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INTRODUCTION: The study explored the failure pattern and clinical outcomes in patients with ependymoma undergoing radiotherapy. METHODS: Between January 2004 and June 2022, we included 32 patients with ependymoma who underwent radiotherapy as part of the multimodality treatment at our institution. Of these, 27 (84.4%) underwent adjuvant radiotherapy, four received radiotherapy after local recurrence, and one received definitive CyberKnife radiotherapy (21 Gy in three fractions). The median prescribed dose was 54 Gy in patients who received conventional radiotherapy. We analyzed the local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and potential prognostic factors. RESULTS: The median age was 29.8 years. Approximately 28.1% were pediatric patients. Fifteen tumors (46.9%) were World Health Organization (WHO) grade II, 10 (31.3%) were WHO grade III, and seven (22.8%) were WHO grade I. Among them, 15 patients (46.9%) had posterior fossa tumors, 10 (31.3%) had supratentorial tumors, and seven (22.8%) had spinal tumors. Of the 31 patients who underwent upfront surgical resection, 19 (61.3%) underwent gross total resection or near total resection. Seventeen of 19 patients with first failures (89.5%) had isolated local recurrences. Of the 19 patients with disease progression, 11 (57.9%) were disease-free or had stable disease after salvage therapy, and five (26.3%) had disease-related mortality. Most of the first local recurrences after radiotherapy occurred in the infield (13 of 16, 81.3%). The 5-year LPFS, DMFS, PFS, and OS rates were 48.5%, 89.6%, 45.1%, and 88.4%, respectively, at a median follow-up of 6.25 years. Subtotal resection was associated with poorer LPFS and PFS in patients with intracranial ependymoma (hazard ratio = 3.69, p = 0.018 for LPFS; hazard ratio = 3.20, p = 0.029 for PFS). CONCLUSION: Incorporating radiotherapy into multimodal treatment has led to favorable outcomes in patients with ependymoma, and the extent of resection is a prognostic factor for the local control of intracranial ependymoma.
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BACKGROUND: Extended field-of-view (eFOV) methods have been proposed to generate larger demonstration FOVs for computed tomography (CT) simulators with a limited scanning FOV (sFOV) size in order to ensure accurate dose calculation and patient collision avoidance. Although the efficacy of these strategies has been evaluated for photon applications, the effect of stopping power ratio (SPR) estimation on proton therapy has not been studied. This study investigated the effect of an eFOV approach on the accuracy of SPR to water estimation in homogeneous and heterogeneous phantoms. MATERIALS AND METHODS: To simulate patient geometries, tissue-equivalent material (TEM) and customized extension phantoms were used. The TEM phantom supported various rod arrangements through predefined holes. Images were reconstructed to three FOV sizes using a commercial eFOV technique. A single-energy CT stoichiometric method was used to generate Hounsfield unit (HU) to SPR (HU-to-SPR) conversion curves for each FOV. To investigate the effect of rod location in the sFOV and eFOV regions, eight TEM rods were placed at off-center distances in the homogeneous phantom and scanned individually. Similarly, 16 TEM rods were placed in the heterogeneous TEM phantom and scanned simultaneously. RESULTS: The conversion curves derived from the sFOV and eFOV data were identical. The average SPR differences of soft-tissue, bone, and lung materials for rods placed at various off-center locations were 3.3%, 4.8%, and 39.6%, respectively. In the heterogeneous phantom, the difference was within 1.0% in the absence of extension. However, in the presence of extension, the difference increased to 2.8% for all rods, except for lung materials, whose difference was 4.8%. CONCLUSIONS: When an eFOV method is used, the SPR variation in phantoms considerably increases for all TEM rods, especially for lung TEM rods. This phenomenon may substantially increase the uncertainty of HU-to-SPR conversion. Therefore, image reconstruction with a standard FOV size is recommended.
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Terapia com Prótons , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Imagens de Fantasmas , Osso e Ossos , Processamento de Imagem Assistida por Computador/métodosRESUMO
BACKGROUND: The Halcyon is a linear accelerator-based treatment machine designed for a high-throughput simplified workflow. The machine features a compact jawless design, dual-layer multileaf collimators, and a single 6-MV flattening filter-free (FFF) beam. However, the machine's 6-MV FFF beam may restrict its applicability to conventional techniques, such as field-in-field (FiF) radiotherapy, for breast cancer treatment. This study developed a practical and efficient hybrid method for imaging, planning, and irradiation procedures for whole-breast irradiation using Halcyon linear accelerators. MATERIALS AND METHODS: The proposed method involves five major steps: (1) field arrangement, (2) planning target volume (PTV) generation and evaluation, (3) basal plan generation, (4) inverse planning intensity-modulated radiation therapy plan generation, and (5) plan evaluation and irradiation. The PTV is generated using isodose curves plotted on the basis of tangential fields, which are applied to create a basal plan. Subsequently, a basal-dose-compensation approach is applied to further optimize the treatment plan. This efficient workflow necessitates executing only one onboard cone-beam computed tomography procedure. This study included 10 patients with early-stage breast cancer who were treated at our center. The performance of the proposed method was evaluated by comparing its corresponding irradiation time and dose statistics with those derived for a dynamically flattened beam-based FiF (DFB-FiF) method. RESULTS: All plans were normalized to ensure that 98% of the prescribed dose covered 95% of the PTV. On average, the global maximum doses in the proposed and DFB-FiF methods were lower than 106%. The homogeneity index for right-sided (left-sided) breast cancer was 0.053 (0.056) in the proposed method and 0.073 (0.076) in the DFB-FiF method. The dose statistics of normal tissues, including the contralateral breast, heart, and lungs, were comparable between the methods. However, the irradiation time per monitor unit in the proposed method was approximately five times faster than that in the DFB-FiF method, but the planning time and complexity were similar between the methods. CONCLUSIONS: This study developed and evaluated an efficient and practical hybrid method for whole-breast irradiation using the Halcyon. This method can significantly reduce the irradiation time, while providing comparable dose statistics to the DFB-FiF method.
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Neoplasias da Mama , Radioterapia de Intensidade Modulada , Neoplasias da Mama/radioterapia , Feminino , Humanos , Aceleradores de Partículas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodosRESUMO
Unresectable anaplastic thyroid cancer (ATC) has a poor prognosis. Chemotherapy and radiotherapy have limited effects on it. Here, we present four cases who underwent immunotherapy for ATC. The patients were aged between 58 and 70 years. Two male patients with pulmonary metastases received pembrolizumab and lenvatinib. However, they died of septic shock and respiratory failure in 2.7 and 1 months, respectively, after the initiation of combination therapy. Another male patient with stage IVB disease was treated with spartalizumab. The tumor remained stable after surgical debulking but slightly progressed after 23 months. He survived for 45.5 months after spartalizumab initiation. A female patient with BRAF-mutant ATC and lung metastases was treated with a combination of pembrolizumab and lenvatinib, which was complicated with grade 4 transaminitis. The patient subsequently received dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) treatment, which was continued for 10.2 months with a best response of partial remission. She died 18 months after the initial diagnosis (11.4 months after treatment with dabrafenib and trametinib). In conclusion, the treatment responses of immunotherapy, either alone or in combination with other therapies, were highly variable in patients with ATC and should be carefully monitored along with the side effects.
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Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Idoso , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/etiologia , Neoplasias da Glândula Tireoide/tratamento farmacológicoRESUMO
C57BL/6 mice implanted in the flank with murine Lewis lung carcinoma cells were randomized into control, anti-angiogenic, anti-PD-L1, radiotherapy (RT), RT + anti-angiogenic, RT + anti-PD-L1, and RT + anti-PD-L1 + anti-angiogenic therapy groups. Immune response and immunophenotyping were determined by flow cytometry. Vasculature analysis after RT and anti-angiogenic therapy was assessed by quantified power Doppler sonography. Antitumor response, survival, and rechallenged tumor growth were evaluated. RT increased PD-L1 expression on CD8+ T, CD4+ T, dendritic, myeloid-derived suppressor cells (MDSCs), and tumor cells and increased PD-1 expression on CD8+ and CD4+ T cells. Anti-angiogenic therapy insignificantly decreased the RT-induced PD-1 expression on CD8+ and CD4+ T cells, implying a weak reversal of the immune-suppressive environment. Transient vessel collapse was observed within days after RT, and blood flow recovered at 1 week after RT. RT + anti-PD-L1 suppressed the tumor growth, improved survival, and prolonged immune memory capable of protecting against tumor recurrence, evidenced by local accumulation of CD8+ T cells and reduction in MDSCs in microenvironment. Similar and more prominent effects were observed when anti-VEGF was added to RT + anti-PDL1 therapies, implying an additive, rather than synergistic, antitumor immunity. Phenotypic analyses revealed that anti-cancer treatments increased the proportion of effector memory T cells in TILs and splenocytes, and RT, alone or in combination with other treatments, further increased the proportion of central memory T cells in splenocytes. These results provide evidence on operating the immunosuppressive tumor environment and offer insights into the design of the new combination treatment.
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Inibidores da Angiogênese/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores da Angiogênese/farmacologia , Animais , Terapia Combinada , Modelos Animais de Doenças , Humanos , Neoplasias Pulmonares/patologia , CamundongosRESUMO
OBJECTIVES: To evaluate the effect of botulinum toxin type A (BTX)-induced masticatory muscle hypofunction on the maxillofacial suture bone growth of growing rats. SETTING AND SAMPLE POPULATION: Department of Orthodontics at Taipei Medical University. Forty-eight male 4-week-old Wistar rats were divided into four groups. The N group received injections of normal saline into each of the masseter and temporalis muscles. The M group received injections of normal saline into each of the temporalis muscle and injections of BTX into each of the masseter muscle. The T group received injections of normal saline into each of the masseter muscle and injections of BTX into each of the temporalis muscle. The MT group received injections of BTX into each of the masseter and temporalis muscles. MATERIAL & METHODS: Rats were sacrificed after 42 days of growth. Changes in body and muscle weight were measured. Anthropometric measurements of the maxillary arch, sutural bone mineral density and sutural bone deposition distances were recorded. Statistical comparisons were performed using analysis of variance. RESULTS: No significant change in body weight was found across groups. However, significant decreases were observed in muscle weight, anthropometric measurements, sutural bone mineral density and bone apposition distance in the BTX-injected group. CONCLUSIONS: Reduced masticatory muscle function in growing rats can affect maxillofacial suture bone growth.
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Toxinas Botulínicas Tipo A , Animais , Desenvolvimento Ósseo , Injeções Intramusculares , Masculino , Músculo Masseter , Músculos da Mastigação , Ratos , Ratos WistarRESUMO
Berberine and the methylenedioxy ring-opening derivatives palmatine and jatrorrhizine are active ingredients in immunomodulatory plants, such as goldenseal. This study aimed to illustrate the effects of protoberberines on aryl hydrocarbon receptor (AhR) activation and cytochrome P450 (CYP) 1 in the estrogen receptor (ER)α(+) MCF-7 breast cancer cells. Among protoberberines at non-cytotoxic concentrations (≤10 µM), berberine had the most potent and statistically significant effects on AhR activation and CYP1A1/1A2/1B1 mRNA induction. The 24-h exposure to 10 µM berberine did not change CYP1A1 mRNA stability, protein level and function. Berberine significantly increased micro RNA (miR)-21-3p by 36% and the transfection of an inhibitor of miR-21-3p restored the induction of CYP1A1 protein with a 50% increase. These findings demonstrate that the ring opening of the methylenedioxyl moiety in berberine decreased AhR activation in MCF-7 cells. While CYP1A1 mRNA was elevated, berberine-induced miR-21-3p suppressed the increase of functional CYP1A1 protein expression.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Berberina/farmacologia , Neoplasias da Mama/metabolismo , Citocromo P-450 CYP1A1/genética , MicroRNAs/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Berberina/análogos & derivados , Berberina/química , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacologia , Neoplasias da Mama/genética , Citocromo P-450 CYP1A1/metabolismo , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Estrutura Molecular , Receptores de Hidrocarboneto Arílico/genéticaRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis. Despite intensive research, markers for the early diagnosis, prognosis, and targeting therapy of PDAC are not available. This study aimed to investigate the protein expressions of Jagged1 and DLL4 in PDAC tumor, benign pancreatic and normal pancreatic tissues, and analyze the associations of the two proteins with the clinical and pathological characteristics of PDAC. METHODS: A total of 106 PDAC tumor tissues and 35 peritumoral tissues were collected from January 2000 to December 2011 at our hospitals. Thirteen normal pancreatic tissues and 55 benign pancreatic specimens were collected at the same period. Immunohistochemical staining was used to measure Jagged1 and DLL4 protein expressions in these tissues. RESULTS: The percentage of positive Jagged1 and DLL4 was significantly higher in PDAC than in normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P<0.01). The higher Jagged1 and DLL4 expressions in PDAC were significantly associated with poor differentiation, maximum tumor size >5 cm, invasion, regional lymph node metastasis, and TNM III/IV disease (P<0.05). In PDAC, Jagged1 expression positively correlated with DLL4 expression. Univariate Kaplan-Meier analysis showed that positive Jagged1 and DLL4 expressions were significantly associated with shorter survival in patients with PDAC. Multivariate Cox regression analysis showed that positive Jagged1 and DLL4 expressions were independent prognostic factors for poor prognosis of patients with PDAC. CONCLUSION: Positive Jagged1 and DLL4 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in patients with PDAC.
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Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/química , Peptídeos e Proteínas de Sinalização Intercelular/análise , Proteína Jagged-1/análise , Neoplasias Pancreáticas/química , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Proteínas de Ligação ao Cálcio , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
BACKGROUND: Changes in head and neck anatomy during radiation therapy (RT) produce setup uncertainties of nasopharyngeal cancer (NPC) irradiation. We retrospectively analyzed image guidance data to identify clinical predictors of setup errors. PATIENTS AND METHODS: The data of 217 NPC patients undergoing definitive RT on a helical tomotherapy (HT) unit were analyzed. Factors including tumor stage, body mass index, weight loss, and planning target volume (PTV) were assessed as predictors of daily megavoltage computed tomography (MVCT) setup displacements, which were automatically registered using software. RESULTS: Mean daily setup displacements (in mm) were 1.2 ± 0.6, 1.8 ± 0.8, 3.4 ± 1.4 in the medial-lateral (ML), superior-inferior (SI), and anterior-posterior (AP) directions, respectively. Mean weight loss was 4.6 ± 3.3 kg (6.8 ± 4.9%). Patients with weight loss > 5% had significantly larger setup displacements in the AP (3.6 ± 1.5 vs. 2.9 ± 1.1 mm, p < 0.001) and SI (1.6 ± 0.7 vs. 1.9 ± 0.9 mm, p = 0.01) direction, but not in the ML direction (p = 0.279). The AP setup error increased 0.06 mm (y = 0.055x + 2.927, x: percentage of weight loss/PTV, y: AP displacement) per one percent increase in weight loss normalized to PTV. CONCLUSIONS: Patients with weight loss > 5% and smaller PTVs, possibly because of small body frame or neck girth, were more likely to have increased setup errors in the AP direction.
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OBJECTIVE: To investigate the distribution and change of the causes of fever of unknown origin(FUO). METHODS: The clinical data of 500 inpatients with FUO in our center between December 2003 and June 2014 were retrospectively analyzed. The diagnostic methods,etiologies,and their possible relationship with age,sex,fever duration,and period. RESULTS: Of these 500 FUO patients,452(90.4%)were confirmed to be with fever caused by conditions including infectious diseases [(n=231,46.2%;e.g.tuberculosis(32.9%,76/231)],connective tissue diseases(CTD)(n=99,19.8%),neoplasms(n=58,11.6%),miscellaneous causes(n=64,12.8%). The causes were not identified in 48 cases(9.6%).The proportion of CTD in female patients was significantly higher than that in male patients(26.3% vs. 14.5%,P=0.025),whereas the proportion of neoplasms in male patients was significantly higher than that in female patients(14.5% vs. 8.0%,P=0.001). Infectious diseases was the most common cause in all age groups,CTD ranked the second in the 21-39-year group and 40-59-year group,and neoplasm was the second most coomon cause in the over 60 year group. Thus,the distribution of FUO etiologies significantly differed in different age groups(χ(2)=43.10,P=0.000). The duration of fever in patients with neoplasms [60(28,90)d] was longer than that in patients with infectious diseases [28(21,42)d,Z=-4.168,P=0.000] or CTD [30(21,60)d,Z=-2.406,P=0.016)]. Compared with the level in 2003-2008,the proportion of CTD significantly increased in 2009-2014(13.7% vs. 23.8%,χ(2)=8.598,P=0.003),along with the dicrease of the proportions of infectious diseases,neoplasms and miscellaneous diseases were decreased(all P>0.05). CONCLUSIONS: Infectious diseases(in particular,tuberculosis)remains the major cause of FUO. CTD and neoplasms also play important roles in the development of FUO. The distributions of the FUO etiologies have certain differences in terms of age,sex,duration of fever,and period.
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Febre de Causa Desconhecida , Doenças do Tecido Conjuntivo , Feminino , Humanos , Masculino , Neoplasias , Estudos Retrospectivos , TuberculoseRESUMO
A dogma for DNA polymerase catalysis is that the enzyme binds DNA first, followed by MgdNTP. This mechanism contributes to the selection of correct dNTP by Watson-Crick base pairing, but it cannot explain how low-fidelity DNA polymerases overcome Watson-Crick base pairing to catalyze non-Watson-Crick dNTP incorporation. DNA polymerase X from the deadly African swine fever virus (Pol X) is a half-sized repair polymerase that catalyzes efficient dG:dGTP incorporation in addition to correct repair. Here we report the use of solution structures of Pol X in the free, binary (Pol X:MgdGTP), and ternary (Pol X:DNA:MgdGTP with dG:dGTP non-Watson-Crick pairing) forms, along with functional analyses, to show that Pol X uses multiple unprecedented strategies to achieve the mutagenic dG:dGTP incorporation. Unlike high fidelity polymerases, Pol X can prebind purine MgdNTP tightly and undergo a specific conformational change in the absence of DNA. The prebound MgdGTP assumes an unusual syn conformation stabilized by partial ring stacking with His115. Upon binding of a gapped DNA, also with a unique mechanism involving primarily helix αE, the prebound syn-dGTP forms a Hoogsteen base pair with the template anti-dG. Interestingly, while Pol X prebinds MgdCTP weakly, the correct dG:dCTP ternary complex is readily formed in the presence of DNA. H115A mutation disrupted MgdGTP binding and dG:dGTP ternary complex formation but not dG:dCTP ternary complex formation. The results demonstrate the first solution structural view of DNA polymerase catalysis, a unique DNA binding mode, and a novel mechanism for non-Watson-Crick incorporation by a low-fidelity DNA polymerase.
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Vírus da Febre Suína Africana/enzimologia , DNA Polimerase Dirigida por DNA/química , DNA Polimerase Dirigida por DNA/metabolismo , DNA/metabolismo , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/química , Vírus da Febre Suína Africana/metabolismo , Animais , Pareamento de Bases , DNA/química , DNA Polimerase beta/química , DNA Polimerase beta/metabolismo , Nucleotídeos de Desoxicitosina/metabolismo , Nucleotídeos de Desoxiguanina/metabolismo , Guanosina Trifosfato/metabolismo , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Suínos/virologiaRESUMO
BACKGROUND: Neurologic status is one of the major prognostic factors in glioblastoma patients; however, no consensus exists on a clinical index for predicting patient outcomes. The purpose of this study was to evaluate the correlation between neurologic deficits and clinical outcomes in glioblastoma patients, and to develop a prognostic neurologic index for identifying patients with poor outcomes. METHODS: Patients receiving tumor resection with pathologically confirmed glioblastoma were retrospectively evaluated. The patients' preoperative neurologic deficits were categorized, and patients with poor overall survival (OS) were identified. Other common prognostic factors, including age, performance, imaging findings, and extent of resection, were analyzed. RESULTS: We evaluated 162 glioblastoma patients receiving tumor resection between February 2000 and December 2011, of whom 54 received adjuvant radiotherapy (RT) alone and 84 received concurrent chemo-RT with temozolomide. At a median follow-up of 57.6 (range 26.3-88.9) months, 26 patients had survived without loss to follow-up. We defined adverse neurologic status by using an index of combined increased intracranial pressure (IICP) and non-IICP signs. In univariate analysis, the median OS of patients with and without adverse neurologic status were 9.6 and 18.7 months, respectively (p < 0.001). In multivariate analyses, adverse neurologic status remained significantly associated with poor OS (hazard ratio 2.18, 95 % confidence interval 1.54-3.10). CONCLUSIONS: Our proposed neurologic index enables significantly identifying glioblastoma patients receiving tumor resection with poor outcomes, independent of other common prognostic factors. Using the index provides a preoperative predictor of prognosis in glioblastoma patients receiving tumor resection.
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Neoplasias Encefálicas/patologia , Glioblastoma/patologia , Doenças do Sistema Nervoso/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/etiologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Feminino , Seguimentos , Glioblastoma/etiologia , Glioblastoma/mortalidade , Glioblastoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Doenças do Sistema Nervoso/fisiopatologia , Cuidados Pré-Operatórios , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemAssuntos
Mielofibrose Primária/radioterapia , Esplenomegalia/radioterapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/diagnóstico por imagem , Baço/diagnóstico por imagem , Esplenomegalia/diagnóstico por imagemRESUMO
OBJECTIVE: To compare tumor characteristics and clinical outcome of patients with cervical locally advanced adenocarcinoma (AC)/adenosquamous carcinoma (ASC) and squamous cell carcinoma (SCC). DESIGN: Retrospective study. SETTING: National Taiwan University Hospital, Taipei, Taiwan. POPULATION: All patients with cervical SCC (n = 35), AC or ASC (n = 194) with FIGO stage ≥IIB who received definitive radiotherapy or concurrent chemoradiotherapy (CCRT) from January 1995 to December 2009. METHOD: Medical and histopathological record review. MAIN OUTCOME MEASURES: Progression-free survival (PFS), local recurrence-free survival, distant metastasis-free survival, and overall survival (OS). RESULTS: Compared with the SCC subgroup, patients with AC/ASC were significantly younger (p = 0.007), more of them without clinical symptoms were diagnosed by abnormal Pap smear findings (p = 0.043), and less responded to treatment (p = 0.018). After a median follow-up of 59.3 months, patients with AC/ASC had worse 5-year PFS (30.0% vs. 47.6%, p = 0.044), worse 5-year distant metastasis-free survival (41.5% vs. 69.9%, p = 0.005), and trends toward worse 5-year local recurrence-free survival (64.4% vs. 76.2%, p = 0.165) and worse 5-year OS (41.3% vs. 58.1%, p = 0.090) than patients with SCC. In univariate analysis, early FIGO stage and complete treatment response were significantly associated with PFS and OS. Histology of non-AC/ASC and Point A biologically equivalent doses in 2-Gy fractions >85 Gy were significantly associated with better PFS, and CCRT was significantly associated with better OS. In multivariate analysis, complete treatment response and early FIGO stage remained significant factors for predicting better PFS and OS. CONCLUSIONS: Cervical AC/ASC may be more aggressive than is SCC. For cervical AC/ASC, more comprehensively effective treatments are warranted.
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Adenocarcinoma/radioterapia , Antineoplásicos/uso terapêutico , Carcinoma Adenoescamoso/radioterapia , Carcinoma de Células Escamosas/radioterapia , Colo do Útero/patologia , Cisplatino/uso terapêutico , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Feminino , Seguimentos , Humanos , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Análise de Sobrevida , Falha de Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologiaRESUMO
To date, there has been little improvement in cryopreservation of bull sperm due to lack of understanding of the freezing mechanisms. Therefore, this study set out to investigate expression levels of fertility-associated proteins in bull sperm, and in particular the relationship between the 90 kDa heat-shock protein (HSP90) and the sperm characteristics after freezing-thawing. Semen was collected from eight Holstein bulls by artificial vagina. Characteristics of these fresh semen, including sperm motility, morphology, viability and concentration, were evaluated. Sperm quality was also assessed after freezing-thawing. Eight ejaculates were divided into two groups based on freezing resistance and sperm motility. Sperm proteins were extracted and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis and western blotting were performed. SDS-PAGE results showed that there was substantial diversity in 90 kDa proteins in the frozen-thawed sperm and HSP90 was confirmed as one of the 90 kDa proteins by western blot. This study indicated that HSP90 expression correlated positively with sperm quality. The amount of expressed 90 kDa proteins in the high freezing resistance (HFR) group was significantly higher than that in the low freezing resistance (LFR) group (P < 0.05). Thus, higher expression of HSP90 could probably lead to the higher motility and freezing resistance of sperm found after freezing-thawing. Therefore, we concluded that level of HSP90 expression could be used to predict reliably and simply the freezing resistance of bull sperm.
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Criopreservação/veterinária , Fertilidade/fisiologia , Proteínas de Choque Térmico HSP90/metabolismo , Preservação do Sêmen/veterinária , Motilidade dos Espermatozoides/fisiologia , Espermatozoides/fisiologia , Animais , Western Blotting , Bovinos , Células Cultivadas , Criopreservação/métodos , Eletroforese em Gel de Poliacrilamida , Congelamento , Proteínas de Choque Térmico HSP90/análise , Masculino , Preservação do Sêmen/métodos , Espermatozoides/citologiaRESUMO
Low-density lipoproteins (LDL) is known to protect boar sperm during freezing-thawing, but little information is known about the effects of LDL extracted from different avian egg yolks on post-thaw boar semen quality. The purpose of this study was to compare and analyze the effects of LDL at various concentrations and different species on boar sperm quality after freezing-thawing. LDL extracted from the yolk of hen egg, duck egg, quail egg, pigeon egg or ostrich egg was added to the extender at the concentrations of 0.06, 0.07, 0.08, 0.09 and 0.1 g/ml, respectively, and their effects on frozen-thawed boar sperm quality were assessed. According to all measured parameters, the results showed that sperm motility, acrosome integrity and plasma membrane integrity were 43.20%, 52.57% and 48.13%, respectively, after being frozen-thawed with 0.09 g/ml LDL extracted from pigeon egg yolk. All these quality parameters were higher than that of other groups (P < 0.05). In conclusion, our results confirmed that LDL extracted from pigeon egg yolk had the best cryoprotective effects on frozen-thawed boar sperm among all of the groups supplemented with LDL from five kinds of avian egg in extender. The optimum concentration of LDL extracted from pigeon egg in boar semen freezing extender was 0.09 g/ml.
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Acrossomo/efeitos dos fármacos , Gema de Ovo/química , Lipoproteínas LDL/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/citologia , Espermatozoides/fisiologia , Animais , Células Cultivadas , Criopreservação , Congelamento , Masculino , SuínosRESUMO
A high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed for determining degradation dynamics and final residues of myclobutanil 25% WG in ginseng root, stem, leaf and soil. The samples were extracted with acetonitrile, cleaned-up with primary secondary amine (PSA) solid phase extraction cartridge, separated by Kromasil Eternity-5-C18 (2.1 mm x 150 mm, 5 microm) column with a gradient of acetonitrile and 0.1% formate in water as mobile phases, and analyzed with the multiple reaction monitoring (MRM) in positive ion mode by employing the external standard method. The average recoveries and the relative standard derivations (RSDs) of myclobutanil at the spiked level of 0.01-0.20 mg x kg(-1) were 80.9%-90.7% and 5.54%-9.29%, respectively, and the limit of quantification (LOQ) was 0.005 mg x kg(-1). The method with good reproducible, high precision and low detection limit could meet the requirements of residual analysis on ginseng production. The half-lives of myclobutanil were from 6.25 days to 9.94 days in ginseng root, stem, leaf and soil at spraying dosage of 1 152 g x hm(-2) The final residues were below 0.060 1 mg x kg(-1) in root, below 0.081 7 mg x kg(-1) in stem, 0.006 0-0.102 2 mg x kg(-1) in leaf and below 0.037 6 mg x kg(-1) in soil at spraying dosage range from 576 to 1 152 g x hm(-2). It is recommended that the MRLs of myclobutanil in dried ginseng may be suggested to be 0.10 mg x kg(-1) temporarily, and the preharvest interval was set at 35 days.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Fungicidas Industriais/química , Nitrilas/química , Panax/química , Poluentes do Solo/química , Espectrometria de Massas em Tandem/métodos , Triazóis/química , Contaminação de Medicamentos , Folhas de Planta/química , Raízes de Plantas/química , Caules de Planta/química , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
BACKGROUND: Physical activity (PA) and functional fitness (FF) are crucial for promoting independent living and healthy aging in older adults. However, there is a lack of normative values for the Senior Fitness Test (SFT) among older adults (aged 55-90) living in southern rural Taiwan, particularly in the Chiayi region, which has been relatively underserved in terms of health-related resources compared to northern Taiwan. PURPOSE: This study aimed to determine the age- and gender-specific normative fitness scores for a large representative population of community-dwelling older adults in southern rural Taiwan. METHODS: A cross-sectional descriptive study was conducted to obtain normative FF scores for 3332 community-dwelling elderly people (1057 men and 2275 women) in Chiayi, through the implementation of functional fitness tests across 72 Chiayi communities. The developed normative data served as a reference for exercise prescription for the elderly in southern Taiwan. RESULTS: The study showed that the average normative values of all functional fitness tests declined significantly with increasing age (p < 0.05). Sex differences were also found in all measures of FF tests, with elderly women scoring significantly better than men on flexibility (scratch back: -1.34 ± 9.03 vs. -6.54 ± 11.07; chair sit and reach: 6.56 ± 9.44 vs. 0.56 ± 10.40) (p < 0.05), while men scored significantly higher than women on strength (grip strength: 30.83 ± 8.06 vs. 21.82 ± 5.32; bicep curl: 19.25 ± 5.44 vs. 17.64 ± 4.98) (p < 0.05). Furthermore, four FF normative scores in southern rural Taiwan were found to be significantly higher than their counterparts living in northern Taiwan. CONCLUSION: These findings contribute positively to the evaluation of fitness levels among older adults in southern rural Taiwan and provide a concrete reference for developing sound PA programs for this population. The results suggest that strategies aimed at promoting increased participation in PA among older adults need to consider age-, sex-, and region-specific factors.
RESUMO
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) of the head-and-neck area primarily involves the Waldeyer ring (WR) and sinonasal area (SN). However, the differential clinical outcomes between patients with WR-DLBCL and those with SN-DLBCL in the rituximab era remain unclear. METHODS: To avoid confounding factors contributed by advanced DLBCL with WR and SN involvement, we assessed the clinical outcomes of patients with stage I/II WR-DLBCL and SN-DLBCL and compared them with those having corresponding stages of DLBCL in the lymph nodes but without other extranodal involvement (LN-DLBCL) in the same period. We compared the patients' clinical characteristics, treatment modalities, event-free survival (EFS), and overall survival (OS) among the three subgroups. RESULTS: We analyzed 67, 15, and 106 patients with WR-DLBCL, SN-DLBCL, and LN-DLBCL, respectively, between January 2000 and December 2019. All patients received front-line rituximab-based regimens, and > 80% received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone-based regimens. More patients with SN-DLBCL had revised International Prognostic Index (R-IPI) score 3 (27%) when compared with those with WR-DLBCL (7%) and those with LN-DLBCL (10%, p = 0.181). Patients with WR-DLBCL, LN-DLBCL, and SN-DLBCL had 5-year EFS and OS rates of 80.7%, 59.5%, and 41.9% (p = 0.021) and 83.7%, 70.8%, and 55.8% (p = 0.032), respectively. Compared to patients with LN-DLBCL, those with WR-DLBCL also had a significantly favorable 5-year EFS rate (p = 0.021) and 5-year OS rate (p = 0.023). Three of the 15 patients with SN-DLBCL experienced lymphoma recurrence in the brain after front-line treatment. In multivariate analyses, R-IPI scores of 1-2 and 3 served as significantly poor prognostic factors for patients with poor EFS and OS. CONCLUSIONS: Compared to patients with LN-DLBCL, patients with WR-DLBCL receiving front-line rituximab-based treatments had favorable clinical outcomes; however, patients with SN-DLBCL had worse clinical outcomes. Further studies on molecular prognostic factors and treatment strategies for SN-DLBCL are warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Rituximab , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Rituximab/uso terapêutico , Feminino , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Vincristina/uso terapêutico , Idoso de 80 Anos ou mais , Doxorrubicina/uso terapêutico , Estudos Retrospectivos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Estadiamento de Neoplasias , Resultado do Tratamento , Adulto Jovem , Prognóstico , Neoplasias dos Seios Paranasais/tratamento farmacológico , Neoplasias dos Seios Paranasais/mortalidade , Neoplasias dos Seios Paranasais/patologiaRESUMO
INTRODUCTION: This study aims to investigate the spectrum of magnetic resonance imaging (MRI) features following endoscopic potassium-titanyl-phosphate (KTP) laser nasopharyngectomy. METHODS: From January 2005 to December 2010, a total of 35 patients underwent KTP laser nasopharyngectomy for early recurrent NPC (rT1 or rT2) at our institute. Those who were lost to follow-up (N = 2) were excluded. Among the remaining patients, ten were proved to have locally recurrent disease and the other 23 not locally recurrent within 2 years of postoperative follow-up. Their serial MRIs were evaluated. RESULTS: Postoperative nasopharyngeal mucosal changes were present in all of the subjects on first follow-up MRI, ranged from focal mucosal thinning (19/33, 57.6 %), focal mucosal thickening (8/33, 24.2 %) to mixed thinning and thickening (6/33, 18.2 %). Nasopharyngeal submucosal soft tissue volume loss was found in 23 (23/33, 69.7 %), and parapharyngeal soft tissue necrosis was found in 3 (3/33, 9.1 %). Postoperative bone marrow change involved the clivus in 31 (31/33, 93.9 %) and the petrous or pterygoid in 17 (17/33, 51.5 %). There were no significant differences between the two groups in the changes of mucosa, adjacent soft tissue, and skull base on the first MRI. The evaluation of serial MRIs disclosed that the patients in the recurrent group were more likely to develop new or enlarging mucosal masses (p = 0.01) and enlarging skull base changes (p = 0.0001). CONCLUSIONS: KTP laser nasopharyngectomy induces mucosal and skull base changes that could be misinterpreted as tumor progression on early postoperative MRI scans. Sequential imaging is required to distinguish between postoperative changes and progressive disease.