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1.
Exp Cell Res ; 435(2): 113937, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38242344

RESUMO

Lung carcinoma (LC) is a complicated and highly heterogeneous disease with high morbidity and mortality. Both lysyl oxidase-like (LOXL) 2 and 3 act in cancer progression. This work endeavors to illustrate the influence of LOXL2/LOXL3 on LC progression and the underlying mechanisms. LOXL family genes and CCAAT enhancer binding protein A (CEBPA) were analyzed in the TCGA database for their expression patterns in LC patients and their correlations with the patient's prognosis. CEBPA, LOXL2, and LOXL3 expression levels were determined in LC cells. Gain- and loss-of-function assays were conducted, followed by assays for cell proliferation, epithelial-mesenchymal transition (EMT), apoptosis, invasion, and migration. The binding of CEBPA or B cell lymphoma protein (BCL)-2 to LOXL2/LOXL3 was verified. The ubiquitination level of BCL-2 and histone acetylation level of LOXL2/LOXL3 in LC cells were analyzed. Database analyses revealed that LC patients had high CEBPA, LOXL2, and LOXL3 expression, which were related to poor prognosis. LC cells also exhibited high CEBPA, LOXL2, and LOXL3 levels. LOXL2/LOXL3 knockdown subdued EMT, proliferation, migration, and invasion while enhancing the apoptosis of LC cells. LOXL2/LOXL3 could bind to CEBPA and BCL-2. LOXL2/LOXL3 knockdown upregulated BCL-2 ubiquitination level and diminished BCL-2 expression in LC cells. CEBPA recruited Tip60 to enhance histone acetylation and transcription of LOXL2/LOXL3 in LC cells. BCL-2 overexpression abolished the impacts of LOXL2/LOXL3 knockdown on LC cells. In conclusion, CEBPA boosts LOXL2 and LOXL3 transcription to facilitate BCL-2 stability by recruiting Tip60 and thus contributes to LC cell growth and metastasis.


Assuntos
Carcinoma , Neoplasias Pulmonares , Humanos , Histonas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pulmão/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Aminoácido Oxirredutases/genética , Proteínas Estimuladoras de Ligação a CCAAT
2.
Technol Cancer Res Treat ; 22: 15330338231185013, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37357685

RESUMO

OBJECTIVE: To evaluate the clinical outcomes of volumetric modulated arc therapy (VMAT) followed by brachytherapy (BT), combined with chemotherapy, and local hyperthermia (HT) on locally advanced cervical cancer (LACC). METHODS: In total, 40 patients with FIGO stage IB1-IVB cervical cancer from January 2016 to December 2018 were selectively enrolled in this study. All patients were treated with VMAT (50.4 Gy/1.8 Gy/28 f) concurrent with cisplatin-based chemotherapy (40 mg/m2, q1w, 6 cycles) and local HT (40.5-41°C for 60 min, BIW). BT (30-36 y/5-6 f, 2 f/w) was conducted after VMAT. Objective response rate (ORR), local control (LC) time, LC rate, progression-free survival (PFS) rate, cancer-specific survival (CSS) rate, overall survival (OS), median time to tumor progression and treatment-related toxicity were evaluated. RESULTS: The median follow-up time was 31 months (8-48). The ORR was 100% at 3 months after treatment and 92.1% at 6 months, respectively. The 1-year, 2-year, and 3-year LC rates were 87.4%, 81.9%, and 70.9%, respectively. The average LC time was 31.50 ± 1.89 months (95% CI 27.79-35.21). The 1-year, 2-year, and 3-year PFS rates were 75.85%, 61.2%, and 51.3%, respectively, while the median PFS was 27.07 months. The 1-year, 2-year, and 3-year OS rates were 95%, 84%, and 79.6%, respectively. In total, 12(30%) patients had grade 3/4 bone marrow suppression. One patient had grade 4 leukopenia. In total, 17 patients had grade 1/2 bone marrow suppression. Two patients had grade 3 nausea and grade 3 vomiting reaction, respectively. No grade 3/4 proctitis and bladder reaction were observed. In the late period of treatment, 1 patient had a rectal hemorrhage. In total, 13 patients had vaginal stenosis. CONCLUSION: VMAT concurrent with chemotherapy, BT, and local HT had a favorable short-term efficacy and acceptable toxicity on cervical cancer, which was an alternative option for LACC.


Assuntos
Braquiterapia , Hipertermia Induzida , Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Humanos , Feminino , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Braquiterapia/efeitos adversos , Constrição Patológica/tratamento farmacológico , Constrição Patológica/etiologia , Quimiorradioterapia/efeitos adversos , Vagina , Cisplatino , Resultado do Tratamento
3.
Int J Radiat Oncol Biol Phys ; 115(5): 1197-1204, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36402358

RESUMO

PURPOSE: Nanoparticle albumin-bound (nab) paclitaxel has improved uptake by tumor cells in comparison to paclitaxel. The aim of this study was to determine the maximal tolerated dose (MTD) and the dose-limiting toxicity (DLT) of nab-paclitaxel plus cisplatin with concurrent image guidance volume modulated arc therapy for locally advanced cervical cancer (LACC). METHODS AND MATERIALS: This single-arm phase 1 trial followed the standard 3 + 3 dose escalation design. Patients with histologically proven stage IB2-IVA LACC were eligible. Image guidance volume modulated arc therapy included 50.4 Gy in 28 fractions to the pelvis and 59.4 Gy simultaneous boost in 28 fractions to involved pelvic and para-aortic lymph nodes, and subsequent high-dose-rate intracavitary brachytherapy at a total dose of 30.0 Gy in 5 fractions, twice a week. Concurrent chemotherapy regimen included weekly cisplatin (40 mg/m2) and weekly nab-paclitaxel at escalating doses (10, 20, 33, 50, and 70 mg/m2 per week). Duration of the planned treatment was 8 weeks. Grade 4 hematologic toxicity and grade 3 or above nonhematologic toxicity were considered as DLT. MTD was defined as the highest dose with ≤33% DLT. RESULTS: A total of 22 patients were enrolled from September 2019 to August 2021. The most common adverse events were grade 1 to 3 leukopenia, diarrhea, and nausea/vomiting. A total of 4 patients (18.0%) experienced DLT: grade 3 hypokalemia at 33 mg/m2 (1 of 6 subjects), grade 3 deep vein thrombosis at 50 mg/m2 (1 of 6) and 70 mg/m2 (1 of 4), and grade 3 perineum edema at 70 mg/m2 (1 of 3). The estimated MTD was 50 mg/m2. Complete response was observed in 20 patients (90.9%). CONCLUSIONS: In patients undergoing concurrent IG-VAMT with nab-paclitaxel plus cisplatin for LACC, MTD of nab-paclitaxel was 50 mg/m2. Complete response rate was 90.9%.


Assuntos
Cisplatino , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Paclitaxel , Albuminas/efeitos adversos
4.
J Appl Clin Med Phys ; 23(5): e13578, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35293667

RESUMO

PURPOSE: We compared the setup errors determined by an optical imaging system (OSIS) in women who received breast-conserving surgery (BCS) followed by whole-breast radiotherapy (WBRT) with those from cone-beam computed tomography (CBCT) carried out routinely. METHODS: We compared 130 setup errors in 10 patients undergoing WBRT following BCS by analyzing the translational and rotational couch shifts via CBCT and OSIS. Patients were treated with intensity-modulated radiotherapy (IMRT). The patient outline extracted from the planning reference Computed tomography (CT) was used as the reference for OSIS and CBCT alignment during treatment. We detected the setup uncertainty using CBCT and OSIS at the first five fractionations of RT and then twice a week. RESULTS: The absolute translational setup error (mean ± Standard deviation (SD)) in x (lateral), y (longitudinal), and z (vertical) axes detected by the OSIS was 0.14 ± 0.18, 0.15 ± 0.14, and 0.13 ± 0.13 cm, respectively. The rotational setup error (mean ± SD) in Rx (pitch), Ry (roll), and Rz (yaw) axes was 0.77 ± 0.54, 0.76 ± 0.61, and 1.23 ± 0.95, respectively. Significant difference is observed only in one direction (Rx, p = 0.03) in the paired setup errors obtaining from OSIS and CBCT, without significant differences in five directions. CONCLUSION: OSIS is a repeatable and reliable system that can be used to detect misalignments with accuracy, which is capable of supplementing CBCT for WBRT after BCS. We believe that an OSIS may be easier to use, quicker, and reduce overall dose as this method of patient alignment does not require ionizing radiation.


Assuntos
Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Tomografia Computadorizada de Feixe Cônico/métodos , Feminino , Humanos , Lasers , Mastectomia Segmentar , Planejamento da Radioterapia Assistida por Computador/métodos , Erros de Configuração em Radioterapia/prevenção & controle , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos
5.
Curr Oncol ; 28(6): 4577-4586, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34898560

RESUMO

Cervical cancer is the fourth most common cancer in females worldwide. Patients with stage III and IV cervical cancer based on the Federation of Gynecology and Obstetrics (FIGO) classification have higher recurrence rates. Because of organs at risk (OAR) protection and the low indication rate of salvage surgery, the choice of treatment is always challenging. Systemic chemotherapy is palliative and can be performed in conjunction with surgery or radiotherapy; however, it has no significant benefit to survival. Brachytherapy and stereotactic body radiotherapy (SBRT) are characterized by extremely high radiation doses applied to tumor cells while sparing the normal tissues. Several studies have investigated the efficacy of these technologies in recurrent cervical cancer and showed promising results. The immune checkpoint inhibitors approach was also investigated and showed promising results too. Herein, we report a case of a patient with cervical cancer that recurred five months after adjuvant chemotherapy and concurrent chemoradiotherapy. The disease prognosis after interstitial implantation brachytherapy (IIB) was determined. Then, the patient underwent radioactive 125I-seed implantation combined with PD-1 inhibitor treatment. The patient exhibited a partial response after seed implantation, and up to now, the duration of this partial response was 24 months.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Radioisótopos do Iodo/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia
6.
Thorac Cancer ; 12(23): 3157-3168, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34651449

RESUMO

BACKGROUND: For lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) sensitive mutation and synchronous brain metastasis (syn-BM), when and how to apply radiotherapy (RT) during first-line tyrosine kinase inhibitor (TKI) treatment remains debatable. METHODS: From a real-world multicenter database, EGFR-mutant patients with syn-BM diagnosed between 2010-2020 and treated with first-line TKIs were enrolled and divided into upfront TKI + RT and upfront TKI groups. Median intracranial progression-free survival (mIC-PFS), median overall survival (mOS), and their risk factors were estimated. RESULTS: There were 60 and 186 patients in the upfront TKI + RT group and upfront TKI group, respectively. Their mIC-PFS were 28.9 months (m) and 17.5 m (p = 0.023), and mOS were 42.7 m and 40.1 m (p = 0.51). Upfront brain RT improved mIC-PFS in patients ≤60-year-old (p = 0.035), with symptomatic BM (p = 0.002), and treated with first-generation TKIs (p = 0.012). There was no significant difference in mOS in any subgroup. Upfront brain stereotactic radiosurgery (SRS) showed a trend of better mIC-PFS and mOS. mIC-PFS was independently correlated with symptomatic BM (HR = 1.54, p = 0.030), EGFR L858R mutation (HR = 1.57, p = 0.019), and upfront brain RT (HR = 0.47, p = 0.001). mOS was independently correlated with being female (HR = 0.54, p = 0.007), ECOG 3-4 (HR = 10.47, p < 0.001), BM number>3 (HR = 2.19, p = 0.002), and third-generation TKI (HR = 0.54, p = 0.044) or antiangiogenic drugs (HR = 0.11, p = 0.005) as first/second-line therapy. CONCLUSIONS: Upfront brain RT based on first-line EGFR-TKI might improve IC-PFS but not OS in EGFR-mutant lung adenocarcinoma patients, indicating potential survival benefit from brain SRS and early application of drugs with higher intracranial activity.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Neoplasias Encefálicas/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma de Pulmão/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos Retrospectivos
7.
J Contemp Brachytherapy ; 13(3): 273-279, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34122566

RESUMO

PURPOSE: To investigate the accuracy and dosimetry of 3D-printing non-coplanar template (3D-PNCT)-assisted computed tomography (CT)-guided iodine-125 seed implantation (125I-SI) for recurrent chest wall cancer (rCWC). MATERIAL AND METHODS: This was a retrospective study of 19 patients with 22 rCWC treated with 3D-PNCT-assisted CT-guided 125I-SI, from Mar 2017 to Mar 2020 in our institute. RESULTS: Mean needle entrance deviation was 4.50 ±2.70 mm, mean angular deviation was 3.40 ±3.10 degrees, and mean depth deviation was 5.20 ±5.20 mm. No significant difference was found for dosimetric parameters (except conformity index) between pre-plan and post-plan; D90, D100, V100, V150, and V200 were 157.74 ±24.23 and 151.71 ±33.62 (p = 0.228), 85.36 ±34.09 and 70.46 ±23.48 (p = 0.067), 0.93 ±0.04 and 0.90 ±0.07 (p = 0.068), 0.64 ±0.16 and 0.64 ±0.16 (p = 0.984), and 0.35 ±0.17 and 0.37 ±0.18 (p = 0.382) for pre-plan and post-plan, respectively. Conformity index, external index, and homogeneity index were 0.57 ±0.16 and 0.52 ±0.15 (p = 0.007), 0.73 ±0.55 and 0.79 ±0.53 (p = 0.096), and 0.31 ±0.15 and 0.30 ±0.14 (p = 0.504) for pre-plan and post-plan, respectively. Median follow-up time was 8 months (range, 3-30 months). Complete response was observed in 4/22 (18.1%), partial response in 13/22 (59.1%), stable disease in 4/22 (18.1%), and progression disease in 1/22 (4.5%) of the cancers. Among patients with pain before 125I-SI, pain relief rate was 87.5% (7/8). No peri-operative complications of more than grade 2 were observed. CONCLUSIONS: 3D-PNCT-assisted CT-guided 125I-SI may be safe and feasible as palliative therapy for non-surgical candidates and painful patients with rCWC.

8.
World J Surg Oncol ; 18(1): 307, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239023

RESUMO

PURPOSE: To investigate the accuracy, dosimetric parameters, and safety of 3D-printing non-coplanar template (3D-PNCT)-assisted CT guidance for radioactive iodine-125 (125I) seed implantation brachytherapy (RSI-BT) for retroperitoneal recurrent carcinomas METHODS AND MATERIALS: We enrolled 15 patients with 17 retroperitoneal recurrent carcinomas after external beam radiotherapy (EBRT). All patients received CT-guided 125I RSI-BT assisted by 3D-PNCT successfully. We compared the original needle insertion position, angular, and the needle tip distance deviations of preoperative plan with that of intraoperative in brachytherapy treatment planning system (B-TPS). The dosimetric parameters of RSI-BT were evaluated on preoperative plan, intraoperative real-time plan, and postoperative plan, including D90, D100 (the dose to 90% and 100% of the target volume), V100, V150, and V200 (the volume receives 100%, 150%, and 200% of the prescribed doses). The quality assurance of RSI-BT evaluated on conformal index (CI), external index (EI), and homogeneity index (HI) of the targets were compared among preoperative plan, intraoperative real-time plan, and postoperative plan. The perioperation complications and RSI-BT-related toxicity were assessed. RESULTS: The median follow-up was 8.2 months (range 1-18.5 months). One patient was lost to follow-up after RSI-BT. Fourteen patients were assessed for response rate and toxicity. The mean entrance point distance deviation for all 165 needles was 4.50 ± 4.10 mm (range, 0-30). The mean angular deviation was 2.70 ± 3.00° (range, 0-20). The needle tip distance deviation was 6.90 ± 6.00 mm (range, - 30-28). D90 for preoperative plan, intraoperative plan, and postoperative plan were 140.55 ± 23.93, 124.25 ± 28.04, and 128.98 ± 22.75, respectively. There was significant difference between D90 of preoperative plan with that of intraoperative plan (p = 0.036). Four lesions reached CR, six lesions reached PR, three lesions were SD, and three lesions were PD. Four patients with moderate pain became mild, and two with mild pain relieved completely after RSI-BT. The other parameters showed no differences among preoperative plan, intraoperative plan, and postoperative plan. The perioperative complications were observed in four patients, including three patients of grade 1 and one patient of grade 2. No ≥ grade 3 side effects were observed. CONCLUSION: CT-guided 125I RSI-BT assisted by 3D-PNCT was a safe, accurate, and feasible strategy for recurrent carcinomas located in the retroperitoneal regions.


Assuntos
Braquiterapia , Carcinoma , Neoplasias da Glândula Tireoide , Braquiterapia/efeitos adversos , Humanos , Radioisótopos do Iodo/uso terapêutico , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios X
9.
Cancer Biol Ther ; 21(7): 623-628, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32298199

RESUMO

OBJECTIVE: Retrospective analysis of the long-term clinical outcome and acute toxicity of the primary malignant tumor of cervical spine receiving CBCT image-guided VMAT. METHODS: Thirty patients with primary malignant tumor of the cervical spine included in our center, from December 2013 to January 2016, 28 patients were retrospectively studied. The prescription dosage 95% PTV volume dose was 44 Gy, 2.0 Gy/fraction, and a total of 22 times. The median PGTV synchronized volume dose was 60 Gy (45-62.1 Gy), median 2.5 Gy (2-2.7 Gy)/fraction. In volumetric modulated, two arc volumetric modulated arc therapy (VMAT) was used, with spinal cord dosage DMAX< 45 Gy. Early response rate and acute toxicities were analyzed. RESULT: The follow-up duration was 6-76 months (median 53 months). At the end of follow-up of June 1, 2019, 78.6% (22/28) patients were still alive. 3 and 5-y local control rates were 67.3% and 56.5% while 3 and 5-y OS were both 78.6% in the whole group of patients, respectively. Fourteen patients with chordoma 5-y local control rates and OS were 57.1% and 85.7%, respectively. Nine patients with giant-cell tumor of bone had a 5-y local control rate and OS were 77.8% and 85.7%, respectively. The response rate for moderate pain or above was 80% (8/10). Eleven patients (39.3%) suffered from grade 1 acute skin toxicity. Twenty-four patients (85.7%) had grade 1/2 mucositis. No radiation-induced spinal cord injury was found. CONCLUSION: The image-guided VMAT for primary malignant tumor of the cervical spine provided a satisfactory long-term local control rate.


Assuntos
Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias do Colo do Útero/radioterapia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
J Gynecol Oncol ; 30(1): e9, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30479093

RESUMO

OBJECTIVE: To investigate the efficacy of image-guided radioactive ¹²5I seed (IGRIS) implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy (EBRT), and analyze the influence of clinical and dosimetric factors on efficacy. METHODS: From July 2005 to October 2015, 36 patients with PRCC received IGRIS. We evaluated local progression-free survival (LPFS) and overall survival (OS). RESULTS: The median follow up was 11.5 months. The 1- and 2-year LPFS rate was 34.9% and 20%, respectively. The multivariate analysis indicated recurrence site (central or pelvic wall) (hazard ratio [HR]=0.294; 95% confidence interval [CI]=0.121-0.718), lesion volume (HR=2.898; 95% CI=1.139-7.372), D90 (HR=0.332; 95% CI=0.130-0.850) were the independent factors affecting LPFS. The 1- and 2-year OS rate was 52.0% and 19.6%, respectively. The multivariate analysis suggested pathological type (HR=9.713; 95% CI=2.136-44.176) and recurrence site (HR=0.358; 95% CI=0.136-0.940) were the independent factors affecting OS. The dosimetric parameters of 33 patients mainly included D90 (128.5±47.4 Gy), D100 (50.4±23.7 Gy) and V100 (86.7%±12.9%). When D90 ≥105 Gy or D100 ≥55 Gy or V100 ≥91%, LPFS was extended significantly, but no significant difference for OS. The 79.2% of 24 patients with local pain were suffering from pain downgraded after radioactive ¹²5I seed implantation. CONCLUSION: IGRIS implantation could be a safe and effective salvage treatment for PRCC after EBRT, which could markedly release the pain. Recurrence site, tumor volume and dose were the main factors affected efficacy. Compared with central recurrence, it was more suitable for patients with pelvic wall recurrent cervical cancer after EBRT.


Assuntos
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Carcinoma de Células Escamosas/radioterapia , Radioisótopos do Iodo/administração & dosagem , Recidiva Local de Neoplasia/radioterapia , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Relação Dose-Resposta à Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Radioterapia Guiada por Imagem/métodos , Estudos Retrospectivos , Terapia de Salvação/métodos , Neoplasias do Colo do Útero/mortalidade
11.
ScientificWorldJournal ; 2013: 129793, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23970827

RESUMO

The Fourth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR4) presents twenty-two global climate models (GCMs). In this paper, we evaluate the ability of 22 GCMs to reproduce temperature and precipitation over the Tibetan Plateau by comparing with ground observations for 1961~1900. The results suggest that all the GCMs underestimate surface air temperature and most models overestimate precipitation in most regions on the Tibetan Plateau. Only a few models (each 5 models for precipitation and temperature) appear roughly consistent with the observations in annual temperature and precipitation variations. Comparatively, GFCM21 and CGMR are able to better reproduce the observed annual temperature and precipitation variability over the Tibetan Plateau. Although the scenarios predicted by the GCMs vary greatly, all the models predict consistently increasing trends in temperature and precipitation in most regions in the Tibetan Plateau in the next 90 years. The results suggest that the temperature and precipitation will both increase in all three periods under different scenarios, with scenario A1 increasing the most and scenario A1B increasing the least.


Assuntos
Mudança Climática , Modelos Teóricos , Chuva , Temperatura , Tibet
12.
J Chromatogr A ; 1250: 2-26, 2012 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-22560346

RESUMO

For the proper design of supercritical fluid extraction processes, it is essential to have a sound knowledge of the mass transfer mechanism of the extraction process and the appropriate mathematical representation. In this paper, the advances and applications of kinetic models for describing supercritical fluid extraction from various solid matrices have been presented. The theoretical models overviewed here include the hot ball diffusion, broken and intact cell, shrinking core and some relatively simple models. Mathematical representations of these models have been in detail interpreted as well as their assumptions, parameter identifications and application examples. Extraction process of the analyte solute from the solid matrix by means of supercritical fluid includes the dissolution of the analyte from the solid, the analyte diffusion in the matrix and its transport to the bulk supercritical fluid. Mechanisms involved in a mass transfer model are discussed in terms of external mass transfer resistance, internal mass transfer resistance, solute-solid interactions and axial dispersion. The correlations of the external mass transfer coefficient and axial dispersion coefficient with certain dimensionless numbers are also discussed. Among these models, the broken and intact cell model seems to be the most relevant mathematical model as it is able to provide realistic description of the plant material structure for better understanding the mass-transfer kinetics and thus it has been widely employed for modeling supercritical fluid extraction of natural matters.


Assuntos
Cromatografia com Fluido Supercrítico , Modelos Teóricos , Difusão , Pressão
13.
PLoS One ; 6(8): e23422, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21850271

RESUMO

We have been studying calcineurin signal transduction pathway in fission yeast Schizosaccharomyces pombe (S. pombe) by developing a genetic screen for mutants that show hypersensitivity to the immunosuppressive calcineurin inhibitor FK506 (tacrolimus). In the present study, to identify nonessential genes that are functionally related to the calcineurin signaling pathway, we performed a genome-wide screen of 3004 haploid deletion strains and confirmed 72 deletion strains to be FK506 sensitive. These 72 genes are classified into nine functional groups to include membrane trafficking (16 genes), signal transduction (10 genes), ubiquitination (8 genes), chromatin remodeling (6 genes), cytokinesis (4 genes), ribosomal protein (3 genes), RNA binding protein (3 genes), and a variety of other known functions (17 genes) or still unknown functions (5 genes) in the biological system. In our previous screening of FK506-sensitive mutants we isolated several membrane-trafficking mutants showing defective cell wall integrity. Here, we further examined the vacuolar fusion, the v-SNARE synaptobrevin Syb1 localization, and the sensitivity to the ß-glucan synthase inhibitor micafungin in these 72 FK506-sensitive strains. Results showed that 25 deletion strains exhibited abnormal vacuole fusion, 19 deletion strains exhibited Syb1 mislocalization, and 14 deletion strains exhibited both abnormal vacuole fusion and Syb1 mislocalization, while 42 deletion strains showed both normal vacuole fusion and Syb1 localization. Likewise, 16 deletion strains showed sensitivity to micafungin. Altogether, our present study indicates that calcineurin mediates a plethora of physiological processes in fission yeast, and that calcineurin is extensively involved in cross-talk between signaling pathways.


Assuntos
Calcineurina/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/metabolismo , Tacrolimo/farmacologia , Inibidores de Calcineurina , Schizosaccharomyces/efeitos dos fármacos , Proteínas de Schizosaccharomyces pombe/antagonistas & inibidores
14.
Acta Oncol ; 49(2): 230-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20001497

RESUMO

BACKGROUND: The use of Intensity-modulated radiotherapy (IMRT) and Helical tomotherapy (HT) is increasing in gynecological cancer patients. No published studies have performed a dosimetric evaluation of whole pelvic radiotherapy (WPRT) using HT for postoperative endometrial cancer. The purpose of this study was to perform a direct dosimetric comparison of three-dimensional conformal radiotherapy (3D-CRT), IMRT and HT plans for WPRT in postoperative endometrial cancer patients, and to evaluate the integral dose to organs at risk (OARs) and normal tissue. MATERIAL AND METHODS: We selected ten patients with endometrial cancer undergoing postoperative WPRT. Plans for 3D-CRT, IMRT and HT were developed for each patient. All plans were normalized to deliver 50 Gy to 95% of the PTV. The dosimetry and integral dose to OARs and normal tissue were compared. The significance of differences was tested using a paired two-tailed Student t-test. RESULTS: IMRT were superior to 3D-CRT in dose conformity (conformity index: 0.87 vs. 0.61, p = 0.00) and integral dose to OARs and normal tissue, although a greater volume of normal tissue receiving dose below 10 Gy was observed. The results were similar in HT except that the integral dose to normal tissue increased slightly. Compared directly with IMRT, HT showed better dose homogeneity and lower integral dose to rectum and bladder, but the integral dose to pelvic bones and normal tissue slightly increased. CONCLUSIONS: In postoperative WPRT of endometrial cancer, IMRT and HT result in better conformity and lower integral dose to OARs compared with 3D-CRT. The integral dose to normal tissue did not increase significantly in IMRT, although a greater volume of normal tissue is irradiated to the dose below 10 Gy. HT further improves the dose homogeneity and integral dose to rectum and bladder, at the expense of a slightly higher integral dose to pelvic bones and normal tissue.


Assuntos
Neoplasias do Endométrio/radioterapia , Radioterapia/métodos , Relação Dose-Resposta à Radiação , Feminino , Humanos , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia Adjuvante
15.
Int J Gynecol Cancer ; 19(9): 1574-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19955940

RESUMO

INTRODUCTION: Conventional whole pelvic radiotherapy (WPRT) with 3-dimensional conformal radiotherapy (3D-CRT) exposes most of the contents of the true pelvis to the prescribed dose. Intensity-modulated radiation therapy (IMRT) provides more conformal dose distribution and better sparing of critical structures for WPRT. However, IMRT is more complicated in planning and delivery, requiring more expensive equipment and time-consuming quality assurance. We explore and evaluate a novel conformal arc radiotherapeutic technique for postoperative WPRT for endometrial cancer in this study. METHODS: This technique involves 2-axis conformal arc therapy (2A-CAT) with 180-degree rotation around 2 isocenters each in 2 separate dose-shaping structures. Dosimetric comparison with 3D-CRT and IMRT for 10 endometrial cancer patients undergoing postoperative WPRT was performed to evaluate this new 2A-CAT technique. RESULTS: The mean conformity indices were 0.83, 0.61, and 0.88 for 2A-CAT, 3D-CRT, and IMRT, respectively. The mean homogeneity indices were 1.15, 1.08, and 1.10. The mean doses to bowel, rectum, bladder, and pelvic bone marrow were, respectively, 1.19, 3.39, 4.65, and 1.64 Gy lower with 2A-CAT than with 3D-CRT (P < 0.05), whereas a little higher than with IMRT. The mean dose to normal tissue was 1.87 Gy higher with 2A-CAT than with IMRT (P = 0.00). CONCLUSIONS: In postoperative WPRT for endometrial cancer, 2A-CAT significantly improves the dose conformity and sparing of bowel, rectum, and bladder compared with 3D-CRT. Despite dose uniformity and conformity being still inferior to those of IMRT, its simplicity and extensive availability combined with further improvement warrant it as a potential shortcut alternative to IMRT.


Assuntos
Carcinoma/radioterapia , Carcinoma/cirurgia , Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/cirurgia , Radioterapia Conformacional/métodos , Terapia Combinada , Relação Dose-Resposta à Radiação , Feminino , Humanos , Pelve/efeitos da radiação , Período Pós-Operatório , Lesões por Radiação/prevenção & controle , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante
16.
Ai Zheng ; 28(11): 1121-6, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-19895729

RESUMO

BACKGROUND AND OBJECTIVE: Helical tomotherapy (HT) has shown its dosimetric advantages in the radiotherapy for many cancers. To date, no published studies have performed a dosimetric evaluation of whole pelvic radiotherapy (WPRT) using HT for postoperative endometrial cancer. This study was to compare the dosimetric characteristics of HT and step-and-shoot intensity modulated radiation therapy (SaS-IMRT) for endometrial cancer patients undergoing postoperative WPRT, and to explore whether whole pelvic HT for postoperative endometrial cancer has the advantage of dosimetry. METHODS: Ten patients with endometrial cancer undergoing postoperative WPRT were enrolled in this study. SaS-IMRT and HT Plans were developed for each patient. The dose distributions of the targets, organs at risk and normal tissue were analyzed and compared. RESULTS: The mean PTV100 were 95.6% and 95.8% (P=0.72) for the SaS-IMRT and HT plans, respectively. The mean homogeneity indexes were 1.10 and 1. 07 (P=0.00). The mean conformity indexes were both 0.87. The mean doses to rectum and bladder for HT were decreased by 1.3 Gy and 3.0 Gy compared with SaS-IMRT, respectively, while the mean dose to pelvic bones was increased by 1.1 Gy. The volumes of small intestine and colon, pelvic bones receiving moderate and low dose also increased. The V5, V10 and V20 of normal tissue were increased by 13.0%, 18.0%, and 5.0% (P=0.00). The mean dose to normal tissue was increased by 2.5 Gy (P=0.00). CONCLUSIONS: Compared with SaS-IMRT, HT resulted in more homogeneous PTV dose distribution, better sparing of rectum and bladder. The volumes of small intestine and colon, pelvic bones and normal tissue receiving moderate and low dose for HT increased. The clinical significance of the dosimetric differences needs further investigations.


Assuntos
Neoplasias do Endométrio/radioterapia , Radiometria/métodos , Dosagem Radioterapêutica , Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Colo/efeitos da radiação , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Intestino Delgado/efeitos da radiação , Pessoa de Meia-Idade , Órgãos em Risco , Ossos Pélvicos/efeitos da radiação , Reto/efeitos da radiação , Tomografia Computadorizada Espiral , Bexiga Urinária/efeitos da radiação
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