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1.
Scand J Surg ; 99(1): 38-44, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20501357

RESUMO

BACKGROUND: Fractures of the tibial intercondylar eminence are observed mostly in children and adolescents, often after minimal trauma. The purpose of this paper is to evaluate the use of K-wire fixation for the arthroscopic treatment of tibial eminence fractures in children. PATIENTS AND METHODS: From January 2002 through January 2009 ten patients were treated arthroscopically because of the intercondylar eminence fracture in a Department of pediatric surgery, University Hospital Split. Arthroscopically controlled reposition was done, and using mobile X-ray two crossed K-wires were introduced percutaneously from the proximal part of the tibia to the fractured intercondylar eminence. Subjective outcome was obtained using IKDC subjective questionnaire. RESULTS: Average hospitalization time was 11 days. Average duration of treatment was 12.5 weeks. Average follow-up was 42 months. Follow-up radiographs showed union in all cases. The mean IKDC subjective score was 96/100. Clinically, all patients exhibited a solid endpoint on the Lachman test. The global IKDC objective score was normal in eight knees and nearly normal in two knees. CONCLUSION: Arthroscopic reduction and fixation by Kirschner wires or a small fragment screw is the best way for treatment intercondylar tibial eminence fractures, in the pediatric population, because is not crossing the epiphyseal plate.


Assuntos
Artroscopia , Fios Ortopédicos , Fixação Interna de Fraturas/instrumentação , Fraturas Intra-Articulares/cirurgia , Traumatismos do Joelho/cirurgia , Fraturas da Tíbia/cirurgia , Adolescente , Criança , Estudos de Coortes , Feminino , Consolidação da Fratura , Humanos , Fraturas Intra-Articulares/diagnóstico , Fraturas Intra-Articulares/etiologia , Traumatismos do Joelho/diagnóstico , Traumatismos do Joelho/etiologia , Masculino , Estudos Retrospectivos , Fraturas da Tíbia/diagnóstico , Fraturas da Tíbia/etiologia , Resultado do Tratamento
2.
Scott Med J ; 55(3): 35-8, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20795516

RESUMO

BACKGROUND: Simple or unicameral bone cysts are common benign fluid-filled lesions usually located in the long bones of children before skeletal maturity. Pathological fracture is common, and is often the presenting feature. AIM: The objective of the present study was to evaluate the results of titanium intramedullary nailing for the treatment of unicameral bone cysts with or without a pathological fracture. METHODS: During the period 2001 to 2007, flexible intramedullary nailing for the treatment of a unicameral bone cyst was performed in 18 children. Four of these patients presented with a pathological fracture. The cyst was located in the humerus in 14 patients, in the femur in three, and in the tibia in one. The diagnosis was based on typical radiographs and computed tomography. The mean age of the patients at the time of surgery was 9.4 years, and the mean duration of follow-up was 53 months. Radiographic evaluation was performed, and the cyst was classified as completely healed, healed with residual radiolucency, recurred, or having no response. RESULTS: Mean hospital stay was 24 hours. At one to four weeks postoperatively, all patients were pain free and had full range of motion of adjacent joints. Radiographic signs of cyst healing were present at three months in all patients, and all cysts healed completely. All of the cysts responded to treatment, with no cyst recurrence. No major complications were observed. CONCLUSION: Elastic intramedullary nailing has the twofold benefits of continuous cyst decompression, and early immediate stability to the involved bone segment, which permits early mobilization and return to normal activities.


Assuntos
Cistos Ósseos/cirurgia , Pinos Ortopédicos , Descompressão Cirúrgica/métodos , Procedimentos Ortopédicos/métodos , Adolescente , Cistos Ósseos/diagnóstico por imagem , Criança , Feminino , Fraturas do Fêmur/cirurgia , Fraturas Espontâneas/cirurgia , Humanos , Fraturas do Úmero/cirurgia , Masculino , Radiografia , Estudos Retrospectivos , Fraturas da Tíbia/cirurgia , Titânio
3.
Eur J Cancer Prev ; 29(4): 281-288, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31609810

RESUMO

Lynch syndrome is caused by germline mutations of genes affecting the mismatch repair proteins MLH1, MSH2, MSH6 or PMS2. Identification of Lynch syndrome patients using germline molecular testing in colorectal cancer (CRC) affected patients and in their healthy relatives is a cost-effective model of cancer prevention. Several studies demonstrate that universal tumor testing using immunohistochemical (IHC) analysis of CRC samples is the most efficient approach to identifying patients affected by Lynch syndrome. We studied a cohort of 352 consecutive CRCs for MSH2, MLH1, MSH6 and PMS2 protein expression using universal IHC screening. IHC mismatch repair (MMR) defects were identified in 70 out of 352 cases (19.8%) including six CRCs MSH2/MSH6 defective, two CRCs, respectively, MSH6 and PMS2 defective, 58 CRCs MLH1/PMS2 defective and four CRCs showing atypical MMR pattern. MLH1 promoter methylation and V600E BRAF mutation analysis were investigated on 61 CRCs. Cancer genetic counseling was offered to all 68 patients affected by MMR defective CRCs and 25 patients opted in to this service (36.8% compliance). Pathogenetic variants of MSH2 genes were identified in two cases (55 and 79 years old). Universal screening based on an IHC approach showed a Lynch syndrome incidence of 1/173. The protocol recommended by regional law improved patient compliance. This study demonstrates that the IHC approach for both MMR deficiency and V600E BRAF mutation detections is the most efficient approach for Lynch syndrome screening in the Italian population.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Reparo de Erro de Pareamento de DNA , Detecção Precoce de Câncer/métodos , Mutação em Linhagem Germinativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Humanos , Imuno-Histoquímica , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Reto/patologia , Reto/cirurgia
4.
Orthop Traumatol Surg Res ; 103(5): 765-770, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28330797

RESUMO

BACKGROUND: The aim of this study was to analyze outcomes of treatment and complications in children treated with flexible intramedullary nailing (FIN) due to humeral fracture. HYPOTHESIS: The FIN for treatment of humeral fractures in children would allow an early functional and cast-free follow-up with a quick pain reduction and low complication rate. PATIENTS AND METHODS: From May 2002 until May 2016 case records of all children who underwent fixation with titanium intramedullary nails because of humeral fracture were retrospectively reviewed. The study included 118 patients treated with FIN for proximal humeral or humeral shaft fracture. The average age at the time of trauma was 12 years. Mean follow-up was 77 months. Left hand was affected in 51% of patients. The most common mechanism of injury was fall (n=58), followed by sports injuries, road traffic accidents, pathological fractures, motorbike accidents and bicycle riding. RESULTS: There were no residual valgus/varum deformities. All patients achieved complete radiographic healing at a mean of 7.5 weeks. Nine complications were recorded: 1 humeral shaft fracture in patient with osteogenesis imperfecta, 4 entry site skin irritations, 2 skin infections and 2 radial nerve injuries. There were no cases of delayed union, nonunion or mal-union. After removal of the nails, all patients regained full function and all complications resolved. DISCUSSION: The FIN for humeral fractures is a minimally invasive, simple and well reproducible technique with very low complication rate. CONCLUSION: The FIN for treatment of humeral fractures shows very good functional and cosmetic results. It allows an early functional and cast-free follow-up with a quick pain reduction. LEVEL OF EVIDENCE: Level IV - retrospective study.


Assuntos
Pinos Ortopédicos , Fixação Intramedular de Fraturas/métodos , Fraturas do Úmero/cirurgia , Complicações Pós-Operatórias/etiologia , Fraturas do Ombro/cirurgia , Adolescente , Criança , Pré-Escolar , Diáfises/diagnóstico por imagem , Diáfises/lesões , Feminino , Seguimentos , Fixação Intramedular de Fraturas/efeitos adversos , Humanos , Fraturas do Úmero/diagnóstico por imagem , Masculino , Radiografia , Estudos Retrospectivos , Fraturas do Ombro/diagnóstico por imagem , Resultado do Tratamento , Cicatrização
5.
Oncogene ; 36(40): 5551-5566, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28581528

RESUMO

Widespread genome hypo-methylation and promoter hyper-methylation of epithelium-specific genes are hallmarks of stable epithelial-to-mesenchymal transition (EMT), which in prostate cancer (PCa) correlates with castration resistance, cancer stem cells generation, chemoresistance and worst prognosis. Exploiting our consolidated 'ex-vivo' system, we show that cancer-associated fibroblasts (CAFs) released factors have pivotal roles in inducing genome methylation changes required for EMT and stemness in EMT-prone PCa cells. By global DNA methylation analysis and RNA-Seq, we provide compelling evidence that conditioned media from CAFs explanted from two unrelated patients with advanced PCa, stimulates concurrent DNA hypo- and hyper-methylation required for EMT and stemness in PC3 and DU145, but not in LN-CaP and its derivative C4-2B, PCa cells. CpG island (CGI) hyper-methylation associates with repression of genes required for epithelial maintenance and invasion antagonism, whereas activation of EMT markers and stemness genes correlate with CGI hypo-methylation. Remarkably, methylation variations and EMT-regulated transcripts almost completely reverse qualitatively and quantitatively during MET. Unsupervised clustering analysis of the PRAD TCGA data set with the differentially expressed (DE) and methylated EMT signature, identified a gene cluster of DE genes defined by a CAF+ and AR- phenotype and worst diagnosis. This gene cluster includes the relevant factors for EMT and stemness, which display DNA methylation variations in regulatory regions inversely correlated to their expression changes, thus strongly sustaining the ex-vivo data. DNMT3A-dependent methylation is essential for silencing epithelial maintenance and EMT counteracting genes, such as CDH1 and GRHL2, that is, the direct repressor of ZEB1, the key transcriptional factor for EMT and stemness. Accordingly, DNMT3A knock-down prevents EMT entry. These results shed light on the mechanisms of establishment and maintenance of coexisting DNA hypo- and hyper-methylation patterns during cancer progression, the generation of EMT and cell stemness in advanced PCa, and may pave the way to new therapeutic implications.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Transformação Celular Neoplásica , Metilação de DNA , Células Epiteliais/patologia , Mesoderma/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Meios de Cultivo Condicionados , Citosina/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA de Neoplasias/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Células-Tronco/patologia , Ativação Transcricional
6.
Cancer Res ; 56(19): 4493-8, 1996 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-8813146

RESUMO

Complex karyotypes are often seen in primary surface epithelial ovarian tumors (SEOTs). Conventional cytogenetic as well as fluorescence in situ hybridization analyses coupled with loss of heterozygosity studies identified abnormalities of chromosome 6 as one of the most frequent lesions in these types of tumors. We performed cytogenetic analysis of direct preparations from 40 SEOTs, including borderline tumors and low-, intermediate-, and high-grade carcinomas to verify the frequency of chromosome 6 alterations. We also carried out fluorescence in situ hybridization analysis with a chromosome 6 library and yeast artificial chromosome clones from a region of the same chromosome (6q27). Chromosome 6 abnormalities were identified in 30 of 32 analyzable SEOTs. Twenty-five of 32 cases showed a deletion of 6q irrespective of their histological grade. We wish to underline that this is the first report proving that del(6q) was the most frequent chromosome anomaly in near-diploid SEOTs and that it was the sole anomaly observed in four SEOTs with diploid complement. Our findings suggest that abnormalities of the telomeric region of chromosome 6 (6q27) may be considered one of the earliest lesions in the pathogenesis of ovarian carcinomas.


Assuntos
Cromossomos Humanos Par 6 , Cistadenocarcinoma Papilar/genética , Neoplasias Ovarianas/genética , Aneuploidia , Carcinoma/genética , Carcinoma/patologia , Cistadenocarcinoma Papilar/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Neoplasias Ovarianas/patologia
7.
Oncogene ; 16(12): 1639-42, 1998 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-9569033

RESUMO

A detailed long range restriction map of the region defined by markers D6S149 and D6S193 on chromosome 6q27 has been constructed. This was achieved by YAC cloning and contig assembling of the same region. Seven YAC clones were found to span the almost 1000 Kb region flanked by the two markers which on the genetic map resulted to be 1.9 cM apart. With some of the characterized YAC clones we undertook a molecular cytogenetic analysis of 20 benign ovarian tumors. The rationale for this was the recent mapping to a region of chromosome 6q27, flanked by markers D6281 and D6S133, of a locus for the SV40-mediated immortalization of human cells (SEN6 gene). Noteworthy we found that the the D6S149-D6S193 region (comprised in the larger D6S281-D6S133 physical interval) was altered in all samples analysed adding support to the occurrence of a immortalization step in this type of tumors.


Assuntos
Cromossomos Humanos Par 6/genética , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Mapeamento por Restrição , Deleção Cromossômica , Feminino , Marcadores Genéticos , Humanos , Hibridização in Situ Fluorescente
8.
Clin Cancer Res ; 6(4): 1422-31, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10778973

RESUMO

To assess whether early breast lesions are the precursors of invasive carcinomas, three classes of breast lesions, namely benign tumors (including fibroadenomas), putative premalignant lesions (including cases of atypical hyperplasia), and invasive carcinomas, were compared at the cytogenetic and molecular cytogenetic levels. Genetic relatedness was clearly demonstrated by the sharing of several anomalies, among which 6q deletions outnumbered all of the other alterations detected. Indeed, deletions of the long arm of chromosome 6, most likely occurring in epithelial cells, were present in 83.9% of benign breast tumors, 64% of putative premalignant lesions, and 77.4% of analyzable carcinomas. Furthermore, the interval between 6q24 and qter appeared to be the common region of deletion in all three classes of breast lesions, whereas the minimal common region of deletion was 6q27-qter. Interestingly, the latter region was reported previously to be deleted in benign ovarian tumors and recently found to harbor a gene (SEN6) that is important for SV40-mediated immortalization of human cells.


Assuntos
Neoplasias da Mama/genética , Deleção Cromossômica , Cromossomos Humanos Par 6/genética , Fibroadenoma/genética , Lesões Pré-Cancerosas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Mama/química , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma in Situ/genética , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Análise Citogenética , Feminino , Fibroadenoma/metabolismo , Fibroadenoma/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Cariotipagem , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Índice Mitótico , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia
9.
Clin Cancer Res ; 7(11): 3404-9, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11705855

RESUMO

PURPOSE: We used conventional cytogenetics, molecular cytogenetics, and molecular genetic analyses to study the pattern of allelic loss on chromosome 6q in a cohort of borderline epithelial ovarian tumors. EXPERIMENTAL DESIGN: Fifteen tumor samples were collected from patients undergoing surgery for ovarian tumors. The tumors of borderline malignancy, classified according to the standard criteria, included 4 mucinous and 11 serous tumors. Cytogenetic and molecular cytogenetic (with yeast artificial chromosome clones from 6q26-27) studies were performed on tumor areas contiguous to those used for histological examination ensuring the appropriate sampling. Moreover loss of heterozygosity analysis was performed using PCR amplification of eight microsatellite markers mapping on 6q27 (D6S193, D6S297), 6q26 (D6S305, D6S415, D6S441), 6q21 (D6S287), 6q16 (D6S311), and 6q14 (D6S300). RESULTS: Deletions of this chromosome arm, in particular of 6q24-27, were the most frequent lesions found in this set of tumors. In a tumor with a normal karyotype the only detectable alteration was a deletion of approximately 300 kb within the D6S149-D6S193 interval at band 6q27. This is, to date, the smallest deletion described for borderline tumors. CONCLUSION: Alterations in the above-mentioned interval are a common finding in advanced ovarian carcinomas but also in benign ovarian cysts, implying that some tumors of borderline malignancy may arise from benign tumors and that malignant ones may evolve from tumors of borderline malignancy. Genes located in 6q27 seem to be crucial for this mechanism of early events in ovarian tumorigenesis.


Assuntos
Adenocarcinoma Mucinoso/patologia , Deleção Cromossômica , Cromossomos Humanos Par 6/genética , Cistadenoma Seroso/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma Mucinoso/genética , Bandeamento Cromossômico , Cistadenoma Seroso/genética , DNA de Neoplasias/genética , Progressão da Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Perda de Heterozigosidade , Repetições de Microssatélites , Neoplasias Ovarianas/genética
10.
J Clin Pathol ; 54(1): 37-41, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11271786

RESUMO

BACKGROUND/AIM: Fibroadenomas are benign tumours composed of both glandular and fibrous tissue. The mechanisms regulating the growth of these tumours and the relation between the stromal and epithelial cells are poorly understood. Acidic fibroblast growth factor (aFGF) is a well known fibroblast activator, which acts through four specific cell surface receptors, among which, fibroblast growth factor receptor 4 (FGFR4) is highly specific. The aim of this study was to evaluate the distribution of aFGF and FGFR4 in specific cell types of fibroadenomas to understand their possible role in the growth of these breast lesions. METHODS: Formalin fixed and paraffin wax embedded tissues from 15 fibroadenomas and peritumoral normal breasts were investigated for the expression of aFGF and FGFR4 using immunohistochemistry. The presence of aFGF mRNA was also investigated using in situ hybridisation. RESULTS: Immunoreactivity for aFGF and FGFR4 was seen in epithelial cells, but it was lacking in myoepithelial cells of both normal tissues and fibroadenomas. Strong FGFR4 immunoreactivity was found in stromal fibroblasts, which were also weakly positive for aFGF. aFGF mRNA was detected in epithelial cells and in some stromal fibroblasts. CONCLUSIONS: These results suggest a paracrine/autocrine modulation of epithelial and stromal cells of fibroadenomas through an aFGF-FGFR4 interaction. This interaction might regulate various cell functions and the growth of fibroadenomas.


Assuntos
Neoplasias da Mama/metabolismo , Fibroadenoma/metabolismo , Fator 1 de Crescimento de Fibroblastos/metabolismo , Proteínas de Neoplasias/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Adolescente , Adulto , Células Epiteliais/metabolismo , Feminino , Fator 1 de Crescimento de Fibroblastos/genética , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , RNA Mensageiro/genética , RNA Neoplásico/genética , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos , Células Estromais/metabolismo
11.
Virchows Arch ; 438(1): 39-48, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11213834

RESUMO

Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours.


Assuntos
Neoplasias Colorretais/química , Proteínas de Ligação a DNA , Neoplasias do Endométrio/química , Imuno-Histoquímica , Proteínas de Neoplasias/análise , Neoplasias Ovarianas/química , Proteínas Proto-Oncogênicas/análise , Neoplasias Gástricas/química , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma/química , Adenocarcinoma/genética , Adenocarcinoma/patologia , Carcinoma/química , Carcinoma/genética , Carcinoma/patologia , Proteínas de Transporte , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Cistadenocarcinoma/química , Cistadenocarcinoma/genética , Cistadenocarcinoma/patologia , Reparo do DNA , DNA de Neoplasias/análise , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Humanos , Repetições de Microssatélites , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Mutação , Proteínas Nucleares , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Polimorfismo Conformacional de Fita Simples , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
12.
Virchows Arch ; 439(2): 158-69, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11561756

RESUMO

The relative contribution of tumour histology or molecular changes, compared with invasion pattern or stage, to prognostic assessment of gastric cancer was investigated in a series of 185 advanced (T2 to T4, stage IB to IV) cancers that had undergone intentionally curative surgery at Varese General Hospital. Survival analysis of the histological types considered in commonly used classifications, such as Lauren, Kubo, the World Health Organization (WHO) and related classifications, allowed separation of a small high-grade (Hg, 12 cases) group of adenosquamous, anaplastic and small cell endocrine carcinomas from a large cohesive group (C, 86 glandular or solid cancers) and from another large (87 cases) group of tumours with dissociated cells [29 diffuse (D) and 58 mixed (M) tumours]. Univariate and multivariate analysis showed the independent prognostic value of this C/M+D/Hg classification approach, which proved superior to other classifications and to cell dissociation at the growing front or angio, lympho and neuro-invasion. Expression of sialyl Lewis(c), the DUPAN-2 antigen, proved to be an independent predictor of worse survival among tumours beyond stage I, showing an exclusively or predominantly cohesive structure. Microsatellite instability (MSI) predicted favourable survival in purely cohesive tumours of intermediate (II) stage, especially of solid/medullary and lymphoid stroma/lympho-epithelioma-like structure, among which two distinct tumour subsets were characterised, one MSI-positive and the other Epstein-Barr virus positive. T2NOM0 (stage IB) tumours showed mostly favourable survival independently from histological type, invasive pattern, DUPAN-2 or MSI status. It is concluded that an appropriate histological evaluation, coupled with sialylated glycoproteins histochemistry and, for stage-II tumours, MSI tests may contribute significantly to prognostic assessment of tumours beyond stage I. However, the stage itself, with special reference to lymph-node metastases and invasion level beyond subserosa, remains the most important prognostic clue for gastric cancer.


Assuntos
Adenocarcinoma/patologia , Neoplasias Gástricas/patologia , Adenocarcinoma/química , Adenocarcinoma/classificação , Adenocarcinoma/mortalidade , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Técnicas Imunoenzimáticas , Hibridização In Situ , Repetições de Microssatélites , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Oligossacarídeos/análise , Prognóstico , RNA Viral/análise , Análise de Regressão , Antígeno Sialil Lewis X , Neoplasias Gástricas/química , Neoplasias Gástricas/classificação , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida
13.
Int J Biol Markers ; 8(3): 147-50, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8277205

RESUMO

In only a few years, the technology of antibody engineering has demonstrated its power and a variety of recombinant monoclonal antibodies are now being developed. Recent developments in gene manipulation have allowed the isolation of antibodies, including human antibodies, with or without immunization, by displaying functional antibody fragments on the surface of bacteriophage particles and directly selecting with antigen. In the present review some recent achievements in these areas are highlighted.


Assuntos
Anticorpos Monoclonais/genética , Engenharia Genética , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Antivirais , Humanos , Linfócitos/imunologia , Camundongos
14.
Chem Biol Interact ; 35(2): 189-97, 1981 May.
Artigo em Inglês | MEDLINE | ID: mdl-7194152

RESUMO

The antimitotic and cytotoxic effects of cis-dichlorobis(cyclohexylamine)-platinum(II) (cis-HAD) which among Pt complexes used as antitumoral drugs shows the highest therapeutic index (TI) have been compared to those os cis-dichlorodiamine platinum(II) (cis-DDP), the most commonly used drug of this group, using Chinese hamster ovary cell cultures (CHO line). DNA synthesis inhibition, mitotic index, cell viability, chromosome aberrations and cell survival have been taken into account. The data indicates that the antimitotic agent cis-HAD is active only at doses causing high cell mortality and chromosome damage.


Assuntos
Antineoplásicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Aberrações Cromossômicas , Mitose/efeitos dos fármacos , Compostos Organoplatínicos/toxicidade , Animais , Linhagem Celular , Cisplatino/toxicidade , Cricetinae , Cricetulus , Cicloexilaminas/toxicidade , DNA/biossíntese , Feminino , Ovário
15.
Chem Biol Interact ; 16(1): 1-11, 1977 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-189945

RESUMO

The interaction of cis- and trans-Pt(NH3)2Cl2 with DNAs of different base composition was studied by means of circular dichroism (CD) spectroscopy. The spectra obtained indicated a partial transformation of the secondary structure of DNA (B- less than C transition) with an increased helix winding. Subtle differences were noted between the two isomers, possibly related to changes in base orientation due to the different molecular geometries of the P+(II) complexes.


Assuntos
Cisplatino , DNA , Animais , Bovinos , Fenômenos Químicos , Química , Dicroísmo Circular , Cisplatino/análise , Cisplatino/síntese química , Clostridium perfringens , DNA/análise , Isomerismo , Micrococcus , Serotonina , Timo
16.
Mutat Res ; 294(2): 117-26, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7687004

RESUMO

Human PBL were treated in vitro with the ultimate reactive metabolites of BaP anti- and syn-BaPDE and DNA damage and repair were measured. The incorporation of radioactivity into DNA due to UDS was higher after treatment with anti-BaPDE. Radioactive DNA adduct dosimetry applied to PBL treated with tritiated syn- and anti-BaPDE demonstrated that anti-BaPDE gave more DNA adducts, which were more efficiently removed than syn adducts in the 24 h following the treatment. HPLC analysis of deoxynucleosides obtained from the enzymatic digestion of DNA showed that in treated PBL the major DNA adduct involved deoxyguanosine. DNA strand breaks, detected by FADU, were induced at comparable levels by anti- and syn-BaPDE (0.1-0.4 micrograms/ml), and persisted after 20 h of post-treatment incubation. Only in the case of syn-BaPDE did the percentage of double-stranded DNA tend to increase with time after the treatment.


Assuntos
Benzopirenos/farmacologia , Reparo do DNA/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Adulto , Células Cultivadas , Dano ao DNA , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Mutat Res ; 190(1): 35-9, 1987 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3796669

RESUMO

We used the V79 Chinese hamster cell line to detect the induction by NTA of 6-thioguanine resistance, due to mutation at the HGPRT locus, with direct and indirect mutagens as positive controls. NTA was tested within the 10(-4)-1.5 X 10(-2) M concentration range: although it was cytotoxic above the 10(-2) M dose, it did not increase the frequency of mutations at any of the tested concentrations, independently of metabolic activation (rat-liver S9 fraction). NTA is known to dissolve heavy metals and therefore to increase their genotoxicity. We found that an insoluble Cr(VI) compound, lead chromate (PbCrO4), was not cytotoxic nor mutagenic on V79 cells, probably because it is taken up by the cells very slowly, whereas the presence of NTA (2.5 X 10(-3) M in water) elicited a direct cytotoxicity and mutagenicity, which was dose-dependent from 5 X 10(-5) M to 10(-4) M PbCrO4. This effect was due to solubilization of the chromate anion by NTA, as determined by comparing spectrophotometric determinations of Cr(VI) in PbCrO4 treatment solutions with a mutagenicity titration curve obtained with a completely soluble Cr(VI) salt (potassium dichromate, K2Cr2O7).


Assuntos
Acetatos/toxicidade , Cromatos/toxicidade , Chumbo/toxicidade , Mutação , Ácido Nitrilotriacético/toxicidade , Compostos de Potássio , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatos/farmacologia , Cricetinae , Cricetulus , Resistência a Medicamentos , Solubilidade , Tioguanina/farmacologia
18.
Mutat Res ; 209(3-4): 149-54, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3193978

RESUMO

In cultured human lymphocytes we determined the ability of nitrilotriacetic acid (NTA) to inhibit DNA replication and to stimulate DNA repair synthesis (UDS), as well as to influence the UDS induced by UV irradiation. In phytohemagglutinin-stimulated lymphocytes a strong inhibition of DNA replication was induced by NTA concentrations above 10(-3) M, which was accompanied by a marked cell lethality, whereas at lower doses the incorporation of tritiated thymidine (3H-TdR) into DNA or treated cells was slightly increased in comparison to untreated cells. When, after NTA pretreatment, UDS was determined by scintillation spectrometry or autoradiography in unstimulated G0 lymphocytes, UV-irradiated or unirradiated, an increased incorporation of 3H-TdR was observed, positively correlated with the NTA doses. This effect was only partially due to the expansion of the intracellular TdR pool as a consequence of the stimulation of 3H-TdR uptake by NTA. Even after normalization of the scintillometric data by the radioactivities of the soluble nucleotide fraction, significant increase of DNA repair synthesis was detected after treatment with 7.5 x 10(-3)-10(-2) M NTA.


Assuntos
Acetatos/farmacologia , Dano ao DNA , Reparo do DNA , Mutagênicos , Ácido Nitrilotriacético/farmacologia , Humanos , Técnicas In Vitro , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/ultraestrutura , Fito-Hemaglutininas/farmacologia , Raios Ultravioleta
19.
Toxicol In Vitro ; 8(6): 1269-75, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20693099

RESUMO

Cytotoxicity and mutagenicity were measured in human lymphocytes after treatment in vitro with anti- or syn-benzo[a]pyrene diolepoxide, two diastereoisomer metabolites of benzo[a]pyrene. These compounds were incubated with resting and cycling lymphocytes to determine the inhibition of cell proliferation induced by phytohemoagglutinin and interleukin2 at different times after treatment. Anti-benzo[a]pyrene diolepoxide was more cytotoxic than the syn-adduct under all conditions, and its effect on cell growth was more marked in cycling lymphocytes. In contrast, neither of the compounds induced alteration of the ATP intracellular pool. Cytotoxic effects of anti- and syn-benzo[a]pyrene diolepoxide were also assessed by determining the cloning efficiency. Both compounds affected the cloning efficiency in human lymphocytes and the effect of anti-benzo[a]pyrene was particularly marked. Mutagenic potency of anti- and syn-benzo[a]pyrene diolepoxide at the hgprt locus was measured both in the V79 cell line and in human lymphocytes by selection of mutant cells in medium containing 6-thioguanine. Both compounds increased the mutant frequency in comparison with the control and anti-benzo[a]pyrene diolepoxide was more active than the syn-metabolite.

20.
Scand J Surg ; 100(3): 208-15, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22108751

RESUMO

PURPOSE: To demonstrate the effectiveness of intramedullary fixation of displaced long bones shaft fractures in skeletally immature children using the elastic stable intramedullary nails. PATIENTS AND METHODS: The case records of 173 children who underwent fixation with titanium intramedulary nails because of long bones fractures were reviewed. The average age of the patients was 11.7 years, and mean follow-up was 41.3 months. There were 55 humeral, 42 forearm, 42 femoral and 36 tibial fractures. Subjective satisfaction was assessed. RESULTS: All patients achieved complete healing at a mean of 7.5 weeks. Complications were recorded in 11 (6.3%) patients and included: one neuropraxia, six entry site skin irritations, two protrusions of the wires through the skin and two skin infections at the entry site. In a subjective measure of outcome at follow-up, 89% of patients were very satisfied and 11% satisfied; no patients reported their outcome as not satisfied. The implants were removed at a median time of six months from the index operation. CONCLUSION: Elastic Stable Intra-medullary Nailing is the method of choice for the pediatrics patients, because it is minimaly invasive and shows very good functional and cosmetic results. It allows an early functional and cast-free follow-up with a quick pain reduction.


Assuntos
Pinos Ortopédicos , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas/instrumentação , Fraturas do Úmero/cirurgia , Fraturas do Rádio/cirurgia , Fraturas da Tíbia/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Consolidação da Fratura , Humanos , Fraturas do Úmero/diagnóstico por imagem , Masculino , Medição da Dor , Complicações Pós-Operatórias , Radiografia , Fraturas do Rádio/diagnóstico por imagem , Fraturas da Tíbia/diagnóstico por imagem , Titânio , Resultado do Tratamento
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