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1.
JAMA Neurol ; 79(11): 1199, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36156066

RESUMO

This case report describes neurogenic unilateral leg edema that was a consequence of chronic regional pain syndrome induced by an S1 radiculopathy.


Assuntos
Deslocamento do Disco Intervertebral , Radiculopatia , Humanos , Perna (Membro) , Músculo Esquelético , Edema/diagnóstico por imagem , Edema/etiologia
2.
Clin Radiol ; 76(8): 553-558, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34053731

RESUMO

We present a multimodality pictorial review of axillary lymphadenopathy in patients recently vaccinated against COVID-19. As the mass vaccination programme continues to be rolled out worldwide in an effort to combat the pandemic, it is important that radiologists consider recent COVID-19 vaccination in the differential diagnosis of unilateral axillary lymphadenopathy and are aware of typical appearances across all imaging methods. We review current guidelines on the management of unilateral axillary lymphadenopathy in the context of recent COVID-19 vaccination.


Assuntos
Axila/diagnóstico por imagem , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Linfadenopatia/induzido quimicamente , Linfadenopatia/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Humanos , Vacinação em Massa , Pandemias , SARS-CoV-2
4.
Surg Neurol Int ; 7(Suppl 38): S914-S916, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28028448

RESUMO

BACKGROUND: Transverse fractures of the sacrum are rare, and surgical treatment for these fractures ranges from conservative to challenging. Transverse stress fractures of the sacrum after placement of lumbar-to-sacral instrumentation have been previously described. We report a new technique to repair a transverse Type-2 Roy-Camille fracture with spondylolisthesis of S1 over S2 in a previously fused instrumented high-grade L4-L5, L5-S1 spondylolisthesis. CASE DESCRIPTION: A 64-year-old female who previously had an L4-L5, L5-S1 fusion for spondylolisthesis presented with excruciating lower back pain and radiculopathy for over 6 months. She was found to have an S1-S2 transverse fracture caused by previous implantation of pedicle screws. She underwent repositioning of several failed right lumbar and sacral screws and then had bilateral S1-S2 screws placed directly across the fracture line. The patient had an unremarkable postoperative course. She discontinued most of her pain medications within 6 weeks postoperatively. In the months following surgery, she reported only minimal lower back pain and no radiculopathy with the last appointment 5 years postoperatively. CONCLUSIONS: We describe a novel technique to reduce an iatrogenic transverse type-2 Roy-Camille fracture at S1-S2 in a previously instrumented high-grade L4-L5, L5-S1 spondylolisthesis. The patient's fracture achieved adequate reduction and fusion with symptomatic relief.

5.
Open Orthop J ; 9: 218-25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26161161

RESUMO

Autologous iliac crest bone graft is the preferred option for spinal fusion, but the morbidity associated with bone harvest and the need for graft augmentation in more demanding cases necessitates combining local bone with bone substitutes. The purpose of this study was to document the clinical effectiveness and safety of a novel hybrid biosynthetic scaffold material consisting of poly(D,L-lactide-co-glycolide) (PLGA, 75:25) combined by lyophilization with unmodified high molecular weight hyaluronic acid (10-12% wt:wt) as an extender for a broad range of spinal fusion procedures. We retrospectively evaluated all patients undergoing single- and multi-level posterior lumbar interbody fusion at an academic medical center over a 3-year period. A total of 108 patients underwent 109 procedures (245 individual vertebral levels). Patient-related outcomes included pain measured on a Visual Analog Scale. Radiographic outcomes were assessed at 6 weeks, 3-6 months, and 1 year postoperatively. Radiographic fusion or progression of fusion was documented in 221 of 236 index levels (93.6%) at a mean (±SD) time to fusion of 10.2+4.1 months. Single and multi-level fusions were not associated with significantly different success rates. Mean pain scores (+SD) for all patients improved from 6.8+2.5 at baseline to 3.6+2.9 at approximately 12 months. Improvements in VAS were greatest in patients undergoing one- or two-level fusion, with patients undergoing multi-level fusion demonstrating lesser but still statistically significant improvements. Overall, stable fusion was observed in 64.8% of vertebral levels; partial fusion was demonstrated in 28.8% of vertebral levels. Only 15 of 236 levels (6.4%) were non-fused at final follow-up.

6.
Clin. transl. oncol. (Print) ; 16(5): 476-487, mayo 2014. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-127889

RESUMO

PURPOSE: Suppressor of cytokine signaling 7 (SOCS7) is a member of the SOCS family and is known to interact with phospholipase Cγ-1 (PLCγ-1), one of the insulin-like growth factor-I (IGF-I) receptor downstream molecules. In this study, we sought to observe the effect of knocking down SOCS7 gene on breast cancer cells in vitro growth and migration and to elucidate whether this involves IGF-I-PLCγ1 route using the PLCγ-1 blocker U73122. METHODS: Suitable breast cancer cells (MCF7 and MDA-MB-231) were transfected with anti-SOCS7 ribozymal transgene, to create sub-lines with SOCS7 knockdown verified by RT-PCR. The growth and migration of the cells were evaluated in the presence or absence of IGF-I and PLCγ-1 inhibitor using growth assay, scratch-wound and electrical cell impedance sensing (ECIS) migration assays. RESULTS: IGF-I treatment produced more pronounced influence on MCF7 growth and migration and on MDA-MB-231 migration when SOCS7 gene was knocked down in both lines (p < 0.05). The absence of IGF-I-induced growth response in MDA-MB-231 could be due to the intrinsic characteristics of these cells. PLCγ-1 pharmacological inhibition during their in vitro migration seemed to only occur when SOCS7 gene was knocked down. CONCLUSIONS: To the best of our knowledge, this is the first report of the SOCS7 regulatory role in IGF-I induced in vitro functions in ER-positive and ER-negative breast cancer cells. IGF-I treatment and SOCS7 loss have synergistically resulted in increased growth and migration of MCF7 and in increased migration of MDA-MB-231 cells. The migratory effects could be due to a precise anti-PLCγ-1 role (AU)


No disponible


Assuntos
História do Século XXI , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/radioterapia , Neoplasias da Mama/diagnóstico
7.
Clin Transl Oncol ; 16(5): 476-87, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24046004

RESUMO

PURPOSE: Suppressor of cytokine signaling 7 (SOCS7) is a member of the SOCS family and is known to interact with phospholipase Cγ-1 (PLCγ-1), one of the insulin-like growth factor-I (IGF-I) receptor downstream molecules. In this study, we sought to observe the effect of knocking down SOCS7 gene on breast cancer cells in vitro growth and migration and to elucidate whether this involves IGF-I-PLCγ1 route using the PLCγ-1 blocker U73122. METHODS: Suitable breast cancer cells (MCF7 and MDA-MB-231) were transfected with anti-SOCS7 ribozymal transgene, to create sub-lines with SOCS7 knockdown verified by RT-PCR. The growth and migration of the cells were evaluated in the presence or absence of IGF-I and PLCγ-1 inhibitor using growth assay, scratch-wound and electrical cell impedance sensing (ECIS) migration assays. RESULTS: IGF-I treatment produced more pronounced influence on MCF7 growth and migration and on MDA-MB-231 migration when SOCS7 gene was knocked down in both lines (p < 0.05). The absence of IGF-I-induced growth response in MDA-MB-231 could be due to the intrinsic characteristics of these cells. PLCγ-1 pharmacological inhibition during their in vitro migration seemed to only occur when SOCS7 gene was knocked down. CONCLUSIONS: To the best of our knowledge, this is the first report of the SOCS7 regulatory role in IGF-I induced in vitro functions in ER-positive and ER-negative breast cancer cells. IGF-I treatment and SOCS7 loss have synergistically resulted in increased growth and migration of MCF7 and in increased migration of MDA-MB-231 cells. The migratory effects could be due to a precise anti-PLCγ-1 role.


Assuntos
Neoplasias da Mama/genética , Técnicas de Silenciamento de Genes , Fator de Crescimento Insulin-Like I/farmacologia , Proteínas Nucleares/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Humanos , Células Tumorais Cultivadas/efeitos dos fármacos
8.
Oncol Rep ; 29(5): 1969-74, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23503572

RESUMO

The mammalian target of rapamycin (mTOR) plays a key role in the regulation of cellular metabolism, growth and proliferation. It forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2, respectively. This study examines the relationship between mTORC1, Rictor and Raptor mRNA expression and human breast cancer. Furthermore, the correlation between mTORC1 and hTERT was investigated. Breast cancer tissues (n=150) and normal tissues (n=31) were analysed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher mTOR expression was noted in breast cancer tissue (P=0.0018), higher grade tumours (grade 2 vs. 3, P=0.047), in ductal tumours (P=0.0014), and was associated with worse overall survival (P=0.01). Rictor expression was significantly higher in background breast tissues compared with tumours and was inversely related to the Nottingham Prognostic Index (NPI1 vs. 2, P=0.03) and tumour grade (grade 1 vs. 3, P=0.01) and was associated with better overall (P=0.037) and disease-free survival (P=0.048). The mRNA expression of Raptor was higher in tumours compared with normal tissues. Furthermore, the expression of Raptor was associated with a higher tumour grade (grade 1 vs. 3, P=0.027). A highly significant positive correlation between mTOR and hTERT (P<0.00001) was observed. These observations are consistent with the role of mTORC1 in the anti-apoptosis pathway and suggest that selective inhibitors of mTORC1 may be more efficacious in human breast cancer. Our findings support the hypothesis that mTORC1 is an important upregulator of telomerase in breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proteínas de Transporte/biossíntese , Complexos Multiproteicos/biossíntese , Serina-Treonina Quinases TOR/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/agonistas , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Complexos Multiproteicos/antagonistas & inibidores , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Prognóstico , RNA Mensageiro/genética , Proteína Companheira de mTOR Insensível à Rapamicina , Proteína Regulatória Associada a mTOR , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Telomerase/genética , Telomerase/metabolismo
10.
Cancer Genomics Proteomics ; 9(4): 199-201, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22798505

RESUMO

UNLABELLED: This pilot study is the first to focus on the potential role of death-associated protein 1 (DAP1) in human breast cancer. MATERIALS AND METHODS: A total of 153 samples were studied. DAP1 transcription levels were determined using quantitative polymerase chain reaction (qPCR). Transcript levels within breast cancer specimens were compared to those of normal background tissues and correlated with clinicopathological data accumulated over a 10-year follow-up period. RESULTS: The expression of DAP1 mRNA was demonstrated to decrease with increasing Nottingham Prognostic Index (NPI2 vs. NPI3, p=0.0026), and TNM stage (TNM1 vs. 4, p=0.0039). Lower DAP1 expression levels were significantly associated with local recurrence (p=0.02) and distant metastasis (p=0.001). CONCLUSION: This study demonstrates an inverse association between DAP1 mRNA levels and tumour stage and clinical outcome in breast cancer; thus, providing evidence that DAP1 plays a pro-apoptotic role in human breast cancer. The relationship between oncogenesis and the autophagy pathway merits further investigation.


Assuntos
Proteínas Reguladoras de Apoptose , Neoplasias da Mama , RNA Mensageiro/metabolismo , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estadiamento de Neoplasias , RNA Mensageiro/genética , Resultado do Tratamento
11.
Surg Oncol ; 21(2): e67-74, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22296996

RESUMO

The use of skin-sparing mastectomy (SSM) to facilitate breast reconstruction is increasing due to a wide acceptance of improved cosmetic outcomes and evidence of equivalence in oncologic outcomes. The rates of patients undergoing mastectomy for whom post-mastectomy radiotherapy (PMRT) will be recommended is increasing as evidence of decreased loco-regional recurrence and increased survival mounts. PMRT may adversely effect complication rates and cosmetic outcomes for patients undergoing immediate breast reconstruction and PMRT--although the evidence for this is methodologically flawed. This article summarises the above evidence and highlights a reconstructive algorithm that may be used to mitigate the possible deleterious effects of PMRT on results.


Assuntos
Neoplasias da Mama/cirurgia , Procedimentos Cirúrgicos Dermatológicos , Mamoplastia/métodos , Mastectomia/métodos , Tratamentos com Preservação do Órgão/métodos , Cuidados Pós-Operatórios , Algoritmos , Neoplasias da Mama/radioterapia , Contraindicações , Métodos Epidemiológicos , Feminino , Humanos , Recidiva Local de Neoplasia/etiologia , Radioterapia , Retalhos Cirúrgicos , Conduta Expectante
12.
Anticancer Res ; 32(2): 671-4, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22287761

RESUMO

BACKGROUND: This pilot study is the first to focus on the potential role for death-associated protein 3 (DAP3) in human breast cancer. MATERIALS AND METHODS: A total of 153 samples were studied. The levels of transcription of DAP3 were determined using quantitative polymerase chain reaction (qPCR). Transcript levels within breast cancer specimens were compared to those of normal background tissues and correlated with clinicopathological data accumulated by over a 10-year follow-up period. RESULTS: The expression of DAP3 mRNA was demonstrated to decrease with increasing Nottingham Prognostic Index (NPI2 vs. 3, p=0.036), TNM stage (TNM1 vs. 3, p=0.07), and tumour grade (grade 1 vs. 3, p=0.08). Lower DAP3 expression levels were significantly associated with local recurrence (p=0.013), distant metastasis (p=0.0057) and mortality (p=0.019). CONCLUSION: This study demonstrates an inverse association between DAP3 mRNA levels and tumour stage and clinical outcome in breast cancer, consistent with the pro-apoptosis function of DAP3. Further research is required in order to confirm our findings and clarify the mechanisms that regulate DAP3 expression in human breast cancer.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , RNA Mensageiro/biossíntese , Proteínas Ribossômicas/genética , Proteínas Reguladoras de Apoptose/biossíntese , Neoplasias da Mama/metabolismo , Feminino , Dosagem de Genes , Humanos , Gradação de Tumores , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Projetos Piloto , RNA Mensageiro/genética , Proteínas de Ligação a RNA , Proteínas Ribossômicas/biossíntese , Taxa de Sobrevida , Transcrição Gênica
13.
Eur Radiol ; 21(4): 676-82, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20886340

RESUMO

OBJECTIVE: To compare the diagnostic performance of full-field digital mammography (FFDM) with screen-film mammography (SFM) in a corporate screening programme including younger women. METHODS: Data were available on 14,946 screening episodes, 5010 FFDM and 9936 SFM. Formal analysis was by logistic regression, adjusting for age and calendar year. FFDM is compared with SFM with reference to cancer detection rates, cancers presenting as clustering microcalcifications, recall rates and PPV of recall. RESULTS: Overall detection rates were 6.4 cancers per thousand screens for FFDM and 2.8 per thousand for SFM (p < 0.001). In women aged 50+ cancer detection was significantly higher for FFDM at 8.6 per thousand vs. 4.0 per thousand, (p = 0.002). In women <50, cancer detection was also significantly higher for FFDM at 4.3 per thousand vs. 1.4 per thousand, (p = 0.02). Cancers detected as clustering microcalcifications increased from 0.4 per thousand with SFM to 2.0 per thousand with FFDM. Rates of assessment recall were higher for FFDM (7.3% vs. 5.0%, p < 0.001). FFDM provided a higher PPV for assessment recall, (32 cancers/364 recalls, 8.8%) than SFM, (28 cancers/493 recalls, 5.7%). CONCLUSIONS: Cancer detection rates were significantly higher for FFDM than for SFM, especially for women <50, and cancers detected as clustering microcalcifications.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico , Mamografia/métodos , Adulto , Idoso , Algoritmos , Calcinose/diagnóstico por imagem , Análise por Conglomerados , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Intensificação de Imagem Radiográfica/métodos , Ultrassonografia , População Urbana
14.
Anticancer Res ; 30(9): 3309-11, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20944102

RESUMO

BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. We previously demonstrated SETD2 to be a potential tumour suppressor gene in breast cancer. The aim of this study was to compare SETD2 expression in breast cancer with that in adjacent non-cancerous breast tissue (ANCT) in paired samples. A hypothesis is proposed that explains the mode of action of SETD2 as a tumour suppressor gene. MATERIALS AND METHODS: Paired samples of tumour and adjacent non-cancerous tissue (ANCT) from 25 patients were analysed. The levels of transcription of SETD2 were determined using quantitative polymerase chain reaction and normalized against cytokeratin 19. Immunohistochemical staining with appropriate antibodies against SETD2 protein was also performed in selected samples. RESULTS: Levels of SETD2 mRNA were significantly higher in ANCT when compared to those in tumour samples (p=0.01). Immunohistochemistry also demonstrated a higher protein expression in ANCT. CONCLUSION: This study offers further evidence that SETD2 behaves like a tumour suppressor gene. Our hypothesis links SETD2 mode of action with telomerase regulation through human telomerase reverse transcriptase (hTERT). Several studies have emphasised the importance of histone methylation of hTERT promotor in telomerase regulation. SETD2 function of histone methylation could be the missing link in this chain which could explain the potential tumour suppressor function of SETD2.


Assuntos
Neoplasias da Mama/genética , Genes Supressores de Tumor , Histona-Lisina N-Metiltransferase/genética , Neoplasias da Mama/metabolismo , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Histona-Lisina N-Metiltransferase/biossíntese , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Anticancer Res ; 30(9): 3693-7, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20944155

RESUMO

BACKGROUND: The potential for radiofrequency ablation (RFA) therapy is an area of increasing interest in the context of breast conserving therapy for breast cancer. This non surgical technique potentially provides a non invasive, cosmetically pleasing result that is preferable to surgeon and patient. MATERIALS AND METHODS: A literature review was carried out facilitated by PubMed and Medline databases. Cross referencing of the obtained articles was used to identify other relevant studies. A total of 17 studies were reviewed. RESULTS: RFA is emerging as a promising treatment for breast cancer. Pilot and phase II studies have shown RFA to be effective at ablation with few complications or adverse effects experienced by patients. However, complete ablation of tumours is still not achieved in all patients. CONCLUSION: RFA represents a promising therapeutic modality for breast lesions. However, there is a clear need for further research and refinement of the procedure before it can be offered as a therapeutic alternative to surgical excision for operable breast cancer.


Assuntos
Neoplasias da Mama/terapia , Ablação por Cateter/métodos , Ensaios Clínicos como Assunto , Feminino , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
17.
Anticancer Res ; 30(6): 2287-90, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20651381

RESUMO

UNLABELLED: The aim of this retrospective study was to assess whether open surgical excision is required following a B3 diagnosis on 11-gauge vacuum-assisted core biopsy (VACB) of radiologically indeterminate breast lesions. PATIENTS AND METHODS: Twenty-four women with a histological diagnosis of the B3 category on VACB of radiologically indeterminate breast lesions were identified over a 3-year period. The VACB procedure was performed under stereotactic (n=21), ultrasound (n=2) or magnetic resonance imaging (MRI) (n=1) guidance using the Suros system. Nineteen patients underwent open surgical excision. The remaining 5 patients who had 'complete' removal of the radiological abnormality using VACB under ultrasound (n=2, papilloma) or stereotactic (n=4, atypical ductal hyperplasia) guidance were followed up clinically and radiologically. RESULTS: The median patient age was 49 years. The disease status in three patients was upgraded to ductal carcinoma in situ at open surgical excision. The VACB showed atypical lobular hyperplasia in these 3 patients, associated with microcalcification (n=2) or mass lesion (n=1). No single case of upgrading to invasive breast cancer was identified in our series. The remaining patients (16 out of 19) had a benign biopsy. The upgrade to malignancy was significantly associated with the presence of atypical lobular hyperplasia, a BI-RADS category of 4 and incomplete removal of the radiological abnormality by VACB. After a mean follow-up of 18 months, no malignancy was detected in the 5 patients who did not undergo open surgical biopsy. CONCLUSION: Open surgical excision is strongly recommended for atypical lobular hyperplasia identified in VACB specimens. VACB can be a safe alternative to surgery in the treatment of B3 lesions in selected cases, providing thorough multidisciplinary discussion has taken place.


Assuntos
Biópsia por Agulha/métodos , Neoplasias da Mama/cirurgia , Mama/patologia , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Hiperplasia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Anticancer Res ; 30(4): 1079-82, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20530412

RESUMO

UNLABELLED: DLEC1 (deleted in lung and oesophageal cancer), located on 3p22.3, is a candidate tumour suppressor gene in lung, esophageal, and renal cancer. The aim of this study was determine whether the mRNA expression levels of DLEC1 were consistent with a tumour suppressive function. MATERIALS AND METHODS: A total of 153 samples were analysed. The levels of transcription of DLEC1 were determined using quantitative PCR and normalised against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues. RESULTS: Levels of transcription were lower [corrected] in tumour samples compared to adjacent non cancerous tissue (ANCT) samples but this was not statistically significant (median 0.167 vs. 0.03; p=0.138). DLEC1 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for >10 years (p=0.041). DISCUSSION: These findings are consistent with a possible tumour suppressor function of DLEC1 in breast cancer.


Assuntos
Neoplasias da Mama/genética , Proteínas Supressoras de Tumor/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Genes Supressores de Tumor , Humanos , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Transcrição Gênica , Proteínas Supressoras de Tumor/biossíntese
19.
Surg Oncol ; 19(1): e11-21, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19097883

RESUMO

INTRODUCTION: HER-2 over-expression is implicated in the pathogenesis of breast cancer and represents a key marker and determinant of patient outcome. Trastuzumab/Herceptin (TZ) is a recombinant humanised monoclonal antibody which targets HER-2. Introduction into clinical practice has significantly improved the natural history of HER-2 over-expressing tumors and has altered the standard of care for these women. This article reviews the established and emerging roles of TZ in the management of breast cancer (BC). METHODS: Literature review facilitated by Medline and PubMed databases. FINDINGS: The clinical utility of TZ was first established in the management of HER-2 over-expressing metastatic breast cancer (MBC), with improvements recognised in both the quality and quantity of life. Prospective randomized controlled trials have consistently demonstrated the efficacy of TZ for early breast cancer (EBC) in the adjuvant setting with significant improvements in disease free and overall survival. Emerging roles for TZ include neo-adjuvant therapy and the treatment of progressive disease. TZ is well tolerated and safe, however, associated cardiac dysfunction remains a significant clinical concern. CONCLUSION: HER-2 status is critically important in the management algorithm for BC and should be determined in all cases. Quality assurance of laboratory testing is of paramount importance. TZ has an established role in the management of HER-2 positive MBC and EBC in conjunction with conventional chemotherapy. Appropriate patient selection and monitoring for cardiac dysfunction are required.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/efeitos dos fármacos , Algoritmos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Receptor ErbB-2/biossíntese , Fatores de Risco , Trastuzumab , Resultado do Tratamento
20.
BMC Cancer ; 9: 290, 2009 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-19698110

RESUMO

BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). CONCLUSION: This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica , Histona-Lisina N-Metiltransferase/genética , Neoplasias da Mama/metabolismo , Feminino , Seguimentos , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Estadiamento de Neoplasias , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
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