Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 158
Filtrar
1.
Eur Rev Med Pharmacol Sci ; 26(2): 391-398, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35113414

RESUMO

OBJECTIVE: The current study aimed to explore the risk factors for bone metastasis (BMT) in patients with newly diagnosed prostate cancer (PCa). PATIENTS AND METHODS: The clinical data of 322 patients newly diagnosed with PCa following transrectal prostate biopsy at our hospital from October 2016 to March 2021 were analyzed. According to the results of whole-body bone emission computed tomography (ECT) scanning, patients were divided into the following two groups: bone metastasis group (BMT) and none-bone metastasis group (None-BMT). Univariate and multivariate logistic regression analyses were performed to assess the BMT-related factors associated with PCa. A receiver operating characteristic curve was also used to compare the diagnostic value of total prostate-specific antigen (TPSA), prostate-specific antigen density (PSAD), Gleason score and alkaline phosphatase (ALP) for prostate cancer bone metastasis (PCBM). RESULTS: The results revealed that the incidence of BMT in newly diagnosed patients with PCa was ~22.05% (71/322). Univariate analysis demonstrated that Gleason score, clinical T stage, TPSA, PSAD and ALP were associated with PCBM (p<0.001). Furthermore, the results of multivariate regression analysis revealed that TPSA, PSAD, Gleason score and ALP were independent risk factors for BMT (p <0.05). The cutoff values for TPSA, PSAD, ALP and Gleason score were 39.58 ng/ml, 1.489 ng/(ml/cm3), 93.15 U/l and 7.5, respectively. Additionally, the respective sensitivities for TPSA, PSAD, ALP and Gleason score were 67.6, 62.0, 57.7 and 46.5%, and the respective specificities were 88.4, 98.0, 100 and 98.8%. CONCLUSIONS: The current study determined that TPSA, PSAD, Gleason score and ALP were predictors of PCBM. In patients with PSA levels >39.58 ng/ml, PSAD levels >1.489 ng/(ml/cm3), Gleason scores >7.5 and ALP levels >91.0 U/l, a whole-body bone ECT scan is recommended.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Biópsia , Humanos , Masculino , Gradação de Tumores , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Curva ROC , Fatores de Risco
2.
Clin Oncol (R Coll Radiol) ; 32(7): 433-441, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32169302

RESUMO

AIMS: Stereotactic body radiotherapy (SBRT) is a locally ablative therapy used for the treatment of patients with spine metastases. However, it is associated with higher rates of vertebral compression fractures (VCF) than conventionally fractionated palliative radiotherapy. The purpose of this study was to determine the rate of VCF following spine SBRT and to identify the risk factors associated with this outcome. MATERIALS AND METHODS: We retrospectively reviewed patients treated at two Australian institutions from January 2015 to March 2019. Descriptive statistics were used to assess patient, tumour and treatment factors. The Log-rank test and Cox proportional hazards model were applied in univariate and multivariable analyses to identify factors associated with VCF, local control and overall survival. RESULTS: We evaluated 113 spinal segments from 84 patients, with a median follow-up time of 11.9 months. The median dose and fractionation utilised was 30 Gy in three fractions (67.3%), with a single-fraction rate of 0.9%. The median Spinal Instability Neoplastic Score (SINS) of the lesions was 4/18, with most (84.1%) being SINS stable, scoring between 0 and 6. Five VCFs were observed (three progression of pre-existing fractures and two de novo), a cumulative VCF risk of 4.4%. Four of five fractures occurred within the first year after treatment, with a median time to VCF of 9.2 months. A pre-existing VCF (P = 0.011) was associated with subsequent fracture on multivariable analysis, whereas all VCF segments displayed lytic disease appearance. All fractures were managed conservatively with analgesia, without requirement for subsequent surgical intervention. CONCLUSION: SBRT to spine metastases is safe with respect to VCF, with rates around the lower limit observed in similar studies. Knowledge of factors that predispose to post-treatment fracture, such as pre-existing compression, lytic vertebral disease and SINS >6 will aid in the counselling and selection of patients for this therapy.


Assuntos
Radiocirurgia/efeitos adversos , Fraturas da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Neoplasias da Coluna Vertebral/secundário , Taxa de Sobrevida
3.
Clin Oncol (R Coll Radiol) ; 32(2): 101-109, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31607612

RESUMO

AIM: To assess the intrafraction motion of the urinary bladder and delineate the appropriate margin size for radiotherapy planning, for both the full and empty bladder. MATERIALS AND METHODS: This was a single-site, single-arm study of 20 patients planned to undergo radical cystectomy for histologically confirmed muscle-invasive bladder cancer. Patients underwent magnetic resonance imaging (cineMRI) of the entire pelvis using a 3-Tesla system, prior to cystectomy. Patients first underwent a cineMRI with a full bladder, then voided and underwent a second MRI with an empty bladder. All MRI sequences were acquired over 18 min. We assessed the differences in bladder filling and subsequent bladder wall displacement, between the empty and full bladder, during a time period consistent with radiotherapy treatment delivery. RESULTS: Twenty patients underwent cineMRI of the entire pelvis. The maximum mean directional displacements of the bladder walls over the 18 min duration of the scan for the empty bladders were 9.8 mm superiorly, 1.1 mm inferiorly, 2.39 mm anteriorly, 3.73 mm posteriorly, 2.74 mm to the left and 2.48 mm to the right. The maximal mean displacements for the full bladders were 9.2 mm superiorly, 1.1 mm inferiorly, 2.28 mm anteriorly, 1.08 mm posteriorly, 1.85 mm to the left and 1.73 mm to the right. Statistically significant differences were seen in the posterior, left and right displacements but were quantitatively small. CONCLUSIONS: Intrafractional motion secondary to bladder filling showed minimal variation between the full and empty bladder. Similar clinical target volume to planning target volume margins can be applied for the delivery of radiotherapy for a full and empty bladder.


Assuntos
Imageamento por Ressonância Magnética/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias da Bexiga Urinária/radioterapia , Feminino , Humanos , Masculino , Estudos Prospectivos
4.
J Oncol Pract ; 15(9): e758-e768, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31322990

RESUMO

PURPOSE: In the United States, lung cancer accounts for 14% of cancer diagnoses and 28% of cancer deaths annually. Because no cure exists for advanced lung cancer, the primary treatment goal is to prolong survival. OBJECTIVES: The study aim was to determine whether individual preferences, characteristics, and treatment experiences affect the meaning of treatment success. MATERIALS AND METHODS: A quantitative study using an observational, longitudinal cohort of patients with advanced stage non-small-cell lung cancer was conducted. Data sources included medical records and patient interviews. Data were analyzed using χ2, Fisher's exact, and McNemar's tests, as well as logistic regressions. RESULTS: At the first interview of 235 individuals, 12% considered survival alone as their definition of treatment success; others defined treatment success as survival plus other aspects, such as quality of life and reaching an important personal goal. As they moved through chemotherapy, 47% of the patients changed their definition of treatment success. Bivariate analysis showed that patients with lower incomes tended to be more likely to change their definition of treatment success compared with their counterparts with higher income (P = .0245). CONCLUSION: By taking chemotherapy, patients expect to increase their odds of survival and want to maintain the quality of life and functionality. A patient's definition of treatment success is often changing as treatment continues, making it appropriate to ensure patient-provider communication throughout their clinical care. The study results are limited to patients with advanced non-small-cell lung cancer and drawn from a predominantly white patient population, mainly from the US Midwest.


Assuntos
Neoplasias Pulmonares/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Idoso , Idoso de 80 Anos ou mais , Gerenciamento Clínico , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Fatores Socioeconômicos , Inquéritos e Questionários , Estados Unidos/epidemiologia
5.
Eur Rev Med Pharmacol Sci ; 23(3): 1134-1144, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30779082

RESUMO

OBJECTIVE: Long noncoding RNA LINC00313 (LINC00313) has been reported to be dysregulated in several tumors, including papillary thyroid carcinoma (PTC). Our present study aimed to further explore the potential mechanism of LINC00313 in the progression of papillary thyroid carcinoma (PTC). PATIENTS AND METHODS: RT-PCR was performed to detect the expression of LINC00313 in both PTC tissues and cell lines. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to explore whether SP1 could bind to the promoter region of LINC00313 and activate its transcription. The biological functional correlation of LINC00313 was determined by down-regulating the expression of LINC00313 on PTC cell proliferation, apoptosis, migration and invasion. The regulating relationship between LINC00313 and miR-422a was investigated in PTC cells using luciferase reporter assays. RESULTS: We observed that LINC00313 expression was significantly up-regulated in both PTC tissues and cell lines. Next, the results of bioinformatics analysis and luciferase reporter assays indicated that the transcription factor SP1 can bind to the promoter region of LINC00313 resulting in the overexpression of LINC00313 in PTC. Moreover, functional study revealed that knockdown of LINC00313 significantly suppressed cells proliferation, migration, invasion and EMT. Finally, our results indicated that LINC00313 functioned as an oncogene in PTC in part through serving as a competing endogenous RNA to modulate mi-422a expression. CONCLUSIONS: Overall, our data demonstrated that SP1-induced LINC00313 contributed to PTC progression by via competitively binding to miR-422a, which may provide a novel therapeutic strategy for PTC.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/genética , Fator de Transcrição Sp1/metabolismo , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Apoptose/genética , Ligação Competitiva , Linhagem Celular Tumoral , Movimento Celular/genética , Humanos , Regiões Promotoras Genéticas , Fator de Transcrição Sp1/genética , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
7.
Clin Oncol (R Coll Radiol) ; 30(10): 634-641, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30049649

RESUMO

AIMS: Intensity-modulated radiotherapy (IMRT) is increasingly used in the treatment delivery of chemoradiotherapy in anal cancer with the ability to reduce toxicity. We report on 4 year outcomes since the introduction of IMRT and identify the most predictive bowel organ at risk that correlates with acute diarrhoea. MATERIALS AND METHODS: Fifty-eight patients receiving definitive chemoradiotherapy for squamous or basaloid cell anal carcinoma (T1-4NanyM0) were reviewed. Fifty-four per cent of patients had stage III disease and most (79%) were treated with a dose of 54 Gy in 30 fractions. Patient acute gastrointestinal toxicity was recorded using Common Terminology Criteria of Adverse Events (CTCAE) diarrhoea grading. Four different methods of bowel were re-contoured for each patient and correlated with acute diarrhoea. Locoregional control and overall survival were analysed. RESULTS: CTCAE grade 3 or more diarrhoea occurred in 11/58 patients (19%). Seven patients did not complete treatment; 10 patients (17%) required a treatment break of 3 or more days. 'Bowel cavity' was the best predictor of acute grade 3 toxicity using volume (P = 0.002) or volume to bowel cavity in 5 Gy bins (V5-V50Gy); P < 0.05. Bowel cavity V30Gy ≤ 300 cm3 predicts a 6% grade 3 diarrhoea risk versus > 300 cm3 predicts a 42% risk. Four year progression-free survival was 84% (95% confidence interval 73-92%) and overall survival was 88% (95% confidence interval 75-95%). CONCLUSION: Chemoradiation using IMRT provides excellent local control and acceptable acute gastrointestinal toxicity. Bowel cavity is the most sensitive predictor for grade 3 versus grade 0-2 diarrhoea, with any volume receiving 5-50 Gy discriminatory.


Assuntos
Cavidade Abdominal/efeitos da radiação , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Diarreia/etiologia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Estadiamento de Neoplasias , Órgãos em Risco , Intervalo Livre de Progressão , Doses de Radiação , Taxa de Sobrevida
8.
Allergy ; 73(11): 2192-2204, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29672862

RESUMO

BACKGROUND: Exposure to environmental pollutants promotes Th2 cell responses. Aryl hydrocarbon receptor (AhR) activation aggravates allergic responses. Epithelium-derived thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33 are implicated in the dysregulation of Th2 immune responses in severe allergic asthma. METHODS: Bronchial biopsies of 28 allergic severe asthma and 6 mild asthma subjects from highly polluted areas were analyzed for AhR nuclear translocation (NT), cytokine expression, and gene activation. Cultured primary epithelial cells were stimulated with diesel exhausted particles (DEP) to determine AhR-mediated IL-33, Il-25, and TSLP synthesis and release. RESULTS: Primary bronchial epithelial cells exposed to DEP showed upregulation of IL-33, IL-25, and TSLP. These effects were abolished by knockdown of AhR by siRNA. Increased AhR/ARNT binding to promoters of IL-33, IL-25, and TSLP was found using chromatin immunoprecipitation (ChIP) assay. Allergic severe asthma with high AhR NT had higher bronchial gene and protein expression of IL-33, IL-25, and TSLP. These patients derived clinical benefit from anti-IgE treatment. CONCLUSION: Aryl hydrocarbon receptor activation by DEP mediates upregulation of IL-33, IL-25, and TSLP with Th2 activation, potentially linking environmental pollution and allergic severe asthma.


Assuntos
Asma/etiologia , Asma/metabolismo , Citocinas/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Emissões de Veículos , Alérgenos/imunologia , Anticorpos Anti-Idiotípicos/farmacologia , Anticorpos Anti-Idiotípicos/uso terapêutico , Asma/diagnóstico , Asma/terapia , Biópsia , Citocinas/genética , Feminino , Imunofluorescência , Regulação da Expressão Gênica , Humanos , Imunoglobulina E/imunologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Transporte Proteico , Testes de Função Respiratória , Mucosa Respiratória/patologia , Células Th2/imunologia , Células Th2/metabolismo , Linfopoietina do Estroma do Timo
9.
Hernia ; 22(4): 661-669, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29243214

RESUMO

PURPOSE: To evaluate the safety, efficacy and merits of laparoscopic repair in children with hydroceles by comparing the outcomes of laparoscopic repair and the traditional open repair (OR) procedure. The outcomes of the following three laparoscopic percutaneous extra-peritoneal closure (LPEC) approaches were also compared: conventional two-port surgery, transumbilical single-site two-port surgery and single-port surgery. METHODS: We retrospectively compared the demographic, perioperative and follow-up data from the consecutive records obtained for 382 boys who underwent OR and 950 boys who underwent LPEC at two children's medical centres in China. In the LPEC group, regardless of the hydrocele form, one of the three approaches with percutaneous aspiration was performed: conventional two-port surgery was performed in 387 cases, single-site two-port surgery was performed in 468 cases and single-port surgery was performed in 95 cases. The clinical data and complications were statistically analysed. RESULTS: Postoperative follow-up data were obtained for all the patients. The mean follow-up time was 36 months (24-48 months) in the OR group and 32.5 months (20-44 months) in the LPEC group. Significant differences in recurrence were not observed between the groups (five in the OR and 10 in the LPEC; P = 0.69). However, the operation time, postoperative hospital stay, incidence of scrotal oedema, incision infection and contralateral metachronous hernia or hydrocele were significantly higher in the OR group than those in the LPEC group (P < 0.01). Eighteen children (4.71%) had a negative exploration of the patent processus vaginalis (PPV) in the OR group. Fourteen children (1.47%) in the LPEC group had a closed internal ring and were converted to a scrotal procedure. Significant differences in the clinical data or complications were not observed between the two centres for the laparoscopic procedure (P > 0.05). Contralateral PPV (cPPV) was found in 18 patients in the single-port group (18.9%). Of the patients affected with cPPV, significant differences were observed between the single-port group and the two-port LPEC group (122 patients, 31.5%, P = 0.016) and the single-site two-port group (the 148 patients, 31.6%, P = 0.013). A contralateral metachronous hernia or hydrocele was found in zero, zero and two cases in these groups, respectively, and significant differences were observed (P < 0.01) between the single-site surgery and the other two laparoscopic approaches. CONCLUSIONS: LPEC is safe, feasible and effective for treating hydroceles in children and has the same recurrence rate as OR. However, LPEC is superior in operation time, hospital stay, occurrence of scrotal oedema, incision infection and occurrence of metachronous hernia or hydrocele. The transumbilical single-site two-port procedure has the same cosmetic effect as the single-port LPEC. According to our experience, the two-port LPEC approach is better for diagnosing cPPV and reducing metachronous hernia or hydrocele than the single-port LPEC procedure.


Assuntos
Herniorrafia/métodos , Laparoscopia/métodos , Hidrocele Testicular/cirurgia , Criança , Pré-Escolar , Hérnia Inguinal/cirurgia , Herniorrafia/instrumentação , Humanos , Lactente , Masculino , Estudos Retrospectivos
10.
BMJ Open ; 6(1): e008166, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26733563

RESUMO

OBJECTIVE: To determine if injection of vitamin K3 in an acupuncture point is optimal for the treatment of primary dysmenorrhoea, when compared with 2 other injection treatments. SETTING: A Menstrual Disorder Centre at a public hospital in Shanghai, China. PARTICIPANTS: Chinese women aged 14-25 years with severe primary dysmenorrhoea for at least 6 months not relieved by any other treatment were recruited. Exclusion criteria were the use of oral contraceptives, intrauterine devices or anticoagulant drugs, pregnancy, history of abdominal surgery, participation in other therapies for pain and diagnosis of secondary dysmenorrhoea. Eighty patients with primary dysmenorrhoea, as defined on a 4-grade scale, completed the study. Two patients withdrew after randomisation. INTERVENTIONS: A double-blind, double-dummy, randomised controlled trial compared vitamin K3 acupuncture point injection to saline acupuncture point injection and vitamin K3 deep muscle injection. Patients in each group received 3 injections at a single treatment visit. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the difference in subjective perception of pain as measured by an 11 unit Numeric Rating Scale (NRS). Secondary measurements were Cox Pain Intensity and Duration scales and the consumption of analgesic tablets before and after treatment and during 6 following cycles. RESULTS: Patients in all 3 groups experienced pain relief from the injection treatments. Differences in NRS measured mean pain scores between the 2 active control groups were less than 1 unit (-0.71, CI -1.37 to -0.05) and not significant, but the differences in average scores between the treatment hypothesised to be optimal and both active control groups (1.11, CI 0.45 to 1.78) and (1.82, CI 1.45 to 2.49) were statistically significant in adjusted mixed-effects models. Menstrual distress and use of analgesics were diminished for 6 months post-treatment. CONCLUSIONS: Acupuncture point injection of vitamin K3 relieves menstrual pain rapidly and is a useful treatment in an urban outpatient clinic. TRIAL REGISTRATION NUMBER: NCT00104546; Results.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura/métodos , Dismenorreia/terapia , Manejo da Dor , Dor/tratamento farmacológico , Vitamina K 3/uso terapêutico , Vitaminas/uso terapêutico , Adolescente , Adulto , China , Método Duplo-Cego , Dismenorreia/tratamento farmacológico , Feminino , Humanos , Injeções , Gravidez , Vitamina K 3/administração & dosagem , Vitaminas/administração & dosagem , Adulto Jovem
11.
Klin Padiatr ; 227(3): 157-65, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25985449

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative therapy for the severe hematopoietic complications associated with Fanconi anemia (FA). In Germany, it is estimated that 10-15 transplants are performed annually for FA. However, because FA is a DNA repair disorder, standard conditioning regimens confer a high risk of excessive regimen-related toxicities and mortality, and reduced intensity regimens are linked with graft failure in some FA patients. Moreover, development of graft-versus-host disease is a major contributing factor for secondary solid tumors. The relative rarity of the disorder limits HSCT experience at any single center. Consensus meetings were convened to develop a national approach for HSCT in FA. This manuscript outlines current experience and knowledge about HSCT in FA and, based on this analysis, general recommendations reached at these meetings.


Assuntos
Anemia de Fanconi/terapia , Transplante de Células-Tronco Hematopoéticas , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Anemia de Fanconi/sangue , Alemanha , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Fidelidade a Diretrizes , Hospitais Especializados , Humanos , Terapia de Imunossupressão , Estudos Retrospectivos , Fatores de Risco , Condicionamento Pré-Transplante
12.
Ann Hematol ; 94(8): 1311-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25862235

RESUMO

Fanconi anemia (FA) is a genomic instability syndrome associated with bone marrow failure, myelodysplastic syndrome (MDS), and/or acute myeloid leukemia (AML) requiring hematopoietic stem cell transplantation (HSCT) to restore normal hematopoiesis. Although low-intensity fludarabine-based preparative regimens without radiation confer excellent outcomes in FA HSCTs with HLA-matched sibling donors, outcomes for FA patients with alternative donors are less encouraging, albeit improving. We present our experience with 17 FA patients who completed mismatched related or unrelated donor HSCT using a non-radiation fludarabine-based preparative regimen at Charité University Medicine Berlin. All patients engrafted; however, one patient had unstable chimerism in the setting of multi-viral infections that necessitated a stem cell boost to revert to full donor chimerism. Forty-seven percent of patients developed grade I acute graft-verus-host disease (aGVHD). No grade II-IV aGVHD or chronic graft-versus-host disease of any severity occurred. At a median follow-up of 30 months, 88 % of patients are alive with normal hematopoiesis. Two patients died of infections 4 months post-transplantation. These results demonstrate that short-term outcomes for FA patients with mismatched and unrelated donor HSCTs can be excellent using chemotherapy only conditioning. Viral reactivation, however, was a major treatment-related complication.


Assuntos
Antineoplásicos/administração & dosagem , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Doadores não Relacionados , Adolescente , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Resultado do Tratamento , Adulto Jovem
14.
Oncogene ; 33(28): 3648-59, 2014 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23975427

RESUMO

Nasopharyngeal carcinoma (NPC), which is closely associated with Epstein-Barr virus (EBV), is a metastasis-prone epithelial cancer. We previously showed that tumor necrosis factor α-induced protein 2 (TNFAIP2) is highly expressed in NPC tumor tissues and is correlated with metastasis and poor survival in NPC patients. However, the underlying mechanism remains unclear. In this study, we demonstrate that the EBV oncoprotein, latent membrane protein 1 (LMP1), can transcriptionally induce TNFAIP2 expression via NF-κB. Quantitative RT-PCR and western blotting revealed that LMP1 induces TNFAIP2 expression through its C-terminal-activating region (CTAR2) domain, which is required for transduction of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling. Inhibition of NF-κB activation or depletion of p65 (a component of NF-κB) by RNA interference abolished the LMP1-induced expression of TNFAIP2, whereas ectopic expression of p65 was sufficient to induce TNFAIP2 expression. Luciferase reporter assays showed that LMP1 transcriptionally induces TNFAIP2 expression through a newly identified NF-κB-binding site within the TNFAIP2 promoter (-3,869 to -3,860 bp). Immunohistochemical analysis of NPC biopsy specimens further revealed a significant correlation between the protein levels of TNFAIP2 and activated p65 (R=0.689, P<0.001), indicating that our findings are clinically relevant. Immunofluorescence microscopy and co-immunoprecipitation assays showed that TNFAIP2 associates with actin and is involved in the formation of actin-based membrane protrusions. Furthermore, transwell migration assays demonstrated that TNFAIP2 contributes to LMP1-induced cell motility. Collectively, these findings provide novel insights into the regulation of TNFAIP2 and its role in promoting NPC tumor progression.


Assuntos
Movimento Celular , Citocinas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Nasofaríngeas/patologia , Fator de Transcrição RelA/metabolismo , Transcrição Gênica , Proteínas da Matriz Viral/metabolismo , Actinas/metabolismo , Carcinoma , Linhagem Celular Tumoral , Extensões da Superfície Celular/metabolismo , Sequência Conservada , Citocinas/metabolismo , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/virologia , Regiões Promotoras Genéticas/genética , Estrutura Terciária de Proteína , Transporte Proteico , Regulação para Cima , Proteínas da Matriz Viral/química
15.
Clin Ter ; 164(4): 301-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24045512

RESUMO

BACKGROUND AND AIMS: Helicobacter pylori strains secrete a vacuolating cytotoxin (VacA), plays an important role for the development of peptic ulcer disease and gastro-duodenal diseases. vacA gene is responsible to regulate the activity of the vacuolating cytotoxin. The objective of this study was molecular detection of vacA gene and observes the vacuolating activity on human gastric adenocarcinoma (AGS) cells. MATERIALS AND METHODS: H. pylori vacA gene was determined by polymerase chain reaction. Vacuolation activity of VacA toxin in broth culture filtrates was assessed in AGS cells and quantified by neutral uptake assay. Different concentration dosages of VacA and incubation time were used in the measurement of the vacuolating activity on AGS cells. RESULTS: The results showed that VacA toxin could stimulate vacuolating activity on AGS cells with minimum concentration 1.0 µg/ml from both of s1m1 and s1m2 alleles (vacA gene). The toxin produced optimal reaction at 5.0 µg/ml with significant differences observed between the alleles. The results also showed that both alleles commenced the vacuolating activity at the minimum of 3 hr incubation time, and the activity showed in time-dependent manner. CONCLUSION: Optimal concentration of VacA toxin (s1m1 allele) causes more interaction with AGS cell producing more vacuolating activities. Time-dependent vaculation of both alleles might allow H. pylori for persistent infection without rapid destruction of gastric cells might promote gastro-duodenal diseases. The study provided us better understanding of the pathogenesis of the diseases associated with H. pylori infection which is an emerging problem in developing countries.


Assuntos
Adenocarcinoma/complicações , Adenocarcinoma/microbiologia , Proteínas de Bactérias/genética , Infecções por Helicobacter/complicações , Helicobacter pylori/genética , Neoplasias Gástricas/complicações , Neoplasias Gástricas/microbiologia , Proteínas de Bactérias/análise , Humanos , Reação em Cadeia da Polimerase , Células Tumorais Cultivadas , Vacúolos
16.
Ann Oncol ; 24(5): 1344-51, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23293112

RESUMO

BACKGROUND: We evaluated the long-term results of radiotherapy for patients with gastric marginal zone lymphoma (GMZL). PATIENTS AND METHODS: We carried out a retrospective, multi-centre study of patients with low-grade GMZL treated by radiotherapy between 17 July 1981 and 25 March 2004. RESULTS: There were 102 eligible patients. Fifty-eight patients were previously untreated and 44 had recurrent/residual disease after prior treatment (HP eradication, chemotherapy and surgery in 35, 9 and 8 patients, respectively, and 7 had >1 prior therapy). Radiation fields included the stomach /involved nodes in 61 patients and whole abdomen in 41. The median radiotherapy dose to stomach was 40 Gy (range 26-46 Gy) in a median 22 fractions. With a median follow-up after radiotherapy of 7.9 years (range 0.3-24 years), 10- and 15-year freedom from treatment failure (FFTF) was 88% (95% CI 82%-95%). Risk factors for TF were a large-cell component (P = 0.036) and an exophytic growth pattern (P = 0.042). Radiotherapy field size, radiotherapy dose, and failure of prior therapy were not associated with inferior FFTF. Ten-year overall survival was 70% (95% CI 60%-82%). CONCLUSIONS: Radiotherapy achieves cure for the majority of patients with low-grade GMZL, including patients who have had prior therapy. Several features may predict a poorer outcome.


Assuntos
Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/radioterapia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
17.
ISRN Oncol ; 2012: 609439, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22690342

RESUMO

Despite marked improvement in the prognosis of patients with nonmetastatic Ewing sarcoma (ES), the outcome for patients with recurrent or metastatic disease remains poor. Insight into key biologic processes in ES could provide new therapeutic targets. The particular biologic feature of ES, the fusion of the EWS gene with a member of the ETS family of genes, is present in >95% of cases. The EWS-ETS chimeric protein leads to aberrant transcription that promotes tumor initiation and propagation via prosurvival and antiapoptotic pathways. Recent research has identified cooperating mutations important for ES tumorigenesis. This paper provides a summary of the latest research in ES and discusses potential novel targets for therapy.

18.
Med Phys ; 39(6Part16): 3805-3806, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28517187

RESUMO

PURPOSE: A three-dimensional conformal radiotherapy (3DCRT) has been recently introduced to helical tomotherapy, allowing the user to plan and treat patients that do not require sophisticated IMRT planning and delivery. This study aims to test treatment planning on this modality and evaluate its performance by comparing to conventional LINAC-based 3DCRT planning. METHODS: Four clinical cases (whole brain, extremity, lung, and partial breast irradiation) were retrospectively selected from a Pinnacle planning system (Philips Medical System, Fitchburg, WI) and planned on Tomotherapy (Accuray Inc., Sunnyvale, CA). Computed tomography (CT) images together with contours of target and critical structures were exported from Pinnacle to the Tomotherapy planning station. The same prescription and fractionation scheme was adopted. The pitch factor for all clinical cases was set to 0.287. A 2.5 cm jaw was employed except in the lung case the field size was set to 1.0 cm for better dose conformity. The dose grid size was chosen to be half of that of the planning CT images. On Pinnacle 100% prescription dose was delivered to the treatment isocenter while onTomotherapy it was stipulated that at least 95% of the target volume received the prescribed dose. Comparison between two planning strategies was performed, in terms of dose volume histograms (DVH), dosimetric and radiobiological parameters, for plan quality assessment. RESULTS: Comparison of DVHs reveals that up to 25% healthy tissue sparing in volume can be accomplished with Tomotherapy 3DCRT while the same target coverage is ensured. Dosimetric and radiobiological indices between Tomotherapy and Pinnacle planning agree to within 3.0%. Additional beam modifiers and non-coplanar beams associated with LINAC-based 3DCRT are not needed on Tomotherapy, making it more favorable. CONCLUSIONS: Tomotherapy 3DCRT has similar dosimetric performance when compared to conventional LINAC-based 3DCRT while it is substantially easier to use.

19.
Med Phys ; 39(6Part3): 3619, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28517411

RESUMO

PURPOSE: On-treatment megavoltage computed tomography on Helical Tomotherapy (Accuray Inc., Sunnyvale, CA) is critical for image guided radiotherapy. A strategy was developed to assess the impact of various jaw widths on image quality and imaging dose with Tomotherapy. METHODS: A cheese phantom (Gammex RMI, Middleton, WI) made of water equivalent materials was employed in this study. Three sets of measurements were independently carried out. Firstly, in the imaging dose measurement, the phantom was placed on the couch and aligned with a stationary green laser and beam isocenter. The measurement point was 10 mm up from the cente of the phantom. Three slices on either side of the middle slice were selected. Secondly, two inserts with different rows of holes of various sizes were placed inside the phantom for image contrast and resolution investigation. Lastly, twelve density inserts were placed into the outer holes in the phantom for measurement of the image value to density table (IVDT). A comparison of imaging dose, image resolution and contrast, IVDT table between different jaw configurations was performed to evaluate the imaging system. RESULTS: Imaging dose was 2.93 cGy with a jaw size of one mm as opposed to 1.62 cGy with a four mm jaw, both of which are below the vendor's requirement: 3 cGy. However, image quality is improved significantly with the smaller jaw. Four lines of holes can be readily identified on images using smaller jaw while only three lines visible with the larger jaw. Image contrast is similarly enhanced when reducing the jaw size. On average CT numbers are 6% higher with the smaller jaw than those obtained with the larger one. CONCLUSIONS: Significant improvement in image quality is achieved with the smaller jaw field in Tomotherapy while the imaging dose is kept at a clinically acceptable level.

20.
Bone Marrow Transplant ; 46(7): 929-35, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20935684

RESUMO

Our purpose was to present the clinical feasibility of TBI with helical tomotherapy (HT) in four patients with AML. Treatment planning, delivery, dose verification and summation, toxicity and patient outcomes for each patient are presented. TBI prescription was set in such a manner that 80% of the clinical target volume received 12 Gy in six fractions, at two fractions per day. Dose reconstruction was carried out by recontouring the regions of interest in the daily pretreatment megavoltage computed tomography of each individual fraction and calculating its corresponding dose. A deformable registration model was used for dose summation of all individual fractions. Differences between planned and delivered doses were calculated. Average planned and delivered doses to the regions of interest differed by up to 2.7%. TBI toxicity was limited to radiotherapy oncology group grade 1 dermatitis in all patients and grade 1 headache in one patient. Two patients are alive with no evidence of disease and no GVHD. Two patients died of GVHD, but there was no evidence of disease at the time of death. We conclude that HT simplifies the process of TBI. Dose verification is possible with HT showing small differences between plan and delivered doses.


Assuntos
Leucemia Mieloide Aguda/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Irradiação Corporal Total/efeitos adversos , Irradiação Corporal Total/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA