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1.
Z Orthop Unfall ; 161(5): 500-510, 2023 Oct.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-35196738

RESUMO

INTRODUCTION: After reconstruction of the anterior cruciate ligament, the modification processes in the transplanted tendon tissue directly influence the biomechanical properties of the knee. The histopathological alterations in failed grafts have hardly been studied. OBJECTIVE: Our study focused on examining the presence and extent of tendinosis (low or high grade) in the tendon tissue of failed anterior cruciate ligament reconstructions. We considered its relationship to the type of transplant, the symptoms, the arthroscopic appearance, the mode of trauma, and the timing of the failure. MATERIALS AND METHODS: The tendon tissue of failed anterior cruciate ligament reconstructions in 30 patients was gathered during revision surgery and its histopathology was analysed for the occurrence of structural alterations. The classification of the tendinosis as low or high grade was semiquantitative based on five qualities. We used a standardised questionnaire to collect patient data and we used the Marburg Arthroscopy Score for the intraoperative evaluation of the graft. RESULTS: We found histological vitality and, except for two samples, structural alterations consistent with tendinosis, predominantly high grade, in all failed anterior cruciate ligament grafts. No direct link could be proved between the degree of tendinosis and the type of graft used, the symptoms (except for instability) or the timing of the graft failure, the mode of trauma, or the arthroscopic appearance of the failed plasty. However, the accumulation of high-grade tendinosis in patients with hamstring tendons, subjective instability, and graft failure between 1 to 5 years postoperatively was noteworthy. CONCLUSION: Structural alterations consistent with tendinosis could be detected, with different expressions, in the vital tendon tissue of anterior cruciate ligament reconstructions. This indicates that the graft is subject to repetitive microtrauma. However, it is still unclear how tendinosis influences the failure of anterior cruciate ligament reconstructions.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Humanos , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Transplante Autólogo , Articulação do Joelho/cirurgia , Resultado do Tratamento
2.
Cancers (Basel) ; 12(8)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806571

RESUMO

Soft tissue sarcoma (STS) is a heterogeneous group of rare malignancies with a five-year survival rate of approximately 50%. Reliable molecular markers for risk stratification and subsequent therapy management are still needed. Therefore, we analyzed the prognostic potential of miR-155-5p and miR-203a-3p expression in a cohort of 79 STS patients. MiR-155-5p and miR-203a-3p expression was measured from tumor total RNA by qPCR and correlated with the demographic, clinicopathological, and prognostic data of the patients. Elevated miR-155-5p expression was significantly associated with increased tumor stage and hypoxia-associated mRNA/protein expression. High miR-155-5p expression and low miR-203a-3p expression, as well as a combination of high miR-155-5p and low miR-203a-3p expression, were significantly associated with poor disease-specific survival in STS patients in the Kaplan-Meier survival analyses (p = 0.027, p = 0.001 and p = 0.0003, respectively) and in the univariate Cox regression analyses (RR = 1.96; p = 0.031; RR = 2.59; p = 0.002 and RR = 4.76; p = 0.001, respectively), but not in the multivariate Cox regression analyses. In conclusion, the oncomiR miR-155-5p and the tumor suppressor-miR miR-203a-3p exhibit an association with STS patient prognosis and are suggested as candidates for risk assessment.

3.
Int J Mol Sci ; 19(12)2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30513863

RESUMO

In various tumors, the hypoxia inducible factor-1α (HIF-1α) and the epidermal growth factor-receptor (EGFR) have an impact on survival. Nevertheless, the prognostic impact of both markers for soft tissue sarcoma (STS) is not well studied. We examined 114 frozen tumor samples from adult soft tissue sarcoma patients and 19 frozen normal tissue samples. The mRNA levels of HIF-1α, EGFR, and the reference gene hypoxanthine phosphoribosyltransferase (HPRT) were quantified using a multiplex qPCR technique. In addition, levels of EGFR or HIF-1α protein were determined from 74 corresponding protein samples using ELISA techniques. Our analysis showed that a low level of HIF-1α or EGFR mRNA (respectively, relative risk (RR) = 2.8; p = 0.001 and RR = 1.9; p = 0.04; multivariate Cox´s regression analysis) is significantly associated with a poor prognosis in STS patients. The combination of both mRNAs in a multivariate Cox's regression analysis resulted in an increased risk of early tumor-specific death of patients (RR = 3.1, p = 0.003) when both mRNA levels in the tumors were low. The EGFR protein level had no association with the survival of the patient's cohort studied, and a higher level of HIF-1α protein associated only with a trend to significance (multivariate Cox's regression analysis) to a poor prognosis in STS patients (RR = 1.9, p = 0.09). However, patients with low levels of HIF-1α protein and a high content of EGFR protein in the tumor had a three-fold better survival compared to patients without such constellation regarding the protein level of HIF-1α and EGFR. In a bivariate two-sided Spearman's rank correlation, a significant correlation between the expression of HIF-1α mRNA and expression of EGFR mRNA (p < 0.001) or EGFR protein (p = 0.001) was found, additionally, EGFR mRNA correlated with EGFR protein level (p < 0.001). Our results show that low levels of HIF-1α mRNA or EGFR mRNA are negative independent prognostic markers for STS patients, especially after combination of both parameters. The protein levels showed a different effect on the prognosis. In addition, our analysis suggests a possible association between HIF-1α and EGFR expression in STS.


Assuntos
Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Sarcoma/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sarcoma/patologia , Análise de Sobrevida , Adulto Jovem
4.
Int J Mol Sci ; 18(12)2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29215551

RESUMO

The capillary morphogenesis gene 2 (CMG2), also known as the anthrax toxin receptor 2 (ANTXR2), is a transmembrane protein putatively involved in extracellular matrix (ECM) adhesion and tissue remodeling. CMG2 promotes endothelial cell proliferation and exhibits angiogenic properties. Its downregulation is associated with a worsened survival of breast carcinoma patients. Aim of this study was to analyze the CMG2 mRNA and protein expression in soft tissue sarcoma and their association with patient outcome. CMG2 mRNA was measured in 121 tumor samples of soft tissue sarcoma patients using quantitative real-time PCR. CMG2 protein was evaluated in 52 tumor samples by ELISA. CMG2 mRNA was significantly correlated with the corresponding CMG2 protein expression (rs = 0.31; p = 0.027). CMG2 mRNA expression was associated with the mRNA expressions of several ECM and tissue remodeling enzymes, among them CD26 and components of the uPA system. Low CMG2 mRNA expression was correlated with a worsened patients' disease-specific survival in Kaplan-Meier analyses (mean patient survival was 25 vs. 96 months; p = 0.013), especially in high-stage tumors. A decreased CMG2 expression is a negative prognostic factor for soft tissue sarcoma patients. CMG2 may be an interesting candidate gene for the further exploration of soft tissue sarcoma genesis and progression.


Assuntos
Biomarcadores Tumorais/metabolismo , Receptores de Peptídeos/metabolismo , Sarcoma/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Biomarcadores Tumorais/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Peptídeos/genética , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Análise de Sobrevida
6.
Breast J ; 23(2): 215-219, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27868315

RESUMO

The number of performed core biopsies of the breast as diagnostic workup is increasing in many European countries. We measured the intraobserver variability in pathological assessment of breast core biopsies. Furthermore, we studied potential modifiers of agreement between the assessments. Two hundred and fifty-six breast biopsies were evaluated twice in a blinded fashion by two pathologists. We calculated the observed and the chance-corrected (weighted) intraobserver agreement (kappa) using the B-categorization scheme (B1: normal or not interpretable, B2: benign, B3: benign but of uncertain biological potential, B4: suspicious of malignancy, B5: malignant). The observed agreement between the first and the second assessments were 0.80 (95% CI: 0.75-0.85) for pathologist 1 and 0.81 (95% CI: 0.76-0.86) for pathologist 2. The chance-corrected agreements were 0.85 (95% CI: 0.80-0.89) and 0.81 (95% CI: 0.76-0.87), respectively. The most frequent disagreement was between B1 and B2 for pathologist 1 (N = 34 out of 50 disagreements, 68%) and between B2 and B3 for pathologist 2 (N = 23 out of 48 disagreements, 48%). Our study shows that the chance-corrected agreement between the histopathological evaluations of breast biopsies based on the B-categorization scheme is almost perfect. The level of agreement is modified by biopsy technique and by the level of suspicion of the mammographic lesion.


Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Neoplasias da Mama/patologia , Variações Dependentes do Observador , Idoso , Densidade da Mama , Feminino , Humanos , Pessoa de Meia-Idade
7.
Neuroradiol J ; 29(3): 236-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27000208

RESUMO

The advent of new and acute headaches poses a diagnostic challenge. The differential diagnosis comprises numerous diseases and syndromes, the prevalence of which varies depending on the geographical region. Due to increased magnitudes in international migration, the usual differential diagnostic spectrum has to be enlarged in individual cases. The presented case illustrates this dilemma and shows that, for example, tuberculosis deserves to be taken into consideration.


Assuntos
Encéfalo/diagnóstico por imagem , Cefaleia/etiologia , Tuberculose do Sistema Nervoso Central/complicações , Adulto , Feminino , Cefaleia/diagnóstico por imagem , Humanos , Tomografia Computadorizada por Raios X , Tuberculose do Sistema Nervoso Central/diagnóstico por imagem
8.
Acta Radiol ; 57(4): 444-50, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25907117

RESUMO

BACKGROUND: Thyroid metastases (TM) are uncommon. Dependent on study design, the reported frequency of TM is in the range of 0.1-6% in different analyses. While clinical and histopathological features of TM were well described in the literature, radiological publications consist predominantly of isolated case reports or small series. PURPOSE: To estimate the prevalence, clinical signs, and radiological appearances of TM. MATERIAL AND METHODS: From 1997 to 2013, a total of 8849 patients with various disorders of the thyroid gland were treated in our institution. In 33 patients TM were diagnosed. Ultrasound (US) images were available in all patients, computed tomography (CT) of the neck in 16 patients, and magnetic resonance imaging (MRI) in nine patients. RESULTS: Clinically, most patients (85%) presented with a painless neck mass. Primary tumors were renal cell carcinoma (79%), colorectal cancer (12%), lung cancer (3%), rhabdomyosarcoma (3%), and breast carcinoma (3%). On US, most lesions were irregular in shape with inhomogenous texture. On CT, all TM were hypodense. On T1-weighted images, most TM were inhomogenously iso-to-hyperintense in comparison to the normal thyroid tissue, and slightly hyperintense on T2-weighted images with an inhomogenous contrast enhancement. CONCLUSION: The prevalence of TM was 0.4%. Most of the TM originated from renal cell carcinoma. The identified radiological features of TM should be taken into consideration in the differential diagnosis of thyroid lesions.


Assuntos
Imageamento por Ressonância Magnética , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/secundário , Tomografia Computadorizada por Raios X , Ultrassonografia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Adulto Jovem
9.
Oncoimmunology ; 4(1): e985082, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25949868

RESUMO

Tumor-associated immune cells have been discussed as an essential factor for the prediction of the outcome of tumor patients. Lymphocyte-specific genes are associated with a favorable prognosis in colorectal cancer but with poor survival in renal cell carcinoma (RCC). Flow cytometric analyses combined with immunohistochemistry were performed to study the phenotypic profiles of tumor infiltrating lymphocytes (TIL) and the frequency of T cells and macrophages in RCC lesions. Data were correlated with clinicopathological parameters and survival of patients. Comparing oncocytoma and clear cell (cc)RCC, T cell numbers as well as activation-associated T cell markers were higher in ccRCC, whereas the frequency of NK cells was higher in oncocytoma. An intratumoral increase of T cell numbers was found with higher tumor grades (G1:G2:G3/4 = 1:3:4). Tumor-associated macrophages slightly increased with dedifferentiation, although the macrophage-to-T cell ratio was highest in G1 tumor lesions. A high expression of CD57 was found in T cells of early tumor grades, whereas T cells in dedifferentiated RCC lesions expressed higher levels of CD69 and CTLA4. TIL composition did not differ between older (>70 y) and younger (<58 y) patients. Enhanced patients' survival was associated with a higher percentage of tumor infiltrating NK cells and Th1 markers, e.g. HLA-DR+ and CXCR3+ T cells, whereas a high number of T cells, especially with high CD69 expression correlated with a worse prognosis of patients. Our results suggest that immunomonitoring of RCC patients might represent a useful tool for the prediction of the outcome of RCC patients.

10.
Clin Imaging ; 38(6): 826-30, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25103962

RESUMO

From 1997 to 2013, 8849 patients with several disorders of the thyroid were treated in our surgical department. In nine patients (0.1%), primary thyroid sarcoma (PTS) was diagnosed. In eight patients, PTS manifested as a thyroid mass (range, 25-90 mm). In one case, a global enlargement of the thyroid was seen. Clinically, all patients presented with neck swelling. On ultrasound, PTS was predominantly hypoechoic. On computed tomography, the sarcomas were hypodense. On magnetic resonance imaging, PTS had inhomogeneous signal increase on T2-weighted images and signal decrease on T1-weighted images with inhomogeneous enhancement.


Assuntos
Diagnóstico por Imagem/métodos , Sarcoma/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Idoso , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia
11.
Open Orthop J ; 8: 242-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25136392

RESUMO

OBJECTIVES: The study investigated the impact of occupational workloads on disc surgery specimens. We report the relationship between workload and histological features. METHODS: Specimens were collected prospectively from patients suffering from lumbar disc prolapse (n=90) or spinal osteochondrosis (n=19). Histomorphology and occupational workload data and histomorphological features were evaluated. Occupational data were collected in a structured, standardized patient interview assessing lifting and carrying loads. In this way the exposure was assessed for each test subject's entire working life up to surgery. RESULTS: There was no association between cumulative workload and histological patterns. In a subgroup of patients with a workload period of 12 months prior to surgery a relevant formation of chondrocyte clusters (p=0.055) was apparent. Chondrocyte cluster formation was found in 83% (n=74) of the prolapse patients and in 58% (n=11) of the osteochondrosis patients (p=0.02). Fibrocyte mediated scar formation was found in 55% of the prolapse patients and in 45% of the spinal stenosis patients. Chondrocyte clusters and their de novo collagen matrix did not integrate biomechanically sufficient with collagen fibers of the disc. Disintegration of clusters from disc matrix and formation of intra-discal sequesters were observed. CONCLUSION: Matrix degeneration was common but displayed no relationship to occupational workload or other histological features. Scar formation was observed in every second specimen. Regenerative chondrocyte cluster proliferation was a common feature in disc specimens and tended to be associated in patients with a workload one year before surgery.

12.
Int J Cancer ; 135(9): 2096-106, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24676787

RESUMO

Chemokines are involved in both the negative and positive regulation of inflammatory processes, angiogenesis and cancer/cancer stem cell proliferation as well as the chemoattraction of tumor cells to metastatic sites. The aim of this study was to measure the mRNA expression levels of three chemokines, CCL2, CCL7 and CX3CL1, in soft tissue sarcomas (STSs) and to assess the correlations between these levels as well as their correlations with clinicopathological data and the disease-specific survival of STS patients. The mRNA levels of CCL2, CCL7 and CX3CL1 were analyzed in tumor tissues from 126 STS patients using qPCR. Low mRNA expression of CCL2 and CX3CL1 was significantly correlated with a worse prognosis (RR = 1.98; p = 0.019 and RR = 2.10; p = 0.014; multivariate Cox's regression analysis). A combined low expression of CCL2 and CX3CL1 was associated with a significantly increased risk of tumor-related death as compared to patients with high expression levels of both chemokines (RR = 3.08; p = 0.003). A gender-specific multivariate analysis revealed that female STS patients with low CX3CL1 mRNA expression had a 3.46-fold increased risk of death (p = 0.004). Low expression of both CCL2 and CX3CL1 mRNAs resulted in an additive 5.37-fold increased risk of tumor-related death (p = 0.003) as compared to those with high expression of both parameters in female patients. In conclusion, this is the first study to show a significant correlation between combined low expression of CCL2 and CX3CL1 and a poor prognosis for STS patients, particularly in female patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CX3CL1/metabolismo , Sarcoma/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Biomarcadores Tumorais/genética , Western Blotting , Proliferação de Células , Quimiocina CCL2/genética , Quimiocina CX3CL1/genética , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma/genética , Sarcoma/mortalidade , Fatores Sexuais , Taxa de Sobrevida , Células Tumorais Cultivadas , Adulto Jovem
14.
PLoS One ; 8(12): e80520, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24349002

RESUMO

Sialic acids (Sia) are widely expressed as terminal monosaccharides on eukaryotic glycoconjugates. They are involved in many cellular functions, such as cell-cell interaction and signal recognition. The key enzyme of sialic acid biosynthesis is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE), which catalyses the first two steps of Sia biosynthesis in the cytosol. In this study we analysed sialylation of muscles in wild type (C57Bl/6 GNE (+/+)) and heterozygous GNE-deficient (C57Bl/6 GNE (+/-)) mice. We measured a significantly lower performance in the initial weeks of a treadmill exercise in C57Bl/6 GNE (+/-) mice compared to wild type C57Bl/6 GNE (+/+) animals. Membrane bound Sia of C57Bl/6 GNE (+/-) mice were reduced by 33-53% at week 24 and by 12-15% at week 80 in comparison to C57Bl/6 GNE (+/+) mice. Interestingly, membrane bound Sia concentration increased with age of the mice by 16-46% in C57Bl/6 GNE (+/+), but by 87-207% in C57Bl/6 GNE (+/-). Furthermore we could identify specific morphological changes in aged muscles. Here we propose that increased Sia concentrations in muscles are a characteristic feature of ageing and could be used as a marker for age-related changes in muscle.


Assuntos
Envelhecimento/fisiologia , Músculo Esquelético/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
15.
Histopathology ; 63(6): 817-25, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24236511

RESUMO

AIMS: Because of the introduction of mammography screening programmes in Europe, the number of breast biopsies performed is increasing. We investigated the influence of immunohistochemistry (IHC) on the final diagnosis of breast biopsies by comparing the primary diagnoses (based on the results of haematoxylin and eosin staining only) with the final diagnoses (based on the additional information provided by IHC). METHODS AND RESULTS: We analysed the breast biopsies which were performed at the University of Halle-Wittenberg between 2006 and 2010 and for which the pathologist requested IHC for making the final diagnosis. According to the B-categorization scheme, the primary diagnosis changed in 37 of a total of 429 biopsies (8.6%). In 18 of these biopsies (48.6%) the category changed from B1-B2 to B3-B5 or vice versa, which would imply a different work-up. Only 77% of the primary diagnoses of breast cancer in situ were confirmed. CONCLUSION: IHC has a considerable influence on the final diagnosis of breast biopsies in several situations, including those in which the biopsied women are at risk of inadequate therapeutic intervention. The influence is particularly notable among those biopsies for which IHC is performed in order to assess the suspicion of breast cancer in situ.


Assuntos
Doenças Mamárias/diagnóstico , Neoplasias da Mama/diagnóstico , Mama/patologia , Imuno-Histoquímica , Biópsia/métodos , Doenças Mamárias/metabolismo , Doenças Mamárias/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Erros de Diagnóstico , Feminino , Alemanha , Humanos
16.
Mol Cancer Res ; 11(11): 1462-77, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24025972

RESUMO

UNLABELLED: The cyclic (c)AMP responsive element binding protein (CREB) plays a key role in many cellular processes, including differentiation, proliferation, and signal transduction. Furthermore, CREB overexpression was found in tumors of distinct origin and evidence suggests an association with tumorigenicity. To establish a mechanistic link between HER-2/neu-mediated transformation and CREB protein expression and function, in vitro models of HER-2/neu-overexpressing and HER-2/neu-negative/silenced counterparts as well as human mammary carcinoma lesions with defined HER-2/neu status were used. HER-2/neu overexpression resulted in the induction and activation of CREB protein in vitro and in vivo, whereas short hairpin RNA (shRNA)-mediated inhibition of HER-2/neu correlated with downregulated CREB activity. CREB activation in HER-2/neu-transformed cells enhanced distinct signal transduction pathways, whereas their inhibition negatively interfered with CREB expression and/or activation. CREB downregulation in HER-2/neu-transformed cells by shRNA and by the inhibitors KG-501 and lapatinib caused morphologic changes, reduced cell proliferation with G0-G1 cell-cycle arrest, which was rescued by CREB expression. This was accompanied by reduced cell migration, wound healing, an increased fibronectin adherence, invasion, and matrix metalloproteinase expression. In vivo shCREB-HER-2/neu(+) cells, but not control cells, exerted a significantly decreased tumorgenicity that was associated with decreased proliferative capacity, enhanced apoptosis, and increased frequency of T lymphocytes in peripheral blood mononuclear cells. Thus, CREB plays an important role in the HER-2/neu-mediated transformation by altering in vitro and in vivo growth characteristics. IMPLICATIONS: These data suggest that CREB affects tumor immunogenicity and is a potential target for cancer therapy.


Assuntos
Neoplasias da Mama/metabolismo , Transformação Celular Neoplásica/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Neoplasias Mamárias Experimentais/metabolismo , Receptor ErbB-2/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Masculino , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos DBA , Células NIH 3T3 , Fenótipo , Receptor ErbB-2/genética , Transdução de Sinais/genética , Análise Serial de Tecidos
17.
J Neurooncol ; 112(3): 323-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23404622

RESUMO

Meningioma is a common intracranial neoplasm derived from meningothelial cells. Meningiomas are associated with a benign clinical course. However, malignant behaviour such as metastatic disease has been also described. Our aim was to analyze the metastatic pattern taking tumor grading into consideration, and to determine clinical signs of distant metastases in meningiomas. In this systematic review PubMed database was screened for distant meningioma metastases from 1990 to 2012. 95 articles were identified. Only cases with metastasized meningiomas were included in the analysis. Our analysis comprised 115 cases with 164 metastatic lesions. Primary tumors were in 33.9 % grade 1, 20.9 % grade 2, and 40 % grade 3. In 5.2 % the grade was not reported. In 93 % meningiomas were diagnosed and resected before distant metastases occurred. In 6.1 % metastases were identified simultaneously with primary tumors and in 0.9 % metastases were identified before the primary tumor was found. The metastatic lesions were localized most frequently in the lung (37.2 %), bones (16.5 %), intraspinally (15.2 %), and in the liver (9.2 %). Other locations were rarer. The size of the metastases varied from 0.6 to 28 cm (median size, 3 cm). There were no significant differences between sizes of the identified metastases in relation to tumor grading. 50.4 % of distant metastases were clinically manifest and 31.3 % were identified incidentally. In 18.3 % clinical signs were missing. In our review 31.3 % of metastatic meningiomas were found to be clinically silent. The prevalence of metastases in meningioma may be underreported.


Assuntos
Neoplasias Meníngeas/patologia , Meningioma/secundário , Metástase Neoplásica/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Adulto Jovem
18.
Langenbecks Arch Surg ; 398(3): 403-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23408061

RESUMO

PURPOSE: Calcitonin screening aims at uncovering occult medullary thyroid cancer (MTC) in patients with nodular thyroid disease. Elevated basal calcitonin serum levels call for calcitonin stimulation, the level of which may direct the extent of surgery. Because pentagastrin has become restricted, calcium has increasingly been used instead for stimulation. This study identified a new spectrum of patients demonstrating a false-positive hypercalcitoninemia in the absence of C-cell disease, carrying multinodular goiter (MNG), thyroiditis, and non-MTC thyroid malignancy, and endeavored to explore the feasibility of extrapolating pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. METHODS: Altogether, 43 (9.5 %) of 455 patients with nodular thyroid disease revealed increased basal calcitonin serum levels between 2005 and 2012, for which they underwent intravenous stimulation with pentagastrin (31 patients) or calcium gluconate (12 patients) before and after primary thyroidectomy. RESULTS: Stimulation with calcium gluconate resulted in significantly higher and more variable preoperative calcitonin serum levels after 2 (241.2 vs. 104.9 pg/mL; P = 0.018) and 5 min (240.6 vs. 87.4 pg/mL; P = 0.007) than stimulation with pentagastrin. Stimulation with calcium gluconate produced 10-fold (nodular goiter), 15-fold (thyroiditis), and 21-fold (thyroid neoplasia other than MTC) calcitonin increases over baseline, as opposed to 5-fold, 10-fold, and 8-fold increases after stimulation with pentagastrin. None of the 43 patients, all of whom reverted to undetectable calcitonin serum levels after thyroidectomy, had immunohistochemical evidence of C-cell disease. Subgroup analyses according to gender and thyroid disease, being limited by the low number of patients in each subgroup, did not yield significant differences. CONCLUSIONS: Calcium stimulation yields significantly greater calcitonin levels than pentagastrin stimulation, precluding generalization of pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. After calcium stimulation, false-positive findings appear to be more common in patients of female gender and patients with thyroiditis and thyroid neoplasia other than MTC, potentially effecting surgical overtreatment.


Assuntos
Biomarcadores Tumorais/sangue , Calcitonina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/cirurgia , Análise de Variância , Gluconato de Cálcio , Carcinoma Neuroendócrino , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pentagastrina , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Estimulação Química , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/patologia , Doenças da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Resultado do Tratamento
19.
BMC Cancer ; 12: 554, 2012 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-23176326

RESUMO

BACKGROUND: As high percentage of mammographic densities complicates the assessment of imaging findings, mammographic density may influence the histopathological evaluation of core-biopsies of the breast. We measured the influence of mammographic density on the inter-observer variability of histopathological findings of breast biopsies. METHODS: Histological slides of 695 women who underwent core biopsies of the breast at University of Halle between 2006 and 2008 were evaluated in a blinded fashion by two pathologists using the five levels of the B-categorization scheme (B1-B5). To quantify mammographic density, we used a computer-based threshold method (Madena). We calculated observed and chance-corrected agreements (weighted kappa) and 95% confidence intervals (95% CI) according to four categories of mammographic density (<10%, 10<25%, 25<50%, ≥50%). RESULTS: The weighted kappa decreased monotonically from 89.6% (95% CI: 85.8%, 93.3%) among women with less than 10% of mammographic density to 80.4% (95% CI: 69.9%, 90.9%) for women with more than 50% of mammographic density, respectively. Results of a kappa regression analysis showed that agreement of pathologists on clinically relevant categories (B1-B2 versus B3-B5) decreased with mammographic density. CONCLUSIONS: Mammographic density is a relevant modifier of the agreement between pathologists who assess breast biopsies using the B-categorization scheme. The influence of mammographic density on the inter-observer variability can be explained to some extent by varying prevalences of histological entities across B categories that have typically different inter-observer agreement. Women with high mammographic density are at higher risk of inter-observer variability compared to women with low mammographic density and should possibly undergo a second pathology review.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Mama/patologia , Adulto , Idoso , Biópsia/métodos , Densidade da Mama , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Glândulas Mamárias Humanas/anormalidades , Glândulas Mamárias Humanas/patologia , Mamografia/métodos , Pessoa de Meia-Idade , Variações Dependentes do Observador
20.
Clin Imaging ; 36(5): 539-46, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22920359

RESUMO

From January 2005 to January 2010, 668 consecutive patients with lymphoproliferative disease were retrospectively identified. Hepatic infiltration was present at initial staging in patients with non-Hodgkin's lymphoma [12 of 364=3.3%; age median=45; male:female (M:F)=10:2] but also Hodgkin's disease (5 of 41=12.2%; age median=19; M:F=0:5) and multiple myeloma (3 of 162=1.8%; age median=60; M:F=2:1). There were no cases of hepatic infiltration in 101 patients with leukemia. There are typical radiological patterns of hepatic involvement in lymphoproliferative disease with typical lesions characteristics.


Assuntos
Hepatopatias/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Progressão da Doença , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Humanos , Hepatopatias/epidemiologia , Hepatopatias/patologia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/patologia , Prevalência , Estudos Retrospectivos , Esplenopatias/diagnóstico , Esplenopatias/epidemiologia , Esplenopatias/patologia , Tomografia Computadorizada por Raios X
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