , Brasil/epidemiología , Carcinógenos Ambientales/efectos adversos , Cocarcinogénesis , Culinaria/métodos , Cotinina/orina , Exposición a Riesgos Ambientales , Neoplasias Esofágicas/epidemiología , Calor/efectos adversos , Incidencia , Carne , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Pirenos , Encuestas y Cuestionarios
15.
Eur J Cancer Prev ; 15(6): 548-50, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17106336

RESUMEN

The objective of this study was to determine whether immunologic competence, as measured by lymphocyte stimulation indices from three different ex vivo challenges, is associated with subsequent risk of cancer or total mortality in Linzhou, China, a population at high risk for upper gastrointestinal cancers. Cellular immune function tests were conducted on a subgroup of 381 trial participants after 5.25 years of intervention to evaluate whether nutrient supplementation affected the cellular immune system and found significantly higher T-lymphocyte mitogenic responsiveness to phytohemagglutinin-M among men receiving daily supplementation of beta-carotene (15 mg) plus selenium (50 mug) plus alpha-tocopherol (30 mg) (supplementation factor D) compared with those who did not receive this supplement (P<0.05). The current analysis reports 10 years of post-trial prospective follow-up of these 381 trial participants and identifies 53 incident cancers, 48 (92%) of which were upper gastrointestinal cancers, including 22 esophageal cancers, 22 gastric cardia cancers, and four noncardia gastric cancers. Ninety-one deaths occurred among the 381 participants, including 33 upper gastrointestinal cancer deaths, 23 heart disease deaths, 16 stroke deaths, and seven fatal accidents. Multivariate Cox proportional hazards models including variables for age at time of tests, sex, tobacco smoking, alcohol drinking, and original trial treatment group showed no significant associations between phytohemagglutinin-M, concanavalin-A, or anti-CD3 stimulation indices and subsequent cancer incidence or total mortality. This implies that immune competence, as measured by these stimulation indices, is not associated with incident cancer or total mortality in this population.


Asunto(s)
Inmunidad Celular/fisiología , Neoplasias/epidemiología , Neoplasias/mortalidad , Linfocitos T/inmunología , Anciano , China/epidemiología , Neoplasias Esofágicas/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias Gástricas/epidemiología
16.
Oncol Rep ; 15(6): 1591-7, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16685400

RESUMEN

Esophageal squamous cell carcinoma (ESCC) is a common cancer with a very poor prognosis. New methods are needed to screen high-risk populations and identify curable tumors and precursor lesions early. Molecular markers may be useful in such screening efforts. This study was designed to determine the prevalence of p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in patients with ESCC to evaluate the variation of gene methylation across a spectrum of preneoplastic lesions, and assess the feasibility of using gene methylation in a primary screening test utilizing frozen esophageal cells collected by balloon cytology samplers. Samples were obtained from high-risk subjects from north central China. These samples included 11 foci of histologically normal mucosa, 8 foci of low-grade squamous dysplasia, 7 foci of high-grade squamous dysplasia, and 13 foci of ESCC from 6 fully embedded resection specimens; endoscopic biopsies from 6 individuals with no histological evidence of disease; and frozen esophageal balloon samples from 12 asymptomatic subjects. Promoter CpG site-specific hypermethylation status was determined for each gene using real-time methylation-specific PCR (qMS-PCR) based on Taqman chemistry. Of the 6 ESCC patients, 5 showed methylation of at least one gene. For most genes, methylation occurred with increasing frequency during neoplastic progression, with the largest increase found between low- and high-grade dysplasia. There was considerable variation in methylation patterns among different foci of the same histological grade, even within individual patients, but 16/20 (80%) of high-grade dysplastic and cancer foci had >or= 2 methylated genes, while 17/19 (89%) of normal and low-grade dysplastic foci had <2 methylated genes. These genes were rarely methylated in histologically normal mucosa from patients with or without ESCC. Gene methylation was common and easily detectable in the frozen esophageal cells collected by balloon cytology samplers. Our data suggest that methylation of p16, MGMT, RARbeta2, CLDN3, CRBP, and MT1G is common in the esophageal mucosa of patients with ESCC in this high-risk population, and tends to increase in prevalence in foci with increasing histological severity of disease. Methylation data from panels of genes may be able to identify patients with high-grade lesions. Balloon cytology may be able to screen the length of the esophagus effectively for a subset of cells with abnormal methylation, and may be useful in a primary screening test for ESCC and its precursor lesions.


Asunto(s)
Carcinoma de Células Escamosas/genética , Metilación de ADN , Neoplasias Esofágicas/genética , Lesiones Precancerosas/genética , Adulto , Anciano , Claudina-3 , Metilasas de Modificación del ADN , Enzimas Reparadoras del ADN , Femenino , Genes p16 , Humanos , Masculino , Proteínas de la Membrana/genética , Metalotioneína/genética , Persona de Mediana Edad , Receptores de Ácido Retinoico/genética , Proteínas de Unión al Retinol/genética , Proteínas Celulares de Unión al Retinol , Proteína p14ARF Supresora de Tumor/genética , Proteínas Supresoras de Tumor
17.
Cancer Res ; 63(14): 3872-6, 2003 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-12873975

RESUMEN

Tumor and matched normal tissue from 19 esophageal squamous cell carcinoma patients from a high-risk area of China were analyzed with 7680 gene cDNA microarrays. Forty-one genes were differentially expressed (P < 0.001; >/==" BORDER="0">2-fold change) between tumor and matched normal samples (13 overexpressed and 28 underexpressed). Hierarchical clustering showed consistent molecular profiles across patients. Multidimensional scaling plots visually distinguished cases by family history status, which was confirmed statistically using a global permutation test (P = 0.007); we then identified 152 genes of which the expression differed in tumors from family history positive versus negative cases (55 overexpressed and 97 underexpressed at P < 0.001). These data indicate that molecular profiles in esophageal squamous cell carcinoma are highly consistent and that expression patterns in familial cases differ from those in sporadic cases.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Anciano , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Salud de la Familia , Femenino , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos
18.
PLoS One ; 11(3): e0151775, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26999048

RESUMEN

Precision medicine promises to enhance patient treatment through the use of emerging molecular technologies, including genomics, transcriptomics, and proteomics. However, current tools in surgical pathology lack the capability to efficiently isolate specific cell populations in complex tissues/tumors, which can confound molecular results. Expression microdissection (xMD) is an immuno-based cell/subcellular isolation tool that procures targets of interest from a cytological or histological specimen. In this study, we demonstrate the accuracy and precision of xMD by rapidly isolating immunostained targets, including cytokeratin AE1/AE3, p53, and estrogen receptor (ER) positive cells and nuclei from tissue sections. Other targets procured included green fluorescent protein (GFP) expressing fibroblasts, in situ hybridization positive Epstein-Barr virus nuclei, and silver stained fungi. In order to assess the effect on molecular data, xMD was utilized to isolate specific targets from a mixed population of cells where the targets constituted only 5% of the sample. Target enrichment from this admixed cell population prior to next-generation sequencing (NGS) produced a minimum 13-fold increase in mutation allele frequency detection. These data suggest a role for xMD in a wide range of molecular pathology studies, as well as in the clinical workflow for samples where tumor cell enrichment is needed, or for those with a relative paucity of target cells.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Microdisección/métodos , Animales , Núcleo Celular/metabolismo , Epitelio/metabolismo , Humanos , Ratones , Células 3T3 NIH , Coloración y Etiquetado
19.
Oncogene ; 22(2): 314-8, 2003 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-12527901

RESUMEN

Previous studies have shown frequent allelic loss on chromosome 13 in esophageal squamous cell carcinoma (ESCC). We assessed the frequency of allelic loss on chromosome 13q14 and mutations of deleted in cancer 1 (DICE1) (also found on 13q14) in ESCC patients to determine if this candidate tumor suppressor gene has a role in the development of ESCC, and whether this gene was an inactivation target for allelic loss on chromosome 13q14. Initially, we examined allelic loss at five markers flanking DICE1 in 56 ESCC patients from Shanxi Province, China, and then examined the entire coding sequence of this gene for mutations using polymerase chain reaction-single-strand confirmation polymorphism (PCR-SSCP) analysis and DNA sequencing. Subsequently, we extended our evaluation to an additional 80 ESCC patients and 232 healthy individuals to confirm the germline variant found in the initial 56 ESCC patients. The frequencies of allelic loss were 71, 58, and 75% for D13S325, D13S757, and D13S887, respectively, in the initial 56 ESCC patients studied. Overall, 73% of informative patients had loss of heterozygosity (LOH) for at least one of these three markers. Somatic mutations were identified in three patients (3/56, 5%), and one novel polymorphism was identified in 3% of ESCC patients (4/136) and 3% of healthy individuals (6/232). We conclude that DICE1 mutations occur in ESCC but are infrequent. The candidate tumor suppressor gene corresponding to the frequent allelic loss on chromosome 13q14 in ESCC remains unknown.


Asunto(s)
Carcinoma de Células Escamosas/genética , Cromosomas Humanos Par 13 , Neoplasias Esofágicas/genética , Pérdida de Heterocigocidad , Mutación , ARN Helicasas , Proteínas Supresoras de Tumor/genética , Alelos , China , Humanos , Polimorfismo Genético , Polimorfismo Conformacional Retorcido-Simple , Proteínas de Unión al ARN , Proteínas Ribosómicas , Análisis de Secuencia de ADN
20.
Cancer Epidemiol Biomarkers Prev ; 14(6): 1576-8, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15941977

RESUMEN

We explored whether serum leptin response to alcohol ingestion was related to common leptin receptor gene polymorphisms, K109R (Lys109Arg), Q223R (Gln223Arg), S343S [Ser(T)343Ser(C)], and K656N (Lys656Asn), of reported physiologic significance during a controlled intervention. Fifty-three participants rotated through three 8-week treatment periods and consumed 0, 15 (equivalent to one drink), or 30 g (equivalent to two drinks) of alcohol (95% ethanol in 12 ounces of orange juice) per day, in random order. During the controlled feeding periods, all food and beverages including alcoholic beverages were prepared and supplied by the staff of the Beltsville Human Nutrition Research Center's Human Study Facility (Beltsville, MD), and energy intake was adjusted to maintain a constant weight. Blood was collected after an overnight fast on 3 separate days during the last week of each controlled feeding period and pooled for hormone analysis. Circulating serum leptin concentration was measured in duplicate by RIA and genotype analysis was done on DNA extracted from WBC using real-time PCR analysis amplification (TaqMan). Linear mixed models with a single random intercept reflecting a participant effect were used to estimate changes in serum leptin levels at 15 and 30 g of alcohol per day relative to 0 g of alcohol per day. No significant effects were found between common leptin receptor polymorphisms and serum leptin levels (P > or = 0.26).


Asunto(s)
Consumo de Bebidas Alcohólicas , Leptina/sangre , Polimorfismo Genético , Receptores de Superficie Celular/genética , Adulto , ADN/análisis , Dieta , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Reacción en Cadena de la Polimerasa , Receptores de Leptina
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