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1.
Anticancer Res ; 41(9): 4417-4422, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34475063

RESUMEN

BACKGROUND/AIM: Ovarian carcinoma is the fifth leading cause of cancer-related deaths in women in the United States. Serous papillary carcinoma is the most common histological type of ovarian carcinoma that often goes undetected until it has spread within the pelvis and abdomen leading to poor prognosis. Translation of next-generation sequencing (NGS) technology into personalized medicine and identification of new potential targets for therapeutic applications may be helpful. CASE REPORT: We report a case of a 59-year-old female who initially presented in the emergency department with increasing abdominal girth, and bloating. Computed tomography showed ascites and omental and pelvic masses. Fine needle biopsy of the omental mass showed high-grade papillary adenocarcinoma consistent with high-grade ovarian serous carcinoma. She was treated with chemotherapy followed by debulking surgery. Primary ovarian serous carcinoma and synchronous primary fallopian tube serous carcinoma with multiple leiomyomas were identified in the surgical specimen. Pleural biopsy was also positive for carcinoma. NGS and programmed death-ligand 1 (PD-L1) expression testing were performed in the ovarian serous carcinoma. The results showed mutations of breast cancer type 1 (BRCA1) and type 2 (BRCA2), tumor protein p53 (TP53) (c.524G>A at pR175H), and heat shock protein 90 alpha family class B member 1 (HSP90AB1) (p.R456C), as well as low RNA expression score of PD-L1. CONCLUSION: Identification of these mutations and PD-L1 abnormality at the diagnosis of ovarian carcinoma may shed light for clinicians to provide targeted therapy with poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors for ovarian serous carcinoma. This is the first documented case of ovarian serous carcinoma to have found a HSP90AB1 (p.R456C) mutation.


Asunto(s)
Cistadenocarcinoma Seroso/genética , Neoplasias de las Trompas Uterinas/genética , Proteínas HSP90 de Choque Térmico/genética , Leiomiomatosis/genética , Neoplasias Primarias Múltiples/genética , Neoplasias Ováricas/genética , Biopsia con Aguja Fina , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/cirugía , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias de las Trompas Uterinas/cirugía , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leiomiomatosis/tratamiento farmacológico , Leiomiomatosis/patología , Leiomiomatosis/cirugía , Persona de Mediana Edad , Mutación , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos X , Estados Unidos
2.
Sci Total Environ ; 783: 147102, 2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34088167

RESUMEN

While biochar supported iron materials have been widely studied in advanced oxidation processes (AOPs), little is known about the effect and mechanism of goethite/biochar in sulfate radical (SO4-) based AOPs. Herein, a novel goethite/biochar composite was applied as peroxymonosulfate (PMS) activator for tetracycline (TC) degradation in the water. The superior catalytic efficiency of goethite/biochar was achieved through radical (OH and SO4-) and non-radical (1O2) processes according to the radicals quenching experiments and electron paramagnetic resonance analysis. Carbonyl group and Fe species were the main active sites on the surface of goethite/biochar, which was demonstrated by combining Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and reaction kinetic experiments. Furthermore, nine main by-products of TC degradation were detected by liquid chromatography-mass spectrometry and the reasonable degradation pathway was proposed according to the molecular structure analysis. Overall, the goethite/biochar materials could be applied to activate PMS for TC degradation, and this study will benefit the application of iron/biochar materials in practical water treatment.


Asunto(s)
Carbón Orgánico , Peróxidos , Compuestos de Hierro , Minerales
3.
Dev Biol ; 464(1): 11-23, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32450229

RESUMEN

Development of the complex structure of the vertebrate limb requires carefully orchestrated interactions between multiple regulatory pathways and proteins. Among these, precise regulation of 5' Hox transcription factor expression is essential for proper limb bud patterning and elaboration of distinct limb skeletal elements. Here, we identified Geminin (Gmnn) as a novel regulator of this process. A conditional model of Gmnn deficiency resulted in loss or severe reduction of forelimb skeletal elements, while both the forelimb autopod and hindlimb were unaffected. 5' Hox gene expression expanded into more proximal and anterior regions of the embryonic forelimb buds in this Gmnn-deficient model. A second conditional model of Gmnn deficiency instead caused a similar but less severe reduction of hindlimb skeletal elements and hindlimb polydactyly, while not affecting the forelimb. An ectopic posterior SHH signaling center was evident in the anterior hindlimb bud of Gmnn-deficient embryos in this model. This center ectopically expressed Hoxd13, the HOXD13 target Shh, and the SHH target Ptch1, while these mutant hindlimb buds also had reduced levels of the cleaved, repressor form of GLI3, a SHH pathway antagonist. Together, this work delineates a new role for Gmnn in modulating Hox expression to pattern the vertebrate limb.


Asunto(s)
Embrión de Mamíferos/embriología , Geminina/metabolismo , Regulación del Desarrollo de la Expresión Génica , Miembro Posterior/embriología , Proteínas de Homeodominio/metabolismo , Factores de Transcripción/metabolismo , Animales , Embrión de Mamíferos/citología , Geminina/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Miembro Posterior/citología , Proteínas de Homeodominio/genética , Ratones , Ratones Transgénicos , Receptor Patched-1/genética , Receptor Patched-1/metabolismo , Factores de Transcripción/genética
4.
Genes Cancer ; 8(9-10): 725-744, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29234490

RESUMEN

Medulloblastoma is the most common malignant brain cancer of childhood. Further understanding of tumorigenic mechanisms may define new therapeutic targets. Geminin maintains genome fidelity by controlling re-initiation of DNA replication within a cell cycle. In some contexts, Geminin inhibition induces cancer-selective cell cycle arrest and apoptosis and/or sensitizes cancer cells to Topoisomerase IIα inhibitors such as etoposide, which is used in combination chemotherapies for medulloblastoma. However, Geminin's potential role in medulloblastoma tumorigenesis remained undefined. Here, we found that Geminin is highly expressed in human and mouse medulloblastomas and in murine granule neuron precursor (GNP) cells during cerebellar development. Conditional Geminin loss significantly enhanced survival in the SmoA1 mouse medulloblastoma model. Geminin loss in this model also reduced numbers of preneoplastic GNPs persisting at one postnatal month, while at two postnatal weeks these cells exhibited an elevated DNA damage response and apoptosis. Geminin knockdown likewise impaired human medulloblastoma cell growth, activating G2 checkpoint and DNA damage response pathways, triggering spontaneous apoptosis, and enhancing G2 accumulation of cells in response to etoposide treatment. Together, these data suggest preneoplastic and cancer cell-selective roles for Geminin in medulloblastoma, and suggest that targeting Geminin may impair tumor growth and enhance responsiveness to Topoisomerase IIα-directed chemotherapies.

5.
Mayo Clin Proc ; 89(7): 926-33, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24835528

RESUMEN

MV-NIS is an engineered measles virus that is selectively destructive to myeloma plasma cells and can be monitored by noninvasive radioiodine imaging of NIS gene expression. Two measles-seronegative patients with relapsing drug-refractory myeloma and multiple glucose-avid plasmacytomas were treated by intravenous infusion of 10(11) TCID50 (50% tissue culture infectious dose) infectious units of MV-NIS. Both patients responded to therapy with M protein reduction and resolution of bone marrow plasmacytosis. Further, one patient experienced durable complete remission at all disease sites. Tumor targeting was clearly documented by NIS-mediated radioiodine uptake in virus-infected plasmacytomas. Toxicities resolved within the first week after therapy. Oncolytic viruses offer a promising new modality for the targeted infection and destruction of disseminated cancer.


Asunto(s)
Virus del Sarampión , Mieloma Múltiple/terapia , Viroterapia Oncolítica/métodos , Virus Oncolíticos , Anciano , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico por imagen , Cintigrafía
6.
Biol Blood Marrow Transplant ; 19(9): 1395-8, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23792270

RESUMEN

A rare, multisystem, plasma cell neoplasm, POEMS (polyradiculoneuropathy, organomegaly, endocrinopathy, M-spike, skin changes) syndrome is characterized by an abundance of proinflammatory and angiogenic cytokines. Patients with POEMS are known to have a high incidence of engraftment syndrome after autologous stem cell transplantation. We conducted a pilot study assessing levels of 30 different pro- and anti-inflammatory cytokines before and serially after transplantation in 18 patients with plasma cell neoplasms: POEMS syndrome (n = 9), multiple myeloma (n = 4), and amyloidosis (n = 5). We show that POEMS patients have higher pretransplantation levels of IL-4, IL-10, IL-13, IFN-α, and EGF as compared with those with non-POEMS plasma cell neoplasms. Higher pre- and posttransplantation IL-13 levels correlated with delayed neutrophil engraftment in POEMS patients. Low posttransplantation IL-1RA levels correlated with engraftment syndrome in both POEMS and non-POEMS patients. We conclude that differences in the peri-transplantation cytokine milieu may explain the higher transplantation morbidity in patients with POEMS syndrome. Our results need validation in a larger cohort.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Proteína Antagonista del Receptor de Interleucina 1/sangre , Neoplasias de Células Plasmáticas/sangre , Neoplasias de Células Plasmáticas/cirugía , Síndrome POEMS/sangre , Adulto , Anciano , Citocinas/sangre , Citocinas/inmunología , Femenino , Supervivencia de Injerto/inmunología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Proteína Antagonista del Receptor de Interleucina 1/inmunología , Masculino , Persona de Mediana Edad , Neoplasias de Células Plasmáticas/inmunología , Síndrome POEMS/inmunología , Síndrome POEMS/cirugía , Proyectos Piloto , Valor Predictivo de las Pruebas , Receptores de Interleucina-1/sangre , Receptores de Interleucina-1/inmunología , Trasplante Autólogo
7.
J Clin Invest ; 120(7): 2537-48, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20516639

RESUMEN

Somatic activating mutations in Notch1 contribute to the pathogenesis of T cell acute lymphoblastic lymphoma (T-ALL), but how activated Notch1 signaling exerts this oncogenic effect is not completely understood. Here we identify HIV-1 Rev-binding protein (Hrb), a component of the clathrin-mediated endocytosis machinery, as a critical mediator of Notch-induced T-ALL development in mice. Hrb was found to be a direct transcriptional target of Notch1, and Hrb loss reduced the incidence or delayed the onset of T-ALL in mouse models in which activated Notch1 signaling either contributes to or drives leukemogenesis. Consistent with this observation, Hrb supported survival and proliferation of hematopoietic and T cell precursor cells in vitro. We demonstrated that Hrb accelerated the uptake of transferrin, which was required for upregulation of the T cell protooncogene p21. Indeed, iron-deficient mice developed Notch1-induced T-ALL substantially more slowly than control mice, further supporting a critical role for iron uptake during leukemogenesis. Taken together, these results reveal that Hrb is a critical Notch target gene that mediates lymphoblast transformation and disease progression via its ability to satisfy the enhanced demands of transformed lymphoblasts for iron. Further, our data suggest that Hrb may be targeted to improve current treatment or design novel therapies for human T-ALL patients.


Asunto(s)
Linfocitos T/metabolismo , Animales , Diferenciación Celular/genética , Células/metabolismo , Clatrina/genética , Clatrina/metabolismo , Endocitosis/genética , VIH-1/genética , VIH-1/metabolismo , Células Madre Hematopoyéticas/metabolismo , Humanos , Hierro/metabolismo , Leucemia/genética , Linfoma de Células T/genética , Ratones , Ratones Noqueados , Modelos Biológicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Transducción de Señal/genética , Transducción de Señal/fisiología
8.
Cancer Res ; 69(4): 1459-68, 2009 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-19208845

RESUMEN

Oncolytic measles virus (MV) induces cell fusion and cytotoxicity in a CD46-dependent manner. Development of fully retargeted oncolytic MVs would improve tumor selectivity. The urokinase-type plasminogen activator receptor (uPAR) is a tumor and stromal target overexpressed in multiple malignancies. MV-H glycoproteins fully retargeted to either human or murine uPAR were engineered and their fusogenic activity was determined. Recombinant human (MV-h-uPA) and murine (MV-m-uPA) uPAR-retargeted MVs expressing enhanced green fluorescent protein (eGFP) were rescued and characterized. Viral expression of chimeric MV-H was shown by reverse transcription-PCR and Western blot. In vitro viral replication was comparable to MV-GFP control. The receptor and species specificity of MV-uPAs was shown in human and murine cells with different levels of uPAR expression. Removal of the NH(2)-terminal fragment ligand from MV-uPA by factor X(a) treatment ablated the MV-uPA functional activity. Cytotoxicity was shown in uPAR-expressing human and murine cells. MV-h-uPA efficiently infected human endothelial cells and capillary tubes in vitro. I.v. administration of MV-h-uPA delayed tumor growth and prolonged survival in the MDA-MB-231 breast cancer xenograft model. Viral tumor targeting was confirmed by immunohistochemistry. MV-m-uPA transduced murine mammary tumors (4T1) in vivo after intratumor administration. MV-m-uPA targeted murine tumor vasculature after systemic administration, as shown by dual (CD31 and MV-N) staining of tumor capillaries in the MDA-MB-231 model. In conclusion, MV-uPA is a novel oncolytic MV associated with potent and specific antitumor effects and tumor vascular targeting. This is the first retargeted oncolytic MV able to replicate in murine cells and target tumor vasculature in a uPAR-dependent manner.


Asunto(s)
Virus del Sarampión/genética , Viroterapia Oncolítica/métodos , Células 3T3 , Animales , Células CHO , Carcinoma Hepatocelular , Fusión Celular , Línea Celular Tumoral , Chlorocebus aethiops , Neoplasias del Colon , Cricetinae , Cricetulus , Eliminación de Gen , Haplorrinos , Humanos , Neoplasias Hepáticas , Virus del Sarampión/inmunología , Virus del Sarampión/fisiología , Ratones , Virus Oncolíticos/genética , Virus Oncolíticos/inmunología , Virus Oncolíticos/fisiología , ARN Neoplásico/genética , ARN Neoplásico/aislamiento & purificación , Receptores del Activador de Plasminógeno Tipo Uroquinasa/deficiencia , Receptores del Activador de Plasminógeno Tipo Uroquinasa/genética , Células Vero , Proteínas Virales/genética
9.
J Natl Cancer Inst ; 98(11): 756-64, 2006 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-16757700

RESUMEN

BACKGROUND: We and others have previously shown that plasminogen activators generate endogenous angiogenesis inhibitors and induce antiangiogenic activity. Here we assessed the effects of plasminogen activator overexpression on tumor progression in a syngeneic mammary cancer model. METHODS: Genes encoding murine tissue plasminogen activator (tPA), urokinase (uPA), and vector controls were stably transfected into 4T1 murine mammary cancer cells, and cell proliferation in vitro was analyzed. Cells were also implanted into female BALB/c mice (n = 12 per group), and tumor growth, lung metastases, and survival were compared. Tumor cell proliferation and microvessel formation were analyzed by immunohistochemistry using antibodies to proliferating cell nuclear antigen and CD31, respectively. 4T1 cells transfected with proteolytically inactive uPA mutants (A and B) were assayed for proliferation in vitro and tumor growth in vivo by using the same syngeneic model (eight to 10 mice per group). All statistical tests were two-sided. RESULTS: In vitro growth of uPA- and tPA-overexpressing and control 4T1 cells was similar. In vivo, however, inhibition of tumor growth and lung metastasis were inhibited in the mice carrying tPA- and uPA-overexpressing tumors, compared with controls (tumor weight at day 34: control, mean = 1760 mg, 95% confidence interval [CI] = 1434 to 2087 mg; tPA, mean = 921, 95% CI = 624 to 1217 mg; P < .001; uPA, mean = 395 mg, 95% CI = 161 to 629 mg; P < .001; number of lung metastases at day 34: control, mean = 117, 95% CI = 74 to 159; tPA, mean = 33, 95% CI = 13 to 52; uPA, mean = 15, 95% CI = 4 to 25; P < .001). Median survival was 42 (95% CI = 36 to 44), 55 (95% CI = 48 to 61), and 73 (95% CI = 51 to 86) days in the control, tPA, and uPA groups, respectively (P < .001). uPA- and tPA-expressing tumors had reduced angiogenesis and cell proliferation compared with controls. Tumors overexpressing uPA mutants grew faster than tumors expressing wild-type uPA (tumor volume at day 30: wild-type uPA, mean = 203, 95% CI = 121 to 285 mm3; control, mean = 534, 95% CI = 460 to 608 mm3; P < .001; mutant A, mean = 600, 95% CI = 520 to 679 mm3; P < .001; and mutant B, mean = 435, 95% CI = 358.9 to 511 mm3; P = .005). CONCLUSIONS: In this mouse model, uPA expression delayed tumor progression and had antiangiogenic and antiproliferative effects that may be mediated by uPA's protease activity. These results challenge the current dogma of proteases being exclusively tumor promoting and provide further rationale for exploring plasminogen activators as antitumor agents.


Asunto(s)
Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/patología , Mutación , Activador de Tejido Plasminógeno/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Animales , Northern Blotting , Proliferación Celular , Células Clonales , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Regulación Neoplásica de la Expresión Génica , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Péptido Hidrolasas/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Antígeno Nuclear de Célula en Proliferación/análisis , Análisis de Supervivencia , Activador de Tejido Plasminógeno/genética , Transfección , Trasplante Isogénico , Células Tumorales Cultivadas , Regulación hacia Arriba , Activador de Plasminógeno de Tipo Uroquinasa/genética
10.
Mol Cell Biol ; 26(3): 789-809, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16428436

RESUMEN

The global transcriptional coactivators CREB-binding protein (CBP) and the closely related p300 interact with over 312 proteins, making them among the most heavily connected hubs in the known mammalian protein-protein interactome. It is largely uncertain, however, if these interactions are important in specific cell lineages of adult animals, as homozygous null mutations in either CBP or p300 result in early embryonic lethality in mice. Here we describe a Cre/LoxP conditional p300 null allele (p300flox) that allows for the temporal and tissue-specific inactivation of p300. We used mice carrying p300flox and a CBP conditional knockout allele (CBPflox) in conjunction with an Lck-Cre transgene to delete CBP and p300 starting at the CD4- CD8- double-negative thymocyte stage of T-cell development. Loss of either p300 or CBP led to a decrease in CD4+ CD8+ double-positive thymocytes, but an increase in the percentage of CD8+ single-positive thymocytes seen in CBP mutant mice was not observed in p300 mutants. T cells completely lacking both CBP and p300 did not develop normally and were nonexistent or very rare in the periphery, however. T cells lacking CBP or p300 had reduced tumor necrosis factor alpha gene expression in response to phorbol ester and ionophore, while signal-responsive gene expression in CBP- or p300-deficient macrophages was largely intact. Thus, CBP and p300 each supply a surprising degree of redundant coactivation capacity in T cells and macrophages, although each gene has also unique properties in thymocyte development.


Asunto(s)
Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Proteína de Unión a CREB/fisiología , Proteína p300 Asociada a E1A/fisiología , Timo/crecimiento & desarrollo , Alelos , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Proteína de Unión a CREB/genética , Diferenciación Celular , Proteína p300 Asociada a E1A/genética , Eliminación de Gen , Expresión Génica , Ionóforos/farmacología , Recuento de Linfocitos , Linfoma de Células T/genética , Macrófagos/metabolismo , Ratones , Ratones Noqueados , Ésteres del Forbol/farmacología , Receptores de Antígenos de Linfocitos T , Bazo/citología , Bazo/crecimiento & desarrollo , Timo/citología , Transcripción Genética , Factor de Necrosis Tumoral alfa/genética
11.
Cancer Cell ; 5(2): 177-89, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14998493

RESUMEN

CBP can function as a tumor suppressor, but the mechanisms that govern oncogenesis in its absence are unknown. Here we show that CBP inactivation in mouse thymocytes leads to lymphoma. Although CBP has been implicated in the transactivation functions of p53, development of these tumors does not seem to involve loss of p53 activity. CBP-null tumors show reduced levels of p27Kip1 and increased levels of cyclin E and Skp2, two oncoproteins that can promote p27Kip1 proteolysis. Reduction of p27Kip1 by introduction of a p27Kip1-null allele into CBP knockout mice accelerates lymphomagenesis and seems to obviate the requirement for Skp2 and cyclin E upregulation. These data suggest that CBP loss mediates lymphomagenesis in cooperation with a mechanism that reduces p27Kip1 abundance.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Linfoma de Células T/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Represoras , Linfocitos T/metabolismo , Transactivadores/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Proteína de Unión a CREB , Clonación Molecular , Ciclina E/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Daño del ADN/fisiología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genes myc/fisiología , Predisposición Genética a la Enfermedad , Linfoma de Células T/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Noqueados , Microscopía Fluorescente , Proteínas Nucleares/genética , Complejo Represivo Polycomb 1 , Proteínas Proto-Oncogénicas/metabolismo , Receptores Notch , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Linfocitos T/patología , Transactivadores/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba/fisiología
12.
Laryngoscope ; 112(2): 402-8, 2002 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11889405

RESUMEN

OBJECTIVES/HYPOTHESIS: Cyclin D1 expression and the rate of apoptosis have been reported to serve as important prognostic indicators in human cancers. The purpose of the present study was to determine the prognostic significance of both initial cyclin D1 expression and the apoptotic index in nasopharyngeal carcinoma. STUDY DESIGN: Cohort study. METHODS: Cyclin D1 protein levels and apoptosis in tumors and their corresponding adjacent, histologically normal tissues were determined at the time of initial diagnosis using immunohistochemical staining, Western blot analysis, and in situ end labeling, respectively, in 64 patients with T1-T4/N0-N2, poorly differentiated squamous cell carcinoma of the nasopharynx. All cases were treated by routine radiation therapy with a total median dose of 70 Gy and followed up for 10 years. RESULTS: High levels of cyclin D1 were found in 35 of 64 tumor specimens (54.7%); no cyclin D1--positive cells were determinable in normal epithelium of the nasopharynx. Rates of early local recurrence (within 5 y) were significantly higher (P <.01) for patients with high levels of cyclin D1 before radiation therapy (24 of 35 patients [68.6%]) as compared with patients with low or no expression (3 of 29 [10.3%]). Furthermore, patients bearing high levels of cyclin D1 had a poorer prognosis concerning 10-year survival than the others (P <.001), whereas overexpression of cyclin D1 did not correlate with the initial TMN classification (P >.05). According to the rate of spontaneous apoptosis in tumors below or above the median, patients were divided into two groups. There was no statistically significant difference for the overall survival between the two groups (P >.05). CONCLUSIONS: The present study demonstrates that cyclin D1 can be used as an indicator of recurrence and subsequent prognosis in nasopharyngeal carcinoma after radiation therapy. At the same time, the apoptotic state before radiation therapy is of no value in predicting the prognosis of patients with nasopharyngeal carcinoma.


Asunto(s)
Biomarcadores de Tumor/análisis , Carcinoma/patología , Ciclina D1/análisis , Neoplasias Nasofaríngeas/patología , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Análisis de Varianza , Biopsia con Aguja , Western Blotting , Carcinoma/radioterapia , China , Estudios de Cohortes , Técnicas de Cultivo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/radioterapia , Estadificación de Neoplasias , Probabilidad , Pronóstico , Sensibilidad y Especificidad
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