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1.
J Int Med Res ; 50(7): 3000605221078484, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35904051

RESUMO

Cardiac amyloidosis usually presents with diastolic dysfunction, but sometimes systolic dysfunction develops, particularly at its advanced stage. However, the therapeutic strategy for patients with cardiac amyloidosis and systolic dysfunction remains unknown. We report a 77-year-old man who was diagnosed with wild-type cardiac amyloidosis and systolic dysfunction with a left ventricular ejection fraction of 27%. Following 6-month medical therapy of tafamidis 80 mg and neurohormonal blockers (carvedilol 5.0 mg, enalapril 2.5 mg, and spironolactone 25 mg), the left ventricular ejection fraction improved to 55%. Tafamidis-incorporated neurohormonal blocker therapy might be a promising strategy to facilitate cardiac reverse remodeling in patients with cardiac amyloidosis and systolic dysfunction.


Assuntos
Amiloidose , Cardiomiopatias , Idoso , Amiloidose/complicações , Amiloidose/tratamento farmacológico , Benzoxazóis , Cardiomiopatias/tratamento farmacológico , Carvedilol , Humanos , Masculino , Volume Sistólico , Função Ventricular Esquerda
2.
J Cardiovasc Dev Dis ; 9(2)2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35200692

RESUMO

Post-transplant lymphoproliferative diseases (PTLD) are potentially fatal complications after cardiac transplantation. Most cases are Epstein-Barr virus (EBV)-related B-cell tumors, and reduction of immunosuppression treatment as well as the use of rituximab in combination with other chemotherapy are effective. However, patients with T/NK-cell PTLD post-cardiac transplantation are rarely reported. We had a patient with a fever that lasted for three weeks, with lung infiltrations and hepatosplenomegaly, who had EBV-associated hemophagocytosis 7 years after heart transplantation and was eventually diagnosed with T/NK-cell PTLD by autopsy. Although rare diseases, regular monitoring of EBV-DNA levels might be crucial for early diagnosis and treatment of PTLD.

3.
J Cardiol Cases ; 25(1): 34-36, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35024066

RESUMO

A wild-type ATTR amyloidosis is a systemic disease with multi-organ dysfunction, involving heart, kidney, skin, and gastrointestinal tract, due to deposition of wild-type transthyretin in each organ. We had a 76-year-old man diagnosed with wild-type ATTR cardiac amyloidosis, whose heart failure symptom improved by anti-heart failure medications but constipation refractory to multiple conventional medications persisted. Following the conversion from lubiprostone to Kampo medicine mashiningan, his average days per one evacuation decreased from around 7.0 days down to 1.6 days. Mashininigan might be an alternative option to improve refractory constipation in patients with cardiac amyloidosis. .

4.
Intern Med ; 61(7): 1015-1019, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544954

RESUMO

A de novo cardiac malignant tumor is rare and sometimes challenging to diagnose. We encountered a 67-year-old man without any medical history complaining of dyspnea on effort. On admission, his hemodynamics were deteriorated due to cardiac tamponade, which was improved by percutaneous drainage of 1,200 mL pericardial effusion, showing 11.0 g/dL of hemoglobin. We suspected primary cardiac malignancy following multidisciplinary tests, and a cardiac biopsy via sternotomy demonstrated the definitive diagnosis of primary malignant tumor (angiosarcoma) infiltrating the right atrial myocardium. We initiated weekly paclitaxel therapy. Further studies are warranted to establish the optimal diagnostic and therapeutic strategy for de novo cardiac malignancy.


Assuntos
Tamponamento Cardíaco , Neoplasias Cardíacas , Hemangiossarcoma , Derrame Pericárdico , Idoso , Tamponamento Cardíaco/diagnóstico por imagem , Tamponamento Cardíaco/etiologia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico por imagem , Hemangiossarcoma/complicações , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/patologia , Humanos , Masculino , Derrame Pericárdico/complicações , Derrame Pericárdico/diagnóstico por imagem
5.
Intern Med ; 60(17): 2807-2809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34470986

RESUMO

Sacubitril/valsartan has demonstrated its prognostic advantageousness over enalapril in patients with heart failure with a reduced ejection fraction. However, the optimal therapeutic strategy using sacubitril/valsartan in real-world practice, particularly among a Japanee cohort, remains uncertain. A 75-year-old man with systolic heart failure and chronic kidney disease was administered sacubitril/valsartan. Plasma B-type natriuretic peptide transiently increased, accompanied by an increase in the urine volume, which allowed us to terminate loop diuretics. The estimated glomerular filtration rate as well as heart failure symptom improved at the one-month follow-up. Sacubitril/valsartan might be a promising option to preserve the renal function and improve clinical outcomes when the dose of concomitant diuretics can be decreased, although further large-scale studies are warranted to validate our hypothesis.


Assuntos
Insuficiência Cardíaca Sistólica , Insuficiência Cardíaca , Insuficiência Renal Crônica , Idoso , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Japão , Masculino , Neprilisina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Volume Sistólico , Tetrazóis/uso terapêutico , Resultado do Tratamento , Valsartana/uso terapêutico
6.
Med Mol Morphol ; 54(3): 245-252, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33963949

RESUMO

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.


Assuntos
Quimiorradioterapia , Regulação Neoplásica da Expressão Gênica , Inflamação , Microambiente Tumoral/imunologia , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígenos CD8/genética , Proteínas de Ligação a DNA/genética , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Japão , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/metabolismo
7.
Int Heart J ; 62(2): 441-444, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33731533

RESUMO

We had a 58-year-old man with advanced heart failure and progressive end-organ dysfunction refractory to inotropes. Following detailed discussions, he decided not to receive ventricular assist device therapy considering his comorbidity of schizophrenia. A palliative care team initiated 2.5 mg of morphine together with low-dose anti-heart failure medications, which improved not only his heart failure symptoms but also the congestive heart failure itself. Aggressive commitments of the palliative care team might improve not only patients' quality of life but also advanced heart failure itself.


Assuntos
Insuficiência Cardíaca/terapia , Coração Auxiliar , Cuidados Paliativos/métodos , Qualidade de Vida , Esquizofrenia/complicações , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade
8.
Jpn J Clin Oncol ; 50(11): 1290-1297, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089868

RESUMO

OBJECTIVE: To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients. METHODS: We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues. RESULTS: In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230. CONCLUSION: The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.


Assuntos
Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Intervalo Livre de Doença , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
9.
Cancer Med ; 9(22): 8579-8588, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32964674

RESUMO

BACKGROUND: To best employ radium-223 dichloride (Ra-223) for patients with castration-resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone-predominant status in patients treated with Ra-223. METHODS: We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra-223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra-223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression-free survival (PFS). RESULTS: During the median follow-up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P < .001). In multivariate analysis, the type of the new progressive lesions in bone metastasis (HR 1.45, 95% CI 1.13-1.66, P = .003), performance status of >1 (HR 1.74, 95% CI 1.04-2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02-2.50, P = .043), and PSA doubling time (PSADT) of <3 months (HR 1.53, 95% CI 1.11-2.03, P = .007) were independent unfavorable predictive factors for PFS. The risk assessment for PFS was highlighted when the type of dynamic changes of bone metastasis was combined with PSADT just before Ra-223 treatment. This was associated with non-bone metastasis progression, especially visceral metastasis, and overall survival. CONCLUSIONS: Risk assessment in combination with dynamic changes of bone metastasis and PSADT determines the bone-predominant metastasis type to benefit from Ra-223.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Rádio (Elemento)/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/secundário , Tomada de Decisão Clínica , Humanos , Masculino , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/patologia , Radioisótopos/efeitos adversos , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/efeitos adversos , Rádio (Elemento)/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
10.
In Vivo ; 34(5): 2865-2872, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871826

RESUMO

Background/Aim: Accurate prediction of radiotherapy results is indispensable for the individualized selection of treatment modalities of cancer. We examined the application of the artificial neural network (ANN) model in predicting radiotherapy results using clinical factors and immunohistochemical staining of Ku70 as inputs. Patients and Methods: We analyzed 79 prostate cancer patients with localized adenocarcinoma treated with radiotherapy between August 2001 and October 2010. We also analyzed 46 hypopharyngeal cancer patients with squamous cell carcinoma treated with radiotherapy between March 2002 and December 2009. The properly trained ANN analysis using a standard feedforward, back-propagation neural network was used to predict the radiotherapy treatment results. Results: The areas under the receiver-operating characteristic curve (AUC) were 0.939 for patients treated with intensity modulated radiotherapy (IMRT)+androgen deprivation therapy (ADT), 0.803 for IMRT alone, and 0.960 for 3D-conformal radiotherapy (CRT) alone in prostate cancer. Sensitivity and specificity were 85.7% and 90.4% for IMRT+ADT, 75.0% and 88.5% for IMRT alone, and 92.3% and 100% for 3D-CRT alone. The AUC was 0.901 for hypopharyngeal cancer. Sensitivity and specificity were 66.7% and 88.2%, respectively. Conclusion: We demonstrated a possibility to predict the radiotherapy treatment results in prostate and hypopharyngeal cancer using ANN in combination with Ku70 expression and clinical factors as inputs.


Assuntos
Neoplasias da Próstata , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Antagonistas de Androgênios , Humanos , Masculino , Redes Neurais de Computação , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica
11.
Brachytherapy ; 19(3): 290-297, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32249179

RESUMO

PURPOSE: To assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer. METHODS AND MATERIALS: The minimum urethral dose (UD10, 30, and 90) and the percent volume of the urethra receiving the prescription dose (V100, V150) were calculated from the postimplant dose-volume histograms of 182 patients. We then calculated various urethral biologically equivalent doses (uBEDs) using different values of the α/ß ratio and tissue repair half-time (t1/2) and examined the correlations with GU toxicity. RESULTS: Common dosimetric quantifiers, such as UD90 (brachytherapy) + UD50 (external beam radiotherapy), showed no correlation with Grade ≥ 2 GU toxicity. There was a significant correlation between Grade ≥2 GU toxicity and uBED when the α/ß value was 0.5 or 1 Gy and t1/2 was 0.5-2.5 h. An uBED (α/ß = 1.0, t1/2 = 0.5) had the largest hazard ratio for GU toxicity, and it was also significantly correlated with Grade ≥ 2 GU toxicity according to multivariate analysis. CONCLUSIONS: We observed a significant correlation of uBED with GU toxicity when α/ß was 0.5 or 1.0 Gy and t1/2 was 0.5-2.5 h. As the simple formula we used has not been verified in basic experiments, more data are needed to validate our results.


Assuntos
Braquiterapia/efeitos adversos , Neoplasias da Próstata/radioterapia , Lesões por Radiação/etiologia , Uretra/efeitos da radiação , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Dosagem Radioterapêutica
12.
J Radiat Res ; 61(2): 265-274, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32009177

RESUMO

Combining external beam radiotherapy (EBRT) with intracavitary brachytherapy (ICBT) is important for definitive treatment of cervical cancer. In cervical cancer patients receiving radiotherapy, we evaluated treatment outcomes in relation to dose-volume histogram parameters, including the computed tomography (CT)-based high-risk clinical target volume (HR-CTV) for ICBT. Between 2010 and 2015, 89 consecutive cervical cancer patients were mostly treated with 40 Gy of EBRT in 20 fractions and 18 Gy of ICBT prescribed to point A in 3 fractions. CT scans were obtained during ICBT. The HR-CTV D90 was calculated and the total doses of ICBT and EBRT were converted to the equivalent dose in 2 Gy fractions (EQD2). When the patients were divided into four groups according to EQD2 of the HR-CTV D90, the 3-year local recurrence-free survival rates were 95.2, 78.4, 52.7 and 42.9% for patients receiving >80 , 70-80 , 60-70 and <60 Gy, respectively. There was a significant negative correlation between EQD2 of the HR-CTV D90 and the HR-CTV volume at first ICBT (r = -0.713). Local recurrence was more frequent when the HR-CTV volume was ≥22 cc and EQD2 of the HR-CTV D90 was <70 Gy. Multivariate analysis showed that EQD2 of the HR-CTV D90 and concurrent chemotherapy (≥4 cycles) were significant determinants of overall survival. HR-CTV D90 was an important prognostic indicator for local recurrence. HR-CTV D90 >70 Gy is required for the better local control, especially in patients with a larger HR-CTV (≥22 cc at initial ICBT).


Assuntos
Braquiterapia , Dosagem Radioterapêutica , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Resultado do Tratamento
13.
Strahlenther Onkol ; 196(8): 725-735, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31953603

RESUMO

PURPOSE: To evaluate radiotherapy-induced changes in the expression of programmed death ligand 1 (PD-L1), programmed death 1 (PD-1), and human leukocyte antigen class I (HLA-1) in patients with uterine cervical cancer, as well as infiltration of CD8+ and Forkhead box P3+ (FoxP3+) T lymphocytes into tumor tissue and the prognostic value of these parameters. MATERIALS AND METHODS: We performed immunohistochemical analysis of pre-radiotherapy biopsies and corresponding post-radiotherapy resected tissues in 104 uterine cervical cancer patients undergoing preoperative chemoradiotherapy or radiotherapy alone. We scored the expression of various proteins to distinguish positive from negative samples. RESULTS: PD-L1-expressing tumor cells (PD-L1 TC) increased significantly after chemoradiotherapy (p = 0.043). CD8+ T cell infiltration (p = 0.002) and FoxP3+ T cell infiltration (p = 0.003) decreased significantly after chemoradiotherapy. Expression of PD­1, PD-L1-expressing immune cells (PD-L1 IC), and HLA­1 did not change after chemoradiotherapy. In biopsy specimens obtained before chemoradiotherapy or radiotherapy, greater infiltration of CD8+ T cells (p = 0.001) and FoxP3+ T cells (p = 0.003) were significant predictors of better overall survival (OS). In surgical specimens obtained after chemoradiotherapy or radiotherapy, greater infiltration of PD-L1 TC was the only significant predictor of better OS (p < 0.001) and was related to a significantly lower probability of out-of-field recurrence (p = 0.005). CONCLUSION: Chemoradiotherapy induced an immunologic shift that increased PD-L1 TC. Chemoradiotherapy has immunological effects that can influence the results of treatment for uterine cervical cancer.


Assuntos
Antígeno B7-H1/análise , Carcinoma de Células Escamosas/radioterapia , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Antígenos HLA/análise , Terapia Neoadjuvante , Proteínas de Neoplasias/análise , Subpopulações de Linfócitos T/imunologia , Neoplasias Uterinas/radioterapia , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Linfócitos T CD8-Positivos/química , Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante , Cisplatino/uso terapêutico , Feminino , Fatores de Transcrição Forkhead/análise , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/efeitos da radiação , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Subpopulações de Linfócitos T/química , Resultado do Tratamento , Neoplasias Uterinas/imunologia , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/terapia
14.
Radiother Oncol ; 129(2): 409-414, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30249348

RESUMO

BACKGROUND AND PURPOSE: To investigate influences of proteins involved with tumor immunity on outcomes of radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC). MATERIAL AND METHODS: We performed immunohistochemical staining to examine expressions of p16 and proteins involved with tumor immunity in 92 OPSCC patients treated with radiotherapy. RESULTS: Patients with abundant infiltrating CD8-positive cells had the significantly better overall survival (OS) rate than patients with fewer CD8-positive cells (p = 0.026). Patients with higher PD-L1 expression in tumor cells (TC 1-3) had a better outcome than those with low PD-L1 expression in tumor cells (TC 0) for both OS (p = 0.019) and progression-free survival (PFS) rate (p = 0.032). Patients with high PD-L1 expression in infiltrating immune cells (IC 3) showed significantly better OS (p = 0.009) and PFS (p = 0.011) than those with low PD-L1 expression (IC 0-2). Patients with p16-negative and IC 3 showed similar OS to patients with p16-positive and IC 0-2. P16-positive tumors had a significantly higher CD8-positive cell infiltration and PD-L1 expression in tumor cells than p16-negative tumors. CONCLUSIONS: In addition to tumor p16 expression, PD-L1 expression in TC and IC can be useful for predicting the response of OPSCC to radiotherapy.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Orofaríngeas/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Neoplasias Orofaríngeas/imunologia , Neoplasias Orofaríngeas/patologia , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
15.
J Radiat Res ; 59(4): 484-489, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29659987

RESUMO

This study aims to demonstrate the feasibility of a method for estimating the strength of a moving brachytherapy source during implantation in a patient. Experiments were performed under the same conditions as in the actual treatment, except for one point that the source was not implanted into a patient. The brachytherapy source selected for this study was 125I with an air kerma strength of 0.332 U (µGym2h-1), and the detector used was a plastic scintillator with dimensions of 10 cm × 5 cm × 5 cm. A calibration factor to convert the counting rate of the detector to the source strength was measured and then the accuracy of the proposed method was investigated for a manually driven source. The accuracy was found to be under 10% when the shielding effect of additional needles for implantation at other positions was corrected, and about 30% when the shielding was not corrected. Even without shielding correction, the proposed method can detect dead/dropped source, implantation of a source with the wrong strength, and a mistake in the number of the sources implanted. Furthermore, when the correction was applied, the achieved accuracy came close to within 7% required to find the Oncoseed 6711 (125I seed with unintended strength among the commercially supplied values of 0.392, 0.462 and 0.533 U).


Assuntos
Braquiterapia , Radioisótopos do Iodo/química , Calibragem , Humanos
16.
Jpn J Clin Oncol ; 48(2): 167-174, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29281088

RESUMO

BACKGROUND: To search for novel biomarkers that can predict acute radiation toxicity, we conducted microRNA expression analysis of peripheral blood lymphocytes (PBLs). METHODS: The discovery cohort was 69 patients with localized adenocarcinoma of the prostate who received intensity-modulated radiation therapy between October 2007 and October 2010. The validation cohort was 72 patients treated with low-dose-rate brachytherapy between May 2008 and March 2014. After13 microRNAs were selected by TaqMan® Array analysis in a preliminary experiment, expression of these microRNAs in all samples was analyzed by RT-PCR. RESULTS: In the discovery cohort, the average prostate volume, the rectal volume receiving 70 Gy, and expression of miR-410 and miR-221 were significant risk factors for Grade 1-2 gastrointestinal toxicity. Receiver operating characteristic analysis showed that the area under the curve (AUC) was 0.807. The maximum dose to the urinary bladder, prostate volume, pretreatment urinary function score, and miR-99a and miR-221 expression were risk factors for Grade 2 genitourinary toxicity. The corresponding AUC was 0.796. In the validation cohort, reproducibility of these markers was confirmed for gastrointestinal toxicity, but not for genitourinary toxicity. CONCLUSION: Combining radiation dose parameters with microRNA expression in PBLs may be useful for predicting acute gastrointestinal toxicity of radiation therapy, thus contributing to personalized treatment of prostate cancer.


Assuntos
Trato Gastrointestinal/patologia , Linfócitos/patologia , MicroRNAs/metabolismo , Neoplasias da Próstata/complicações , Neoplasias da Próstata/patologia , Lesões por Radiação/etiologia , Lesões por Radiação/genética , Sistema Urogenital/patologia , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Humanos , Modelos Logísticos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROC , Dosagem Radioterapêutica , Reprodutibilidade dos Testes
17.
J Radiat Res ; 58(2): 225-231, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28399576

RESUMO

Repair of DNA damage is critical for genomic stability, and DNA-dependent protein kinase (DNA-PK) has an important role in repairing double-strand breaks. We examined whether the DNA-PK activity of peripheral blood lymphocytes (PBLs) was related to biochemical (prostate-specific antigen: PSA) relapse and radiation toxicity in prostate cancer patients who have received radiotherapy. A total of 69 patients with localized adenocarcinoma of the prostate participated in this study. Peripheral blood was collected 2 years or later after radiotherapy and centrifuged, then DNA-PK activity was measured by a filter binding assay. The high DNA-PK activity group had a significantly higher PSA relapse-free survival rate than the low DNA-PK activity group. The 10-year PSA relapse-free survival was 87.0% in the high DNA-PK activity group, whereas it was 52.7% in the low DNA-PK activity group. Multivariate analysis showed the Gleason score and the level of DNA-PK activity were significant predictors of PSA relapse after radiotherapy. In addition, the low DNA-PK activity group tended to have a higher incidence of Grade 1-2 urinary toxicity than the high DNA-PK activity group. Prostate cancer patients with low DNA-PK activity had a higher rate of PSA relapse and a higher incidence of urinary toxicity. DNA-PK activity in PBLs might be a useful marker for predicting PSA relapse and urinary toxicity, possibly contributing to personalized treatment of prostate cancer.


Assuntos
Proteína Quinase Ativada por DNA/sangue , Leucócitos Mononucleares/enzimologia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/radioterapia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/urina , Recidiva , Fatores de Risco
18.
Strahlenther Onkol ; 193(1): 29-37, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27465041

RESUMO

BACKGROUND AND PURPOSE: Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse. PATIENTS AND METHODS: We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens. RESULTS: Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D'amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained. CONCLUSION: Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/radioterapia , Autoantígeno Ku/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional/métodos , Adenocarcinoma/diagnóstico , Idoso , Biomarcadores Tumorais/sangue , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Prevalência , Prognóstico , Neoplasias da Próstata/diagnóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Resultado do Tratamento
19.
Med Mol Morphol ; 50(1): 25-33, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27338590

RESUMO

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/radioterapia , Idoso , Idoso de 80 Anos ou mais , Proteína Quinase Ativada por DNA/metabolismo , Feminino , Humanos , Autoantígeno Ku/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Resultado do Tratamento
20.
Med Mol Morphol ; 49(4): 210-216, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26867665

RESUMO

DNA double-strand breaks (DSB) are severe damages induced by ionizing radiation. Non-homologous end joining (NHEJ) is a major mechanism for repairing DSB. Immunohistochemical analysis of proteins involved in NHEJ, such as Ku86 and XRCC4 (X-ray repair cross-complementing protein 4) may be useful for predicting tumor radiosensitivity. We examined the relationship between expression of DSB-related proteins in biopsy specimens of uterine cervical cancer and the pathological effect of 40 Gy of preoperative radiotherapy. 119 patients with uterine cervical cancer were treated between 2000 and 2011. Pathological effects of preoperative radiotherapy were classified by examining hysterectomy specimens. Patients with complete response (pCR) had a significantly better overall 5-year survival rate than those without pCR (96.3 vs. 76.9 %, P = 0.02). The pCR rate was significantly higher in patients with low Ku86 and XRCC4 expression than in other patients (47.4 vs. 21.3 %, P = 0.04). Logistic regression analysis also demonstrated that low Ku86 and XRCC4 expression was a significant predictor of pCR (P = 0.03). Patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others (79.3 vs. 93.5 %, P = 0.02). Proteins involved with NHEJ might have an influence on results of radiotherapy for uterine cervical cancer.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Autoantígeno Ku/metabolismo , Cuidados Pré-Operatórios , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Biópsia , Contagem de Células , Reparo do DNA por Junção de Extremidades/genética , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
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