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1.
Med Mycol Case Rep ; 43: 100621, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38187996

RESUMEN

Cerebral phaeohyphomycosis (CP) is a serious form of phaeohyphomycosis. We report a case of CP caused by Fonsecaea species in a 66-year-old immunocompromised renal transplant recipient female. Craniotomy was performed on an irregularly enhancing right cerebellar hemisphere lesion and abscess and tissue samples collected for microbiological and histological evaluation, showing fungal elements and Fonsecaea species was isolated. Antifungal treatment with voriconazole & liposomal amphotericin B was initiated with a temporary improvement in the patient's condition. Deep vein thrombosis jeopardized patient's prognosis. Despite aggressive surgical and medical intervention, our patient succumbed to the disease. Historically, CP has been linked with fatality rates as high as 65 %, despite surgical intervention and systemic antifungal medication.

2.
BJR Case Rep ; 9(3): 20220117, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37265750

RESUMEN

Renal affection is common in disseminated non-Hodgkin's lymphoma (NHL) which is known as secondary renal lymphoma (SRL). Primary renal lymphoma (PRL) is an exceedingly uncommon disease, which accounts for less than 1% of all renal masses. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL in both primary as well as secondary renal lymphomas. PRL is of paramount importance clinically as it is usually managed with neo-adjuvant chemotherapy followed by nephrectomy in contrast to the more frequently seen renal cell carcinoma, which is treated surgically. This outstanding difference in management challenges the longstanding approach that preoperative biopsies are not mandatory prior to nephrectomy for renal masses. Because of its relative rarity, the imaging features of PRL have been described in a few studies, and having an understanding of these typical imaging patterns is crucial for making an accurate diagnosis and differentiation from other renal malignancies. Here, we present a case of a secondary renal lymphoma and discuss its differential imaging features.

3.
Urol Case Rep ; 38: 101700, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34007791

RESUMEN

Primary tumors of the epididymis are mostly benign in nature, and the most common type is adenomatoid tumors followed by leiomyomas. Leiomyoadenomatoid tumors are very rare benign epididymal neoplasms composed of two components: gland-like structures lined by cuboidal cells and bundles of smooth muscle components. The goal of treatment is testicular-preserving surgery. A preoperative and intraoperative evaluation plays an important role in proper management. To the best of our knowledge, few cases have been reported in the literature. We report a case of a right epididymal tail leiomyoadenomatoid tumor in a 49-year-old male who underwent trans-scrotal exploration and tumor excision.

4.
Cancer Invest ; 38(7): 394-405, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32643440

RESUMEN

The study investigated the human cytomegalovirus (HCMV) and human papillomavirus (HPV) in gliomas. A retrospective study was conducted on 112 samples. HCMV was investigated by PCR, in situ hybridization (ISH) and immunohistochemistry. HPV was tested by PCR and DNA ISH. HCMV was identified in 60 gliomas, including 55 GBM. However, RNA ISH and immunohistochemistry failed to detect HCMV positivity. HPV was identified in 44 GBM. No significant relationship was identified between HCMV and HPV and tumour characteristics (p > 0.05). Our findings support the HCMV and HPV presence in gliomas. Further assays are required to more explore the potential efficient antiviral management.


Asunto(s)
Neoplasias Encefálicas/virología , Citomegalovirus/aislamiento & purificación , Glioma/virología , Papillomaviridae/aislamiento & purificación , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Citomegalovirus/genética , Infecciones por Citomegalovirus/virología , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Túnez , Adulto Joven
5.
J Neurovirol ; 26(3): 347-357, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32124265

RESUMEN

The gliomagenesis remains not fully established and their etiological factors still remain obscure. Polyomaviruses were detected and involved in several human tumors. Their potential implication in gliomas has been not yet surveyed in Africa and Arab World. Herein, we investigated the prevalence of six polyomaviruses (SV40, JCPyV, BKPyV, MCPyV, KIPyV, and WUPyV) in 112 gliomas from Tunisian patients. The DNA sequences of polyomaviruses were examined by PCR assays. Viral infection was confirmed by DNA in situ hybridization (ISH) and/or immunohistochemistry (IHC). The relationships between polyomavirus infection and tumor features were evaluated. Specific SV40 Tag, viral regulatory, and VP1 regions were identified in 12 GBM (10.7%). DNA ISH targeting the whole SV40 genome and SV40 Tag IHC confirmed the PCR findings. Five gliomas yielded JCPyV positivity by PCR and DNA ISH (2.7%). However, no BKPyV, KIPyV, and WUPyV DNA sequences were identified in all samples. MCPyV DNA was identified in 30 gliomas (26.8%). For GBM samples, MCPyV was significantly related to patient age (p = 0.037), tumor recurrence (p = 0.024), and SV40 (p = 0.045) infection. No further significant association was identified with the remaining tumor features (p > 0.05) and patient survival (Log Rank, p > 0.05). Our study indicates the presence of SV40, JCPyV, and MCPyV DNA in Tunisian gliomas. Further investigations are required to more elucidate the potential involvement of polyomaviruses in these destructive malignancies.


Asunto(s)
Neoplasias Encefálicas/virología , Glioma/virología , Virus JC/genética , Poliomavirus de Células de Merkel/genética , Recurrencia Local de Neoplasia/virología , Infecciones por Polyomavirus/virología , Virus 40 de los Simios/genética , Adulto , Factores de Edad , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , ADN Viral/genética , ADN Viral/metabolismo , Femenino , Estudios de Seguimiento , Glioma/genética , Glioma/mortalidad , Glioma/patología , Humanos , Inmunohistoquímica , Hibridación in Situ , Virus JC/crecimiento & desarrollo , Virus JC/patogenicidad , Masculino , Poliomavirus de Células de Merkel/crecimiento & desarrollo , Poliomavirus de Células de Merkel/patogenicidad , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Infecciones por Polyomavirus/genética , Infecciones por Polyomavirus/mortalidad , Infecciones por Polyomavirus/patología , Virus 40 de los Simios/crecimiento & desarrollo , Virus 40 de los Simios/patogenicidad , Análisis de Supervivencia , Carga Viral
6.
Ann Biol Clin (Paris) ; 77(3): 307-317, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-31131831

RESUMEN

The study investigated the pattern of MGMT promoter methylation and the expression of MGMT, P53, EGFR, MDM2 and PTEN proteins in glioblastomas multiforme (GBM) and evaluated their prognostic significance. We carried out a retrospective study of 80 GBM. Expression of MGMT as well as of P53, EGFR, MDM2 and PTEN was investigated by immunohistochemistry. MGMT promoter methylation was investigated by methylation specific-PCR of bisulfite-treated DNA. Twenty-five GBM exhibited MGMT expression. Methylation of MGMT promoter was detected in 35.1% of cases. No significant concordance was reported between MGMT promoter methylation and protein expression (κ=-0.047, p=0.11). MGMT promoter methylation was significantly associated only with PTEN expression (p=0.001): no other significant association was identified with clinical parameters as well as with expression of P53, EGFR and MDM2 (p >0.05). Tumor recurrence was significantly associated with unmethylated MGMT promoter (p=0.01) but not with MGMT expression (p=0.51). Recurrence-free survival (RFS) was significantly better among patients with methylated MGMT promoter (log rank, p <0.0001) and PTEN expression (log rank, p=0.025) but not with MGMT expression (log rank, p=0.308). As well, using univariate analysis, MGMT promoter methylation (p=0.001) and PTEN expression (p=0.044) were significantly associated with RFS. In multivariate analysis, only MGMT promoter methylation was significantly associated with RFS (p=0.003). Together, our findings support that MGMT protein expression doesn't reflect the MGMT promoter methylation status. Furthermore, MGMT promoter methylation remains a useful prognostic marker in Tunisian patients with GBM. PTEN expression could be a potential prognostic marker of this tumor.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Metilasas de Modificación del ADN/genética , Metilasas de Modificación del ADN/metabolismo , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Glioblastoma/diagnóstico , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Niño , Preescolar , Metilación de ADN , Metilasas de Modificación del ADN/análisis , Enzimas Reparadoras del ADN/análisis , Receptores ErbB/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Fosfohidrolasa PTEN/metabolismo , Valor Predictivo de las Pruebas , Pronóstico , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/análisis , Túnez , Adulto Joven
7.
Pathol Res Pract ; 215(3): 446-452, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30558966

RESUMEN

Hydatidiform moles (HM) are characterized by an abnormal proliferating trophoblast with a potential for a malignant transformation. Similar to other human tumors, trophoblastic pathogenesis is likely a multistep process involving several molecular and genetic alterations. The study was performed to investigate the expression patterns of c-erbB-2 and Bcl-2 oncoproteins, p53, p21WAF1/CIP1 and p63 tumor suppressor proteins and Ki-67 cell proliferation marker in HM. We conducted a retrospective study of 220 gestational products, including 39 hydropic abortions (HA), 41 partial HM (PHM) and 140 complete HM (CHM). The expression of c-erbB-2, Bcl-2, p53, p21WAF1/CIP1, p63 and Ki-67 was investigated by immunohistochemistry on archival tissues. c-erbB-2 expression was observed in three PHM and 10 CHM. Bcl-2 immunostaining was significantly higher in PHM (61%) and CHM (70.7%) compared with HA (7.7%, p = 0.001 and p < 0.0001, respectively). p53 expression was stronger in CHM (73.6%) compared with PHM (24.4%, p < 0.0001) and HA (12.8%, p < 0.0001). p21WAF1/CIP1 staining was observed as well in molar and non-molar gestations (p > 0.05). p63 immunoexpression was significantly described in CHM (85.7%) and PHM (78%) compared with HA (10.2%, p < 0.0001 and p = 0.0001, respectively). Ki-67 was significantly expressed in CHM (72.1%) compared with HA (46.2%, p = 0.005). Altered expression of Bcl-2, p53, p63 and Ki-67 reflects the HM pathological development. Immunohistochemical analysis is beneficial to recognize the HM molecular and pathogenic mechanisms. Furthermore, it could serve as a useful adjunct to conventional methods for refining HM diagnosis.


Asunto(s)
Biomarcadores de Tumor/análisis , Mola Hidatiforme/patología , Neoplasias Uterinas/patología , Adolescente , Adulto , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/análisis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Femenino , Humanos , Mola Hidatiforme/metabolismo , Inmunohistoquímica , Antígeno Ki-67/análisis , Antígeno Ki-67/biosíntesis , Proteínas de la Membrana/análisis , Proteínas de la Membrana/biosíntesis , Persona de Mediana Edad , Embarazo , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Receptor ErbB-2/análisis , Receptor ErbB-2/biosíntesis , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/análisis , Proteína p53 Supresora de Tumor/biosíntesis , Neoplasias Uterinas/metabolismo , Adulto Joven
8.
Asian Pac J Cancer Prev ; 19(9): 2545-2551, 2018 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-30256049

RESUMEN

Background: Ovarian cancer is the leading cause of gynecologic cancer-related death. Histological assessment remains the standard clue for the diagnosis of ovarian carcinoma. Misinterpretation and inconsistent application of histological criteria may lead to significant interobserver variability and poor reproducibility of the diagnosis. In this study, we investigated the discrepancy in histological diagnosis and the significance of a designed panel of immunohistochemical markers for the improvement of the diagnostic reproducibility of ovarian carcinomas. Methods: We performed a retrospective study on 74 ovarian carcinomas. All tumor slides were independently reviewed by two pathologists. The results for seven available immunomarkers as p53, WT-1, p16INK4A, CK7, CK20, and estrogen and progesterone receptors were determined for all cases by immunohistochemistry. Results: The histological diagnosis review performed using standard histology showed a concordance of diagnoses in 86% of cases with Cohen's kappa of 0.80. Immunohistochemical results increased significantly the diagnosis reproducibility with a concordance of 91% and a Cohen's kappa of 0.86 (P = 0.001). Conclusion: Although the histological diagnosis remains reliable, the use of a designed panel of immunohistochemical markers improves significantly the interobserver concordance and the classification accuracy of ovarian carcinomas.


Asunto(s)
Adenocarcinoma de Células Claras/diagnóstico , Adenocarcinoma Mucinoso/diagnóstico , Biomarcadores de Tumor/metabolismo , Cistadenocarcinoma Seroso/diagnóstico , Neoplasias Endometriales/diagnóstico , Inmunohistoquímica/métodos , Neoplasias Ováricas/diagnóstico , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma Mucinoso/metabolismo , Cistadenocarcinoma Seroso/metabolismo , Neoplasias Endometriales/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Ováricas/metabolismo , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos
9.
Can J Physiol Pharmacol ; 96(11): 1076-1083, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30075092

RESUMEN

This study examined the effects of vanadyl sulfate (VOSO4) on the livers of nondiabetic and streptozotocin-induced diabetic rats. Rats were divided into 6 groups. Groups 1, 2, and 3 consisted of nondiabetic rats that were, respectively, control animals or those receiving an intraperitoneal (i.p.) injection of either 5 or 10 mg·kg-1 (i.p.) VOSO4 for 30 days. Groups 4, 5, and 6 consisted of diabetic animals that were, respectively, control animals or those treated with 5 or 10 mg·kg-1 (i.p.) VOSO4 for 30 days. Results showed that VOSO4 reduced body mass in nondiabetic rats, whereas it increased body mass in diabetic groups. Plasma transaminases (aspartate aminotransferase, alanine aminotransferase), lactate dehydrogenase, and alkaline phosphatase activities and malondialdehyde levels were increased, while liver catalase and superoxide dismutase activities were profoundly decreased in diabetic animals in comparison with enzyme activities in the nondiabetic group. Rats in the diabetic group also showed notable oxidative damage to the liver. Treatment of diabetic rats with VOSO4 decreased the hepatotoxic markers, significantly restored the activities of antioxidant enzymes, and attenuated histopathological changes in liver tissue. In nondiabetic rats, VOSO4 treatment increased most of the hepatotoxic markers, reduced antioxidant enzyme activities, and induced pronounced oxidative damage in liver tissue. These data suggest that treatment with VOSO4 exerts toxic effects in healthy animals and significantly prevents liver oxidative damage in streptozotocin-induced diabetic rats, but without total safety. Further studies are needed to clarify its mechanism of action.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Hígado/efectos de los fármacos , Compuestos de Vanadio/efectos adversos , Animales , Glucemia , Peso Corporal/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Diabetes Mellitus Experimental/inducido químicamente , Humanos , Hígado/patología , Pruebas de Función Hepática , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Estreptozocina/toxicidad , Resultado del Tratamiento
10.
World J Clin Cases ; 5(8): 344-348, 2017 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-28868307

RESUMEN

Langerhans cell histiocytosis (LCH) is a rare condition mostly seen in children and adolescents. Eosinophilic granuloma (EG) is one of its three clinical entities and is considered as a benign osteolytic lesion. Many reports of patients with spine histiocytosis are well documented in the literature but it is not the case of atlantoaxial localization. We report here a new observation of atlantoaxial LCH in a 4-year-old boy revealed by persistent torticollis. He was successfully treated with systemic chemotherapy and surgery. Inter-body fusion packed by autologous iliac bone was performed with resolution of his symptoms. It is known that conservative treatment is usually sufficient and surgery should be reserved for major neurologic defects in spine EG. In atlantoaxial lesion, surgical treatment should be frequently considered.

11.
Am J Forensic Med Pathol ; 38(2): 91-93, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28106684

RESUMEN

Takayasu arteritis is an uncommon inflammatory disease with usually a good prognosis. However, sometimes, the evolution can be fatal essentially by a coronary arteries involvement. We present a case of a 19-year-old woman who died suddenly from cardiogenic shock complicating an unknown Takayasu arteritis.At the autopsy, the aorta showed a significant thickening of the wall. The coronary arteries were slightly thickened and did not show any occlusion. Microscopic examination of the aorta showed an abundant granulomatous and a lymphoplasmacytic infiltrate. Microscopic sections of other internal organs showed signs of cardiac hypertrophy and an extensive edema of the lung. Death was attributed to acute heart failure complicating a supravalvular aortic stenosis secondary to unknown Takayasu arteritis.Takayasu arteritis can be life-threatening by an occlusion of the ascending aorta and its major branches, without any coronary arteries involvement.


Asunto(s)
Estenosis Aórtica Subvalvular/patología , Muerte Súbita/etiología , Arteritis de Takayasu/complicaciones , Estenosis Aórtica Subvalvular/complicaciones , Cardiomegalia/patología , Vasos Coronarios/patología , Femenino , Humanos , Edema Pulmonar/patología , Choque Cardiogénico/etiología , Arteritis de Takayasu/diagnóstico , Adulto Joven
12.
Environ Sci Pollut Res Int ; 24(1): 519-526, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27734311

RESUMEN

The 2,4-dichlorophenoxyacetic acid (2,4-D) is used worldwide in agriculture as a selective herbicide. It has been shown to produce a wide range of adverse effects on the health of both animals and humans from embryotoxicity and teratogenicity to neurotoxicity. In the present study, we have examined the effect of 2,4-D on male reproductive function of rats. Male Wistar rats received daily by force-feeding 100 or 200 mg of 2,4-D/kg body weight for 30 consecutive days. Rats exposed to 100 and 200 mg of 2,4-D/kg showed a significant decrease in body weights only after 24 days of treatment and in relative weights of testis, seminal vesicles and prostate at killing day, when compared with controls. Moreover, a decrease in testosterone and an increase in FSH and LH serum levels were detected in treated rats. Besides, exposure to this herbicide induced pronounced testicular histological alterations with enlarged intracellular spaces, tissue loosening and dramatic loss of gametes in the lumen of the seminiferous tubules. In addition, a decreased motility and a number of epididymal spermatozoa with an increased sperm abnormality rate were found in treated rats in comparison with control. With the highest dose, histological observations of seminal vesicles indicated a considerable decrease of secretions in the lumen, a thinness of the muscle layer surrounding the epithelium with branched mucosal crypts and reduced luminal space. In prostate, the heights of the cells decreased while acinar lumen were enlarged and they lost the typical invaginations. Our results suggest that a subacute treatment of 2,4-D promotes reproductive system toxicity.


Asunto(s)
Ácido 2,4-Diclorofenoxiacético/toxicidad , Contaminantes Ambientales/toxicidad , Genitales Masculinos/efectos de los fármacos , Herbicidas/toxicidad , Reproducción/efectos de los fármacos , Administración Oral , Animales , Masculino , Ratas , Ratas Wistar , Pruebas de Toxicidad Subaguda
13.
Toxicol Ind Health ; 33(2): 97-106, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26419261

RESUMEN

Hexavalent chromium (CrVI)-containing compounds, present in industrial settings and in the environment, are known as carcinogens and mutagens. The present study is designed to test the hypothesis that oxidative stress mediates CrVI-induced apoptosis in testis. Male Wistar rats received an intraperitoneal injection of potassium dichromate at doses of 1 and 2 mg kg-1. Superoxide anion production was assessed by the determination of the reduction of cytochrome c and iodonitrotetrazolium, lipid peroxidation (LPO), metallothioneins (MTs), and catalase (CAT) activity. Apoptosis was evaluated by DNA fragmentation detected by agarose gel electrophoresis. Germinal cells apoptosis was detected by toluidine blue staining. The expression of Bax and Bcl-2 proteins (Pts) was also investigated. After 15 days of treatment, an increase of LPO and MT levels occurred, while CAT activity was decreased. Testicular tissues of treated rats showed pronounced degradation of the DNA into oligonucleotides as seen in the typical electrophoretic DNA ladder pattern. Intense apoptosis was observed in germinal cells of Cr-exposed rats. Bax Pt expression was induced in spermatogonia and spermatocytes cells of CrVI-treated rats. In contrast, Bcl-2 Pt was occasionally observed in germ cells of CrVI-exposed rats. These results clearly suggest that CrVI subacute treatment causes oxidative stress in rat testis leading to apoptosis.


Asunto(s)
Apoptosis/efectos de los fármacos , Carcinógenos Ambientales/toxicidad , Cromo/toxicidad , Testículo/efectos de los fármacos , Animales , Catalepsia/metabolismo , Fragmentación del ADN/efectos de los fármacos , Electroforesis en Gel de Agar , Masculino , Ratas , Ratas Wistar , Superóxidos/análisis , Testículo/química
14.
Mol Neurobiol ; 54(4): 2381-2394, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-26957305

RESUMEN

It has become increasingly evident that morphologically similar gliomas may have distinct clinical phenotypes arising from diverse genetic signatures. To date, glial tumours from the Tunisian population have not been investigated. To address this, we correlated the clinico-pathology with molecular data of 110 gliomas by a combination of HM450K array, MLPA and TMA-IHC. PTEN loss and EGFR amplification were distributed in different glioma histological groups. However, 1p19q co-deletion and KIAA1549:BRAF fusion were, respectively, restricted to Oligodendroglioma and Pilocytic Astrocytoma. CDKN2A loss and EGFR overexpression were more common within high-grade gliomas. Furthermore, survival statistical correlations led us to identify Glioblastoma (GB) prognosis subtypes. In fact, significant lower overall survival (OS) was detected within GB that overexpressed EGFR and Cox2. In addition, IDH1R132H mutation seemed to provide a markedly survival advantage. Interestingly, the association of IDHR132H mutation and EGFR normal status, as well as the association of differentiation markers, defined GB subtypes with good prognosis. By contrast, poor survival GB subtypes were defined by the combination of PTEN loss with PDGFRa expression and/or EGFR amplification. Additionally, GB presenting p53-negative staining associated with CDKN2A loss or p21 positivity represented a subtype with short survival. Thus, distinct molecular subtypes with individualised prognosis were identified. Interestingly, we found a unique histone mutation in a poor survival young adult GB case. This tumour exceptionally associated the H3F3A G34R mutation and MYCN amplification as well as 1p36 loss and 10q loss. Furthermore, by exhibiting a remarkable methylation profile, it emphasised the oncogenic power of G34R mutation connecting gliomagenesis and chromatin regulation.


Asunto(s)
Neoplasias Encefálicas/clasificación , Neoplasias Encefálicas/diagnóstico , Glioma/clasificación , Glioma/diagnóstico , Patología Molecular , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Niño , Preescolar , Análisis por Conglomerados , Estudios de Cohortes , Metilación de ADN/genética , Epigénesis Genética , Femenino , Glioma/genética , Glioma/terapia , Humanos , Inmunohistoquímica , Lactante , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Análisis de Matrices Tisulares , Túnez , Adulto Joven
15.
Asian Pac J Cancer Prev ; 16(16): 6871-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26514459

RESUMEN

BACKGROUND: The meningeal hemangiopericytoma (MHPC) is a vascular tumor arising from pericytes. Most intracranial MHPCs resemble meningiomas (MNGs) in their clinical presentation and histological features and may therefore be misdiagnosed, despite important differences in prognosis. MATERIALS AND METHODS: We report 8 cases of MHPC and 5 cases of MNG collected from 2007 to 2011 from the Neuro-Surgery and Histopathology departments. All 13 samples were re reviewed by two independent pathologists and investigated by immunohistochemistry (IHC) using mesenchymal, epithelial and neuro-glial markers. Additionally, we screened all tumors for a large panel of chromosomal alterations using multiplex ligation probe amplification (MLPA). Presence of the NAB2-STAT6 fusion gene was inferred by immunohistochemical staining for STAT6. RESULTS: Compared with MNG, MHPCs showed strong VIM (100% of cases), CD99 (62%), bcl-2 (87%), and p16 (75%) staining but only focal positivity with EMA (33%) and NSE (37%). The p21 antibody was positive in 62% of MHPC and less than 1% in all MNGs. MLPA data did not distinguish HPC from MNG, with PTEN loss and ERBB2 gain found in both. By contrast, STAT6 nuclear staining was observed in 3 MHPC cases and was absent from MNG. CONCLUSIONS: MNG and MHPC comprise a spectrum of tumors that cannot be easily differentiated based on histopathology. The presence of STAT6 nuclear positivity may however be a useful diagnostic marker.


Asunto(s)
Hemangiopericitoma/química , Hemangiopericitoma/genética , Neoplasias Meníngeas/química , Neoplasias Meníngeas/genética , Meningioma/química , Meningioma/genética , Antígeno 12E7 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Moléculas de Adhesión Celular/análisis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Receptores ErbB/genética , Femenino , Hemangiopericitoma/patología , Humanos , Inmunohistoquímica , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Fosfohidrolasa PTEN/genética , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Receptor ErbB-2/genética , Factor de Transcripción STAT6/análisis , Proteína p53 Supresora de Tumor/genética , Vimentina/análisis
16.
Arch Environ Occup Health ; 70(4): 189-95, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-24965329

RESUMEN

The present study is designed to test the hypothesis that oxidative stress mediates hexavalent chromium (VI)-induced apoptosis in uterus. Female Wistar rats received an intraperitoneal (i.p.) injection of potassium dichromate at doses of 1 and 2 mg/kg. Superoxide anion production was assessed by determination of the reduction of cytochrome c and iodonitrotetrazolium (INT), lipid peroxidation (LPO), metallothioneins (MTs), and catalase (CAT) activity. The expression of Bax and Bcl-2 proteins was investigated. After 15 days of treatment, an increase of LPO and MT levels occurred, whereas CAT activity decreased. Intense apoptosis was observed in endometriotic stromal cells of Cr-exposed rats. Bax protein expression was induced in endometriotic stromal cells with 1 mg of Cr(VI)/kg, and in stromal and epithelial cells at the higher dose. These results clearly suggest that Cr(VI) subacute treatment causes oxidative stress in rat uterus, leading to endometriotic stromal cells apoptosis.


Asunto(s)
Cromo/toxicidad , Estrés Oxidativo/efectos de los fármacos , Útero/efectos de los fármacos , Animales , Biomarcadores/metabolismo , Endometrio/efectos de los fármacos , Endometrio/patología , Femenino , Inmunohistoquímica , Ratas , Ratas Wistar , Útero/patología
17.
Braz. j. pharm. sci ; 51(3): 681-688, July-Sept. 2015. tab, graf
Artículo en Inglés | LILACS | ID: lil-766306

RESUMEN

The aim of this study was to investigate both functionally and structurally bronchodilator effects of Pituitary adenylate cyclase activating peptide (PACAP38) and acetyl-[Ala15, Ala20] PACAP38-polyamide, a potent PACAP38 analog, in rats challenged by methacholine (MeCh). Male Wistar rats were divided randomly into five groups. Groups 1 and 2 inhaled respectively aerosols of saline or increasing doses of MeCh (0.5, 1, 2.12, 4.25, 8.5, 17, 34 and 68mg/L). The other groups received terbutaline (Terb) (250 µg/rat) (10-6 M), PACAP38 (50 µg/rat) (0.1 mM) or PACAP38 analog (50 µg/rat) associated to MeCh from the dose of 4.25 mg/L. Total lung resistances (RL) were recorded before and 2 min after MeCh administration by pneumomultitest equipment. MeCh administration induced a significant and a dose-dependent increase (p<0.05) of RL compared to control rats. Terb, PACAP38 and PACAP38 analog reversed significantly the MeCh-induced bronchial constriction, smooth muscle (SM) layer thickness and bronchial lumen mucus abundance. PACAP38 analog prevents effectively bronchial smooth muscle layer thickness, mucus hypersecretion and lumen decrease. Therefore, it may constitute a potent therapeutic bronchodilator.


O objetivo deste estudo foi investigar funcionalmente e estruturalmente efeito broncodilatador do peptídeo ativador da adenilato ciclase pituitária (PACAP1-38) e da acetil-[Ala15, Ala20]PACAP 38-poliamida, potente análogo do PACAP-38, nos ratos desafiados pelo metacolina (MeCh). Ratos Wistar machos foram aleatoriamente divididos em cinco grupos. Grupos 1 e 2, inalando aerossóis de solução salina ou doses crescentes de MeCh (0,5, 1, 2,12, 4,25, 8,5, 17, 34 e 68 mg/L). Os outros grupos recebendo terbutalina (Terb) (250 µg/rato) (10-6M), PACAP-38 (50 µg/rato) (0.1 mM) ou análogo do PACAP-38 (50 µg/rato) associados a MeCh na dose de 4,25 mg/L. A resistência pulmonar total (RL) foi registrada antes e 2 min após a administração de Mech pelo equipamento pneumomultiteste. A administração MeCh induziu aumento significativo e dose dependente (p<0,05) de RL em comparação com ratos do grupo controle. Terb e PACAP1-38 e análogo do PACAP-38 reverteram, significativamente, a constrição brônquica induzida por Mech, a espessura do músculo liso (SM) e abundância de muco do lume brônquico. O análogo PACAP-38 do mesmo modo que a Terb impediu a responsividade brônquica a MeCh e pode se constituir em um importante regulador no desenvolvimento da doença inflamatório pulmonar. Contudo, o uso do peptídeo nativo para aplicações terapêuticas é limitado por sua baixa estabilidade metabólica. Consequentemente, o análogo metabolicamente estável representa ferramenta promissora no tratamento de doenças pulmonares inflamatórias.


Asunto(s)
Ratas , Adenilil Ciclasas/análisis , Cloruro de Metacolina/análisis , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/análisis , Broncodilatadores/efectos adversos , Cloruro de Metacolina/farmacocinética , Enfermedades Pulmonares/rehabilitación
19.
Asian Pac J Cancer Prev ; 15(20): 8753-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25374202

RESUMEN

BACKGROUND: Glioma is a heterogeneous central nervous system (CNS) tumor group that encompasses different histological subtypes with high variability in prognosis. The lesions account for almost 80% of primary malignant brain tumors. The aim of this study is to extend our understanding of the glioma epidemiology in the central Tunisian region. MATERIALS AND METHODS: We analyzed 393 gliomas recorded in cancer registry of central Tunisia from 1993 to 2012. Crude incidence rates (CR) and world age-standardized rates (ASR) were estimated using annual population data size and age structure. Statistic correlations were established using Chi-square and Kaplan-Meier test. RESULTS: Tunisian glioma patients were identified with a mean age at diagnosis of 48 years and 1.5 sex ratio (male/female). During the 19 years period of study the highest incidence value was observed in male group between 1998 and 2002 (CR: 0.28, ASR: 0.3). Incidence results underline increasing high grade glioma occurring in the adulthood in the last period (2007-2012). Median survival was 27 months, with 1-, 2- and 5-year survival rates of 42%, 30% and 26%, respectively. Survival was greater in patients with younger age, lower tumor grade, infratentrial tumor location and undergoing a palliative treatment. CONCLUSIONS: This central Tunisia gliomas registry study provides important information that could improve glioma management and healthcare practice.


Asunto(s)
Neoplasias Encefálicas/epidemiología , Glioma/epidemiología , Sistema de Registros , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Distribución de Chi-Cuadrado , Países en Desarrollo , Supervivencia sin Enfermedad , Femenino , Glioma/patología , Glioma/terapia , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Estudios Retrospectivos , Distribución por Sexo , Análisis de Supervivencia , Túnez/epidemiología , Adulto Joven
20.
Int J Surg Case Rep ; 5(11): 787-8, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25290382

RESUMEN

INTRODUCTION: Choriocarcinoma is a highly malignant trophoblastic neoplasm. Its association with ectopic pregnancy is very rare and usually with aggressive behavior. PRESENTATION OF CASE: We report a new case arising in an interstitial pregnancy occurring in a 46-year-old woman. The patient was admitted for severe pelvic pain and abundant metrorrhagia. One month ago, she had had a laparoscopic resection of an interstitial pregnancy subsequent to failure of chemotherapy by methotrexate. The raise of serum ßhCG level and the hyperechoic intrauterine mass were in favor of gestational trophoblastic disease. Urgent laparotomy was performed for circulatory collapse. Hysterectomy was done. Histological examination revealed a choriocarcinoma. The patient underwent chemotherapy. Two years later, neither metastasis nor recurrence was detected. DISCUSSION: Clinical diagnosis of primary interstitial choriocarcinoma is difficult, since it is rare and manifesting by non-specific abnormal vaginal bleeding. Imaging findings are also not helpful in ectopic location. The frequency of metastasis is related to the delayed diagnosis. Serial measurement of ßhCG level was the most useful marker of diagnosis and follow up. Histopathological examination remains the only tool of the precise diagnosis. Choriocarcinoma has a very good prognosis even in advanced stages, since it is very chemosensitive. CONCLUSION: The current trend of the treatment of ectopic pregnancy by conservative surgery requires adequate monitoring of ßhCG and careful examination of pathologic specimens to avoid misdiagnosis of ectopic gestational trophoblastic disease.

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