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INTRODUCTION: Persistent withdrawal occlusion (PWO) is a specific catheter malfunction characterized by the inability to withdraw blood through the device. The most common cause of PWO in ports is the presence of a fibroblastic sleeve (FS). If malfunction occurs, medication can be applied incorrectly with the increased risk of complications. METHODS: One hundred seventy-seven cases of PWO in venous ports were managed. We focused on evaluating the cause of PWO, the frequency of occurrence of FS, and the options to address the malfunction. The patients underwent fluoroscopy with a contrast agent administration. Mechanical disruption (MD) with a syringe of saline using the flush method was used; in case of its failure, subsequent administration of a lock solution with taurolidine and urokinase, or low-dose thrombolysis with alteplase was indicated. Demographic data were compared with a control group. RESULTS: A significantly higher proportion of female patients was found in the cohort of patients with PWO (80.3% vs 66.3%, p = 0.004), dominantly patients with ovarian cancer (12.8% vs 4.8%, p = 0.022). No effect of the cannulated vein or the type of treatment on the incidence of PWO was demonstrated. The presence of FS was verified in 70% of cases. MD with a syringe was successful in 53.5% of cases. A significantly shorter time to referral (3 weeks) was demonstrated with successful management. The overall success rate of achieving desobliteration by MD alone or in combination with a thrombolytic (urokinase or alteplase) administration was 97.4%. CONCLUSION: We created a method for resolving PWO using MD +/- application of thrombolytics with 97.4% success rate. Current evidence showed that FS is not likely to be affected by thrombolytic drugs; however, we have ascertained an effect of these drugs, proposing a hypothesis of microthrombotic events at the tip of the catheter if fibroblastic sleeve is present.
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Neoplasias , Humanos , Femenino , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Anciano , Adulto , Cateterismo Venoso Central/efectos adversos , Catéteres de Permanencia/efectos adversos , Obstrucción del Catéter/etiologíaRESUMEN
INTRODUCTION: Multidisciplinary management of patients with rectal cancer presents a gold standard of care; neoadjuvant therapy indications are based on magnetic resonance imaging (MRI) description of the local stage of the carcinoma. Although the accuracy of MRI-based assessment of cancer depth of invasion is satisfactory, its accuracy in the assessment of mesorectal lymphadenopathy is very questionable. METHODS: This was a prospective, single-centre, cohort study focused on the accuracy of preoperative MRI in the assessment of mesorectal lymph nodes (LN). MRI findings of each patient were compared with detailed histopathological examination of rectal specimens. RESULTS: Forty patients with rectal cancer, undergoing rectal resection with total mesorectal excision were enrolled in the study. MRI assessment of the T-stage was correct in 22 of the 40 study patients (55.0%). T-stage overstaging was noted in 14 (35.0%), and understaging in 4 (10.0%) study patients. According to preoperative MRI (using Horvat's criteria), there were 50 suspicious/malignant lymph nodes. Only 13 of these 50 LNs (26.0%) were proved malignant on histopathology examination. In total, our study group included 18 patients with suspicious/positive LNs (according to preoperative MRI) who were classified as cN+. MRI diagnosis of malignant lymphadenopathy was correct in only 33.3% of these patients. CONCLUSION: MRI shows very low accuracy in the evaluation of mesorectal lymph nodes in patients with rectal cancer. Therefore neoadjuvant therapy should be offered particularly with respect to MRI description of the depth of carcinoma invasion (T-stage and relationship to fascia propria of the rectum).
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Carcinoma , Linfadenopatía , Neoplasias del Recto , Humanos , Estudios de Cohortes , Estudios Prospectivos , Estadificación de Neoplasias , Neoplasias del Recto/cirugía , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Carcinoma/patología , Linfadenopatía/patología , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Bladder cancer is 11th most common cancer worldwide. Histologically, most of the tumors are classified as urothelial carcinomas. Less common variants (squamous cell or adenocarcinomas) usually comprise up to 10% of cases. Other types of tumors are exceptional. The finding of Ewing's sarcoma in the bladder is considered extremely rare. CASE: We present the case of a 54-year-old female patient examined for painless hematuria. During the follow-up examination, a bulky tumor of the bladder was detected, but considering the extent of the bladder tumor, only a diagnostic transurethral resection was possible. According to the primary staging, the disease was already advanced at the time of admission with metastatic spread, anemia and present obstruction of the upper urinary tract. RESULTS: Histologically, Ewing's sarcoma was surprisingly demonstrated in the urinary bladder. Anemia caused by hematuria and advanced disease was corrected by blood transfusions and obstruction of the right kidney by puncture nephrostomy. However, despite a very quick diagnosis, completion of staging and preparation of the patient for further treatment, the patient had died before the planned systemic treatment began. CONCLUSION: The diagnosis of Ewing's sarcoma is identical to that of the other bladder tumors, i.e. transurethral resection. In the case of confirmation of this histological type, it is necessary to complete staging examinations and start multimodal treatment. Early systemic chemotherapy plays a key role and if metastatic spread is excluded, radical cystectomy or radiotherapy are included, too. The aim of our communication is to present a rare case of this disease, discuss the differential diagnosis and point out the principles and possibilities of its treatment.
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Anemia , Sarcoma de Ewing , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Persona de Mediana Edad , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/terapia , Vejiga Urinaria , Hematuria , Diagnóstico DiferencialRESUMEN
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is associated with specific coagulopathy that frequently occurs during the different phases of coronavirus disease 2019 (COVID-19) and can result in thrombotic complications and/or death. This COVID-19-associated coagulopathy (CAC) exhibits some of the features associated with thrombotic microangiopathy, particularly complement-mediated hemolytic-uremic syndrome. In some cases, due to the anti-phospholipid antibodies, CAC resembles catastrophic anti-phospholipid syndrome. In other patients, it exhibits features of hemophagocytic syndrome. CAC is mainly identified by: increases in fibrinogen, D-dimers, and von Willebrand factor (released from activated endothelial cells), consumption of a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS13), over activated and dysregulated complement, and elevated plasma cytokine levels. CAC manifests as both major cardiovascular and/or cerebrovascular events and dysfunctional microcirculation, which leads to multiple organ damage. It is not clear whether the mainstay of COVID-19 is complement overactivation, cytokine/chemokine activation, or a combination of these activities. Available data have suggested that non-critically ill hospitalized patients should be administered full-dose heparin. In critically ill, full dose heparin treatment is discouraged due to higher mortality rate. In addition to anti-coagulation, four different host-directed therapeutic pathways have recently emerged that influence CAC: (1) Anti-von Willebrand factor monoclonal antibodies; (2) activated complement C5a inhibitors; (3) recombinant ADAMTS13; and (4) Interleukin (IL)-1 and IL-6 antibodies. Moreover, neutralizing monoclonal antibodies against the virus surface protein have been tested. However, the role of antiplatelet treatment remains unclear for patients with COVID-19.
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Trastornos de la Coagulación Sanguínea , COVID-19 , Anticuerpos Monoclonales/uso terapéutico , Trastornos de la Coagulación Sanguínea/etiología , COVID-19/complicaciones , Enfermedad Crítica , Citocinas , Células Endoteliales , Heparina/uso terapéutico , Humanos , SARS-CoV-2RESUMEN
AIMS: The aim of the study was to analyse the prognostic and predictive value of LC3A positive' 'Stone Like Structures'' (SLSs) in a large cohort of patients with non-small cell lung carcinoma (NSCLC) and to check its relationship with tumor infiltrating lymphocytes (TILs) and PD-L1 expression. METHODS: Tissue microarrays from 1015 patients diagnosed at the Institute of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland, were stained for LC3A, PD-L1, CD3 and CD68 using automated tissue stainer Ventana Benchmark Ultra (Roche). TILs were assessed in matched haematoxylin and eosin stained slides. RESULTS: LC3A positive SLSs, were significantly associated with worse overall (OS) and disease-free survival (DFS) outcomes in patients with lung adenocarcinoma (LADC) (HR = 2.4, 95 %CI(.994-1.008, p = 0.029) and HR = 3.9, 95 %CI (1.002-1.014), p = 0.002 respectively), whilst it was associated with better OS and DFS in patients with lung squamous cell carcinoma (LUSC), with marginal significance (HR = .99, 95 %CI(.975-1.011),p = 0.042 and HR = .99, 95 %CI (.975-1.008), p = 0.026). Multivariate analysis showed that LC3A SLSs are independent poor prognostic factor only in patients with LADC. In addition, LC3A SLSs, were negatively associated with CD68 count in LADC, whilst there was a positive correlation in LSCC. CONCLUSIONS: LC3A SLSs are differentially associated with the survival outcomes and CD68 count in LADC and LSCC. Further studies are justified for the understanding the underlying biological mechanisms of this phenomenon.
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Adenocarcinoma del Pulmón , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Macrófagos , Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Antígeno B7-H1 , Humanos , Linfocitos Infiltrantes de Tumor , Proteínas Asociadas a Microtúbulos , Pronóstico , SuizaRESUMEN
Recently, miR-23b has emerged as a promising new cancer biomarker but its role in lung cancer has not been established yet. Patients still do not respond well to available treatments, probably due to expression of multidrug resistance (MDR) proteins, such as P-gp, MRP and LRP/MVP. The aim of this study was to determine the role of miR-23b in non-small cell lung cancer (NSCLC) and its relationship to the patient outcome together with MDR transporter proteins. We immunohistochemically evaluated expression of P-gp, MRP and LRP/MVP and quantified the relative levels of miR-23b in 62 NSCLC patients´ samples. The prognostic significance of miR-23b and MDR proteins was tested by Kaplan-Meier and Cox-regression analysis. Our results showed that miR-23b is mostly downregulated in NSCLC samples (57/62) and that its upregulation in tumors is connected with longer progression-free survival (PFS; P = 0.065) and overall survival (OS; P = 0.048). The Cox proportional hazard model revealed that the risk of death or relapse in NSCLC patients with miR-23b downregulation increases together with LRP/MVP expression and both risks decrease with miR-23b upregulation (HRPFS = 4.342, PPFS = 0.022; HROS = 4.408, POS = 0.015). Our findings indicate that miR-23b, especially in combination with LRP/MVP expression, might serve as a suitable prognostic biomarker for NSCLC patients.
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Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , PronósticoRESUMEN
An actin-binding protein filamin A connects the actin filament network to cell membrane receptors, and acts as a scaffold for various signaling pathways related to cancer growth and progression. Recently, it has been reported that filamin A is required for efficient regulation of early stages of DNA repair process. Moreover, some in vitro studies showed that the overexpression of filamin A determines resistance to various cytotoxic drugs, including cisplatin. We aimed to analyse the expression of filamin A protein in resected NSCLC (Non Small Cell Lung Cancer) specimens, to investigate the association of the level of filamin A protein expression and other clinicopathological features, and possible relationship between the expression of filamin A and survival outcome in NSCLC patients, treated with platinum-based combination chemotherapy. We performed filamin A protein immunohistochemistry on formalin-fixed and paraffin-embedded (FFPE) tissue sections from 135 NSCLC patients, using EP2405Y antibody against C-terminus of filamin A. Cytoplasmic, membranous and nuclear positivity of filamin A was evaluated semi-quantitatively and correlated with available clinicopathological data. Patients were divided into two groups for survival analysis (I group - patients treated with adjuvant platinum-based chemotherapy, II group - patients with surgical treatment only). We found significant positive correlation between filamin A protein expression and NSCLC stage (r=0.249; p<0,05), presence of lymph node (N)(r=0.205; p<0,05) and distant metastases (M) (r=0.332; P<0.01). Increased filamin A protein expression was significantly related with poor survival outcomes in patients with adjuvant platinum-based chemotherapy: OS (HR=1.005, 95%CI[1.000;1.010], p=0.037), DFS (HR=1.004, 95%CI [1.001:1.008], p=0,017). Multivariate Cox proportional hazards regression analysis also showed that overexpression of filamin A represents an independent risk factor for disease relapse, in addition to tumor size, stage, and metastases status (HR=1.723, 95%CI [1.021:2.909], p<0.05). Thus, filamin A expression might be a new prognostic marker in patients with NSCLC.
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Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/uso terapéutico , Filaminas/biosíntesis , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Femenino , Filaminas/genética , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/mortalidad , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Resultado del TratamientoRESUMEN
Matrix metalloproteinases (MMPs) are potential biomarkers for disease activity in inflammatory bowel disease (IBD). However, clinical trials targeting MMPs have not succeeded, likely due to poor understanding of the biological functions of individual MMPs. Here, we explore the role of MMP-19 in IBD pathology. Using a DSS-induced model of colitis, we show evidence for increased susceptibility of Mmp-19-deficient (Mmp-19(-/-)) mice to colitis. Absence of MMP-19 leads to significant disease progression, with reduced survival rates, severe tissue destruction, and elevated levels of pro-inflammatory modulators in the colon and plasma, and failure to resolve inflammation. There was a striking delay in neutrophil infiltration into the colon of Mmp-19(-/-) mice during the acute colitis, leading to persistent inflammation and poor recovery; this was rescued by reconstitution of irradiated Mmp-19(-/-) mice with wild-type bone marrow. Additionally, Mmp-19-deficient macrophages exhibited decreased migration in vivo and in vitro and the mucosal barrier appeared compromised. Finally, chemokine fractalkine (CX3CL1) was identified as a novel substrate of MMP-19, suggesting a link between insufficient processing of CX3CL1 and cell recruitment in the Mmp-19(-/-) mice. MMP-19 proves to be a critical factor in balanced host response to colonic pathogens, and for orchestrating appropriate innate immune response in colitis.
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Quimiocina CX3CL1/metabolismo , Colitis/inmunología , Colon/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Mucosa Intestinal/inmunología , Macrófagos/inmunología , Metaloproteinasas de la Matriz Secretadas/metabolismo , Animales , Movimiento Celular , Células Cultivadas , Colitis/inducido químicamente , Citocinas/metabolismo , Sulfato de Dextran , Progresión de la Enfermedad , Humanos , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/patología , Metaloproteinasas de la Matriz Secretadas/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infiltración Neutrófila/genéticaRESUMEN
UNLABELLED: Chronic kidney disease-mineral and bone disorder (CKD-MBD) ranks among clinically and pathogenetically significant complications in patients with CKD. Numerous factors are involved in its development, and histomorphometric analysis of the bone tissue is still necessary for accurate diagnosis. METHODS: The open, pilot, prospective study aimed at performing a comprehensive histomorphometric bone analysis in 26 dialysis patients and assessing the relationships of different types of CKD-MBD to selected parameters of calcium and phosphate metabolism, densitometry, activity of parathyroid glands, presence of diabetes mellitus, and duration of dialysis treatment. RESULTS: Comparison of the histomorphometric characteristics demonstrated statistically significant correlations between the volume of bone trabeculae and s-procollagen 1 (.754) as well as s-calcitonin (.856). Similarly, there was a positive correlation between the size of tetracycline lines and volume of bone trabeculae (.705) and a strong negative correlation with the thickness of trabeculae (-.442). When assessing the serum levels of s-osteoprotegerin and serum RANKL, there was a correlation with osteoid thickness and bone trabeculae thickness. In case of s-osteoprotegerin, a statistical power was demonstrated in relation to osteoid thickness (.880); in case of s-RANKL, a statistical power was demonstrated in relation to the thickness of trabeculae (.830). When assessing the influence of dialysis duration, relationships to the volume of trabecular bone (.665) and volume of bone trabeculae (.949) were demonstrated. Finally, a relationship between s-1,25-hydroxyvitamin D and s-osteoprotegerin was observed (.739); also the relationships demonstrated were significantly lower volume of bone trabeculae in men (p = 0.067) and lower values of s-osteocalcin and s-procollagen 1 in diabetic patients (p = 0.014). CONCLUSION: The results provide new noninvasive possibilities of CKD-MBD detection that are based on selected serum parameters of bone metabolism. Presented are possibilities of noninvasive assessment of different types of CKD-MBD using serum osteomarkers in relation to comprehensive CKD-MBD histomorphometry.
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Densidad Ósea , Calcio/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Riñón/metabolismo , Insuficiencia Renal Crónica , Anciano , Biomarcadores/metabolismo , Huesos/patología , Calcitriol/metabolismo , Enfermedades Cardiovasculares/epidemiología , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico , República Checa , Femenino , Humanos , Masculino , Osteocalcina/sangre , Osteoprotegerina/sangre , Hormona Paratiroidea/metabolismo , Proyectos Piloto , Estudios Prospectivos , Ligando RANK/sangre , Diálisis Renal/métodos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/terapia , Reproducibilidad de los Resultados , Factores de RiesgoRESUMEN
INTRODUCTION: Minimal systemic disease (MSD) means the presence of circulating or disseminated tumour cells in mesenchymal compartments of a patientts' body (lymphatic nodes, blood or bone marrow). The aim of our pilot study was to identify sensitive and specific markers for MSD detection in 50 lung cancer patients, who underwent curative surgery in the I. Department of Surgery, Faculty of Medicine and Dentistry, Palacky University and Faculty Hospital Olomouc in 2009 and 2010. MATERIAL AND METHODS: Absolute gene expression of carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR1), lung-specific X protein (LUNX) and hepatocyte growth factor receptor (c-met) was determined in peripheral blood, bone marrow and pulmonary blood of 50 lung cancer patients using real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR). RESULTS: (1) The LUNX marker is specific and sensitive for MSD detection in lung cancer patients. (2) The CEA positivity for MSD in the bone marrow correlated significantly with histopathological grading (GI-GIII). (3) Higher expression of CEA and c-met was found in pulmonary blood of patients with hilar or mediastinal lymphadenopathy. (4) Higher expression of MSD markers (CEA in bone marrow, c-met in peripheral blood and LUNX in pulmonary blood) correlated with higher pTNM classification. CONCLUSION: Minimal systemic disease detection in lung cancer patients is technically feasible using sufficiently sensitive and specific markers for RT-PCR. Minimal systemic disease detection can be used to guide further systemic treatment. This theory must be validated in a larger group of patients and correlated with clinical data, especially with survival data.
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Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Anciano , Antígeno Carcinoembrionario/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/sangre , Femenino , Glicoproteínas/sangre , Humanos , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasia Residual , Células Neoplásicas Circulantes , Fosfoproteínas/sangre , Proteínas Proto-Oncogénicas c-met/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Cancer stem cells (CSCs) share many features with embryonic stem cells (ESCs) such as the ability for self-renewal and differentiation. Signaling pathways that are involved in these processes are also involved in chemo- and radioresistance (e.g. Wnt, Notch and Hedgehog pathways). This review is focused on the influence of three important differentiation pathways on carcinogenesis and on chemo- and radioresistance in ESCs and CSCs.
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Diferenciación Celular/fisiología , Transformación Celular Neoplásica , Resistencia a Antineoplásicos/fisiología , Tolerancia a Radiación/fisiología , Animales , Células Madre Embrionarias/citología , Células Madre Embrionarias/fisiología , Regulación del Desarrollo de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteínas Hedgehog/fisiología , Humanos , Proteínas de Neoplasias/fisiología , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/efectos de la radiación , Células Madre Pluripotentes/citología , Células Madre Pluripotentes/fisiología , Receptores Notch/fisiología , Proteínas Wnt/fisiologíaRESUMEN
Lung cancers are still divided into two major subgroups: small-cell and non-small cell lung cancer (NSCLC) irrespective of biological heterogeneity of NSCLC. It is a key task of the pathologist to provide an accurate classification of tumorous lesions to avoid the term NSCLC and to use it only in the vast minority of cases. Moreover, the most recent reclassification of pulmonary adenocarcinomas should be reflected in the standard biopsy protocol reporting. There is also an increasingly urgent need to provide high quality material for testing of the genetic characteristics of NSCLC, especially the presence and functional status of the EGFR receptor (epidermal growth factor receptor), as well as other potential prognostic markers. The requirement for the quality and swiftness of diagnosis puts major emphasis on the close multidisciplinary collaboration with the central role of a specialized pathologist, who coordinates the differential-diagnostic procedure. This in turn implies the necessity of accounting for the increasing financial burden of diagnostic departments.
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Adenocarcinoma/clasificación , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Neoplasias Pulmonares/clasificación , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mutación , PronósticoRESUMEN
BACKGROUND: Matrix metalloproteinases (MMPs) belong to proteolytic enzymes. Degradation of the cell basement membrane and the extracellular matrix is one of their functions. In malignant tumors they can hypothetically contribute to the invasion and metastasis formation. They are mostly produced by stromal cells (fibroblasts and endothelial cells) as a response to the presence of tumor cells. MMP-2 (gelatinase A), MMP-9 (gelatinase B) and MMP-11 (stromelysin 3) are often mentioned in regard to Non-small Cell Lung Cancer (NSCLC). METHODS AND RESULTS: The relation between the expression of the above-mentioned matrix metal-loproteinases in stromal cells and the cancer-related survival in 80 patients after curative resection of NSCLC in stage I according to TNM was studied. The expression of MMP-2 was associated with cancer-related survival but without significant correlation. No correlation was found in MMP-9. There was a statistically near-significant relation between the expression of MMP-11 and cancer-related survival. CONCLUSIONS: The expression of MMP-11 in stromal cells in surgically treated NSCLC patients in stage I appears useful for evaluation of their prognosis.
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Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Neoplasias Pulmonares/enzimología , Metaloproteinasas de la Matriz/análisis , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Humanos , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Pronóstico , Células del Estroma/enzimología , Tasa de SupervivenciaRESUMEN
This study tested and compared the anti-proliferative and proliferative activities of two anti-oestrogens and three anti-progestins on four separate mouse model systems: young intact and adult ovariectomized (OV-X) females, and young intact and adult castrated males. Pure steroidal anti-oestrogen ICI 182,780 (ICI) decreased mammary and uterine growth stimulated by endogenous hormones in young intact females and by exogenous hormones [progesterone (Prog), 17beta-oestradiol (E) or E plus Prog] in both young intact and adult ovariectomized (OV-X) females. Non-steroidal anti-oestrogen EM-800 (EM), on the other hand, had no effect on mammary and uterine growth stimulated by endogenous hormones in young intact females and in adult OV-X females. Uterine growth was even stimulated by EM alone, and a combination of EM plus Prog not only stimulated uterine growth but also mammary growth (an oestrogenic agonistic activity). However, EM showed anti-oestrogenic activities in both mammary and uterine tissues in females treated with E or E plus Prog. In males, ICI and EM decreased mammary growth stimulated by exogenous hormones (E or E plus Prog) in both young intact and adult castrated animals. In young intact, but not in adult castrated males, ICI increased seminal vesicle growth affected by both endogenous and exogenous (Prog, E or E plus Prog) hormones. EM, on the other hand, decreased seminal vesicle weights in E or E plus Prog and increased its weights in Prog-treated young intact males. Thus, under certain conditions EM possess mixed agonist and antagonist activity in the mammary gland, uterus and seminal vesicles. Norethindrone acetate (NA)-stimulated mammary growth was decreased by anti-progestins onapristone (ON), RU 46556 (RU), and RU 38486 (MI) by 34-59% in females and by 35-93% in males. Uterine weights of NA-treated females were decreased by ON and RU by 29-55% but not by MI. In NA-treated young intact males, seminal vesicle weights were stimulated by RU (by 63%) and not affected by ON and MI. In NA-treated adult castrated males, seminal vesicle weights were decreased by ON, increased by RU and not affected by MI. The results obtained in these and our earlier studies show clearly that mouse four-model systems could serve as in vivo tool for the detection of steroid hormone agonist and antagonist activities of natural and man-made chemicals.
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Antagonistas de Estrógenos/farmacología , Glándulas Mamarias Animales/efectos de los fármacos , Progesterona/antagonistas & inhibidores , Vesículas Seminales/efectos de los fármacos , Útero/efectos de los fármacos , Animales , Bioensayo , Castración , Femenino , Masculino , Glándulas Mamarias Animales/crecimiento & desarrollo , Ratones , Ratones Endogámicos C3H , Modelos Animales , Tamaño de los Órganos/efectos de los fármacos , Vesículas Seminales/crecimiento & desarrollo , Útero/crecimiento & desarrolloRESUMEN
Young intact and adult gonadectomized C3H male and female mice were utilized as bioassay models to detect endocrine disruption chemicals. Animals treated with oestradiol (E) or progesterone (Prog) or E plus Prog were used to assess steroid hormone agonist and antagonist activities of 4-OH-tamoxifen (TAM), diethylstilbestrol (DES) and genistein (GEN) by bioassay. The stimulation or inhibition of mammary growth by TAM depended on sex, the state of animal (intact or gonadectomized), hormonal treatment (Prog, E, E plus Prog) and dose of TAM. TAM stimulated mammary growth in untreated ovariectomized (OV-X) females and in Prog-treated intact males and OV-X females. In intact males, mammary growth was increased by TAM at dose 0.1-1 microg day(-1) and decreased at dose 10 microg day(-1). Mammary growth was inhibited by TAM in Prog-treated intact females and in E or E plus Prog-treated intact and gonadectomized males and females. Uterine weights were increased by TAM in both untreated and treated (E, Prog, E plus Prog) intact and OV-X females; however, seminal vesicle weights were decreased by TAM in both untreated and treated (E, Prog, E plus Prog) intact males. DES alone affected mammary growth (an inverted-U-shaped dose-response curve) both in male and female mice. DES increased uterine weights; however, seminal vesicle weights were decreased. GEN increased mammary and uterine growth in OV-X females, GEN plus Prog stimulated mammary growth in intact males. The results obtained in these studies show clearly that only a bioassay consisting of several endpoints reflective to the mechanism of oestrogen and anti-oestrogen action has the ability to evaluate activities of a molecule.
Asunto(s)
Antagonistas de Estrógenos/farmacología , Estrógenos/farmacología , Glándulas Mamarias Animales/efectos de los fármacos , Tamoxifeno/análogos & derivados , Útero/efectos de los fármacos , Animales , Dietilestilbestrol/farmacología , Estradiol/agonistas , Estradiol/farmacología , Femenino , Genisteína/farmacología , Masculino , Ratones , Ratones Endogámicos C3H , Modelos Animales , Progesterona/farmacología , Vesículas Seminales/efectos de los fármacos , Bazo/efectos de los fármacos , Tamoxifeno/farmacologíaRESUMEN
Young intact and adult castrated outbred C3H/Di male mice were used to characterize steroid hormone agonist and antagonist activities of anti-androgens by bioassay. Animals were injected subcutaneously with flutamide (Flut), chlormadinone acetate (CMA), cyproterone acetate (CA) or Casodex (Cas) alone or simultaneously with oestradiol (E), E plus progesterone (Prog) or norethindrone acetate (NA; a steroid exhibiting progestational and oestrogenic activities) and testosterone (T) for 15 days. Mammary gland growth was not affected with anti-androgen alone. However, all anti-androgens decreased seminal vesicle weights in intact males. In E (0.01 microg day(-1))-treated intact males, mammary growth was stimulated by CMA (progestational activity) and inhibited by CA. The inhibitory effect of CA on mammary growth (glucocorticoid activity) was overcome with high dose of E (0.1 microg day(-1)). When seminal vesicles weights were decreased with a moderate dose of E (0.01 microg day(-1)) anti-androgens injected simultaneously acted synergistically with E and decreased seminal vesicles weights more than E alone. However, in animals overloaded with E (0.1 microg day(-1)), anti-androgen CA was unable to decrease seminal vesicles weights. E (0.01 or 0.05 microg day(-1)) or E + Prog (500 or 1000 microg day(-1)) or NA (12.5 to 50 microg day(-1)) stimulated mammary growth was inhibited by T at doses 20-200 microg day(-1) and these effects were decreased or abolished by simultaneous application of Flut, CMA or Cas in both young intact and adult castrated males. In the same animals, the seminal vesicles weights were increased by T and decreased by anti-androgens. The effects of higher doses of T (300 microg day(-1)) were not inhibited by anti-androgens both in the mammary gland and seminal vesicles. Spleen weights were not consistently affected with Flut, CMA or Cas, but decreased with CA by dose dependent manner. These results demonstrated that anti-androgenic activities could be detected not only on seminal vesicle but also on the mammary gland. Our model system also detected a glucocorticoid activity of CA and progestational activity of CMA.
Asunto(s)
Antagonistas de Andrógenos/farmacología , Glándulas Mamarias Animales/efectos de los fármacos , Noretindrona/análogos & derivados , Vesículas Seminales/efectos de los fármacos , Bazo/efectos de los fármacos , Esteroides/farmacología , Anilidas/farmacología , Animales , Animales no Consanguíneos , Bioensayo , Acetato de Clormadinona/farmacología , Acetato de Ciproterona/farmacología , Quimioterapia Combinada , Estradiol/farmacología , Flutamida/farmacología , Masculino , Ratones , Ratones Endogámicos C3H , Nitrilos , Noretindrona/farmacología , Acetato de Noretindrona , Orquiectomía , Progesterona/farmacología , Compuestos de TosiloRESUMEN
Young intact (18 days of age) and adult ovariectomized (OV-X, ovariectomized between 21 to 24 days of age) C3H/Di mice were used to measure the estrogenicity on the basis of the growth response of mammary epithelial structures and weight of the uterus. The percentage area of the mammary fat pad occupied by mammary epithelial structures was progressively increased by 17beta estradiol from dose 0.001 microg.d(-1). The maximum effective dose of estradiol was 0.01 microg.d(-1) and the dose 10 microg.d(-1) of estradiol decreased mammary size to control levels (inverted-U-shaped dose-response curve). Progesterone alone progressively stimulated mammary growth in young intact females from dose 125 microg.d(-1), in adult OV-X animals from dose 1000 microg.d(-1). Both in young intact and adult OV-X animals, uterine weight progressively increased during estradiol treatment. Progesterone alone had no effect on uterine weight in young intact animals; in adult OV-X animals, uterine weight was increased starting from dose 250 microg.d(-1). Progesterone acted synergistically with estradiol to produce higher mammary growth than that in females treated with estradiol alone. The effects of a combination of estradiol plus progesterone in the mammary gland were mimicked by norethindrone acetate and inhibited by cortisol in both young intact and adult OV-X animals. Testosterone inhibited estradiol plus progesterone stimulated growth of mammary gland only in OV-X animals, but stimulated uterine weights in both young intact and adult OV-X animals. Spleen weight and size of mammary lymph nodes were not affected by estradiol, progesterone, norethindrone acetate or testosterone, but were decreased by cortisol. Cortisol also decreased the percent area of the mammary fat pad occupied by mammary epithelial structures, but had no effect on weight of the uterus. These results show that bioassay of estrogenicity in females is not specific. Mammary and uterine growth is stimulated not only by estrogens but also by progesterone and testosterone, respectively.
Asunto(s)
Estradiol/farmacología , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/crecimiento & desarrollo , Noretindrona/análogos & derivados , Tamaño de los Órganos/efectos de los fármacos , Útero/anatomía & histología , Animales , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Estradiol/administración & dosificación , Femenino , Hormonas Esteroides Gonadales/farmacología , Hidrocortisona/farmacología , Ratones , Ratones Endogámicos C3H , Noretindrona/farmacología , Acetato de Noretindrona , Ovariectomía , Progesterona/administración & dosificación , Progesterona/antagonistas & inhibidores , Progesterona/farmacología , Testosterona/farmacologíaRESUMEN
Young intact (18 days old) and adult castrated males of CBA and C3H/Di mice were used for measuring the estrogenicity on the basis of growth response of mammary epithelial structures and the weight of seminal vesicles. It was demonstrated that heavier young males had disproportionally heavier seminal vesicles (sex steroid-responsive organs) than small animals at day 33 of age (that is on the day when experimental animals were killed and organs dissected). However, the weight of the spleen (sex steroid-nonresponsive organ) was proportionally related to body weight. To minimize variability in hormone responsiveness, all animals were weighed at the age of 18 days and only males weighing 8+/-1 g were used for hormone treatment. The percentage area of mammary fat pad occupiedby mammary epithelial structures was progressively increased by 17beta estradiol from dose 0.01 microg x d(-1). The maximum effective dose of estradiol was 0.1 microg x d(-1) and dose 10 microg x d(-1) of estradiol decreased mammary size to control level (inverted-U-shaped dose-response curve). Progesterone alone stimulated mammary growth only in high doses (500 microg x d(-1) and higher) in young intact males, but had no effect on mammary growth in adult castrated animals. In young intact males, estradiol alone, or progesterone alone decreased the weight of seminal vesicles. No such inhibitory effect of these hormones was noted in adult castrated males. Progesterone acted synergistically with estradiol to produce higher mammary growth compared to that in males treated with estradiol alone. In the presence of progesterone seminal vesicles weight was decreased by estradiol given in such low doses as 0.001 microg x d(-1) of estradiol, which is 10 times lower than that effective in animals treated with estradiol alone. On the other hand, in the adult castrated males a combination of estradiol plus progesterone stimulated seminal vesicles weight. The effects of a combination of estradiol plus progesterone in the mammary gland were mimicked by norethindrone acetate (a synthetic steroid exhibiting progestantial and estrogenic activities) and inhibited by both testosterone and cortisol. Estradiol, progesterone, norethindrone acetate, or testosterone did not affect spleen weight and size of mammary lymph nodes.However, cortisol significantly decreased not only spleen weights but also size of mammary lymph nodes. These results showthat simultaneous evaluation of mammary gland growth, seminal vesicles, and the spleen weight in the same animal is suitable for bioassay of estrogenicity as well as for detection of androgenic and antiandrogenic activities.
Asunto(s)
Bioensayo/métodos , Estradiol/farmacología , Glándulas Mamarias Animales/efectos de los fármacos , Vesículas Seminales/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Hidrocortisona/farmacología , Masculino , Glándulas Mamarias Animales/citología , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos CBA , Orquiectomía , Tamaño de los Órganos , Progesterona/farmacología , Vesículas Seminales/citología , Sensibilidad y Especificidad , Bazo/citología , Bazo/efectos de los fármacosRESUMEN
The surgeon is frequently faced with the task of bioptic sampling of tissues from patients with tumourous diseases. The importance of such frequently minor procedures is incorrectly underrated. The importance of biopsy is in the foreground in particular at present at a time of individualization of treatment of malignant tumours, based on the development of new diagnostic-therapeutic methods. The bioptic specimen is the fundamental link in the basic decision--benignity or malignity--and also a unique source for assessment of prognostic and predictive factors on the basis of which we select the optimal therapeutic procedure. Contrary to current histopathological examination where the principles of correct collection of tissues specimens are generally known, in recent years the importance of molecular examinations is increasing where the surgeon must respect certain different principles to make the sampling successful. The authors working in a department of surgical oncology along with authors from specialized laboratories formulate rules of correct implementation of biopsies and transport of biological material in conjunction with recent laboratory methods, and based on examples of their own practice, they demonstrate how the initial approach of the surgeon can influence in a decisive way the correct diagnosis and therapeutic procedure in oncological patients.
Asunto(s)
Biopsia/métodos , Neoplasias/patología , Biopsia con Aguja/métodos , Citodiagnóstico , Análisis Citogenético , Humanos , Neoplasias/diagnóstico , Manejo de Especímenes/métodosRESUMEN
BACKGROUND: We reviewed 36 patients with liver metastases from islet cell tumors of the pancreas (n = 18) and carcinoid tumors (n = 18) who were treated with surgical resection (n = 16) or hepatic chemoembolization (n = 20). METHODS: All resections were complete and included 4 lobectomies, 6 segmental resections, and 6 wedge resections. There were no operative deaths. RESULTS: Median survival has not yet been reached, and the actuarial 5-year survival rate is 70%. Prognostic variables associated with improved disease-free survival included prior resection of the primary tumor and 4 or fewer metastases resected (P <.05). With an average of 3 chemoembolization procedures per patient, 17 of 20 patients (90%) demonstrated either a significant radiographic response (n = 5), stabilization of tumor mass (n = 2), or improvement of clinical symptoms (n = 10). Factors related to a sustained response (more then 1 year) included surgical resection of the primary tumor, 4 or more chemoembolization procedures, and liver metastases of 5 cm or smaller. Median survival after treatment was 32 months (range, 7-63 months), and the actuarial 5-year survival rate was 40%. CONCLUSIONS: Surgical resection of metastatic neuroendocrine tumors provides the best chance for extended survival. Chemoembolization effectively improves clinical symptoms and, in selected patients, may provide sustained tumor control.