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1.
Medicina (Kaunas) ; 57(2)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525370

RESUMEN

Background and Objectives: Large cell neuroendocrine cancer is characterised by poor prognosis. The standard of treatment is still not established. The aim of this study was to assess the predictive factors of overall survival (OS) and progression-free survival (PFS) of pulmonary large cell neuroendocrine carcinoma (LCNEC) and combined LCNEC. Materials and Methods: All patients had confirmed pathology stage I-IV disease recorded between period 2002-2018. Survival curves were estimated by Kaplan-Meier method. Uni- and multivariable analysis was conducted using Cox-regression analysis. Results: A total of 132 patients with LCNEC and combined LCNEC were included. Half of them had clinical stage IIIB/C-IV. Patients were treated with radical (n = 67, including surgery alone; resection with neo-adjuvant or adjuvant chemotherapy, radiochemotherapy, or adjuvant radiotherapy; patients treated with radiochemotherapy alone), palliative (n = 41) or symptomatic (n = 24) intention. Seventeen patients were treated with resection margin R1 or R2. Non-small cell carcinoma (NSCLC) chemotherapy (platinum-vinorelbine; PN schedule) and small-cell lung carcinoma (SCLC) chemotherapy approaches (platinum/carboplatinum-etoposide; PE/KE schedule) were administered in 20 and in 55 patients, respectively. The median (95% Confidence Interval (CI)) OS and PFS were 17 months (9.0-36.2 months) and 7 months (3.0-15.0 months), respectively. Patients treated with negative resection margin, with lower clinical stage, without lymph node metastasis, and with size of primary tumour ≤4 cm showed significantly better OS and PFS. The main risk factors with an adverse effect on survival were advanced CS and positive resection margin. Conclusions: Patients with LCNEC characterized poor prognosis. Independent prognostic factors influencing PFS were initial clinical stage and resection margin R0 vs. R1-2.


Asunto(s)
Carcinoma de Células Grandes , Carcinoma Neuroendocrino , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Células Grandes/patología , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/cirugía , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Estadificación de Neoplasias , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico
2.
J Clin Med ; 9(5)2020 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-32392725

RESUMEN

Large-cell neuroendocrine carcinoma (LCNEC) is a rare malignancy with poor prognosis. The rationale of the study was to determine the survival of LCNEC patients in I-IIIA clinical stages who underwent resection. A total of 53 LCNEC (89%) and combined LCNEC (11%) patients in stages I-IIIA who underwent surgery with radical intent between 2002-2018 were included in the current study. Overall survival (OS) and time to recurrence (TTR) were estimated. Uni- and multivariable analyses were conducted using Cox-regression model. Patients were treated with surgery alone (51%), surgery with radiochemotherapy (4%), with radiotherapy (2%), with adjuvant chemotherapy (41%), or with neoadjuvant chemotherapy (2%). The median (95% Confidence Interval (CI)) OS and TTR was 52 months (20.1-102.1 months) and 20 months (7.0-75.6 months), respectively. Patients treated in clinical stage I showed better OS than patients in stages II-IIIA (p = 0.008). Patients with R0 resection margin (negative margin, no tumor at the margin) and without lymph node metastasis had significantly better TTR. In the multivariate analysis, age was an independent factor influencing OS. Recurrence within 1 year was noted in more than half cases of LCNEC. R0 resection margin and N0 status (no lymph node metastasis) were factors improving TTR. Age >64 years was observed as a main independent factor influencing OS.

3.
Mol Clin Oncol ; 6(2): 243-248, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28357103

RESUMEN

Angiogenesis in the primary tumor is known to be necessary for tumor progression in adenocarcinomas of the colon. However, whether angiogenesis in the primary tumors of patients with colorectal cancer affects their prognosis has yet to be fully elucidated. The aim of the present study was to assess the association between selected pathoclinical parameters and overall survival of resectable colorectal cancer patients with the expression of angiogenesis-promoting factors, including vascular endothelial growth factor (VEGF) and Fms-like tyrosine kinase receptor (Flt-1), and microvessel density (MVD) in the primary tumor. VEGF and Flt-1 expression were assessed, as well as MVD (with anti-CD34) by immunohistochemistry in 139 archived primary colorectal cancer tissue samples. These results were compared with the overall survival of the patients and potential prognostic pathoclinical parameters. A higher MVD in the tumors expressing Flt-1 (P=0.04) was identified. However, there was no correlation between the pathoclinical parameters of colon cancer and Flt-1 expression, VEGF expression, or MVD in the tumor. Furthermore, the intensity of VEGF expression, Flt-1 expression and tumor MVD did not correlate with the overall survival of the patients. Therefore, although increased expression of VEGF and Flt-1 was correlated with an increased expression of MVD in the primary tumors of resectable colorectal cancer patients, these factors were not correlated with prognostic pathoclinical factors and overall survival.

4.
Sarcoidosis Vasc Diffuse Lung Dis ; 30(4): 317-20, 2013 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-24351624

RESUMEN

A pulmonary alveolar proteinosis (PAP) is a rare disease characterized by an accumulation of surfactant components in lung alveoli. In diagnosis and monitoring of the disease high resolution computed tomography (HRCT) is usually used. Unfortunately, repeated exposure to CT scanning may be associated with an increased risk of radiation. We present a patient in whom repeated transthoracic lung ultrasonography (TLUS) brought parallel to HRCT data in assessing PAP extent. It may indicate that TLUS might be potentially a relevant tool in monitoring of PAP.


Asunto(s)
Proteinosis Alveolar Pulmonar , Tomografía Computarizada por Rayos X , Lavado Broncoalveolar , Humanos , Pulmón/diagnóstico por imagen , Alveolos Pulmonares , Surfactantes Pulmonares , Enfermedades Raras
5.
Hepatobiliary Pancreat Dis Int ; 12(4): 377-84, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23924495

RESUMEN

BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients. METHODS: A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP. RESULTS: Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serum markers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found. CONCLUSIONS: Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.


Asunto(s)
Hígado Graso/sangre , Hígado Graso/complicaciones , Hepatitis C Crónica/complicaciones , Antígenos de Histocompatibilidad Clase I/genética , Sobrecarga de Hierro/sangre , Sobrecarga de Hierro/complicaciones , Cirrosis Hepática/patología , Proteínas de la Membrana/genética , Adulto , Hígado Graso/genética , Hígado Graso/patología , Femenino , Ferritinas/sangre , Hemocromatosis/sangre , Hemocromatosis/genética , Hemocromatosis/patología , Proteína de la Hemocromatosis , Hepatitis C Crónica/patología , Hepatocitos/metabolismo , Humanos , Hierro/sangre , Metabolismo de los Lípidos , Cirrosis Hepática/sangre , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Polimorfismo Genético , Índice de Severidad de la Enfermedad , Transferrina/metabolismo
6.
Clin Lung Cancer ; 14(6): 666-673.e2, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23870818

RESUMEN

BACKGROUND: There is increasing evidence that suggests that particular histopathologic types of non-small-cell lung cancer (NSCLC) display distinct molecular characteristics. We analyzed, in lung squamous cell carcinoma (SCC) and adenocarcinoma (AC), the expression of 8 genes that constitute 2 previously reported prognostic expression signatures in NSCLC. METHODS: Fresh-frozen tumor and normal lung samples were obtained at surgery from 135 patients with stage I-III NSCLC (89 (65.9%) SCC, 46 (34.1%) AC). Expression of CSF1 (colony stimulating factor for macrophages), carbonic anhydrase 9 (CA9), epithelial growth factor receptor (EGFR), dual specificity phosphatase 6 (DUSP6), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3), monocyte to macrophage differentiation-associated (MMD), lymphocyte-specific protein tyrosine kinase (LCK) and signal transducer and activator of transcription 1 (STAT1) was assessed in SCC, AC, and in normal lung by quantitative reverse transcriptase - polymerase chain reaction (qRT-PCR). Metastasis-free survival was analyzed according to the median value of gene expression in the entire NSCLC cohort and separately in SCC and AC. RESULTS: Expression of CA9, CSF1, DUSP6, STAT1, and MMD differed between NSCLC and normal lung. EGFR was more abundant in SCC compared with AC, whereas the reverse was true for DUSP6 and ERBB3. A high expression of CSF1 correlated with shorter metastasis-free survival in the entire NSCLC group (P = .016) and in SCC (P = .049) and AC (P = .034) cohorts. CONCLUSIONS: Several genes considered prognostic in NSCLC showed significantly different expression in SCC and AC, and thus should be analyzed separately in these 2 subtypes for their prognostic significance. CSF1 is similarly expressed in SCC and AC, and portends a poor outcome in the entire group of patients with NSCLC, and in SCC and AC when considered separately.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Factor Estimulante de Colonias de Macrófagos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Anhidrasa Carbónica IX , Anhidrasas Carbónicas/genética , Anhidrasas Carbónicas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Fosfatasa 6 de Especificidad Dual/genética , Fosfatasa 6 de Especificidad Dual/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/genética , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/metabolismo , Linfocinas/genética , Linfocinas/metabolismo , Factor Estimulante de Colonias de Macrófagos/genética , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismo , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo
7.
Surg Innov ; 19(3): 275-80, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22143746

RESUMEN

Duodenal fistula is a significant ongoing surgical problem. Minimal invasive treatment might be an alternative to conventional open surgery. This study aimed to investigate whether addition of gentamicin to fibrin adhesive can augment current surgical methods. Having established a fistula, the defect was closed using the following: simple suturing, suturing covered with fibrin sealant only, or suturing with fibrin sealant mixed with gentamicin. Bursting pressure and macroscopic and microscopic examination were evaluated on the second and sixth day after surgery. The study demonstrated there was no significant difference in overall outcome between the 3 groups. However, on macroscopic examination, the mixture of antibiotic and fibrin adhesive decreased formation of adhesions and abscesses. Microscopically, there was decreased inflammation, improved granulation, and earlier onset of fibrin filament deposition, possibly leading to enhanced wound healing. The addition of gentamicin to fibrin sealant can be a useful adjunct to standard surgical closure in duodenal fistula management.


Asunto(s)
Técnicas de Cierre de Herida Abdominal , Antibacterianos/administración & dosificación , Enfermedades Duodenales/cirugía , Adhesivo de Tejido de Fibrina/administración & dosificación , Gentamicinas/administración & dosificación , Fístula Intestinal/cirugía , Técnicas de Sutura , Animales , Fenómenos Biomecánicos/efectos de los fármacos , Modelos Animales de Enfermedad , Histocitoquímica , Masculino , Ratas , Ratas Wistar , Resultado del Tratamiento
8.
Dis Markers ; 29(5): 207-12, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21206005

RESUMEN

Estimation of HER2 membranous expression is routinely used in breast and gastric cancers, as both a prognostic and a predictive factor. To date there is no evidence for similar application of HER2 expression in colorectal cancer (CRC) cells. In CRC, HER2 is sometimes overexpressed in the cell membrane and very often in the cytoplasm. This study was conducted to determine possible correlations between both membranous and cytoplasmatic expression of HER2 in CRC cells and the outcome of the disease. The prognostic significance of combined staining intensity in the cell membrane and cytoplasm in the entire CRC cell was also investigated. HER2 expression in resectable colorectal adenocarcinoma cells was evaluated by immunohistochemistry in specimens taken from 202 patients. The percentage of cancer cells with membranous or cytoplasmatic reactions and the staining intensity of the reaction in the whole cell were recorded. A membranous reaction was present in 27% of cases, and cytoplasmatic reaction in 66% of cases. The total staining intensity in the entire cell was evaluated as moderate (2+) in 32% of cases and strong (3+) staining in 15%. There was no correlation found between either membranous or cytoplasmatic HER2 expression and survival. Furthermore combined staining intensity did not provide any prognostic information. We conclude that HER2 expression in CRC does not correlate with prognosis.


Asunto(s)
Adenocarcinoma Mucinoso/patología , Adenocarcinoma/patología , Biomarcadores de Tumor/biosíntesis , Neoplasias Colorrectales/patología , Receptor ErbB-2/biosíntesis , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Membrana Celular/metabolismo , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/mortalidad , Citoplasma/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante
9.
Pol J Pathol ; 61(4): 192-8, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21290341

RESUMEN

Neuroblastoma (NB) represents one of the most common paediatric tumours. Despite advance in NB research and treatment, the outcome of the patients from the high-risk group remains poor. PI3K/AKT/mTOR signalling pathway which is involved in oncogenesis and cancer progression of many tumours, in parallel constitutes the target for the biologically based oncological therapy. In this study we analyzed the status of PI3K/AKT/mTOR signalling route in the primary tumour tissue samples from a group of 39 high-risk NB. The pathway activation state was assessed immunohistochemically using antibodies with specificity towards PI3Kp85, PI3Kp110, phospho-AKT, phospho-mTOR, phospho-p70S6K and phospho-4EBP1. Moreover, expression of PTEN, bcl2 and cyclin D1 was examined. We found that most of tumours were positive for PI3Kp85 and PI3Kp110, as well as for p-AKT, p-mTOR and its downstream effectors p-p70S6K and p-4EBPI. PTEN was expressed in all cases, bcl2 and cyclin D1 staining was found in more than 90% of examined NB. Statistical analysis revealed that p-AKT expression was correlated with p-mTOR and strong cyclin D1 labelling. Furthermore, high expression of p-4EBP1 was significantly associated with p-p70S6K expression, high cyclin D1 and lower differentiation of the tumour. PI3K/AKT/mTOR signalling pathway activation is a common event in high-risk NB and it seems that this group of patients may benefit from targeted therapy with kinase inhibitors.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/patología , Neuroblastoma/patología , Proteína Oncogénica v-akt/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Neoplasias Abdominales , Adolescente , Neoplasias de las Glándulas Suprarrenales/metabolismo , Neoplasias de las Glándulas Suprarrenales/cirugía , Biomarcadores de Tumor/metabolismo , Núcleo Celular/metabolismo , Núcleo Celular/patología , Niño , Preescolar , Humanos , Lactante , Estadificación de Neoplasias , Neuroblastoma/metabolismo , Neuroblastoma/cirugía , Transducción de Señal
11.
Ann Surg Oncol ; 16(5): 1287-94, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19259744

RESUMEN

BACKGROUND: Experiments on cancer cell lines and animal models indicated that alteration in expression of N-myc down-regulated gene 1 (NDRG1) is associated with development of colon cancer. However, few clinical data are available to assess the role of NDRG1 in progression of human colorectal cancer. This study was undertaken to reveal the prognostic and predictive usefulness of NDRG1 expression determination in colorectal cancer. METHODS: The expression of NDRG1 mRNA was investigated in 108 colorectal cancer tissues by real-time polymerase chain reaction. The level of NDRG1 protein was investigated by immunohistochemistry. RESULTS: Patients with lowered level of NDRG1 mRNA had a statistically significantly shorter 5-year survival rate compared with patients with unchanged expression of NDRG1 (P = .01). The overall survival time for patients with II tumor, node, metastasis system (TNM) stage disease and tumors displaying reduced expression of NDRG1 was significantly shorter compared with patients with preserved NDRG1 expression (P = .024). Moreover, the survival rate of patients with TNM stage II disease and T4 lesion was significantly lower (P = .0005) for patients with reduced level of NDRG1 expression compared with patients with unchanged NDRG1 expression. The stepwise multivariate regression analysis revealed that advanced TNM stage and lowered NDRG1 expression level were independent unfavorable prognostic factors for patient survival. CONCLUSIONS: The assessment of NDRG1 expression offers valuable prognostic information for patients with colorectal cancer, especially for those with stage II disease. We propose that NDRG1 expression level could be used to select patients with stage II disease who are at increased risk of unfavorable outcome, and who may benefit from adjuvant therapy.


Asunto(s)
Proteínas de Ciclo Celular/genética , Neoplasias Colorrectales/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Anciano , Neoplasias Colorrectales/patología , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia
12.
Int J Cancer ; 122(9): 2030-7, 2008 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-18183578

RESUMEN

A soluble complement inhibitor factor H (FH) and its splice variant factor H-like protein (FHL) have been recently discovered to play a major role in malignant cell escape from complement-mediated cytotoxicity in lung-, ovarian- and glia-derived neoplasms. The role of FH in colon cancer has not yet been examined. Here, we studied immunocytochemically FH/FHL expression in tumor samples derived from 40 patients, with both primary colon adenocarcinoma and metastatic foci in the liver. FH/FHL immunoreactivity was present in stroma of both primary and metastatic tumors, in virtually all patients. The cellular immunoreactivity was observed infrequently. Importantly, when analyzed quantitatively, FH/FHL immunoreactivity was significantly increased in liver metastases when compared with the primary sites. In addition, we have analyzed FH and FHL expression in 5 colon cancer cell lines: SW480, SW620, HCT116, HT-29 and Lovo. FH mRNA and FH secretion were observed in SW620 and HT-29 cells, whereas FHL was produced only by HT-29 cell-line. By confocal and electron microscopy, FH immunoreactivity was associated with the plasma membrane and intracellular vesicular structures. Finally, we have analyzed the role of FH in the susceptibility of SW620 colon cancer cells to complement-mediated damage. When FH function was blocked, using specific antibody, the cells became more susceptible to lysis. Taken together, our results suggest an important role of FH/FHL in colon cancer cells defense against complement-mediated cytotoxicity, and in metastatic process.


Asunto(s)
Adenocarcinoma/inmunología , Neoplasias del Colon/inmunología , Factor H de Complemento/metabolismo , Inactivadores del Complemento/metabolismo , Neoplasias Hepáticas/inmunología , Neoplasias del Colon/patología , Proteínas Inactivadoras del Complemento C3b , Factor H de Complemento/genética , Técnica del Anticuerpo Fluorescente Indirecta , Regulación Neoplásica de la Expresión Génica , Humanos , Immunoblotting , Inmunohistoquímica , Neoplasias Hepáticas/secundario , Microscopía Electrónica , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
13.
Dig Dis Sci ; 53(3): 785-8, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17846888

RESUMEN

Fatty liver in obese patients is emerging as one of the most common causes of chronic liver disease. Obese patients are at risk of developing type 2 diabetes mellitus (DM), and aggravating non-alcoholic fatty liver disease (NAFLD), developing into steatohepatitis (NASH) and hepatic fibrosis. Little is known of the possible impact on liver fibrogenesis of diabetes type 2 associated with obesity and NAFLD. Fifty-two morbidly obese patients were evaluated with complete clinical and laboratory medical assessment. Liver biopsy material was fixed in formalin, routinely processed to paraffin blocks, cut into 4-microm sections, stained with HE, PAS, Masson's trichrome and reticulin. Immunohistochemical stains included collagen IV, SMA and laminin. Within the initial group of 52, 25 patients had DM type 2, mean age 45.8 years. Patients with diabetes were older; had higher BMI, liver enzyme tests, glucose, cholesterol, and triglycerides; and lower albumin concentration. Livers of diabetics had significantly more severe steatosis and rich perisinusoidal collagen IV, laminin and SMA accumulation without histologically detectable NASH and irrespective of the degree of steatosis. Obese patients with type 2 DM and insulin resistance develop more severe NAFLD and early sinusoidal fibrosclerosis.


Asunto(s)
Diabetes Mellitus Tipo 2/patología , Hígado Graso/patología , Cirrosis Hepática/patología , Hígado/patología , Obesidad/patología , Adulto , Biopsia , Diabetes Mellitus Tipo 2/complicaciones , Hígado Graso/complicaciones , Femenino , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/complicaciones
14.
J Cell Physiol ; 215(1): 151-60, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17941087

RESUMEN

Recently it was demonstrated that the elevated concentration of glucose but not lack of insulin is responsible for suppression of equilibrative nucleoside transporter (ENT1) in diabetic rat cardiac fibroblasts (CFs). The present study was undertaken to determine the signaling pathway utilized by glucose to regulate the expression of ENT1 in the primary culture of rat CFs. Pretreatment of CFs with Go 6983, an isozyme non-selective PKC inhibitor, prevented the high glucose (25 mM) effect on ENT1 mRNA level and nitrobenzylthioinosine (NBTI)-sensitive adenosine uptake. Similar effect was observed with a cell-permeable PKC-zeta pseudosubstrate, whereas Go 6976 a selective inhibitor of Ca(2+)-dependent PKC-alpha and PKC-beta isozymes had little effect on high glucose-induced suppression of ENT1 mRNA level. Incubation of CFs with nitric oxide (NO) donors (SNAPE, SNP) or NO synthase inhibitors (L-NAME, L-NMMA) prior to exposition of CFs to high glucose did not change the glucose effect on ENT1 mRNA level. The high glucose-induced suppression of ENT1 expression was blocked by PD9859 (an inhibitor of MEK), whereas neither wortmannin (an inhibitor of PI3K) nor rapamycin (an inhibitor of mTOR) affected the glucose action on ENT1 transcript level. Highly effective in preventing the high glucose effect on ENT1 mRNA level were GW 5074 (an inhibitor of Raf kinase) and SB 203580 (selective p38 MAPK inhibitor). These findings indicate that high glucose suppresses the expression of ENT1 in CFs by NO independent manner involving the signaling through PKC-zeta, Raf-1, MEK, and p38 MAPK pathways.


Asunto(s)
Proteínas Portadoras/metabolismo , Fibroblastos/enzimología , Glucosa/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Miocardio/citología , Miocardio/enzimología , Proteína Quinasa C/metabolismo , Animales , Proteínas Portadoras/genética , Células Cultivadas , Relación Dosis-Respuesta a Droga , Tranportador Equilibrativo 1 de Nucleósido , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Modelos Biológicos , Óxido Nítrico/metabolismo , Donantes de Óxido Nítrico/farmacología , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-raf/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
15.
Folia Neuropathol ; 45(1): 1-8, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17357004

RESUMEN

The aim of the study was to determine microscopic angiogenic parameters of neuroblastoma (NB) Schwannian stroma-poor tumours. Furthermore the associations between vascular parameters and clinicopathological features of tumours and basic prognostic factors were analysed. Examined tissue samples from 62 NB came from 39 untreated and 23 chemotherapy pretreated tumours. The clinicopathological data comprised: patients' age, gender, survival, tumour site and stage, tumour histology and MYCN status.The morphological analysis of the angiogenic potential concentrated on examination of vascular patterns - classical type or pathological angiogenesis with mural microvascular proliferation (MVP). The quantitative study included semi-automatic assessment of vascular density (VD) in CD34 stained tumour sections. Pathologic angiogenesis with MVP, including simple and/or glomeruloid type, was encountered in 25 cases and was more frequent in differentiating histology subtype and extraadrenal tumours. VD value ranged from 56 to 385 vessels/mm2 (median 149). Higher VD was connected with younger patient's age. In untreated tumours VD was significantly higher in infants than in children over one year of age. Pathologic type angiogenesis and lower VD were found to be associated with shorter survival. Our study confirmed high vascularization of NB and revealed common occurrence of vascular pattern with MVP. Angiogenic potential in the analysed group showed diversity related to some clinicopathological tumour features. This points toward heterogeneity of NB tumours in vascular aspects, possibly affecting tumours' reactivity to antiangiogenic therapy.


Asunto(s)
Neovascularización Patológica/patología , Neuroblastoma/irrigación sanguínea , Neuroblastoma/patología , Factores de Edad , Antígenos CD34/metabolismo , Niño , Preescolar , Femenino , Dosificación de Gen , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Proteína Proto-Oncogénica N-Myc , Neuroblastoma/mortalidad , Proteínas Nucleares/genética , Proteínas Oncogénicas/genética , Pronóstico , Células de Schwann/patología
16.
Otolaryngol Pol ; 61(5): 687-93, 2007.
Artículo en Polaco | MEDLINE | ID: mdl-18552001

RESUMEN

BACKGROUND: Pleomorphic adenoma (PA) is the most common neoplasm of the major salivary glands. There are three subtypes of malignant PA: carcinoma ex pleomorphic adenoma (CXPA); carcinosarcoma (true malignant mixed tumor) and metastasizing pleomorphic adenoma. The most common subtype of malignant PA is CXPA which develops in primary or recurrent PA. For proper diagnosis of CXPA, a statement of coexistence of pleomorphic adenoma and carcinoma (or carcinoma after prior PA surgery) is needed. Own material is presented because of rarity and clinicopathologic specificity of this neoplasm. METHODS: Retrospective analysis of the medical data of 19 patients who were treated at our department because of CXPA from 1990 to 2002 was done. The following clinical factors were evaluated: age, sex, symptoms (time of lasting, evolution), tumor size, invasion of the adjacent structures and facial nerve, neck nodes, clinical stage, treatment outcome. One pathologist reviewed histological material of 18 out of 19 patients who had been operated and pathological factors such as sensitivity and accuracy of fine needle aspiration biopsy, grade, histology and proportion of malignant component in tumor, lymph nodes metastases were analyzed. RESULTS: There were 11 men and 8 women, the mean age was 57 years. In 15 cases, tumor was localized in the parotid and in 4 in the submandibular gland. Two patients had history of prior surgery of PA. Duration of symptoms of benign PA was from 2 to 40 years (mean 17.8 years). Symptoms of malignant transformation occurred in 15 patients, the most common were rapid enlargement of tumor, pain and facial nerve palsy. Tumor size varied from 2 to 20 cm with a mean of 6 cm. In 14 patients, the neck was evaluated clinically as No, in 5, examination identified enlarged lymph nodes. Adjacent structures were invaded by neoplasm in 5 cases. Sensitivity and accuracy of fine needle aspiration biopsy in detection of malignant character of PA were 60% and 46% respectively. 17 out of 18 tumors reviewed by the pathologist were high grade. Only in 6 patients, proportion of carcinoma in the mass was less than 50%. The most common malignant component in CXPA was adenocarcinoma (9 cases) and undifferentiated carcinoma (6 cases). Pathologic examination showed metastases to the lymph nodes in 7 out of 10 patients with prior neck dissection. 16 patients were treated surgically (12 of them had also radiation therapy) and 3 patients underwent only (chemo)radiotherapy. Determinate survival at 5 years was 73.6% and in the group treated surgically (alone or with postoperative irradiation) 87.5%. CONCLUSIONS: Malignant transformation of PA occurs in 5 to 25% untreated patients, usually after 15-20 years and warning symptoms are present in the most cases. Fine needle aspiration biopsy has insufficient sensibility and accuracy in detection of malignant character of PA. Clinical picture and histopathological examination determinate the diagnosis of CXPA. Proper histological classification of malignant component can be found difficult. Surgical treatment (alone or with postoperative irradiation), if possible, allows to achieve good locoregional control of CXPA. 5-years survival varied between 30 to 76%. The best method of prevention and treatment of CXPA is early and radical removal of all major salivary glands tumors.


Asunto(s)
Adenoma Pleomórfico/patología , Carcinoma/patología , Neoplasias Primarias Múltiples/patología , Neoplasias de las Glándulas Salivales/patología , Glándulas Salivales/patología , Adenoma Pleomórfico/cirugía , Biopsia con Aguja , Carcinoma/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/cirugía , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/cirugía , Glándulas Salivales/cirugía , Sensibilidad y Especificidad
17.
Otolaryngol Pol ; 61(5): 694-7, 2007.
Artículo en Polaco | MEDLINE | ID: mdl-18552002

RESUMEN

Noninvasive fungal sinusitis (fungus ball) is usually found in one sinus and the most frequently is caused by Aspergillus. Diagnostic criteria are based on histopathology, and fungal cultures are frequently negative. The clinical symptomatology mimics chronic rhinosinusitis and radiology, specially CT and MRI are helpful for making decision of surgery. The authors present 4 cases of fungus ball of the paranasal sinus. In one case clinical symptoms, endoscopic examination of nasal cavity and CT scans suggested foreign body in the maxillary sinus. In other case clinical and radiological evidences made us to thing of neoplasmatic disease of the frontal sinus. In remaining two cases mycetoma was found in the sphenoid sinus. Surgical removal was the treatment in all cases and followed by systemic antifungal therapy in one case because of bone destruction. Histopathology revealed hyphae of Aspergillus without evidence of tissue invasion, fungal cultures in two cases were negative, an in other two Aspergillus fumigatus culture were obtained.


Asunto(s)
Aspergilosis/diagnóstico , Aspergillus fumigatus/aislamiento & purificación , Sinusitis/diagnóstico , Sinusitis/microbiología , Adulto , Anciano , Antifúngicos/uso terapéutico , Aspergilosis/microbiología , Aspergilosis/terapia , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Sinusitis/terapia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
18.
Eur Arch Otorhinolaryngol ; 264(1): 89-92, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17053927

RESUMEN

The authors present the report of the first ever case of angiomyolipoma arising in the larynx. The tumor was found in a 61-year-old man and was resected through laryngofissure. Histopathologic examination of the tumor revealed numerous smooth muscle cells, mature adipose tissue and numerous thin and large irregular vessels. Both histological and immunohistochemical findings were typical for tumors of the mucocutaneous angiomyolipoma group.


Asunto(s)
Angiomiolipoma/patología , Angiomiolipoma/cirugía , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Angiomiolipoma/complicaciones , Humanos , Grasa Intraabdominal , Neoplasias Laríngeas/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/complicaciones
19.
Folia Neuropathol ; 44(4): 274-81, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17183454

RESUMEN

A group of 119 cases of cerebellopontine angle (CPA) tumours was studied looking at the pathological composition, relative incidence of tumour types, their radiological features and the pathological-radiological correlations. Tumours with preoperative radiological diagnosis and verified pathologically were analyzed. Histopathologically the material consisted of 77 schwannomas and 42 non-acoustic tumours. Radiological retrospective evaluation of CT and/or MRI documentation was performed in 84 patients. The tumours were classified according to Koos's staging scale. Diagnostic discrepancies (histopathological vs radiological) according to the clinical stage of CPA tumours were analyzed. In our series non-acoustic tumours made up 37% of CPA lesions. Sharp tumour-pyramis angle and intracanalicular fraction are not exclusive features of schwannomas. Tumours in stage IV are the most heterogeneous and diagnostically difficult group.


Asunto(s)
Neoplasias Cerebelosas/diagnóstico , Ángulo Pontocerebeloso , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Neoplasias Cerebelosas/epidemiología , Neoplasias Cerebelosas/patología , Diagnóstico Diferencial , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos
20.
Dig Dis Sci ; 51(2): 241-4, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16534662

RESUMEN

Lymphocytic colitis (LC) and collagenous colitis (CC), both known as microscopic colitis (MC), are uncommon entities with increasing incidence as more clinicians take biopsies from macroscopically normal colons and as pathologists use more rigorous diagnostic criteria to be confident of the diagnosis. Information on the incidence of this type of colitis is limited and based on reported cases. The purpose of this work is to estimate the incidence of LC and CC in reviewed routine colonoscopies. We reviewed 2815 colonoscopies performed at a tertiary referral center with an open-access service using restricted histological criteria in order to establish the frequency rate of LC and CC in routine colonoscopic biopsy material. Cases suspicious for MC were stained with Masson's trichrome or Congo red stain and immunohistochemically for lymphocytes, where appropriate. Review of routine colonoscopic biopsies showed that MC is underreported in our colonoscopic material. Incidence rates of LC and CC (0.9 and 0.4, respectively) were based on morphological assessment of colonoscopic biopsies using stringent criteria together with clinical data and after differentiation with other lesions which can mimic MC. The 10.2% rate of this type of colitis in patients with chronic watery diarrhea indicates the necessity to consider these lesions in older individuals with diarrhea and normal endoscopical colonic mucosa.


Asunto(s)
Colitis Colagenosa/patología , Colitis Linfocítica/patología , Colonoscopía , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Colitis Colagenosa/epidemiología , Colitis Linfocítica/epidemiología , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos
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