RESUMEN
Proper temporal and spatial activation of stem cells relies on highly coordinated cell signaling. The primary cilium is the sensory organelle that is responsible for transmitting extracellular signals into a cell. Primary cilium size, architecture, and assembly-disassembly dynamics are under rigid cell cycle-dependent control. Using mouse incisor tooth epithelia as a model, we show that ciliary dynamics in stem cells require the proper functions of a cholesterol-binding membrane glycoprotein, Prominin-1 (Prom1/CD133), which controls sequential recruitment of ciliary membrane components, histone deacetylase, and transcription factors. Nuclear translocation of Prom1 and these molecules is particularly evident in transit amplifying cells, the immediate derivatives of stem cells. The absence of Prom1 impairs ciliary dynamics and abolishes the growth stimulation effects of sonic hedgehog (SHH) treatment, resulting in the disruption of stem cell quiescence maintenance and activation. We propose that Prom1 is a key regulator ensuring appropriate response of stem cells to extracellular signals, with important implications for development, regeneration, and diseases.
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Antígeno AC133/metabolismo , Cilios/metabolismo , Incisivo/citología , Antígeno AC133/genética , Animales , Núcleo Celular/metabolismo , Células Cultivadas , Humanos , Incisivo/metabolismo , Ratones , Modelos Biológicos , Mutagénesis Sitio-Dirigida , Transporte de Proteínas , Transducción de Señal , Células Madre/citología , Células Madre/metabolismoRESUMEN
OBJECTIVE: To establish model of dental pulp cells with activated Notch signaling pathway, and investigate the effect of activating Notch signaling pathway on senescence of human dental pulp cells in vitro. METHODS: Human dental pulp cells were isolated, cultured as usual, and used from the 4(th) passage. The cells were divided into the activated group and the negative control group. In the activated group, the way of coating dishes with Jagged1 protein (10 mg/L) was used to activate Notch signaling pathway. The negative control group cells received no treatment. In the 4(th), 8(th), and 10(th) passages, the expression levels of the Notch signaling pathway downstream gene Hes1 were verified by real-time quantitative PCR (RT-qPCR). The cell changes after activating Notch signaling pathway were observed at three levels: (1) The cell morphology changes were observed through invert phase contrast microscope. The cell activity was detected with MTT assay. (2) The alkaline phosphatase (ALP) expression and its activity, and senescence-associated &bgr;-galatosidase (SA-ß-Gal) expression were observed with the kit. (3) The expression changes of senescence related genes were verified using RT-qPCR. The difference between the negative control group and the activated group was analyzed using student's t test. RESULTS: The expression level of the downstream gene Hes1 of Notch signaling pathway increased after coating the dishes with Jagged1 protein, indicating the establishment of the model of dental pulp cells with activated Notch signaling pathway. Compared with the negative control group, the aging cells of the activated group appeared relatively late. In the 8(th) and 10(th) passage, the cell activity increased. In the 10th passage, ALP activity increased, but SA-ß-Gal expression decreased. p16 gene expression decreased in each passage, and p53 gene expression decreased in the 8(th) and 10(th) passages. CONCLUSION: Jagged1 could activate Notch signaling pathway effectively. Through activating Notch signaling pathway, the dental pulp cells showed a trend of senescence delay at different levels, such as cell morphology, metabolic enzyme expressions and related gene expressions.
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Senescencia Celular , Pulpa Dental/citología , Células Epiteliales/metabolismo , Receptores Notch/fisiología , Transducción de Señal , Proteínas de Unión al Calcio/metabolismo , Células Cultivadas , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteína Jagged-1 , Proteínas de la Membrana/metabolismo , Proteínas Serrate-JaggedRESUMEN
Leachate comprising organic contaminants such as dichloromethane is frequently discharged into groundwater at contaminated sites and unlined landfills. Soil-bentonite backfills in vertical cutoff walls are extensively employed to contain the flow of contaminated groundwater, thereby safeguarding the downstream groundwater environmental quality and ecosystem. This study presented a comprehensive evaluation of effects of dichloromethane-impacted groundwater on hydraulic conductivity and microscopic characteristics of soil-bentonite backfills amended with polymer namely polyanionic cellulose and microscale zero-valent iron. The results showed the amended backfills exhibited lower hydraulic conductivity than the unamended backfill regardless of the permeant type, i.e., tap water and dichloromethane solution. Scanning electron microscopy coupled with energy-dispersive spectrometry analyses demonstrated that polyanionic cellulose hydrogel could effectively coat sand, bentonite, and microscale zero-valent iron particles, providing protection of bentonite particles against attacks imposed by the dichloromethane and multivalent iron ions, and diminish aggregation of microscale zero-valent iron particles in the amended backfills. X-ray diffraction results indicated there was no intercalation of polyanionic cellulose and microscale zero-valent iron into the montmorillonite platelets of bentonite particles. Based on the Fourier Transform Infrared Spectroscopy Spectra analysis, a new functional group (-CH2) was identified on the polyanionic cellulose amended bentonite particles. The results demonstrated that amendment with polyanionic cellulose and microscale zero-valent iron is a promising approach to improve the performance of soil-bentonite backfills in containing flow of dichloromethane-impacted groundwater.
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OBJECTIVE: To explore whether the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT) could inhibit Notch signaling pathway in human dental pulp cells, and its effects on the proliferation ability of the cells. METHODS: Human dental pulp cells were primarily cultured from healthy premolars or wisdom teeth extracted intactly. The γ-secretase inhibitor DAPT (5 µmol/L) was added to the culture medium from passage 4 to the end. The cells of passages 4, 8 and 10 were used as check points in this study. The Real-time RT-PCR and RT2 Profiler PCR Array were applied to analyze the expression changes of Notch signaling pathway downstream genes. And the methyl thiazolyl tetrazolium (MTT) method was used to test the proliferation ability of the cells. RESULTS: After DAPT was added, Hes1 gene expression level decreased significantly in the cells of passages 4, 8 and 10 as compared with that of the same passage cells in the control group. The relative gene expression ratio (experimental/control) decreased to 0.20 in the cells of passage 10, and the difference was significant (t=33.143,P=0.001). The PCR Array results of passage 10 dental pulp cells also showed a decline of Notch signaling pathway downstream genes Hey1 and NR4A2 in the experimental group as compared with the control group. The proliferation of passages 8, and 10 experimental cells were slowed down, and the difference was significant. CONCLUSION: Notch signaling pathway of human dental pulp cells could be inhibited by DAPT effectively. The proliferation of the cells was slowed down by the effect of DAPT, and the normal life cycle of the cells was affected.
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Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Proliferación Celular/efectos de los fármacos , Pulpa Dental/citología , Dipéptidos/farmacología , Receptores Notch/metabolismo , Pulpa Dental/efectos de los fármacos , Humanos , Cultivo Primario de Células , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
OBJECTIVE: To identify and investigate clinicopathological features of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations ("double-hit" lymphoma). METHODS: Tissue microarray was constructed from formalin-fixed and paraffin-embedded tissue samples of aggressive B cell lymphomas diagnosed between 2009 and 2012, including 129 cases of diffuse large B cell lymphoma (DLBCL), 5 cases of B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU), 7 cases of Burkitt lymphoma and 4 cases of high-grade follicular lymphoma with diffuse large B cell lymphoma component. Interphase fluorescence in-situ hybridization (FISH) was performed with a panel of probes including myc, bcl-2/IgH and bcl-6 to document related gene translocation and copy number changes. Medical record review was performed and follow-up data was recorded. RESULTS: Among 145 cases, 5 cases (3.4%) of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 rearrangements (double-hit lymphomas) were identified, including 2 cases involving myc and bcl-2 translocations (1 DLBCL and 1 BCLU), and 3 cases involving myc and bcl-6 translocations (all DLBCLs). Three cases with concurrent bcl-2/IgH and bcl-6 translocations were found. Single gene translocations or increase of copy numbers were found in 66 cases, representing 51.2% (66/129) of all de novo DLBCLs. Ki-67 index of the 5 "double-hit" lymphomas ranged from 60% to 100%. Clinical follow-up data were available in 4 of the 5 "double-hit" lymphoma patients, three of whom died within 2 years and 1 patient was alive after 36 months of follow-up. CONCLUSIONS: "Double-hit" B-cell lymphomas are rare and can only be identified by molecular detection. They should not be considered synonymous with BCLU morphologically, and may present entities within other morphological spectra. Most of the patients have a poor prognosis. Further in-depth studies of larger case numbers are required to determine the pathologic and genetic variables of the lesion.
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Linfoma de Células B/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-myc/genética , Translocación Genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/genética , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Genes bcl-2 , Genes myc , Humanos , Hibridación Fluorescente in Situ , Linfoma de Células B/tratamiento farmacológico , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/genética , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/genética , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Estudios Retrospectivos , Vincristina/uso terapéuticoRESUMEN
OBJECTIVE: To study the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. METHODS: The clinicopathologic features of 139 cases of neuroendocrine neoplasm occurring in digestive system were retrospectively reviewed and graded according to the 2010 World Health Organization classification of tumours of the digestive system. Immunohistochemical study for synaptophysin, chromogranin A and Ki-67 was carried out. The follow-up and survival data were analysed using Kaplan-Meier method. Prognostic factors were tested by Log-rank testing and independent risk factors were analysed using Cox regression model. RESULTS: Amongst the 139 cases studied, there were 88 cases (63.3%) of grade 1 tumors, 9 cases (6.5%) of grade 2 tumors and 42 cases (30.2%) of grade 3 tumors. There was diffusely positive staining for synaptophysin and chromogranin A in most of the grade 1 and grade 2 tumors. The staining in grade 3 tumors however was focal (P < 0.05). The differences in tumor size, depth of invasion, presence of tumor emboli, perineural permeation, nodal involvement, distant metastasis and survival rate amongst the three groups was statistically significant (P < 0.05). CONCLUSIONS: There is significant difference in the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. It is considered as an independent prognostic factor and represents a useful tool for prognostic evaluation of such tumors, both in clinical practice and research.
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Neoplasias del Sistema Digestivo/patología , Clasificación del Tumor , Tumores Neuroendocrinos/patología , Adulto , Anciano , Anciano de 80 o más Años , Cromogranina A/metabolismo , Neoplasias del Sistema Digestivo/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Antígeno Ki-67/metabolismo , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Células Neoplásicas Circulantes , Tumores Neuroendocrinos/metabolismo , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tasa de Supervivencia , Sinaptofisina/metabolismo , Carga Tumoral , Adulto JovenRESUMEN
OBJECTIVE: To study the immunophenotype and overall survival of diffuse large B-cell lymphoma (DLBCL) classified according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues. METHODS: Five hundred cases of DLBCL were retrospectively analyzed with histologic review, immunohistochemistry, gene rearrangement study, in situ hybridization and fluorescence in situ hybridization. Follow-up data were collected. The overall survival rates of germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB) subtypes, as well as those of DLBCL, not otherwise specified (NOS) and Epstein-Barr virus (EBV)-positive DLBCL of the elderly, were compared. RESULTS: DLBCL-NOS was the commonest subtype which accounted for 77.2% (386/500) of the cases. EBV-positive DLBCL of the elderly, primary DLBCL of central nervous system, primary mediastinal (thymic) large B-cell lymphoma and T cell/histiocyte-rich large B-cell lymphoma accounted for 9.4% (47/500), 4.4% (22/500), 2.8% (14/500) and 2.6% (13/500), respectively. 68.5% (219/320) of DLBCL-NOS belonged to non-GCB subtype. The percentage of GCB subtype and CD5-positive subtype were 28.4% (91/320) and 3.1% (10/320), respectively. Comparison of the overall survival, GCB and non-GCB immunophenotypic groups have no significant difference (P = 0.93). And the same result in which of the EBV-positive DLBCL of the elderly and DLBCL-NOS group, before and after age matched (P = 0.13 and 0.28, respectively). A double-hit lymphoma was found by FISH detection, which presenting as gray zone lymphoma in morphology. CONCLUSIONS: By using Hans algorithm, GCB and non-GCB subtypes show no significant difference in overall survival. EBV-positive DLBCL of the elderly and DLBCL-NOS also do not have significant difference in overall survival. Fluorescence in situ hybridization technique is helpful in identification of DLBCL with rare phenotypes.
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Antígenos CD5/metabolismo , Infecciones por Virus de Epstein-Barr/patología , Centro Germinal/patología , Linfoma de Células B Grandes Difuso/clasificación , Linfoma de Células B Grandes Difuso/patología , Anciano , Linfoma de Burkitt/metabolismo , Linfoma de Burkitt/patología , Estudios de Seguimiento , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Genes bcl-2 , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunofenotipificación , Factores Reguladores del Interferón/metabolismo , Linfoma de Células B Grandes Difuso/genética , Persona de Mediana Edad , Neprilisina/metabolismo , Fusión de Oncogenes , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To investigate the clinicopathological features of EB virus positive diffuse large B-cell lymphomas (EBV + DLBCL) of the elderly. METHODS: Four hundred and ninety-six cases of DLBCLs were retrospectively studied by in situ hybridization (ISH) to detect the EBV in tumor cells, and by immunohistochemistry to evaluate the expression of CD10, CD20, CD30, CD79a, bcl-6, bcl-2, MUM-1, CD5, CD3, TIA-1 and Ki-67 protein. Their clinicopathological correlations were analyzed. RESULTS: Of the 59 cases of EBV + DLBCL, 48 cases were EBV positive. The median age of these EBV + DLBCLs was 73 years with male predominance (1.4:1). There were 11 cases with nodal presentation only, 18 cases with extra-nodal presentation and 19 cases with both lymph nodal and extra-nodal involvements, whereas about one third cases with more than one extra-nodal involvement. Thirty-five patients presented with advanced disease (Ann Arbor stage III/IV). A performance status was available in 36 cases and 5 cases had performance status of more than 1. Seven of 30 patients were found with high lactate dehydrogenase value (more than twice of the normal). An IPI-score was calculated in 30 cases and 18 cases had an intermediate/high IPI-score (3-5). The median survival for these patients was 35 months. Morphologically, EBV + DLBCLs of the elderly generally showed a diffuse and polymorphic proliferation of large lymphoid cells with varying degrees of reactive components including small lymphocytes, plasma cells, histiocytes, and epithelioid cells. These tumor cells were frequently characterized by a broad range of B-cell maturation, containing centroblasts, immunoblasts, and Hodgkin- and Reed-Sternberg (HRS)-like giant cells. The study cohort was further morphologically divided into large cell lymphoma subtypes (n = 33) and polymorphic lymphoma subtypes (n = 14) and one case with mixed subtype. Immunohistochemical studies showed that tumor cells were positive for CD20 (47/48) and/or CD79a (45/45) in almost cases. Tumor cells were MUM-1-positive in the majority of the cases (44/47) and were stained for CD10 or bcl-6 in a few cases. Expression of bcl-2 and CD30 was observed in 80.0% (28/35) and 28.9% (11/38) cases, respectively, and most of the cases (33/39) had a high proliferative index (by Ki-67 with a 50% cut-off point). Compared with other EBV + DLBCLs, except the older age and low frequency of bcl-6 staining, no other significant differences were observed in EBV + DLBCLs of the elderly. CONCLUSIONS: EBV + DLBCLs of the elderly constitute a distinct clinicopathologic subtype of DLBCL, although many clinical and histological features with EBV + lymphomas are similar with that of younger ages. Differential diagnosis from other types of lymphomas should also be considered.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4/aislamiento & purificación , Linfoma de Células B Grandes Difuso/patología , Anciano , Anciano de 80 o más Años , Antígenos CD20/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígenos CD79/metabolismo , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Factores Reguladores del Interferón/metabolismo , Antígeno Ki-1/metabolismo , L-Lactato Deshidrogenasa/sangre , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/virología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/uso terapéutico , Estudios Retrospectivos , Tasa de Supervivencia , Vincristina/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the epidemiological status of HER2 protein expression in Chinese patients with gastric carcinoma, and to study its clinical and prognostic significance and the association with the clinicopathological features. METHODS: The clinical data were reviewed in 860 patients with gastric carcinoma admitted to Guangdong General Hospital from 2003 to 2010. The HER2 status was evaluated using immunohistochemistry (IHC). The modified HercepTest scoring criterion was used to assess HER2 protein expression. The association between HER2 expression and clinicopathological features was analyzed by χ(2) test. Kaplan-Meier analysis, log-rank test and Cox regression model were used for the survival analysis. RESULTS: The median age of the patients was 59 years, and the male-to-female ratio was 2.06:1. Positive expression of HER2 protein (3+) was found in 77 (9.0%) cases of gastric carcinoma, and in 69 (8.9%) advanced gastric cancers. There was significantly positive association between HER2 over-expression and tumor differentiation, Lauren classification and WHO classification. No significant association was observed between HER2 protein expression and patients' age, gender, tumor location and clinical stage. There was no statistically significant difference in survival rate between patients with positive HER2 expression and negative ones. CONCLUSION: Though there was significantly positive association between HER2 expression status and tumor differentiation, histological type, it may be of limited prognostic value in gastric cancer patients.
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Adenocarcinoma/patología , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/cirugía , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Papilar/metabolismo , Adenocarcinoma Papilar/patología , Adenocarcinoma Papilar/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carcinoma de Células en Anillo de Sello/metabolismo , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células en Anillo de Sello/cirugía , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/cirugía , Tasa de Supervivencia , Adulto JovenRESUMEN
UNLABELLED: Although intraoperative assessment of the sentinel lymph node (SLN) is useful, it has not gained popularity in China as it involves a heavy workload for pathologists. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay performed in 158 SLNs from 97 patients by comparison with postoperative permanent section histopathology, to validate its potential usefulness in China. Every SLN was cut into alternating 1.5 to 3.0 mm slabs. The BLN assay processed 50% of the fresh alternating slabs to detect the presence of cytokeratin 19 and mammaglobin mRNA. Assay results were compared with those for permanent section histopathology and intraoperative imprint cytology. Slides for imprint cytology were prepared from the BLN assay node tissue before it was processed. Full axillary lymph node (ALN) dissections were performed on some patients after a SLN biopsy. The BLN assay was successfully performed on 158 SLNs from 97 patients. Overall performance of the BLN assay compared with permanent section histopathology was sensitivity 83.9% (26/31), specificity 95.5% (63/66), positive predictive value 89.7% (26/29), negative predictive value 92.6% (63/68), and overall agreement 91.8% (89/97). The BLN assay detected about 25% more metastases than imprint cytology. Moreover, the BLN assay correctly identified most of the additional non-sentinel ALNs metastases (P = 0.005). Our results from a large series of Chinese patients with breast cancer indicate that the BLN assay may be a viable alternative for the standard intraoperative procedures used for metastases detection, especially in early stage breast cancer patients. Name of the trial register: GeneSearch Breast Lymph Node (BLN) Assay China Registration Study. CLINICAL TRIAL REGISTRATION NUMBER: NCT00869674.
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Neoplasias de la Mama/patología , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/cirugía , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Persona de Mediana Edad , Estudios Prospectivos , Receptores de Estrógenos/análisisRESUMEN
OBJECTIVE: To study the types of progenitors in dental papilla cells(DPCs) and their differentiation characteristics. METHODS: DPCs of the mandibular first molars of four-day post-natal SD rats were isolated and cultured. The expression of osteocalcin (OCN) and dentin sialoprotein (DSP) were detected using DAB kit. E11 mandible primordias, tooth germs of the mandibular first molars of one-day post-natal SD rats, were isolated and transplanted under renal capsule respectively to observe whether they could survive and continue to develop. Then the pellets with and without dissociated enamel organ were transplanted under renal capsule for 24 days. RESULTS: Cultured DPCs could express positive OCN and DSP. After transplantation, the mandible primordias developed into cap stage. The continuous genesis of dentin and enamel increased the size of tooth germs. DPCs pellets formed dentin-like and bone-like structures, while pellets with enamel organ formed only dentin-like tissue adjacent to the frames. CONCLUSION: There are different progenitors residing in DPCs. The differentiation was closely related to the surrounding environment.
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Diferenciación Celular/fisiología , Papila Dental/citología , Diente Molar/citología , Animales , Animales Recién Nacidos , Trasplante de Células , Células Cultivadas , Proteínas de la Matriz Extracelular/metabolismo , Riñón/cirugía , Osteocalcina/metabolismo , Fosfoproteínas/metabolismo , Ratas , Ratas Sprague-Dawley , Sialoglicoproteínas/metabolismoRESUMEN
OBJECTIVE: To study the clinicopathologic features and prognostic factors of extranodal nasal type NK/T-cell lymphoma (EN-NK/TCL) in Chinese patients. METHODS: Fifty-five cases of EN-NK/TCL diagnosed in Chinese patients during the period from 1998 to 2007 were studied by light microscopy, immunohistochemistry and in-situ hybridization. The follow-up information was analyzed. RESULTS: The male-to-female ratio was 1.89:1. The median age of the patients was 38 years. The commonest sites of involvement included nasal cavity and adjoining tissue (85.5%). Histologically, EN-NK/TCL was composed of small to medium-sized lymphoid cells. Angiocentric and angiodestructive growth patterns, coagulative tumor necrosis and apoptotic bodies were frequently observed. Immunohistochemical study showed that CD20, the B-cell marker, was negative in all cases. The positivity rates for T-cell markers CD3epsilon, CD4, CD5 and CD8 were 100% (49/49), 7% (3/46), 8% (4/48) and 63% (29/46), respectively. Most cases were also positive for NK-cell marker CD56 (79% 42/53). All cases expressed cytotoxic granule-associated proteins TIA-1 and granzyme B. Only 17% (8/46) of the cases were positive for anti-apoptotic protein bcl-2. The proliferation index, as demonstrated by Ki-67 immunostain, varied: 30% (14/47) with a low Ki-67 expression level (< or = 29%), 28% (13/47) with a medium level (30%-59%) and 42% with a high level (> or = 60%). There was a significant positive correlation between the bcl-2 positive expression and a high Ki-67 expression level. In-situ hybridization for EBV-encoded RNA was positive in all cases. Amongst the 41 cases with clinical information available, 63.4% presented with Ann Arbor stage I to II. The performance status score was 1 in 87.8% cases. High lactate dehydrogenase level was demonstrated in some patients (31.8%). Amongst the 27 cases with follow-up data available, the median survival was 13 months. The overall 1-year, 2-year and 5-year survival rates were 52%, 31% and 20%, respectively. In general, cases with high proliferation index carried poor prognosis. CONCLUSIONS: EN-NK/TCL is a mature T-cell and NK-cell neoplasm which can be accurately diagnosed by histologic examination, immunohistochemical study and in-situ hybridization. The prognosis is usually not favorable. Proliferation index of the tumor represents an independent prognostic factor.
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Complejo CD3/metabolismo , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Linfoma Extranodal de Células NK-T , Neoplasias Nasales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígeno CD56/metabolismo , Niño , Infecciones por Virus de Epstein-Barr/virología , Femenino , Estudios de Seguimiento , Granzimas/metabolismo , Humanos , Inmunofenotipificación , Antígeno Ki-67/metabolismo , Linfoma Extranodal de Células NK-T/metabolismo , Linfoma Extranodal de Células NK-T/patología , Linfoma Extranodal de Células NK-T/terapia , Linfoma Extranodal de Células NK-T/virología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Nasales/metabolismo , Neoplasias Nasales/patología , Neoplasias Nasales/terapia , Neoplasias Nasales/virología , Proteínas de Unión a Poli(A)/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Viral/análisis , Estudios Retrospectivos , Tasa de Supervivencia , Antígeno Intracelular 1 de las Células T , Adulto JovenRESUMEN
OBJECTIVE: To explore significance of high-risk human papillomavirus (HR-HPV) testing in atypical squamous cells, cannot exclude high grade squamous intraepithelial lesion (ASC-H). METHODS: Presence of HR-HPV DNA was examined in 45 patients with ASC-H using hybrid capture II (HC-II) test. Colposcopic examination and biopsy were taken all results were evaluated. RESULTS: Overall, 33 of 45 (73.3%) ASC-H cases were biopsy proven cervical intraepithelial lesion (CIN). 36 of 45 ASC-H cases were HPV-DNA positive, including 19 cases of HSIL and over lesion; whereas no HSIL or over was found in 9 HR-HPV negative cases. Sensitivity and negativity predictive value of HR-HPV in ASC-H with HSIL and over lesion were both 100%. CONCLUSIONS: ASC-H strongly predicts the presence of HSIL, HR-HPV may serve as a predict select whether a patient with ASC-H should take colposcopic examination immediately, patients with positive HR-HPV should undergo immediate colposcopic examination, while negative HR-HPV is an excellent predictor of the absence of HSIL.
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ADN Viral/análisis , Infecciones por Papillomavirus , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Biopsia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Colposcopía , Femenino , Humanos , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Lesiones Precancerosas/patología , Lesiones Precancerosas/virología , Neoplasias del Cuello Uterino/virología , Cervicitis Uterina/patología , Cervicitis Uterina/virología , Frotis Vaginal , Adulto Joven , Displasia del Cuello del Útero/virologíaRESUMEN
OBJECTIVE: To assess the sensitivity and positive predictive value (PPV) of intraoperative frozen section diagnosis of the borderline tumor of ovary (BTO). METHODS: A retrospective analysis and comparison were done respectively between the accuracies of diagnoses made by using frozen and paraffin sections from the same tissue blocks for BTO from March 1995 to May 2008 achieved in the Department of Pathology, Guangdong General Hospital. Univariate and multivariate regression models were used to assess the influence of patient and tumor characteristics on the likelihood of underdiagnosis and overdiagnosis. RESULTS: Of the 73 patients analyzed, 39 cases (53.42%) were histologically serous tumors, 32 (43.84%) were mucinous and 2 (2.74%) were endometrioid tumors. Diagnoses identical in those made by using either frozen or routine paraffin sections were 55/73 (75.34%). The sensitivity and positive predictive value of frozen section diagnosis were 87.30% and 85.94%, respectively. Underdiagnosis of frozen section were 18/73 (24.66%). There was no overdiagnosis cases obtained. Univariate analysis showed that tumor diameter and tumor histology were the predictors of underdiagnosis in frozen section analysis. And in multivariate analysis, only tumor diameter, rather than patient age, tumor histology and stage, bilateral side tumor, serum CA-125 and concurrent presence of endometriosis was a predictor of underdiagnosis. CONCLUSIONS: Intraoperative frozen section diagnosis of BTO has a low sensitivity and PPV. Underdiagnosis is not uncommon. Surgical management based on intraoperative frozen section diagnosis should be used with caution.
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Cistoadenoma Mucinoso/patología , Cistadenoma Seroso/patología , Neoplasias Ováricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígeno Ca-125/metabolismo , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/cirugía , Cistoadenoma Mucinoso/metabolismo , Cistoadenoma Mucinoso/cirugía , Cistadenoma Seroso/metabolismo , Cistadenoma Seroso/cirugía , Femenino , Secciones por Congelación , Humanos , Periodo Intraoperatorio , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/cirugía , Adhesión en Parafina , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Stem cells (SCs) receive inductive cues from the surrounding microenvironment and cells. Limited molecular evidence has connected tissue-specific mesenchymal stem cells (MSCs) with mesenchymal transit amplifying cells (MTACs). Using mouse incisor as the model, we discover a population of MSCs neibouring to the MTACs and epithelial SCs. With Notch signaling as the key regulator, we disclose molecular proof and lineage tracing evidence showing the distinct MSCs contribute to incisor MTACs and the other mesenchymal cell lineages. MTACs can feedback and regulate the homeostasis and activation of CL-MSCs through Delta-like 1 homolog (Dlk1), which balances MSCs-MTACs number and the lineage differentiation. Dlk1's function on SCs priming and self-renewal depends on its biological forms and its gene expression is under dynamic epigenetic control. Our findings can be validated in clinical samples and applied to accelerate tooth wound healing, providing an intriguing insight of how to direct SCs towards tissue regeneration.
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Proteínas de Unión al Calcio/metabolismo , Incisivo/citología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Animales , Proteínas de Unión al Calcio/genética , Diferenciación Celular , Linaje de la Célula , Dentina , Epigenómica , Femenino , Expresión Génica , Homeostasis , Humanos , Células Madre Mesenquimatosas/citología , Ratones , Ratones Noqueados , Modelos Animales , Tercer Molar , Ratas , Ratas Wistar , Transducción de Señal , Nicho de Células Madre/fisiología , Cicatrización de HeridasAsunto(s)
Carcinogénesis , Proteínas de Ciclo Celular/genética , Proteínas F-Box/genética , Silenciador del Gen , Genes Supresores de Tumor , Neoplasias , Ubiquitina-Proteína Ligasas/genética , Animales , Proteínas de Ciclo Celular/metabolismo , Ciclina E/metabolismo , Proteínas F-Box/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD , Humanos , Mutación , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Receptores Notch/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
OBJECTIVE: To investigate the role of AIB1 gene in the development of esophageal squamous cell carcinoma (ESCC) and its clinicopathologic significance. METHODS: Two tissue microarrays, including 203 cases of ESCC, were prepared. Fluorescence in-situ hybridization (FISH) and immunohistochemistry were performed to detect the amplification of AIB1 gene and expression of its encoded protein in ESCC. The results were correlated with various clinicopathologic parameters. RESULTS: In the 203 cases of ESCC studied, FISH was successful in 115 cases. Amongst those, amplification/gain of AIB1 gene was observed in 15 cases, including high-level amplification in 5 cases (4.3%) and low-level gain in 10 cases (8.7%). As for immunohistochemical study, AIB1 protein was overexpressed in 94 cases of ESCC. There was a significant association of AIB1 overexpression and tumor staging. AIB1 was overexpressed in 66 of the 123 cases in advanced T stages (T3 to 4), compared with 25 of the 80 cases in early T stages (P = 0.008). Those cases with high-level amplification of AIB1 also showed overexpression of its encoded protein. On the other hand, 8 of the 10 cases with low-level gain of AIB1 showed protein overexpression. The remaining 41 of the 100 cases which did not have AIB1 gene amplification/gain demonstrated overexpression of AIB1 protein. CONCLUSION: Overexpression of AIB1 protein caused by gene amplification/gain or other molecular mechanisms may play an important role in the development and/or progression of a subset of ESCC.
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Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Metástasis Linfática/patología , Coactivador 3 de Receptor Nuclear/metabolismo , Carcinoma de Células Escamosas/patología , Movimiento Celular/genética , Progresión de la Enfermedad , Neoplasias Esofágicas/patología , Femenino , Amplificación de Genes , Histona Acetiltransferasas , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ/métodos , Masculino , Estadificación de Neoplasias , Coactivador 3 de Receptor Nuclear/genética , Células Tumorales CultivadasRESUMEN
OBJECTIVE: Further investigation on the incidence and clinicopathologic features of bronchioloalveolar carcinomas (BAC) including: (1) BAC of strictly defined, (2) adenocarcinoma with bronchioloalveolar features, (3) other different histologic subtypes of lung adenocarcinomas. METHODS: Surgical specimens from 348 lung adenocarcinoma patients admitted in that hospital between 1998 - 2005 were included. And clinical data were collected at the same time. Patients of strictly defined BAC, BAC with focal invasion (BWFI), and adenomas with bronchioloalveolar features (AWBF) were followed-up. Data were analyzed using SPSS statistics software and Kaplan-Meier survival curves were constructed. RESULTS: The resected lung adenocarcinomas consisted of different histologic subtypes. The most frequent one was adenocarcinoma of mixed subtypes (78.2%, 272/348), followed by the acinar type (8.1%, 28/348), the papillary type (4.0%, 14/348), the BAC (3.7%, 13/348), the mucinous (colloid) type (3.4%, 12/348) and the solid types (2.3%, 8/348). The fetal adenocarcinoma was the least component detected. There was no significant difference on the survival curves between groups BAC and BWFI. The survival rate of patients with AWBF was poorer than that of BAC and BWFI. CONCLUSIONS: Since patients with strictly defined (simple) BAC, BWFI, and AWBF have their own distinct clinicopathologic features and prognosis respectively, they should be strictly distinguished from other types of pulmonary adenocarcinomas.
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Adenocarcinoma Bronquioloalveolar/patología , Adenocarcinoma/patología , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Tasa de Supervivencia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Pulmón/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , PronósticoRESUMEN
OBJECTIVE: To investigate the role of bcl-6 gene rearrangement and bcl-6 expression in three molecular subgroups of diffuse large B-cell lymphoma (DLBCL) and its clinicopathological significance. METHODS: Tissue microarray including 163 newly diagnosed DLBCL was constructed. Fluorescence in situ hybridization (FISH) was performed to detect the bcl-6 gene rearrangement and immunohistochemistry (EnVision method) was used to evaluate the expression of bcl-6, Ki-67, cyclin D3, Geminin and P27(Kip1) proteins in DLBCL. The association with clinicopathological features was analyzed. RESULTS: One hundred and forty nine of 163 cases were further classified into three molecular subgroups: 40 cases of germinal center B-cell-like (GCB) type, 75 cases of activated non-germinal center B-cell-like (ABC) type, 34 cases of Type 3. Of these 149 cases, FISH for bcl-6 gene rearrangement was successful in 118 cases. bcl-6 gene rearrangement was observed in 33 of 118 (28.0%) cases. The bcl-6 gene rearrangement was more frequently seen in the ABC subgroup (22/62, 35.5%) than in GCB (6/31, 19.4%) and Type 3 subgroups (5/25, 20.0%, P=0.16). The correlation of bcl-6 gene rearrangement and expression of its encoded protein was further analyzed. Most of DLBCL (26/33, 78.8%) with bcl-6 gene rearrangement presented with overexpression of its encoded protein, which was higher than those without bcl-6 gene rearrangement (53/84, 62.4%, P=0.088). DLBCL with bcl-6 gene rearrangement (24/33, 72.7%) more frequently expressed cyclin D3, and had a higher proliferative activity than those without bcl-6 gene rearrangement (37/81, 45.7% , P=0.009). Twenty-nine of 33 (87.9%) cases of DLBCL with bcl-6 gene rearrangement presented with advanced stage (Ann Arbor stage III/IV), which was higher than those without bcl-6 gene rearrangement (65/85, 76.5% , P=0.167). Univariate Cox proportional hazards regression analysis showed that bcl-6 gene rearrangement was associated with an increased relative risk (at 1.842) of death in DLBCL cases compared with those without bcl-6 gene rearrangement. CONCLUSION: Overexpression of bcl-6 protein caused by bcl-6 gene rearrangement may play some important roles in the development and/or progression of a subset of DLBCL.
Asunto(s)
Ciclina D3/genética , Linfoma de Células B/genética , Linfoma de Células B Grandes Difuso/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Linfocitos B/patología , Cromosomas Humanos Par 14 , Reordenamiento Génico , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Linfoma de Células B/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Estadificación de Neoplasias , Pronóstico , Translocación GenéticaRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0104068.].