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1.
J Cell Physiol ; 234(11): 19249-19255, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31032924

RESUMEN

Noncoding RNAs (ncRNAs) identify a large family of RNAs that do not encode proteins and represent an important group of tumor biomarkers, directly involved in the process of tumor pathogenesis and progression. Many of them have also been identified in biological fluids of patients with cancer, especially blood, suggesting their role as an emerging class of circulating biomarkers. Many ncRNAs, both miRNAs and lncRNAs, are deregulated in sarcoma tissues, with the most consistent data in osteosarcomas. In patients with osteosarcoma, the role of ncRNAs as circulating biomarkers is taking enormous value, above all for their ability to vary expression levels during disease progression and in response to therapy. In this mini-review, we summarize the main studies supporting the role of circulating ncRNAs in monitoring disease status in patients with osteosarcoma.


Asunto(s)
Biomarcadores de Tumor/sangre , Osteosarcoma/genética , ARN Largo no Codificante/sangre , ARN no Traducido/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , MicroARNs/sangre , MicroARNs/genética , Osteosarcoma/sangre , Osteosarcoma/patología , ARN Largo no Codificante/genética , ARN no Traducido/sangre
2.
J Cell Physiol ; 234(1): 395-413, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-30132877

RESUMEN

HOX genes are involved with normal development, cell identity, cell differentiation, cell metabolism, apoptosis, autophagy as well as with diseases such as tumor pathogenesis and progression. In particular, the genes belonging to HOX paralogous 13 seem to carry out a relevant role in both tumor development and disease progression. In recent years, several noncoding RNAs (ncRNA) sequences have been identified in HOX loci, including long noncoding RNA (lncRNA) and microRNA (miRNA), highly conserved during evolution. Many studies have shown that specific intergenic ncRNAs in HOX loci could directly modulate HOX genes expression in normal and pathological conditions. In the present review we attempt to describe the role of these ncRNAs, through the regulation of the HOX gene network, in normal cell biology, and, with particular emphasis, in diseases such as in cancer pathogenesis and progression.


Asunto(s)
Genes Homeobox/genética , MicroARNs/genética , Neoplasias/genética , ARN Largo no Codificante/genética , Diferenciación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes/genética , Humanos , Neoplasias/patología
3.
Int J Mol Sci ; 17(5)2016 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-27213372

RESUMEN

In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues.


Asunto(s)
Antígeno B7-H1/metabolismo , Inmunohistoquímica/normas , Neoplasias/diagnóstico , Humanos , Inmunohistoquímica/métodos , Neoplasias/metabolismo , Especificidad de Órganos , Sensibilidad y Especificidad
4.
Cells ; 12(12)2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37371106

RESUMEN

Dacarbazine is an important drug in the therapeutic landscape of leiomyosarcoma (LMS). Alkylating agents are subjected to resistance mechanisms based on anti-apoptotic pathways and repair mechanisms, including the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). In this retrospective study, the methylation status of the MGMT promoter in histological tumor samples from patients with LMS, dacarbazine-based regimens-treated, was measured and correlated with clinical outcomes aimed at optimizing the use of dacarbazine in soft tissue sarcomas. The patients with unmethylated MGMT had better outcomes than those with methylated MGMT. Patients without MGMT methylation had better Progression Free Survival (PFS) when aged ≥62 years compared to those aged <62 years, while PFS of patients with methylated MGMT was less favorable independently of age (p = 0.0054). The patients without a methylated MGMT gene had higher Disease control rate (DCR). These results are not in agreement with the role of the methylated MGMT gene in other tumors, and with this study, we demonstrated the correlation between methylated MGMT and poor prognosis; despite that, sample smallness, heterogeneity of LMS and of treatment history could be selection bias. Predictive markers of response to chemotherapies in sarcomas remain an unmet need.


Asunto(s)
Neoplasias Encefálicas , Leiomiosarcoma , Humanos , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/patología , Dacarbazina/uso terapéutico , ADN , Metilación de ADN/genética , Metilasas de Modificación del ADN/genética , Metilasas de Modificación del ADN/uso terapéutico , Enzimas Reparadoras del ADN/genética , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/genética , Metiltransferasas/genética , Estudios Retrospectivos , Temozolomida/farmacología , Temozolomida/uso terapéutico , Proteínas Supresoras de Tumor/genética , Persona de Mediana Edad
5.
Curr Nutr Rep ; 12(4): 709-720, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37948008

RESUMEN

PURPOSE OF REVIEW: The review aims to present an overview of inmate health, focusing on lifestyle-related diseases, physical activity levels, and nutritional status. It also presents the B.A.C.I. (Benessere All'interno delle Carceri Italiane, well-being inside the Italian prisons) project, which aims to offers an innovative path of prevention, diagnosis, and treatment of noncommunicable diseases (NCDs) related to unhealthy lifestyles in prisons in the Campania region, Italy. RECENT FINDINGS: The global prison population has risen by 24% since the year 2000, with over 10.77 million people detained worldwide in 2021. In Italy alone, there are currently over 57,000 inmates. Inmates face a higher risk of NCDs such as cardiovascular disease due to unhealthy lifestyles characterized by poor diets and lack of physical activity. Additionally, sleep disorders, particularly insomnia, are prevalent among inmates, further contributing to health disparities. While physical activity has shown positive effects on inmate well-being, there is limited research on nutritional status and interventions in prison populations. Providing quality healthcare to inmates is an international policy norm, but the standards vary globally and are often inadequate. The economic burden of NCDs is rising, and this is exacerbated in prisons, making it challenging for individuals to reintegrate into society after release.


Asunto(s)
Enfermedades no Transmisibles , Prisioneros , Humanos , Prisiones , Salud Pública , Enfermedades no Transmisibles/epidemiología , Factores de Riesgo , Dieta
6.
Vaccines (Basel) ; 10(6)2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35746568

RESUMEN

BACKGROUND: The international strategic plan for COVID-19 vaccines remains the practical option for the protection of health. However, vaccine hesitancy remains an obstacle to full population vaccination, with rapid developments in COVID-19 vaccines and concerns about efficacy acting as influencing factors. AIM: The present study investigated the perception of vaccine hesitancy among parents of adolescents in order to explore the reasons and related emotional states. METHODS: In January-March 2022, an online questionnaire was administered to a sample of parents who brought their children to the vaccine center of a local health unit, ASL Salerno (Campania, Italy). RESULTS: The participants were 1105 parents (F = 64.6%; mean age = 47.37 years, SD = 7.52) of adolescents (F = 47.6%; mean age = 14.83 years, SD = 1.72). All parents had received the COVID-19 vaccine. Regarding the vaccination schedule, 46.8% believed that children receive more vaccinations than they should; 25.1% believed that it is better to develop immunity rather than get vaccinated; 41.2% believed that their child could have side effects; 29.6% were very concerned that vaccines were unsafe, while 35.3% believed vaccines do not prevent disease; 21.5% were very reluctant about pediatric vaccines; and 23.8% did not trust the information received. CONCLUSIONS: In order to increase vaccination and reduce the prevalence of vaccine hesitancy, it is essential to support the value of vaccination among all parents and make information more accessible and usable through competent pediatricians.

7.
Healthcare (Basel) ; 10(2)2022 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-35206999

RESUMEN

Latent Mycobacterium tuberculosis infection (LTBI) and active tuberculosis in prisoners are higher than the general population and are two public health concerns, especially in low- and middle-income countries. We conducted a cross-sectional study to determine the prevalence and the factors associated with LTBI among the inmate population detained in three Southern Italian penitentiaries. Tuberculin intradermal reaction skin test was performed on the inmates who agreed to participate in the study. In case of positivity, the QuantiFERON-TB test was performed. In those positive to QuantiFERON, chest X-ray films were performed, and treatment initiated. A total of 381 inmates accepted to participate. The prevalence of LTBI was 4.2%. In the analysis, LTBI was associated with no self-reported contact with active tuberculosis patients within the prisons, and 10% of subjects admitted the use of inhaled drugs. No HIV coinfections were found. No cases of active symptomatic tuberculosis were identified during the study period. Our results confirm that incarceration increases the risk of tuberculous infection. Non-EU nationality and a history of drug addiction appear to be major risk factors for tuberculosis infection in the penitentiary setting. Reinforcing tuberculosis control is essential to prevent its transmission in prisons.

8.
BMC Cancer ; 11: 472, 2011 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-22047406

RESUMEN

BACKGROUND: The polycomb transcription factor Yin Yang 1 (YY1) overexpression can be causally implicated in experimental tumor growth and metastasization. To date, there is no clinical evidence of YY1 involvement in outcome of patients with osteosarcoma. Prognosis of osteosarcoma is still severe and only few patients survive beyond five years. We performed a prospective immunohistochemistry analysis to correlate YY1 immunostaining with metastatic development and survival in a selected homogeneous group of patients with osteosarcoma. METHODS: We studied 41 patients suffering from osteosarcoma (stage II-IVa). Multivariate analysis was performed using Cox proportional hazard regression to evaluate the correlation between YY1 expression and both metastasis development and mortality. RESULTS: YY1 protein is not usually present in normal bone; in contrast, a high number of patients (61%) showed a high score of YY1 positive cells (51-100%) and 39% had a low score (10-50% positive cells). No statistical difference was found in histology, anatomic sites, or response to chemotherapy between the two degrees of YY1 expression. Cox regression analysis demonstrated that the highest score of YY1 expression was predictive of both low metastasis-free survival (HR = 4.690, 95%CI = 1.079-20.396; p = 0.039) and poor overall survival (HR = 8.353, 95%CI = 1.863-37.451 p = 0.006) regardless of the effects of covariates such as age, gender, histology and chemonecrosis. CONCLUSION: Overexpression of YY1 in primary site of osteosarcoma is associated with the occurrence of metastasis and poor clinical outcome.


Asunto(s)
Neoplasias Óseas/metabolismo , Proteínas de Neoplasias/metabolismo , Osteosarcoma/metabolismo , Factor de Transcripción YY1/metabolismo , Adulto , Análisis de Varianza , Neoplasias Óseas/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Análisis Multivariante , Osteosarcoma/secundario , Osteosarcoma/terapia , Pronóstico , Estudios Prospectivos
9.
Virchows Arch ; 479(3): 565-573, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33768318

RESUMEN

Chromosomal rearrangements involving BCL2, BCL6 and MYC are commonly found in the most frequent B cell lymphomas, namely follicular lymphomas (FLs) and diffuse large B-cell lymphomas (DLBCLs). Particularly, BCL2-rearrangement represents a diagnostic hallmark in FLs, whereas MYC translocation can occur simultaneously with BCL2 and/or BCL6 rearrangements, defining a specific category of DLBCLs with a poorer prognosis. In this study, we aim to validate the diagnostic performance of multiplex BCL2/BCL6 FISH approach in formalin-fixed paraffin-embedded FLs and DBCLs and cytological samples of DLBCL comparing to the classic set of single break-apart probes. We collected a series of lymphomas, including 85 DLBCLs, 45 FLs and 36 other B-cell lymphoma histotypes and 16 cytological samples of DLBCLs. MYC, BCL2 and BCL6 rearrangements were previously assessed by a classic FISH test using single break-apart probes. All samples were analysed by a multiplex FISH assay. In the FL series, 38 cases showed BCL2-R; in the DLBCLs series, MYC-R was detected in 21 out of 85 DLBCL patients, BCL2-R in 10 out of 85 and BCL6-R in 33 out of 85. In the DLBCL cytological series, MYC-R was detected in 4 out of 16, BCL2-R in 4 out of 16 and BCL6-R in 1 out of 16. Notably, in FFPE, 13 double-hit lymphomas (DHLs) and 3 triple-hit lymphomas (THLs) were detected; in the cytological series, only 3 DHL cases were observed. The dual BCL2/BCL6 FISH probe test results were fully concordant with the results obtained using classic BCL2 and BCL6 single break apart. Particularly, multiplex FISH to simultaneously detect BCL2-R and BCL6-R on a single slide could find a wide application in the characterisation of double- and triple-hit DLBCLs.


Asunto(s)
Biomarcadores de Tumor/genética , Reordenamiento Génico , Hibridación Fluorescente in Situ , Linfoma de Células B Grandes Difuso/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-6/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Predisposición Genética a la Enfermedad , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados
10.
Am J Pathol ; 175(6): 2609-17, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19893048

RESUMEN

The roles in brain development. Previous studies have shown the association between OTX2 and OTX1 with anaplastic and desmoplastic medulloblastomas, respectively. Here, we investigated OTX1 and OTX2 expression in Non-Hodgkin Lymphoma (NHL) and multiple myeloma. A combination of semiquantitative RT-PCR, Western blot, and immunohistochemical analyses was used to measure OTX1 and OTX2 levels in normal lymphoid tissues and in 184 tumor specimens representative of various forms of NHL and multiple myeloma. OTX1 expression was activated in 94% of diffuse large B-cell lymphomas, in all Burkitt lymphomas, and in 90% of high-grade follicular lymphomas. OTX1 was undetectable in precursor-B lymphoblastic lymphoma, chronic lymphocytic leukemia, and in most marginal zone and mantle cell lymphomas and multiple myeloma. OTX2 was undetectable in all analyzed malignancies. Analysis of OTX1 expression in normal lymphoid tissues identified a subset of resting germinal center (GC) B cells lacking PAX5 and BCL6 and expressing cytoplasmic IgG and syndecan. About 50% of OTX1(+) GC B cells co-expressed CD10 and CD20. This study identifies OTX1 as a molecular marker for high-grade GC-derived NHL and suggests an involvement of this transcription factor in B-cell lymphomagenesis. Furthermore, OTX1 expression in a subset of normal GC B cells carrying plasma cell markers suggests its possible contribution to terminal B-cell differentiation.


Asunto(s)
Subgrupos de Linfocitos B/metabolismo , Linfocitos B/metabolismo , Biomarcadores de Tumor/análisis , Centro Germinal/metabolismo , Linfoma no Hodgkin/metabolismo , Factores de Transcripción Otx/biosíntesis , Western Blotting , Humanos , Inmunohistoquímica , Mieloma Múltiple/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
11.
Acta Biomed ; 90(4): 587-594, 2019 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-31910191

RESUMEN

We describe radiographic, contrast-enhanced MDCT and MRI findings with pathologic correlations of an unusual recurrence of tumoral calcinosis, also called Teutschlander disease. The disease was silent in the first decade of life, when it appeared with elbows recurring lesions, until the seventh decade of life, when a left hip active growth lesion developed. A review about tumoral calcinosis pathogenesis, clinical course and imaging differential diagnosis is reported. (www.actabiomedica.it).


Asunto(s)
Calcinosis/diagnóstico por imagen , Hiperostosis Cortical Congénita/diagnóstico por imagen , Hiperfosfatemia/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía Computarizada Multidetector , Humanos , Masculino , Persona de Mediana Edad , Recurrencia
12.
Leuk Lymphoma ; 48(4): 723-30, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17454630

RESUMEN

The present study has explored the possible value of sCA-125 as a prognostic factor in Hodgkin's lymphoma (HL). From August 1992 to June 2005 sCA-125 was measured at presentation and at the end of the treatments in 221 newly diagnosed adult patients with HL. In this study 90/221 (41%) patients showed a value greater than the standard upper limit of 35 U/ml, and 79/90 (88%) with an abnormal sCA-125 were at an advanced stage of the disease. Patients with elevated sCA-125 showed a significant reduction in complete remission (CR) rate (76%vs. 98%; p < 0.0001). Failure of normalization of sCA-125 during the treatment revealed that CR had not been reached. Furthermore, no traces of the glycoprotein sCA-125 were found in a series of paraffin-embedded samples coming from 15 patients of this study. In addition, soluble CA-125 was not detected in supernatants coming from four different Hodgkin-derived cell lines. The long-term follow-up revealed that the group of patients with sCA-125 lower than 35 U/ml, at diagnosis, had an estimated 92% event free survival (EFS) rate and a 94% overall survival (OS) rate, while the group of patients with sCA-125 greater than 35 U/ml had only a 60% EFS rate (log-rank 33.43, p < 0.0001) and a 70% OS rate (log-rank 23.52, p < 0.0001). Extranodal disease, severe lymphocytopenia and age proved to be the only standard factors that could represent a poor chance to survive. At multivariate analysis, high sCA-125, E sites >1 and age were the only independent factors producing poor outcomes in terms of CR, EFS and OS. Therefore, we believe that sCA-125 is a simple, reliable and reproducible tool, which may improve existing prognostic systems.


Asunto(s)
Antígeno Ca-125/biosíntesis , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Inducción de Remisión , Factores de Tiempo
13.
Eur J Cancer ; 42(15): 2420-4, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16962318

RESUMEN

The transcription factor Yin Yang 1 (YY1) is known to be present in some human cancer cell lines and its expression correlates with immune-mediated apoptosis. By using Western blot analysis, we have shown that the YY1 protein is strongly expressed in human osteosarcoma cells and localised mainly in the nucleus. Moreover, by using immunohistochemistry and RT-PCR techniques, we have analysed the expression of YY1 protein in biopsies from human osteosarcomas. The YY1 protein was not detectable by immunohistochemistry in osteoid tissue. However, its expression was restricted to osteosarcoma tissues. These data were confirmed by densitometric analysis of RT-PCR for YY1 expression. Thus, YY1 gene activation appears to be an early event in the process of osteoblastic transformation and its detection may represent, together with the analysis of other established markers, a useful diagnostic tool in human osteosarcomas.


Asunto(s)
Neoplasias Óseas/metabolismo , Proteínas de Neoplasias/metabolismo , Osteosarcoma/metabolismo , Factor de Transcripción YY1/metabolismo , Adolescente , Adulto , Western Blotting , Neoplasias Óseas/patología , Línea Celular Tumoral , Técnica del Anticuerpo Fluorescente , Humanos , Osteosarcoma/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
14.
Anticancer Res ; 25(1B): 595-9, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15816633

RESUMEN

BACKGROUND: The aim of our study was to assess the color-Doppler ultrasound (CDU) pattern in the analysis of neoadjuvant preoperative treatment of patients with locally advanced breast carcinoma, improvement after injection of contrast medium (Levovist) and possible correlations between morphological and vascular aspects of the neoplasm and postoperative histopathological findings. MATERIALS AND METHODS: We studied 50 patients affected by locally advanced breast carcinoma (T3a e b-T4), using CDU before and after injection of Levovist, prior to and after neoadjuvant chemotherapeutic treatment. RESULTS: The use of Levovist for ultrasound examinations prior to treatment revealed a higher number of vascular signals in 94% of the lesions compared to the basic color-Doppler examination; in only 3 cases (6%) were no modifications observed after injection of the contrast medium. This finding was also evident after neoadjuvant treatment, as a greater number of vessels in 28 lesions were observed, in addition to residual vascularization in 9 patients in whom the basic color-Doppler examination demonstrated substantial avascularity. Histopathology revealed that this method was more sensitive in disclosing the presence of active neoplastic tissue. CONCLUSION: Color-Doppler ultrasound is the first step in assessing the efficacy of neochemotherapeutic treatment in patients affected by locally advanced breast carcinoma. Levovist increases sensitivity and improves the diagnostic precision, thus allowing for a better image of the vessels, which is an important index of the biological activity of the neoplasm, compared to the basic color-Doppler examination.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Medios de Contraste/farmacología , Ultrasonografía Doppler en Color/métodos , Anciano , Anciano de 80 o más Años , Carcinoma/diagnóstico , Carcinoma/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Persona de Mediana Edad , Terapia Neoadyuvante , Polisacáridos/uso terapéutico , Factores de Tiempo
15.
Anticancer Res ; 25(6C): 4519-26, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16334136

RESUMEN

Adult soft tissue sarcomas (STSs) are a rare group of highly heterogeneous neoplasms arising in different tissues. They are locally aggressive and can produce recurrence and distant metastasis. The most common metastatic sites are lung, lymph nodes, liver, bone and soft tissues. Staging for STSs has been based on some prognostic information: grade (low vs. intermediate/high grade), size (small vs. large tumors), depth of infiltration (superficial vs. deep neoplasms) and presence or not of distant metastasis. In the last 10 years, a plethora of new markers (proliferation markers and DNA alteration, P-gp, p53, TLS-CHOP, cyclins, survivin, TERT, PAX3-PAX7/FKHR, SYT-SSX1/2, VEGF, E-cadherin and beta-catenin, nm23, SKP-2, p27, CD40) has been studied with regard to their role in promoting progression (in a laboratory setting) and then determining prognosis and therapy (in a clinical setting). In the present survey, we focused on the role of new biological prognostic factors in STSs and also reported the quality of such studies with an ad hoc designed questionnaire.


Asunto(s)
Sarcoma/metabolismo , Sarcoma/patología , Neoplasias de los Tejidos Blandos/metabolismo , Neoplasias de los Tejidos Blandos/patología , Adulto , Biomarcadores de Tumor/biosíntesis , Humanos , Pronóstico
16.
Clin Cancer Res ; 10(8): 2824-31, 2004 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-15102691

RESUMEN

PURPOSE: The purpose is to evaluate the expression of CD40, a membrane protein predominantly expressed on B cells, dendritic cells, and macrophages, in a series of adult soft tissue sarcomas and to test its possible prognostic value. EXPERIMENTAL DESIGN: CD40 expression was studied by immunohistochemistry. Correlations with other baseline characteristics of patients and tumors were analyzed with chi(2) test. The prognostic value was studied with univariable and multivariable analysis adjusted by age, sex, tumor size, grade, location, and distant metastases. RESULTS: Eighty-two patients, between January 1994 and May 2001, were analyzed. Membrane or cytoplasmic staining for CD40 protein was absent in 30% of the tumors but present in <10% of cells in 22 (27%), in 10% to 50% in 23 (28%), and in >50% of cells in 12 (15%) tumors. There was no correlation between CD40 expression and age, sex, size, grade, and location of the primary tumor and distant metastases. With 61 patients (74.4%) progressed and 31 (37.8%) dead, CD40 expression was a significant prognostic factor for disease-free and overall survival at univariable and multivariable analysis. Patients with tumors expressing CD40 in >50% of cells had a dramatically unfavorable prognosis with median disease-free and overall survival of 7 and 17 months, respectively, and hazard ratios of relapse and death as compared with patients with CD40-negative tumors of 2.89 (95% confidence interval: 1.26-6.60) and 6.92 (95% confidence interval: 2.18-22.0), respectively. CONCLUSIONS: These data suggest that expression of CD40 protein in >50% of cells might indicate an unfavorable prognosis in adult soft tissue sarcomas.


Asunto(s)
Antígenos CD40/biosíntesis , Sarcoma/diagnóstico , Sarcoma/metabolismo , Neoplasias de los Tejidos Blandos/diagnóstico , Neoplasias de los Tejidos Blandos/metabolismo , Factores de Edad , Anciano , Linfocitos B/metabolismo , Membrana Celular/metabolismo , Citoplasma/metabolismo , Células Dendríticas/metabolismo , Femenino , Humanos , Inmunohistoquímica , Ligandos , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Factores de Tiempo
17.
Oncol Lett ; 10(1): 349-353, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26171028

RESUMEN

Morphological, ultrastructural and immunohistochemical characteristics of clear cell sarcoma (CCS) of the soft tissue frequently overlap with those of malignant melanoma. Thus, the differential diagnosis between the two lesions represents an important diagnostic dilemma. However, a number of genetic factors can be used to differentiate the two tumors; in particular, the t(12;22)(q13;q12) chromosomal translocation is typical of CCS, resulting in fusion of the EWSR1 gene on chromosome 22q12 and the ATF1 gene on chromosome 12q13. The detection of this molecular alteration has proved useful in the differential diagnosis of the two lesions. The present study reports the case of a 71-year-old male patient with a suspicious lymph node mass. Immunohistochemical analysis of the lesion indicated a diagnosis of metastatic melanoma, however, cytogenetic analysis using fluorescence in situ hybridization was additionally performed to investigate the chromosomal rearrangements of the 22q12 region and completely exclude the possibility of CCS. The current case did not demonstrate the presence of the translocation, supporting the diagnosis of melanoma. However, a clear orange amplification signal was observed relative to an ~500-kb region adjacent to the EWSR1 gene in the centromeric direction of chromosome 22q12. To the best of our knowledge, this is the first description of a 22q12 chromosomal alteration in melanoma. Furthermore, despite the presence of numerous genes in this region, their amplification has not previously been associated with the pathogenesis of melanoma.

18.
Tumori ; 88(5): 361-6, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12487551

RESUMEN

BACKGROUND: CD40, a cell surface molecule, is expressed on B-cell malignancies and many different solid tumors. It is capable of mediating diverse biological phenomena such as the induction of apoptosis in tumors and stimulation of the immune response. It has thus been studied as a possible target for antitumor therapy. The general aim of this review is to focus the attention of clinical oncologists on the involvement of CD40 in tumors and the rationale of CD40-activation-based therapies in new, biologically oriented antitumor protocols. METHODS: A Medline review of published papers about the role of CD40 activation in cancer therapy. RESULTS: Many authors have shown that CD40 activation promotes apoptotic death of tumor cells and that the presence of the molecule on the surface of carcinoma lines is an important factor in the generation of tumor-specific T-cell responses that contribute to tumor cell elimination. The CD40 ligand (CD40L) is the natural ligand for CD40; it is expressed primarily on the surface of activated T lymphocytes. Preclinical studies suggest that CD40-CD40L interaction could be useful for cytotoxicity against CD40-expressing tumors and for immune stimulation. Tumor inhibition was observed when tumor cells were treated with agonistic anti-CD40 monoclonal antibodies or with the soluble form of CD40L. The results of the first phase I clinical trial to treat cancer patients with subcutaneous injection of recombinant human CD40L have been recently reported. Immunohistochemical studies have revealed that detection of CD40 in primary cutaneous malignant melanoma and lung cancer may have a negative prognostic value. Interestingly, up-regulation of CD40 was observed in the tumor vessels of renal carcinomas and Kaposi's sarcoma, suggesting possible involvement of CD40 in tumor angiogenesis. Recently, it has also been shown that CD40 engagement on endothelial cells induces in vitro tubule formation and expression of matrix metalloproteinases, two processes involved in the neovascularization and progression of tumors. CONCLUSIONS: CD40 activation represents an exciting target for hematological malignancies and solid tumors expressing the molecule, but its functional role in cancer development still remains unclear and controversial.


Asunto(s)
Antígenos CD40/inmunología , Ligando de CD40/uso terapéutico , Inmunoterapia/métodos , Neoplasias/inmunología , Neovascularización Patológica/inmunología , Linfocitos T Citotóxicos/metabolismo , Animales , Anticuerpos Monoclonales/uso terapéutico , Biomarcadores de Tumor/análisis , Ligando de CD40/metabolismo , Humanos , Neoplasias Renales/inmunología , Neoplasias Pulmonares/inmunología , Activación de Linfocitos , Melanoma/inmunología , Neoplasias/irrigación sanguínea , Neoplasias/terapia , Valor Predictivo de las Pruebas , Pronóstico , Proteínas Recombinantes/uso terapéutico , Factores de Riesgo , Sarcoma de Kaposi/inmunología , Transducción de Señal , Neoplasias Cutáneas/inmunología
19.
Histol Histopathol ; 29(1): 77-87, 2014 01.
Artículo en Inglés | MEDLINE | ID: mdl-23846624

RESUMEN

T(1;14) (p22;q32) involving BCL10 and IGH genes is a rare but recurrent chromosomal aberration in MALT-type lymphoma. It is rarely described in ocular adnexa B cell lymphomas, although nuclear BCL10 shuttling seems to be critical for disease progression in this district. We have evaluated the translocations MALT lymphoma-related in a series of 45 ocular adnexa cases, focusing in particular on their relation with BCL10 expression and its cellular topographic distribution. A prognostic tissue microarray (TMA) with ocular adnexa MALT lymphomas was designed. A study of BCL10 expression and its topographic distribution was performed through immunohistochemistry. In addition the assessment of t(14;18) (q32;q21), t(1;14) (p22;q32) and t(11;18) (q21;q21) was determined by Fluorescent In Situ Hybridization (FISH). Our series revealed t(14;18) (q32;q21) in 6/43 cases (14,3%). t(1;14) (p22;q32), never described in ocular adnexa MALT lymphomas, was observed in 3/31 (9,7%), two of which exhibited the gain of 3' upstream BCL10 gene signal (4%), whereas no case showed t(11;18) (q21;q21). Moreover, BCL10 expression was observed in 18/45 cases. In particular its nuclear expression was revealed in 12/45 cases, cytoplasmic expression in 5/45 and both cytoplasmic and nuclear expression in 1/45. Statistical analysis demonstrated that while BCL10 cytoplasmic expression is significantly related to the presence of the investigated chromosomal aberrations, in particular with t(14;18) (q32;q21), BCL10 nuclear shuttling does not show any correlation with these translocations. Our data support that BCL10 nuclear distribution is neither related to BCL10 rearrangement nor to other known translocations.


Asunto(s)
Neoplasias del Ojo/genética , Neoplasias del Ojo/metabolismo , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/metabolismo , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Adulto , Anciano , Proteína 10 de la LLC-Linfoma de Células B , Biomarcadores de Tumor/análisis , Análisis Citogenético , Neoplasias del Ojo/patología , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Linfoma de Células B de la Zona Marginal/patología , Masculino , Persona de Mediana Edad , Análisis de Matrices Tisulares , Translocación Genética
20.
Infect Agent Cancer ; 7: 8, 2012 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-22472082

RESUMEN

Ocular adnexa MALT-lymphomas represent approximatively 5-15% of all extranodal lymphomas. Almost 75% of OAMLs are localized in orbital fat, while 25% of cases involves conjunctive. MALT-lymphomas often recognize specific environmental factors responsible of lymphoma development and progression. In particular as Helicobacter pylori in gastric MALT lymphomas, other bacterial infections have been recognized related to MALT lymphomas in specific site. Recently Chlamydia psittaci has been identified in Ocular Adnexa MALT lymphomas, with variable frequence dependently from geographic areas. Thus bacterial infection is responsible of clonal selection on induced MALT with subsequent lymphoma development. Moreover Chlamydia psittaci could promote chromosomal aberration either through genetic instability as a consequence of induced proliferation and probably through DNA oxidative damage. The most common translocation described in MALT lymphomas affects NF-kB pathway with a substantial antiapoptotic effect. Several therapeutic approaches are now available, but the use of antibiotic-therapy in specific cases, although with conflicting results, could improve the treatment of ocular adnexa MALT lymphomas. In this review we analyse the most relevant features of Ocular adnexa MALT lymphomas, underlining specific biological characteristics mainly related to the potential role of Chlamydia psittaci in lymphomagenesis.

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