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1.
BJUI Compass ; 3(6): 484-493, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36267204

RESUMO

Objectives: To assess cabazitaxel versus docetaxel re-challenge for the treatment of metastatic castrate refractory prostate cancer (CRPC) patients previously treated with docetaxel at inception of primary hormone therapy. Patients and Methods: The CANTATA trial was a prospective, two-arm, open-label, phase II study conducted in eight UK centres. Patients over the age of 18, with histologically proven, metastatic prostate cancer who had been previously treated with up to 6 cycles of docetaxel as part of the STAMPEDE trial (or treated with the same drug outside of the trial at primary diagnosis) and had a performance status (PS) of 0-2, were eligible. Patients who progressed during primary treatment with docetaxel or had received prior systemic chemotherapy were excluded. Cabazitaxel (25 mg/m2) or docetaxel (75 mg/m2) was administered via intravenous infusion every 3 weeks with oral prednisolone (10 mg) for up to 10 cycles, until disease progression, death or unacceptable toxicity. The primary outcome was clinical progression-free survival (PFS) as defined by either date of pain progression, date of a cancer-related skeletal-related event, or date of death from any cause. Analyses were by intention to treat. EudraCT number: 2012-003835-40. Results: Between 7 March 2013 and 4 January 2016, 15 patients with a median age of 70 years (range 54-76) were recruited; seven received cabazitaxel, eight docetaxel. The study was halted due to slow accrual. The median clinical PFS time in the cabazitaxel group was 6.2 months compared with 8.4 for the docetaxel group (95% confidence intervals were not reached due to the small number of patients). A total of 13 serious adverse events were reported. Conclusion: Due to the low number of patients recruited, meaningful comparisons could not be made. However, toxicity was in line with known outcomes for these agents, demonstrating it is feasible and safe to deliver chemotherapy to men relapsing with CRPC after upfront chemotherapy.

2.
J Tissue Eng ; 13: 20417314221102680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782993

RESUMO

The primary objective was to evaluate performance of low concentration SDS decellularised porcine pulmonary roots in the right ventricular outflow tract of juvenile sheep. Secondary objectives were to explore the cellular population of the roots over time. Animals were monitored by echocardiography and roots explanted at 1, 3, 6 (n = 4) and 12 months (n = 8) for gross analysis. Explanted roots were subject to histological, immunohistochemical and quantitative calcium analysis (n = 4 at 1, 3 and 12 months) and determination of material properties (n = 4; 12 months). Cryopreserved ovine pulmonary root allografts (n = 4) implanted for 12 months, and non-implanted cellular ovine roots were analysed for comparative purposes. Decellularised porcine pulmonary roots functioned well and were in very good condition with soft, thin and pliable leaflets. Morphometric analysis showed cellular population by 1 month. However, by 12 months the total number of cells was less than 50% of the total cells in non-implanted native ovine roots. Repopulation of the decellularised porcine tissues with stromal (α-SMA+; vimentin+) and progenitor cells (CD34+; CD271+) appeared to be orchestrated by macrophages (MAC 387+/ CD163low and CD163+/MAC 387-). The calcium content of the decellularised porcine pulmonary root tissues increased over the 12-month period but remained low (except suture points) at 401 ppm (wet weight) or below. The material properties of the decellularised porcine pulmonary root wall were unchanged compared to pre-implantation. There were some changes in the leaflets but importantly, the porcine tissues did not become stiffer. The decellularised porcine pulmonary roots showed good functional performance in vivo and were repopulated with ovine cells of the appropriate phenotype in a process orchestrated by M2 macrophages, highlighting the importance of these cells in the constructive tissue remodelling of cardiac root tissues.

3.
BJU Int ; 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35908256

RESUMO

OBJECTIVE: To assess feasibility and preliminary efficacy of adding cetuximab to standard chemoradiotherapy for muscle-invasive bladder cancer. PATIENTS AND METHODS: TUXEDO was a prospective, single-arm, open-label, phase I/II trial conducted in six UK hospitals. Cetuximab was administered with an initial loading dose of 400mg/m2 on day 1 of week -1, and then 7-weekly doses of 250mg/m2 . Radiotherapy schedule was 64Gy/32F with day 1 mitomycin C (12g/m2 ) and 5-fluorouracil (500mg/m2 /day) over days 1-5 and 22-26. Patients with T2-4aN0M0 urothelial cancer and a performance status (PS) of 0-1 were eligible. Prior neoadjuvant therapy was permitted. The phase I primary outcome was impact on radiotherapy treatment completion and toxicity experienced during treatment. The phase II primary outcome was local control at three-months post-treatment. ISRCTN identifier: 80733590. RESULTS: Between Sept-2012 and Oct-2016, 33 patients were recruited; 7 in phase I, 26 in phase II. Three patients in phase II were subsequently deemed ineligible and received no trial therapy. Eight patients discontinued cetuximab due to adverse effects. Median age of patients was 70.1 years (range 60.6-75.1), 20 were PS 0, 27 male and 26 had already received neoadjuvant chemotherapy. In phase I, all patients completed planned radiotherapy, with no delays or dose reductions. Of the 30 evaluable patients in phase II, 25 had confirmed local control 3-months post treatment (77%, 95% CI: 58-90). During the trial there were 18 serious adverse events. The study was halted due to slow accrual. CONCLUSION: Phase I data demonstrate it is feasible and safe to add cetuximab to chemoradiotherapy. Exploratory analysis of phase II data provides evidence to consider further clinical evaluation of cetuximab in this setting.

4.
PLoS One ; 17(4): e0265763, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35363787

RESUMO

Decellularised heart valve roots offer a promising option for heart valve replacement in young patients, having the potential to remodel and repair. Replacement heart valves have to undergo billions of opening and closing cycles throughout the patient's lifetime. Therefore, understanding the effect of cyclic loading on decellularised heart valve roots is important prior to human implantation. The aim of this preliminary study was to investigate the influence of low concentration sodium dodecyl sulphate (SDS) decellularisation treatment on the in vitro real time mechanical fatigue of porcine aortic heart valve roots under physiological real time cyclic loading conditions. This required a specific real time in vitro method to be developed, since previous methods relied on accelerated testing, which is non-physiological, and not appropriate for valve replacement materials that exhibit time dependent characteristics. The effects of the real time fatigue on hydrodynamic function and mechanical properties of the heart valve roots were assessed. The mechanical fatigue of decellularised porcine aortic heart valve roots (n = 6) was assessed and compared to cellular porcine aortic heart valve roots (n = 6) in a modified Real time Wear Tester (RWT) at a physiological frequency and under cyclic pressure conditions for a maximum of 1.2 million cycles. Periodically, the heart valve roots were removed from the RWT to assess the influence of cyclic loading on valve competency (static leaflet closure). At the end of testing further hydrodynamic performance parameters were ascertained, along with determination of leaflet material properties. A real time mechanical fatigue assessment method was developed and applied; with two cellular and two decellularised porcine aortic leaflets in different heart valve roots showing tears in the belly region. The decellularised aortic heart valve roots exhibited comparative functionality to the cellular heart valve roots under in vitro static and pulsatile hydrodynamic conditions. However, the material properties of the decellularised aortic leaflets were significantly altered following cyclic fatigue assessment and showed increases in elastin and collagen phase slopes and ultimate tensile strength compared to the cellular porcine aortic leaflets in the circumferential direction. This preliminary study demonstrated that low concentration SDS decellularised porcine aortic heart valve roots can withstand physiological cyclic deformations up to 1.2 million cycles in a RWT whilst maintaining their overall hydrodynamic function and leaflet mechanical properties. This is the first full report of preclinical mechanical fatigue assessment of decellularised porcine aortic heart valve roots under physiological real time conditions.


Assuntos
Bioprótese , Próteses Valvulares Cardíacas , Animais , Valva Aórtica , Fenômenos Biomecânicos , Humanos , Suínos
5.
Lancet Haematol ; 9(4): e250-e261, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35271808

RESUMO

BACKGROUND: Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock. METHODS: Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938. FINDINGS: From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths. INTERPRETATION: The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders. FUNDING: National Institute for Health Research Efficacy and Mechanism Evaluation.


Assuntos
COVID-19 , Serviços Médicos de Emergência , Choque Hemorrágico , Adolescente , Adulto , Transfusão de Sangue , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Choque Hemorrágico/etiologia , Choque Hemorrágico/terapia , Resultado do Tratamento
6.
BMJ Open ; 11(7): e040823, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312190

RESUMO

INTRODUCTION: The improvements in short-term outcome after severe trauma achieved through early resuscitation and acute care can be offset over the following weeks by an acute systemic inflammatory response with immuneparesis leading to infection, multiorgan dysfunction/multiorgan failure (MOF) and death. Serum levels of the androgen precursor dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, steroids with immune-enhancing activity, are low after traumatic injury at a time when patients are catabolic and immunosuppressed. Addressing this deficit and restoring the DHEA(S) ratio to cortisol may provide a range of physiological benefits, including immune modulatory effects. OBJECTIVE: Our primary objective is to establish a dose suitable for DHEA supplementation in patients after acute trauma to raise circulating DHEA levels to at least 15 nmol/L. Secondary objectives are to assess if DHEA supplementation has any effect on neutrophil function, metabolic and cytokine profiles and which route of administration (oral vs sublingual) is more effective in restoring circulating levels of DHEA, DHEAS and downstream androgens. METHODS AND ANALYSIS: A prospective, phase II, single-centre, cross-sectional, randomised study investigating Dehydroepiandrosterone supplementation and its profile in trauma, with a planned recruitment between April 2019 and July 2021, that will investigate DHEA supplementation and its effect on serum DHEA, DHEAS and downstream androgens in trauma. A maximum of 270 patients will receive sublingual or oral DHEA at 50, 100 or 200 mg daily over 3 days. Females aged ≥50 years with neck of femur fracture and male and female major trauma patients, aged 16-50 years with an injury severity score ≥16, will be recruited. ETHICS AND DISSEMINATION: This protocol was approved by the West Midlands - Coventry and Warwickshire Research Ethics Committee (Reference 18/WM/0102) on 8 June 2018. Results will be disseminated via peer-reviewed publications and presented at national and international conferences. TRIAL REGISTRATION: This trial is registered with the European Medicines Agency (EudraCT: 2016-004250-15) and ISRCTN (12961998). It has also been adopted on the National Institute of Health Research portfolio (CPMS ID:38158). TRIAL PROGRESSION: The study recruited its first patient on 2 April 2019 and held its first data monitoring committee on 8 November 2019. DHEA dosing has increased to 100 mg in both male cohorts and remains on 50 mg in across all female groups.


Assuntos
Desidroepiandrosterona , Suplementos Nutricionais , Estudos Transversais , Sulfato de Desidroepiandrosterona , Feminino , Humanos , Masculino , Estudos Prospectivos
7.
J Tissue Eng Regen Med ; 12(2): e841-e853, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-27943656

RESUMO

The clinical use of decellularized cardiac valve allografts is increasing. Long-term data will be required to determine whether they outperform conventional cryopreserved allografts. Valves decellularized using different processes may show varied long-term outcomes. It is therefore important to understand the effects of specific decellularization technologies on the characteristics of donor heart valves. Human cryopreserved aortic and pulmonary valved conduits were decellularized using hypotonic buffer, 0.1% (w/v) sodium dodecyl sulfate and nuclease digestion. The decellularized tissues were compared to cellular cryopreserved valve tissues using histology, immunohistochemistry, quantitation of total deoxyribose nucleic acid, collagen and glycosaminoglycan content, in vitro cytotoxicity assays, uniaxial tensile testing and subcutaneous implantation in mice. The decellularized tissues showed no histological evidence of cells or cell remnants and >97% deoxyribose nucleic acid removal in all regions (arterial wall, muscle, leaflet and junction). The decellularized tissues retained collagen IV and von Willebrand factor staining with some loss of fibronectin, laminin and chondroitin sulfate staining. There was an absence of major histocompatibility complex Class I staining in decellularized pulmonary valve tissues, with only residual staining in isolated areas of decellularized aortic valve tissues. The collagen content of the tissues was not decreased following decellularization however the glycosaminoglycan content was reduced. Only moderate changes in the maximum load to failure of the tissues were recorded postdecellularization. The decellularized tissues were noncytotoxic in vitro, and were biocompatible in vivo in a mouse subcutaneous implant model. The decellularization process will now be translated into a good manufacturing practices-compatible process for donor cryopreserved valves with a view to future clinical use. Copyright © 2016 The Authors Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.


Assuntos
Valva Aórtica/fisiologia , Valva Pulmonar/fisiologia , Dodecilsulfato de Sódio/farmacologia , Doadores de Tecidos , Alicerces Teciduais/química , Células 3T3 , Adulto , Animais , Valva Aórtica/efeitos dos fármacos , Fenômenos Biomecânicos , Morte Celular , Colágeno/metabolismo , DNA/metabolismo , Feminino , Glicosaminoglicanos/metabolismo , Humanos , Hidroxiprolina/metabolismo , Masculino , Camundongos , Valva Pulmonar/efeitos dos fármacos
8.
J Tissue Eng ; 8: 2041731417724011, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28815010

RESUMO

The aim of this study was to adapt a proprietary decellularisation process for human dermis for use with porcine skin. Porcine skin was subject to: sodium chloride (1 M) to detach the epidermis, trypsin paste to remove hair follicles, peracetic acid (0.1% v/v) disinfection, washed in hypotonic buffer and 0.1% (w/v) sodium dodecyl sulphate in the presence of proteinase inhibitors followed by nuclease treatment. Cellular porcine skin, decellularised porcine and human dermis were compared using histology, immunohistochemistry, GSL-1 lectin (alpha-gal epitope) staining, biochemical assays, uniaxial tensile and in vitro cytotoxicity tests. There was no microscopic evidence of cells in decellularised porcine dermis. DNA content was reduced by 98.2% compared to cellular porcine skin. There were no significant differences in the biomechanical parameters studied or evidence of cytotoxicity. The decellularised porcine dermis retained residual alpha-gal epitope. Basement membrane collagen IV immunostaining was lost following decellularisation; however, laminin staining was retained.

9.
BMJ Open ; 7(6): e015081, 2017 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-28674140

RESUMO

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a progressive inflammatory liver disease characterised by relentless liver fibrosis and a high unmet need for new therapies. Preventing fibrosis represents an important area of interest in the development of vital new drugs. Vascular adhesion protein-1 (VAP-1) drives inflammation in liver disease, and provision of an antibody against VAP-1 blunts fibrosis in murine models of liver injury. METHODS AND ANALYSIS: BUTEO is a single-arm, two-stage, open-label, multi-centre, phase II clinical trial. Up to 59 patients will receive treatment with anti-VAP monoclonal antibody, BTT1023, over a 78-day treatment period. Adults with PSC and a serum alkaline phosphatase (ALP) of at least 1.5 times the upper limit of normal will be included. Our primary outcome measure is a reduction in ALP by >25% from baseline to Day 99. Secondary outcome measures include safety and tolerability, changes pre therapy/post therapy in circulating serum VAP-1 as well as imaging findings. The first patient participant was recruited on 08 September 2015. ETHICS AND DISSEMINATION: This protocol has been approved by the Research Ethics Committee (REC, reference 14/EM/1272). The first REC approval date was 06 January 2015 with three subsequent approved amendments. This article refers to protocol V3.0, dated 16 March 2016. Results will be disseminated via peer-reviewed publication and presentation at international conferences. TRIAL REGISTRATION: The trial is registered with the European Medicines agency (EudraCT: 2014-002393-37), the National Institute for Health Research (Portfolio ID: 18051) and ISRCTN: 11233255. The clinicaltrials.gov identifier is NCT02239211. Pre-results.


Assuntos
Fosfatase Alcalina/sangue , Anticorpos Monoclonais/uso terapêutico , Colangite Esclerosante/tratamento farmacológico , Fígado/fisiopatologia , Adolescente , Adulto , Idoso , Amina Oxidase (contendo Cobre)/imunologia , Moléculas de Adesão Celular/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Resultado do Tratamento , Reino Unido , Adulto Jovem
13.
Tumori ; 92(2): 134-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16724693

RESUMO

AIM AND BACKGROUND: The incidence and mortality due to oral cancer have increased worldwide. In India, the use of tobacco has been found to be the major etiological factor for the development of oral cancers. Various studies on serum p53 antibodies have suggested their clinical importance as prognostic markers in cancer. However, there is a dearth of data on serum p53 antibodies in oral cancer patients in India. The present study was carried to evaluate the clinical significance of serum p53 antibodies in oral cancer. MATERIALS AND METHODS: The serum p53 antibody status was analyzed by means of ELISA in 55 healthy individuals, 60 patients with oral precancerous conditions, 75 untreated oral cancer patients, and 86 follow-up blood samples of the oral cancer patients. RESULTS: We found serum p53 antibodies in 23% of cancer patients. The frequency of p53 antibody positivity was higher in patients with lymph node metastasis, advanced disease and well-differentiated tumors. Furthermore, p53 antibody positivity strongly correlated with poor treatment outcome in cancer patients. Kaplan-Meier survival analysis showed significantly poorer disease-free survival in patients with serum p53 antibodies. CONCLUSION: The results of this study suggest the usefulness of serum p53 antibodies in the prognostication of oral cancer patients.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Bucais/sangue , Lesões Pré-Cancerosas/sangue , Proteína Supressora de Tumor p53/sangue , Adulto , Idoso , Anticorpos Antineoplásicos/sangue , Biomarcadores Tumorais/imunologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/patologia , Valor Preditivo dos Testes , Prognóstico , Análise de Sobrevida , Proteína Supressora de Tumor p53/imunologia
14.
J Surg Oncol ; 90(2): 81-8, 2005 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15844188

RESUMO

BACKGROUND AND OBJECTIVES: Oral cancer accounts for one third of all malignancies in India where habit of tobacco consumption is the major etiologic factor, which causes field cancerization in oral mucosa. Multiple molecular events in oral mucosa due to field cancerization may be the cause of local and regional lymph node involvement in oral cancer resulting into low overall survival, high recurrence rate, and poor prognosis. Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (SCC). MMP-2 and MMP-9 are capable of degrading type-IV collagen, which is a major component of basement membrane. Therefore, we studied MMP-2 and MMP-9 activation by gelatin zymography, which is cost effective alternate to ELISA method, in patients with oral SCCs to predict their role in metastatic potentials. MATERIALS AND METHODS: Thirty-nine patients of oral SCCs were classified as non-metastatic (n = 28), and metastatic (n = 11) according to regional lymph node involvement. Malignant and adjacent normal tissues of the patients were collected at the time of surgery. Gelatin zymography was carried out using 7.5% polyacrylamide gel under non-denaturing and non-reducing conditions. Zymograms were analyzed densitometrically. Latent and active forms of MMP-2 and MMP-9 were expressed as ng/50 microg of protein. RESULTS: Latent and active forms of MMP-2 and MMP-9 were significantly elevated in malignant tissues as compared to their adjacent normal tissues (P < 0.05). Total MMP-2 and MMP-9 activities were also significantly elevated in malignant tissues as compared to adjacent normal tissues (P = 0.005 and P = 0.028, respectively). Activation ratio of MMP-2 and MMP-9 were significantly elevated in malignant tissues as compared to adjacent normal tissues. Activation of MMP-2 was prominent (11%) than MMP-9 (5%) in malignant tissues. Activation ratio of MMP-2 was significantly elevated in patients with lymph node metastasis than patients without lymph node metastasis (P = 0.005). Receiver's operating characteristic (ROC) curve analysis revealed that activation ratio of MMP-2 discriminate better than and activation ratio of MMP-9 between patients with and without lymph node metastasis. Activation ratio of MMP-2 could predict risk of lymph node metastasis development in patients without lymph node involvement. CONCLUSION: The study concluded that activation of MMP-2 and MMP-9 was significantly higher in malignant tissues as compared to adjacent normal tissues. Further, activation ratio of MMP-2 was significantly elevated in patients with lymph node metastasis as compared to patients without lymph node metastasis, which could predict risk of lymph node metastasis development in node negative patients.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Linfonodos/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Bucais/enzimologia , Adulto , Idoso , Carcinoma de Células Escamosas/secundário , Ativação Enzimática , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade
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