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Colorectal cancer (CRC) is a serious public health problem known to have a multifactorial etiology. The association between gut microbiota and CRC has been widely studied; however, the link between archaea and CRC has not been sufficiently studied. To investigate the involvement of archaea in colorectal carcinogenesis, we performed a metagenomic analysis of 68 formalin-embedded paraffin fixed tissues from tumoral (n = 33) and healthy mucosa (n = 35) collected from 35 CRC Tunisian patients. We used two DNA extraction methods: Generead DNA FFPE kit (Qiagen, Germantown, MD, USA) and Chelex. We then sequenced the samples using Illumina Miseq. Interestingly, DNA extraction exclusively using Chelex generated enough DNA for sequencing of all samples. After data filtering and processing, we reported the presence of archaeal sequences, which represented 0.33% of all the reads generated. In terms of abundance, we highlighted a depletion in methanogens and an enrichment in Halobacteria in the tumor tissues, while the correlation analysis revealed a significant association between the Halobacteria and the tumor mucosa (p < 0.05). We reported a strong correlation between Natrialba magadii, Sulfolobus acidocaldarius, and tumor tissues, and a weak correlation between Methanococcus voltae and healthy adjacent mucosa. Here, we demonstrated the feasibility of archaeome analysis from formol fixed paraffin-embedded (FFPE) tissues using simple protocols ranging from sampling to data analysis, and reported a significant association between Halobacteria and tumor tissues in Tunisian patients with CRC. The importance of our study is that it represents the first metagenomic analysis of Tunisian CRC patients' gut microbiome, which consists of sequencing DNA extracted from paired tumor-adjacent FFPE tissues collected from CRC patients. The detection of archaeal sequences in our samples confirms the feasibility of carrying out an archaeome analysis from FFPE tissues using a simple DNA extraction protocol. Our analysis revealed the enrichment of Halobacteria, especially Natrialba magadii, in tumor mucosa compared to the normal mucosa in CRC Tunisian patients. Other species were also associated with CRC, including Sulfolobus acidocaldarius and Methanococcus voltae, which is a methanogenic archaea; both species were found to be correlated with adjacent healthy tissues.
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Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous histiocytoma (MFH) and colon carcinoma (RKO), we demonstrate the migration and invasion advantage of tetraploid cells in vitro using several assays, including the wound healing, the OrisTM two-dimensional cell migration, single-cell migration tracking by video microscopy, the Boyden chamber, and the xCELLigence RTCA real-time cell migration. Motility advantage was observed despite tetraploid cell proliferation weakness. We could also demonstrate preferential metastatic potential in vivo for the tetraploid clone using the tail vein injection in mice and tracking metastatic tumors in the lung. Using the Mitelman Database of Chromosome Aberrations in Cancer, we found an accumulation of polyploid karyotypes in metastatic tumors compared to primary ones. This work reveals the clinical relevance of the polyploid subpopulation and the strategic need to highlight polyploidy in preclinical studies as a therapeutic target for metastasis.
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Neoplasias del Colon , Tetraploidía , Humanos , Animales , Ratones , Poliploidía , Aberraciones Cromosómicas , Neoplasias del Colon/genética , Neoplasias del Colon/tratamiento farmacológicoRESUMEN
Background: Congenital epulis is a benign gingival tumor whose differential diagnosis includes other oral-facial masses such as teratoma, hemangioma, lymphatic malformation and dermoid cysts. This tumor can cause obstruction of the airway or feeding problems in the newborn. Surgical excision is the treatment of choice. Case Report: We present a case of congenital epulis, diagnosed prenatally with ultrasonography. Conclusion: Although difficult, a defined prenatal image of congenital epulis is possible by means of accurate high-resolution ultrasonography. It facilitates the narrowing down of differential diagnosis. The confirmatory final diagnosis relies on histopathological examination.
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Neoplasias Gingivales , Hemangioma , Embarazo , Femenino , Recién Nacido , Humanos , Neoplasias Gingivales/diagnóstico por imagen , Neoplasias Gingivales/congénito , Ultrasonografía Prenatal/métodos , Diagnóstico Diferencial , Hemangioma/diagnósticoRESUMEN
Background: Breast phyllodes tumor has a distinct histologic appearance. There are no pediatric phyllodes tumors of the bladder in English literature reported. Case report: A 2-year-old boy presented with a urinary infection and obstructive urinary symptoms. A 3-cm slow-growing bladder mass revealed by repeated transabdominal ultrasonography was initially considered a ureterocele. Cystoscopic and laparoscopic exploration using pneumovesicum confirmed the diagnosis of a bladder neck tumor. Histologically, the features were of a benign phyllodes tumor, morphologically similar to those seen in breast tissue. The patient received no further treatment and showed no recurrence or metastasis. Conclusion: Phyllodes tumor can cause a pediatric bladder tumor.
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Neoplasias de la Mama , Tumor Filoide , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Niño , Preescolar , Tumor Filoide/diagnóstico , Tumor Filoide/cirugía , Tumor Filoide/patología , Vejiga Urinaria , Mastectomía , Neoplasias de la Vejiga Urinaria/diagnósticoRESUMEN
BACKGROUND: CD155 immune checkpoint has recently emerged as a compelling immunotherapeutic target. Epigenetic DNA methylation changes are recognized as key molecular mechanisms in cancer development. Hence, the identification of methylation markers that are sensitive and specific for breast cancer may improve early detection and predict prognosis. We speculate that CD155 promoter methylation can be a valuable epigenetic biomarker, based upon strong indications for its immunoregulatory functions. METHODS: Methylation analyses were conducted on 14 CpGs sites in the CD155 promoter region by bisulfite pyrosequencing. To elucidate the related gene expression changes, a transcriptional study using RT-qPCR was performed. Statistical analyses were performed to evaluate correlations of CD155 methylation profiles with mRNA expression together with clinical-pathological features, prognosis and immune infiltrate. RESULTS: CD155 promoter methylation profile was significantly associated with SBR grade, tumor size, molecular subgroups, HER2 and hormonal receptors expression status. Low CD155 methylation rates correlated with better prognosis in univariate cox proportional hazard analysis and appeared as an independent survival predictor in cox-regression multivariate analysis. Further, methylation changes at CD155 specific CpG sites were consistent with CD155 membranous mRNA isoform expression status. Statistical analyses also showed a significant association with immune Natural Killer cell infiltrate when looking at the CpG7, CpG8, CpG9 and CpG11 sites. CONCLUSION: Altogether, our results contribute to a better understanding of the impact of CD155 immune checkpoint modality expression in breast tumors, revealing for the first time that specific CpG sites from CD155 promoter may be a potential biomarker in breast cancer monitoring.
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Neoplasias de la Mama , Neoplasias de la Mama/metabolismo , Islas de CpG , Metilación de ADN , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Regiones Promotoras Genéticas , Receptores ViralesRESUMEN
BACKGROUND: The tumor phenotype may change between primary and metastatic breast cancer. We compared the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 in a series of primary breast carcinomas (PBC) with their metastatic relapses and analyzed the impact of any changes on survival. MATERIALS AND METHODS: It was a single-center retrospective study, collecting consecutive cases of metastatic breast carcinoma diagnosed in the pathology and medical oncology departments at Habib Bourguiba University Hospital in Sfax, Tunisia. An immunohistochemical study was used to assess ER, PR, and HER2 expression. Overall survival (OS) and post-metastasis survival (PMS) were evaluated using multivariable Cox regression analysis. RESULTS: Our study included 68 patients. ER and PR status changed in 29.4 % and 39.7 % of cases, respectively. Conversions were mainly from positive to negative status (22 % and 23.5 % for ER and PR, respectively). Differences in HER2 status were observed in 19.6 % of cases, with loss of overexpression in 6 patients (10.7 %). Adjuvant trastuzumab therapy and PBC molecular subtype (HR-, HER2+) were associated with HER2 status discordance (p = 0.02 and 0.03, respectively). On multivariable analysis, HR-negative conversion tumors were significantly associated with a worse OS (p = 0.042) and PMS (p < 0.001), compared to HR-concordant positive tumors. CONCLUSION: This study establishes that HR and HER2 status discordance between primary and metastatic breast carcinoma has a prognostic impact on patient outcome. Analyzing these receptors' status in all newly diagnosed cases of metastatic breast carcinoma is strongly recommended and would provide information for changing treatment strategies.
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Neoplasias de la Mama , Metástasis de la Neoplasia , Femenino , Humanos , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Estudios RetrospectivosRESUMEN
BACKGROUND: The incidence of breast cancer (BC) and/or ovarian cancer (OC) is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region. METHODS: We sequenced the entire coding regions of BRCA1and BRCA2 genes using next generation sequencing (NGS) in 134 selected patients with BC and/or OC. RESULTS: Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshift index (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A > T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p = 0.029) and TNBC cases (p = 0.008). In the groups of patients aged between 31 and 40, and 41-50 years, BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p = 0.001, and p = 0.044 respectively). CONCLUSIONS: The overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast/ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA in BRCA2 gene and the c.5030_5033 delCTAA in BRCA1 gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of BC and/or OC.
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Neoplasias de la Mama , Neoplasias Ováricas , Adulto , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Femenino , Genes BRCA2 , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal/genética , Humanos , Persona de Mediana Edad , Mutación/genética , Neoplasias Ováricas/genética , TúnezRESUMEN
Ovarian adrenal rest tumors (OART) are tumors that develop in females with congenital adrenal hyperplasia (CAH). In contrast to their counterpart in testicles, they are exceptional and few cases have been reported in the literature. In this report, we present clinicopathological findings of a female patient with CAH due to 21-hydroxylase deficiency who was incidentally diagnosed with OART with a review of the literature. The 14-year-old patient, who was raised as a boy, developed a virilizing syndrome with high testosterone levels that were attributed to non adherence to her replacement corticosteroid therapy. She consulted for sex reassignment surgery. Pelvic ultrasound was normal. She underwent hysterectomy and bilateral adnexectomy. No abnormalities were noticed during the operation. Grossly, both ovaries were variegated with well circumscribed and lobulated, brownish-yellow nodules. Histologically, the nodules were composed of nests of large polygonal cells with centrally located nuclei and prominent nucleoli. There was mild atypia and no crystals of Reinke. Thus, the findings of the histopathological examination were consistent with bilateral OART. Histological differential diagnosis of OART can be challenging particularly with leydig cell tumor, stromal luteoma and steroid cell tumors, not otherwise specified. OART must be considered in women with CAH and persistent virilizing symptoms despite negative imaging results.
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Hiperplasia Suprarrenal Congénita/complicaciones , Tumor de Resto Suprarrenal/diagnóstico , Neoplasias Ováricas/diagnóstico , Procedimientos de Reasignación de Sexo , Adolescente , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/fisiopatología , Hiperplasia Suprarrenal Congénita/cirugía , Tumor de Resto Suprarrenal/etiología , Tumor de Resto Suprarrenal/cirugía , Femenino , Humanos , Hallazgos Incidentales , Masculino , Neoplasias Ováricas/etiología , Neoplasias Ováricas/cirugía , Personas Transgénero , VirilismoRESUMEN
Male Breast Cancer (MBC) is a rare and aggressive disease that is associated with genetic factors. Mutations in BRCA1 and BRCA2 account for 10% of all MBC cases suggesting that other genetic factors are involved. The aim of the present study is to screen whole BRCA1 and BRCA2 exons using the Ampliseq BRCA panel in Tunisian MBC patients with family history. Furthermore, we performed exome sequencing using the TruSight One sequencing panel on an early onset BRCA negative patient. We showed that among the 6 MBC patients, only one (MBC-F1) harbored a novel frameshift mutation in exon 2 of the BRCA2 gene (c.17-20delAAGA, p.Lys6Xfs) resulting in a short BRCA2 protein of only 6 amino-acids. We selected 9 rare variants after applying several filter steps on the exome sequencing data. Among these variants, and based on their role in breast carcinogenesis, we retained 6 candidate genes (MSH5, DCC, ERBB3, NOTCH3, DIAPH1, and DNAH11). Further studies are needed to confirm the association of the selected genes with family MBC.
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Proteína BRCA2/genética , Neoplasias de la Mama Masculina/genética , Predisposición Genética a la Enfermedad , Adulto , Anciano , Dineínas Axonemales/genética , Proteína BRCA1/genética , Neoplasias de la Mama Masculina/congénito , Neoplasias de la Mama Masculina/diagnóstico por imagen , Neoplasias de la Mama Masculina/patología , Proteínas de Ciclo Celular/genética , Receptor DCC/genética , Forminas/genética , Mutación del Sistema de Lectura , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Linaje , Receptor ErbB-3/genética , Receptor Notch3/genética , Transducción de Señal/genética , Túnez , Secuenciación del ExomaRESUMEN
INTRODUCTION: Mucinous colorectal carcinoma (MC) is a rare subtype of colorectal adenocarcinoma known to be associated with bad prognosis. Lately, research has turned to identify new prognostic markers allowing the use of targeted therapy. The aim of our study is to evaluate the prognostic impact of E-cadherin and Cox-2expression in MC. MATERIALS AND METHOD: A total of 40 formalin-fixed, paraffin-embedded MC specimens were collected within a period of 13 years and were studied for the expression of the two proteins. We used SPSS 22 software to study associations with clinicopathological parameters and overall survival (OS). RESULTS: A reduced or absent E-cadherin expression was noted in 52.5% of cases. It was associated with distant metastases (p = 0.049) and venous invasion (p = 0.049). Cox-2 was overexpressed in 17.5% of cases. It was associated with negative lymph node status (p = 0.020) and with early stage tumor (p = 0.020). A significant association between the two proteins was also noted (p = 0.04). No significant association with OS was found; However, there was an improvement in the survival of patients overexpressing Cox-2 (p = 0.16). CONCLUSION: Our findings link the loss of E-cadherin expression with spread and aggressiveness in MC and Cox-2 overexpression with better prognosis and survival. Because MC has a distinct genetic pathway we encourage the analysis of MSI and Cox-2 expression in all MC. Cox-2 inhibitors may not be effective chemopreventative agents in the setting of defective DNA mismatch repair. More molecular studies are needed to better understand the role of these markers and their prognostic significance in MC.
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Adenocarcinoma Mucinoso/patología , Antígenos CD/metabolismo , Cadherinas/metabolismo , Neoplasias Colorrectales/patología , Ciclooxigenasa 2/metabolismo , Adenocarcinoma Mucinoso/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Pronóstico , TúnezRESUMEN
The transcription factor FOXA1 (forkhead box A1) plays key roles in tumor development and progression. In the present study, we analyzed the expression of FOXA1 in 52 breast tumors and 10 normal tissues, and investigated the relationship between FOXA1 and two EMT markers, namely Twist1 and E-cadherin by RT-PCR and IHC respectively. The expression level of FOXA1 was higher in tumor compared to normal tissues but the difference was not statistically significant (P = 0.138). FOXA1 expression correlated with less aggressive behavior as SBR grade I (P = 0.04), small tumors size (P = 0.05), and longer survival (P = 0.001). Furthermore, estrogen and progesterone positive tumors exhibit high level of FOXA1 (P = 0.002 and P = 0.038 respectively). Survival analysis showed that patients with ER positive/FOXA1 positive (P log rank = 0.001), PR positive/FOXA1 positive (P log rank = 0.044) and HER-2 negative/FOXA1 positive (P log rank = 0.002) tumors have a significant prolonged overall survival. On the other hand, the expression of E-cadherin positively correlated with FOXA1 (P = 0.028), whereas negative association was seen between the expression of Twist1 and FOXA1 (P = 0.016). Kaplan-Meier plots showed that patients with Twist1negative/FOXA1positive tumors have a significant prolonged overall survival (P log rank = 0.001) and FOXA1 appeared as independent predictors of patient survival in multivariate analyses. Overall, our results indicate that FOXA1 could be a useful biomarker to predict prognosis in breast cancer patients.
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Antígenos CD/genética , Neoplasias de la Mama/genética , Cadherinas/genética , Factor Nuclear 3-alfa del Hepatocito/genética , Proteínas Nucleares/genética , Proteína 1 Relacionada con Twist/genética , Adulto , Anciano , Antígenos CD/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Mama/metabolismo , Neoplasias de la Mama/metabolismo , Cadherinas/metabolismo , Femenino , Factor Nuclear 3-alfa del Hepatocito/metabolismo , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Proteínas Nucleares/metabolismo , Pronóstico , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Análisis de Supervivencia , Transcriptoma , Proteína 1 Relacionada con Twist/metabolismoRESUMEN
BACKGROUND: The histopathological examination of cholecystectomy specimens has not been standardized with a debate concerning the routine and the selective approach. The aim of this study was to assess the information obtained from routine histopathological examination of cholecystectomy specimens. METHODS: All histopathological reports of cholecystectomy specimens between January 2003 and December 2016 were analyzed, including a clinical diagnosis of benign gallstone disease or cholecystitis. RESULTS: A total of 20,584 reports were examined. The mean age of patients was 54.2 years. Patients aged more than 60 years represent 37.6% of the study population. Of all patients, 15,973 (77.6%) were females. Incidental gallbladder cancers (GBC) were present in 155 cholecystectomies specimens (0.8%). 67.1% of GBC are at T2 and T3 stage. Granulomatous cholecystitis was diagnosed in only 19 cases (0.1%). GBC were more prevalent in older patients (P < 10-6) and cholesterolosis was more prevalent in young patients (P < 10-6). There was no gender predilection for GBC (P = 0.739). CONCLUSIONS: The rate of incidental gallbladder carcinoma in our study is low, yet, we found a higher proportion of T2 and T3 carcinomas stage. Granulomatous cholecystitis may need further investigations and treatments. When a selective approch of histopathological examination of cholecystectomy specimens is used, it is important to take into account that clinical parameters are significantly associated with gallbladder cancer.
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Colecistectomía , Colecistitis/patología , Colecistitis/cirugía , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/cirugía , Cálculos Biliares/patología , Cálculos Biliares/cirugía , Hallazgos Incidentales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Niño , Preescolar , Colecistitis/epidemiología , Femenino , Cálculos Biliares/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prevalencia , Túnez/epidemiología , Adulto JovenRESUMEN
INTRODUCTION: Tuberculosis (TBC) is a major public health problem with high mortality especially in developing countries. It is associated with a higher risk of developing pulmonary and non-pulmonary malignancies including solid and hematologic cancers. Association between TBC and nonpulmonary malignancies is rarely described in the literature. AIM: To describe the epidemiological, clinical, therapeutic modalities and the evolutive aspects of patients treated for cancer and TBC. METHODS: This is a retrospective study conducted over a period of 19 years (between 1993 and 2012), including 10 patients followed up for cancer and tuberculosis at the department of oncology and the department of infectious disease, CHU Habib Bourguiba Hospital and CHU HediChaker, Sfax, Tunisia. RESULTS: The average age of patients was 55 years old. The sex ratio was 1. The different locations of cancer were represented by the breast (4 cases), the nasopharynx (1 case), the colon (1 case), the kidney (1 case) the gum (1 case), the endometrium (1 case) and the blood (1 case).TBC and cancer were synchronous in 5 cases. Concerning the metachronous presentation that interested 5 patients, the average time betweenthe onset of TBC after cancer diagnosis was 3.5 years. Three of these patients were treated by chemotherapy with radiation therapy. TBClocalization was nodal in 6 cases, spinal one case, nasopharyngeal in one case, peritoneal in one case and urogenital in one case. The diagnosisof TBC was made incidentally in two cases during axillary lymph node dissection. The therapeutic management of cancer was based on surgery,chemotherapy and / or radiotherapy. All patients received anti TBC treatment for at least six months. Surgery was indicated in one case(laminectomy). A complete remission of cancer was observed in 9 patients. Concerning TBC, recovery was observed in 8 patients, 1 patient hada spinal recurrence and 1 patient is being treated. CONCLUSION: Chronic inflammation during TBC can lead to cancer development. The etiopathogenesis of this association is still imperfectly known. Association between TBC and non-pulmonary cancer, although rare, should be always kept in mind in order to handle in time these two diseases in order provide the best chances of recovery for patients.
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Antituberculosos/administración & dosificación , Neoplasias/epidemiología , Tuberculosis/complicaciones , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/patología , Neoplasias/terapia , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Tuberculosis/diagnóstico , Tuberculosis/epidemiologíaRESUMEN
MicroRNAs are emergent players of epigenetics that function as oncogenes or tumor suppressors and that have been implicated in regulating diverse cellular pathways. MiR-10b is an oncogenic microRNA involved in tumor invasion and metastasis in various cancers. Our data have shown that miR-10b is overexpressed in colorectal cancer samples in comparison with non-tumorous adjacent mucosa (p = 0.0025) and that it is associated with severe features such as tumor size >5 cm (p = 0.023), distant metastasis (p = 0.0022), non-differentiated tumors (p = 0.016), and vascular invasion (p = 0.01). Regarding the regulation of its expression, positive correlation between the loss of miR-10b and aberrant DNA methylation (p = 0.02) as well as a loss of TWIST-1 messenger RNA (p = 0.018) have been observed. Furthermore, expression analysis of the downstream miR-10b targets has shown that there are associations between low HOXD10 messenger RNA and E-cadherin protein levels (p < 0.0001, p = 0.0008, respectively) and overexpression of miR-10b. Our data suggests that overexpression of miR-10b results from high levels of TWIST-1 and may induce a decrease of E-cadherin membranous protein levels, thus contributing to the acquisition of metastatic phenotypes in colorectal cancer.
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Cadherinas/biosíntesis , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Metilación de ADN/genética , Proteínas de Homeodominio/genética , MicroARNs/biosíntesis , Proteínas Nucleares/biosíntesis , Factores de Transcripción/genética , Proteína 1 Relacionada con Twist/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Islas de CpG/genética , Femenino , Células HT29 , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Proteínas Nucleares/genética , ARN Mensajero/genética , Proteína 1 Relacionada con Twist/genéticaRESUMEN
BACKGROUND: Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats. METHODS: We determinate the antioxidant activity by ABTS .+ and antioxidant total capacity (TAC) of all extracts of C. scolymus leaves, the inhibition of α-amylase activity in vitro was also investigated. Forty male Wistar rats were induced to diabetes with a single dose intraperitoneal injection (i.p.) of alloxan (150 mg/kg body weight (b.w.)). Diabetic rats were orally and daily administrated of ethanol extract from C. scolymus at two doses (200-400 mg/kg, b.w) or (12 mg/kg, b.w) with anti-diabetic reference drug, Acarbose for one month. Ethanol extract of C. scolymus effect was confirmed by biochemical analysis, antioxidant activity and histological study. RESULTS: The results indicated that the ethanol extract from leaves of C. scolymus showed the highest antioxidant activity by ABTS .+ (499.43g± 39.72 Trolox/g dry extract) and (128.75 ± 8.45 mg VC /g dry extract) for TAC and endowed the powerful inhibition in vitro of α-amylase activity with IC50=72,22 ug/uL. In vivo, the results showed that ethanol extract from the leaves of C. scolymus (200-400 mg/kg) decreased significantly (p < 0.001) the α-amylase levels in serum of diabetic rats, respectively associated with significant reduction (p < 0.001) in blood glucose rate of 42,84% and 37,91% compared to diabetic groups after 28 days of treatment, a significant lowered of plasma total cholesterol (T-Ch) by 18,11% and triglyceride (TG) by 60,47%, significantly and low-density lipoproteins (LDL-C) by 37,77%, compared to diabetic rats, moreover, the administration of ethanol extract appears to exert anti-oxidative activity demonstrated by the increase of CAT, SOD and GSH activities in liver, kidney and pancreas of diabetic rats. This positive effect of the ethanol extract from C. scolymus was confirmed by histological study. CONCLUSION: These observed strongly suggest that ethanol extract from the leaves of C. scolymus has anti-hyperglycemic properties, at least partly mediated by antioxidant and hypolipidemic effects.
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Cynara scolymus/química , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Enfermedades Metabólicas/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Aloxano/efectos adversos , Animales , Glucemia/metabolismo , Diabetes Mellitus/enzimología , Diabetes Mellitus/metabolismo , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Lipoproteínas LDL/metabolismo , Masculino , Enfermedades Metabólicas/enzimología , Enfermedades Metabólicas/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Ratas , Ratas Wistar , alfa-Amilasas/metabolismoRESUMEN
Chronic inflammation increases the risk of development of human malignancies. iNOS is an enzyme dominantly expressed during inflammatory reactions and seems to play a critical role in tumorigenesis. Our aim was to assess the iNOS expression in four types of human tumors: breast, colorectal, nasopharyngeal, and melanoma, of Tunisian patients. The level of iNOS was measured by RT-QPCR in tumor specimens. We showed that the expression of iNOS was higher in breast compared to colorectal and nasopharyngeal tumors, whereas in melanoma, the level of iNOS expression was low. Significant associations were found when comparing the iNOS expression in cancers pairs such as melanoma versus colorectal (p < 0.0001), colorectal versus nasopharyngeal (p = 0.0072), and melanoma versus breast (p < 0.0001). Furthermore, iNOS expression correlated with the Breslow thickness, Clark level, and histological subtype in melanoma, while in nasopharyngeal carcinoma, significant association was seen with age at diagnosis, TNM, metastasis, response to treatment, and expression of COX-2. Furthermore, the expression of iNOS correlated with tumor size, TNM, tumor location, and histological type in colorectal cancer, and with tumor size, tumor stage, SBR grade, and triple negative cases in breast cancer. On the other hand, immunohistochemistry analysis shows that the expression of iNOS is observed in the stroma and tumor cells as well. Overall, our results highlight that iNOS is a reliable marker for advanced stage and aggressive behavior for the four types of cancer and might be a potential promising therapeutic target.
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Neoplasias de la Mama/genética , Neoplasias Colorrectales/genética , Melanoma/genética , Neoplasias Nasofaríngeas/genética , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Adulto , Anciano , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Ciclooxigenasa 2/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Melanoma/epidemiología , Melanoma/patología , Persona de Mediana Edad , Neoplasias Nasofaríngeas/epidemiología , Neoplasias Nasofaríngeas/patología , Estadificación de Neoplasias , Óxido Nítrico Sintasa de Tipo II/genética , Túnez/epidemiologíaRESUMEN
Tubulo-papillary apocrine adenoma (TAA) is a very rare sweat gland tumor. TAA in association with syringocystadenoma papilliferum (SCP) is exceptional. A 2-year-old Tunisian child developed a mixed tumor on the scalp: TAA in association with SCP. Histologically, the tumor consisted of dilated duct-like areas with some apocrine gland-like areas. The superficial part of the tumor was connected to the epidermis and showed the characteristics of SCP. The characteristics and differences in histopathologic and immunohistochemical findings in this mixed tumor are described.
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Adenoma de las Glándulas Sudoríparas/patología , Adenoma/patología , Neoplasias de Cabeza y Cuello/patología , Neoplasias Primarias Múltiples/patología , Cuero Cabelludo/patología , Neoplasias de las Glándulas Sudoríparas/patología , Adenoma de las Glándulas Sudoríparas/diagnóstico , Preescolar , Neoplasias de Cabeza y Cuello/diagnóstico , Humanos , Masculino , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias de las Glándulas Sudoríparas/diagnósticoRESUMEN
BACKGROUND: Myoepthelioma is a rare salivary gland tumor which is usually located in parotid gland and in minor salivary glands. CASE REPORT: We report a case of myoepithelioma arising in an accessory paritid gland in a 47-yearold woman who presented with a slowly expanding subcutaneous nodule on the left cheek, that was within the parotid gland at surgical resection . This tumor was composed of spindle cells. Immunophenotypical characterization demonstrated its myoepithelial nature. CONCLUSION: In the subcutaneous tissue, this unusual neoplasm may be confused with soft tissue tumors showing spindle cell features.
RESUMEN
PURPOSE: Appendicitis is by far the commonest major emergency general surgical operation. Histopathological examination of the appendix is routinely performed. METHODS: This study is a retrospective analysis of 24,697 appendectomies performed from January 2003 to December 2011. Pathological reports were analyzed for the following parameters: age, gender, and pathological diagnosis. RESULTS: Appendectomy specimens represent 17 % of all pathological reports. Acute appendicitis was present in 19,637 (79.5 %) patients. The perforation rate was 6.3 % and was significantly higher in adult patients. The negative appendectomy rate was 15 % and was significantly higher in female and adult patients. The incidence of negative appendectomies had clearly decreased over the 9-year period distribution. Incidental unexpected pathological diagnoses were noted in 226 (0.9 %) appendectomy specimens. Neoplastic lesions were present in 171 cases (0.7 %); they include carcinoid, adenocarcinoma, and mucinous neoplasms. CONCLUSIONS: Routine pathological examination of appendectomy specimens is expensive. With advances in technology and imaging modalities, the diagnosis of acute appendicitis has improved, with a subsequent significant reduction in negative appendectomy. There are still a number of unusual diagnoses found in appendicectomy specimens supporting the continued use of routine histology.
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Apendicectomía , Apéndice/patología , Adulto , Factores de Edad , Femenino , Humanos , MasculinoRESUMEN
INTRODUCTION AND IMPORTANCE: Supernumerary ribs are very rare. They may occur at any level of the spine. We present here a case of an unusual localization of an extra rib that has not been previously described in the literature. CASE PRESENTATION: A 4-year-old girl, with no medical history, presented with a congenital deformity in the sternal region mimicking a tail. The tail-like structure had a bony axis and was covered by normal skin and hairs. A computed tomography of the chest demonstrated that this structure was an abnormal bone articulated with the the sternum. For cosmetic purposes, we have decided to resect the malformation. On histopathological examination, it was a supernumerary rib. CLINICAL DISCUSSION: A review of the literature reveals a global incidence of cervical ribs ranging from 0.04 % up to 4.5 %, intrathoracic ribs in about 50 cases to date and very few reports on supernumerary ribs in the lumbar and sacral region. We were unable to find any similar cases of supernumerary ribs in the sternum. CONCLUSION: Supernumerary ribs are rare and benign congenital anomalies. This case report describes an unusual localization of an extra rib in the sternum mimicking a tail.