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2.
Radiat Oncol ; 15(1): 58, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143669

RESUMO

BACKGROUND: Sublethal radiation induces matrix metalloproteinase 9 (MMP-9)-mediated radioresistance in Lewis lung carcinoma (LLC) cells and their metastatic dissemination. We aim to determine if EGFR/HER2 activation associates with MMP-9-mediated radioresistance and invasiveness in irradiated LLC cells. METHODS: LLC cells were treated with erlotinib or afatinib followed by sublethal radiation. After irradiation, we examined the phosphorylation of EGFR/HER2 and MMP-9 expression. Colony formation assay determined if the kinase inhibitors sensitize LLC cells to radiation. Matrigel-coated Boyden chamber assay assessed cellular invasiveness. Resulting tumors of wild-type LLC cells or HER2 knock-down mutant cells were irradiated to induce pulmonary metastases. RESULTS: Afatinib more effectively sensitized LLC cells to radiation and decreased invasiveness by inhibiting phosphorylation of EGFR, HER2, Akt, ERK, and p38, and down-regulating MMP-9 when compared to erlotinib. Afatinib abolished radiation-induced lung metastases in vivo. Furthermore, LLC HER2 knock-down cells treated with radiation had growth inhibition. CONCLUSION: Dual inhibition of radiation-activated EGFR and HER2 signaling by afatinib suppressed the proliferation and invasion of irradiated LLC cells. Increased radiosensitivity and decreased metastatic dissemination were observed by pharmacological or genetic HER2 inhibition in vivo. These findings indicate that HER2 plays a pivotal role in enhancing radioresistance and reducing metastatic potential of LLC cells.

3.
Clin Lung Cancer ; 20(6): e609-e618, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31377141

RESUMO

INTRODUCTION: Although induction chemotherapy improves the resectability of thymic neoplasms, it is unclear whether surgery after induction chemotherapy can improve outcomes. We compared long-term outcomes of surgery with and without induction chemotherapy in patients with thymic neoplasms. PATIENTS AND METHODS: We retrospectively investigated the clinical information of patients with thymic neoplasms at the National Taiwan University Hospital between 2005 and 2013. RESULTS: Of 204 patients, 119 underwent direct surgery (group 1), 45 underwent surgery after induction chemotherapy (group 2), and 40 underwent no surgery (group 3). The 5-year overall survival rates of groups 1, 2, and 3 were as follows: for 204 patients, 96.3%, 76.4%, and 35.5% (P < .001); for 119 thymoma patients, 96.6%, 88.9%, and 100.0% (P = .835); for 85 thymic carcinoma patients, 94.7%, 69.7%, and 17.7% (P < .001); for 36 American Joint Committee on Cancer (AJCC) stage III-IVA thymoma patients, 92.9%, 83.3%, and 100% (P = .833); and for 28 stage III-IVA thymic carcinoma patients, 75.0%, 76.2%, and 62.5%, (P = .160). Univariate analysis showed that for group 2 (P = .0208) and group 3 (P < .0001), thymic carcinoma pathology type (P = .0010) and stage IVB disease (P < .0001) were poor prognostic factors. Multivariate analysis found thymic carcinoma (P = .0026) and stage IVB disease (P = .0449) to be poor prognostic factors. CONCLUSION: Up-front surgery leads to best overall survival, and induction chemotherapy followed by surgery may improve resectability and outcomes. Only thymic carcinoma and stage IVB disease were poor prognostic factors in multivariate analysis.


Assuntos
Quimioterapia de Indução/métodos , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Timectomia , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Resultado do Tratamento , Adulto Jovem
4.
Oncologist ; 24(12): e1417-e1425, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31127020

RESUMO

BACKGROUND: Immediate whole brain radiation (WBRT) has been the standard for patients with lung cancer with brain metastases. The study aims to evaluate the effect of immediate cranial irradiation in patients with epidermal growth factor receptor (EGFR) mutant lung cancer in the era of a new generation of EGFR inhibitors. MATERIALS AND METHODS: Medical records of 198 patients with EGFR mutant non-small cell lung cancer and brain metastases at initial metastatic diagnosis were reviewed. Patients were categorized into four groups: immediate WBRT, immediate cranial stereotactic radiosurgery (SRS), delayed radiation upon progression of cranial lesions (DRT), and never cranial irradiation (NRT). Overall survival (OS) and progression-free survival related to EGFR inhibitors were analyzed. RESULTS: The SRS group had the fewest brain metastases and fewest extracranial lesions, and the DRT and NRT groups had the smallest brain metastases. Median survival were 18.5, 55.7, 21.1, and 18.2 months for the WBRT, SRS, DRT, and NRT groups, respectively. Patients who had received EGFR T790M inhibitors survived longer (41.1 vs. 19.8 months). In multivariate analysis, the OS of patients in the SRS group was longer than that in the NRT group (adjusted hazard ratio [aHR]: 0.315). Patients who had fewer extracranial lesions and who had received EGFR T790M inhibitor treatments also survived longer (aHR: 0.442 and 0.357, respectively). CONCLUSION: Immediate stereotactic radiosurgery but not whole brain radiation was associated with longer survival. Because of patient heterogeneity and the introduction of EGFR T790M inhibitors, the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted for selected patients. IMPLICATIONS FOR PRACTICE: Immediate whole brain radiation has been the standard for patients with lung cancer with brain metastases. In this study, it was observed that, for patients with epidermal growth factor receptor (EGFR) mutant advanced lung cancer who had brain metastases, there was no difference in survival between patients who never received cranial irradiation and those who received whole brain radiation immediately. Patients who received immediate stereotactic radiosurgery or who had ever received EGFR T790M inhibitors survived longer. Patients who received immediate stereotactic radiosurgery have fewer brain metastases. These findings suggest that the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted in selected patients.

5.
Eur J Surg Oncol ; 45(8): 1498-1504, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30910457

RESUMO

PURPOSE: To compare the locations of recurrences and survival outcomes in esophageal squamous cell carcinoma (ESCC) patients with pathological complete response (pCR) after neoadjuvant concurrent chemoradiotherapy (CCRT) with or without preceding induction chemotherapy (IC) followed by esophagectomy. METHODS: Among 276 patients with locally advanced ESCC undergoing trimodality treatment during 2004-2014, 94 (34.1%) with pCR were eligible. The cohort included 26 patients undergoing IC before CCRT (IC group), and 68 patients who did not receive IC (non-IC group). RESULTS: At a median follow-up of 51.4 months (95% confidence interval; 42.9-62.1), 19 patients experienced recurrences. There was a trend toward fewer distant failures in the IC group (0% vs.14.7%, p = 0.057), while locoregional recurrence was similar (7.7% vs. 7.4%). IC was associated with significantly improved survivals with the 5-year RFS and OS rates for the IC group of 85.1% and 90.5%, respectively, compared to of 46.2% and 48.1% for the non-IC group (p = 0.008 for RFS, and p = 0.015 for OS). By multivariable analyses, IC remained the only significant factor associated with survivals (HR:0.18 for RFS, p = 0.020 and HR:0.18 for OS, p = 0.025). The effect of IC in the whole cohort, irrespective of pathological response, was also assessed. Patients with non-pCR in the IC group had a trend toward worse survivals compared to the non-IC group CONCLUSIONS: In ESCC patients with pCR after trimodality treatment, IC was associated with favorable survivals. The benefits of IC might be a hypothesis generation for adjuvant treatment for patients with pCR.

6.
J Formos Med Assoc ; 118(6): 1024-1030, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30502100

RESUMO

BACKGROUND: In the treatment of esophageal squamous cell carcinoma (ESCC), the optimal use of 18fluorodeoxyglucose positron emission tomography (PET) in measuring metabolic tumor response is undetermined. We launched a phase II trial to evaluate early metabolic response to one-cycle induction chemotherapy in patients with locally advanced ESCC. METHODS: ESCC patients in stage classification T3N0, N1M0, or M1a (American Joint Committee on Cancer, 6th edition) received one-cycle chemotherapy comprising paclitaxel, cisplatin, and 24-h infusional 5-fluorouracil and leucovorin on days 1 and 8, followed by neoadjuvant chemoradiotherapy, 40 Gy, with paclitaxel/cisplatin and then esophagectomy. PET was performed at baseline and day 14 of chemotherapy. The primary endpoint was pathologic complete response (pCR). We hypothesized early metabolic responders with >35% reduction in maximum standardized uptake value (SUVmax), would have better pCR Results. RESULTS: Sixty-six patients were enrolled. The median progression-free survival (PFS) and overall survival (OS) were 16 months (95% confidence interval [CI], 9-27) and 22 months (16-40), respectively. The early metabolic response rate was 55%; and the pCR rate was 34% in the esophagectomy population. The early metabolic response was not associated with pCR or survival. In an exploratory analysis, the postchemotherapy SUVmax was an independent prognostic factor for pCR, PFS, and OS. CONCLUSION: Our study failed to validate the predefined early metabolic response for pCR to neoadjuvant chemoradiotherapy in locally advanced ESCC patients. However, postchemotherapy SUVmax may be prognostic and predictive, and warrants further study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Fluoruracila/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Esofagectomia , Feminino , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Análise de Sobrevida , Taiwan , Resultado do Tratamento
7.
Radiother Oncol ; 126(2): 368-374, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29111173

RESUMO

PURPOSE: The impact of epidermal growth factor receptor (EGFR) mutations on radiotherapy for brain metastases (BM) is undetermined. We evaluated the effects of EGFR mutation status on responses and outcomes in non-small cell lung cancer (NSCLC) patients with BM, treated with upfront or salvage stereotactic radiosurgery (SRS). METHODS AND MATERIALS: From 2008 to 2015, 147 eligible NSCLC patients with 300 lesions were retrospectively analyzed. Patterns of tyrosine kinase inhibitor (TKI) therapy were recorded. Radiographic response was assessed. Brain progression-free survival (BPFS) and overall survival were calculated and outcome prognostic factors were evaluated. RESULTS: Median follow-up time was 13.5 months. Of the EGFR-genotyped patients, 79 (65%) were EGFR mutants, and 42 (35%) were wild type. Presence of EGFR mutations was associated with higher radiographic complete response rates (CRR). Median time to develop new BM after SRS was significantly longer for mutant-EGFR patients (17 versus 10.5 months, p = 0.02), predominantly for those with adjuvant TKI therapy (26.3 versus 15 months, p = 0.01). EGFR mutations independently predicted better BPFS (HR = 0.55, p = 0.048) in multivariate analysis. CONCLUSIONS: In patients with NSCLC treated with SRS for BM, the presence of EGFR mutations is associated with a higher CRR, longer time for distant brain control, and better BPFS. The combination of SRS and TKI in selective patient group can be an effective treatment choice for BM with favorable brain control and little neurotoxicity.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Receptores ErbB/genética , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Valor Preditivo dos Testes , Estudos Retrospectivos , Terapia de Salvação
9.
Hepatology ; 67(2): 586-599, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28646552

RESUMO

Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach is to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or short hairpin RNA to knock down expression of HDAC4 and then irradiated (2.5-10.0 Gy). We evaluated cell survival by a clonogenic assay; apoptosis by Annexin V immunofluorescence; γH2AX, Rad51, and HDAC4 by immunofluorescence staining; HDAC4, Rad51, and ubiquitin-conjugating enzyme 9 (Ubc9) in HCC cell nuclei by cell fractionation and confocal microscopy; physical interaction between HDAC4/Rad51/Ubc9 by immunoprecipitation; and the downstream targets of HDAC4 knockdown by immunoblotting. Both HDAC4 knockdown and HDAC inhibitor enhanced radiation-induced cell death and reduced homologous recombination repair of DNA double-strand breaks and protein kinase B activation, leading to increased apoptosis. HDAC4 knockdown with or without an HDAC inhibitor significantly delayed tumor growth in a radiation-treated xenograft model. Radiation stimulated nuclear translocation of Rad51 in an HDAC4-dependent manner and the binding of Ubc9 directly to HDAC4, which led to Ubc9 acetylation. Moreover, these effects were accompanied by HDAC4/Ubc9/Rad51 complex dissociation through inhibiting nuclear translocation. Conclusion: HDAC4 signaling blockade enhances radiation-induced lethality in HCC cells and xenografts. These findings raise the possibility that HDAC4/Ubc9/Rad51 complex in DNA repair may be a target for radiosensitization of HCC. (Hepatology 2018;67:586-599).


Assuntos
Carcinoma Hepatocelular/radioterapia , Reparo do DNA/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Neoplasias Hepáticas/radioterapia , Radiossensibilizantes/farmacologia , Proteínas Repressoras/antagonistas & inibidores , Enzimas de Conjugação de Ubiquitina/antagonistas & inibidores , Transporte Ativo do Núcleo Celular , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/metabolismo , Humanos , Masculino , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rad51 Recombinase/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Dig Surg ; 35(2): 104-110, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28675905

RESUMO

BACKGROUND: The role of adjuvant radiotherapy for positive lymph nodes (LN) in patients with esophageal cancer who received neoadjuvant concurrent chemoradiotherapy (CCRT) is not well established. This study is aimed at determining the impact of positive LN and the survival benefit of postoperative radiotherapy (PORT) after CCRT plus surgery on esophageal cancer patients. METHODS: Seventy patients with positive LN after neoadjuvant CCRT followed by esophagectomy were enrolled in the study. Patients were grouped into surgery alone following neoadjuvant CCRT (n = 41) and surgery plus PORT following neoadjuvant CCRT (n = 29) groups. The preoperative radiation dose was 36-45 Gy (mean 40 Gy) and the postoperative radiation dose was 20 Gy in 10 fractions. RESULTS: The 5-year survival rate and mean survival was 40% and 58.6 ± 53.9 months for patients with a pathologic complete response (pCR) compared with 8.3% and 22.7 ± 35.5 months, respectively, for non-pCR patients (p = 0.026). Local and distant recurrent patterns were similar for patients who did and did not receive PORT (p = 0.876). The mean survival did not differ significantly between the 2 groups (p = 0.889). Pathological complete response to CCRT was the only significant factor influencing survival (p = 0.026). CONCLUSIONS: Postoperative RT did not improve survival in patients with positive LN after CCRT followed by curative surgery for esophageal cancer.


Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Linfonodos/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Esofagectomia/métodos , Feminino , Humanos , Japão , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Cuidados Pós-Operatórios/métodos , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
11.
J Magn Reson Imaging ; 47(1): 191-199, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28480541

RESUMO

PURPOSE: To evaluate the response in patients undergoing SBRT using dynamic contrast-enhanced (DCE) integrated magnetic resonance positron emission tomography (MR-PET). Stereotactic body radiation therapy (SBRT) is efficacious as a front-line local treatment for non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We prospectively enrolled 19 lung tumors in 17 nonmetastatic NSCLC patients who were receiving SBRT as a primary treatment. They underwent DCE-integrated 3T MR-PET before and 6 weeks after SBRT. The following image parameters were analyzed: tumor size, standardized uptake value (SUV), apparent diffusion coefficient, Ktrans , kep , ve , vp , and iAUC60 . Chest computed tomography (CT) was performed at 3 months after SBRT. RESULTS: SBRT treatment led to tumor changes including significant decreases in the SUVmax (-61%, P < 0.001), Ktrans mean (-72%, P = 0.005), Ktrans standard deviation (SD; -85%, P = 0.046), kep mean (-53%, P = 0.014), kep SD (-63%, P = 0.001), and vp SD (-58%, P = 0.002). The PET SUVmax was correlated with the MR kep mean (P = 0.002) and kep SD (P < 0.001). The percentage reduction in Ktrans mean (P < 0.001) and kep mean (P = 0.034) at 6 weeks post-SBRT were significantly correlated with the percentage reduction in tumor size, as measured using CT at 3 months after SBRT. Univariate analyses revealed a trend toward disease progression when the initial SUVmax > 10 (P = 0.083). CONCLUSION: In patients with NSCLC who are receiving SBRT, DCE-integrated MR-PET can be used to evaluate the response after SBRT and to predict the local treatment outcome. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:191-199.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Imagem por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Meios de Contraste/química , Progressão da Doença , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18/química , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Estudos Prospectivos , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Radiol Oncol ; 50(4): 427-432, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27904451

RESUMO

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.

13.
Case Rep Oncol ; 9(2): 474-480, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27721771

RESUMO

Maintenance pemetrexed offers survival benefit with well-tolerated toxicities for advanced non-squamous non-small cell lung cancer (NSCLC). We present 3 consecutively enrolled patients with advanced non-squamous NSCLC, receiving stereotactic ablative radiotherapy (SABR) for oligoprogressive disease during maintenance pemetrexed. All of them had sustained local control of thoracic oligoprogression after the SABR, while maintenance pemetrexed were kept for additionally long progression-free interval. SABR targeting oligoprogression with continued pemetrexed is an effective and safe approach to extend exposure of maintenance pemetrexed, thus maximizing the benefit from it.

14.
ACS Appl Mater Interfaces ; 8(39): 26309-26318, 2016 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-27602505

RESUMO

Antireflective (AR) silica/polymer composite coatings on glass and poly(methyl methacrylate) (PMMA) substrates were prepared by silica mineralization of layer-by-layer (LbL) assembled films composed of polystyrene-block-poly(l-lysine)/poly(l-glutamic acid) (PS-b-PLL/PGA) complex vesicles without any post-treatments. PS-b-PLL AB and A2B block copolymers with appropriate block ratio can self-assemble to form vesicles, which can be deposited onto substrates without dissociation. Silica deposition specifically onto the complex vesicles in the multilayer films through amine-catalyzed polycondensation results in the continuous, intact composite coatings comprising vesicular nanostructures, which provided an additional parameter for tuning their optical properties. The film thickness and porosity are mainly dictated by the bilayer number and the degree of deformation/fission of vesicles upon complexation and mineralization, depending on polymer composition. The coated PMMA substrate with maximum transmission over 98% can be achieved at the optimized wavelength region. The AR composite films were mechanically stable to withstand both the wipe and adhesion tests due to the preparation of continuous, intact films. This study demonstrated that the concept of preparing composite films comprising vesicular nanostructures through the combination of LbL assembly and biomineralization is feasible.

15.
Liver Cancer ; 5(3): 210-20, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27493896

RESUMO

BACKGROUND: During the past two decades, external-beam radiation technology has substantially changed from traditional two-dimensional to conformal three-dimensional to intensity-modulated planning and stereotactic body radiotherapy (SBRT). SUMMARY: Modern techniques of radiotherapy (RT) are highly focused and capable of delivering an ablative dose to targeted hepatocellular carcinoma (HCC) tumors. SBRT is an option for selected patients with limited tumor volume and non-eligibility for other invasive treatments. Moreover, RT combined with a radiation sensitizer (RS) to increase the therapeutic ratio has shown promising results in select studies, prompting further investigation of this combination. With the undetermined role of RT in treatment guidelines and variation in patterns of treatment failure after RT in patient with HCC, useful biomarkers to guide RT decision-making and selection of patients are needed and emerging. KEY MESSAGE: The objective of this review is to summarize the current RS with SBRT schemes and biomarkers for patient selection used to maximize the effect of RT on HCC.

16.
Asia Pac J Clin Oncol ; 12(4): 380-387, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27312514

RESUMO

AIM: PROCLAIM, a phase III trial of patients with nonsquamous non-small cell lung cancer comparing concurrent pemetrexed-cisplatin and thoracic radiation therapy followed by consolidation pemetrexed, did not meet its primary endpoint of superior overall survival versus etoposide-cisplatin and thoracic radiation therapy followed by a consolidation platinum doublet of choice. The results from an East Asian subgroup analysis are presented here. METHODS: A subgroup analysis was performed for all patients randomized from China (n = 61), Taiwan (n = 25), and Korea (n = 11). RESULTS: Baseline characteristics were balanced between treatment arms for East Asian patients. In the 97 randomized East Asian patients, median overall survival was 26.8 months for the pemetrexed-cisplatin arm and 36.3 months for the etoposide-cisplatin arm (hazard ratio: 1.23; 95% confidence interval: 0.70-2.14; P = 0.469). Median progression-free survival was 10.0 months for the pemetrexed-cisplatin arm and 7.6 months for the etoposide-cisplatin arm (hazard ratio: 0.97; 95% confidence interval: 0.61-1.54; P = 0.890). The objective response rate was 47.7% in the pemetrexed-cisplatin arm and 34.0% in the etoposide-cisplatin arm (P = 0.167). In the 90 treated East Asian patients, the overall incidence of drug-related grade 3-4 treatment-emergent adverse events was significantly lower in the pemetrexed-cisplatin arm versus the etoposide-cisplatin arm (61.4% vs 91.3%; P = 0.001). CONCLUSION: For East Asian patients, pemetrexed-cisplatin combined with thoracic radiation therapy, followed by consolidation pemetrexed, did not improve overall survival but did have a good safety profile with a trend for improved progression-free survival and objective response rate compared to standard chemoradiotherapy for stage III unresectable nonsquamous non-small cell lung cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Quimioterapia de Consolidação/métodos , Pemetrexede/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pemetrexede/administração & dosagem
17.
Nanoscale ; 8(4): 2367-77, 2016 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-26752150

RESUMO

We report a versatile approach to synthesize silica coatings with antireflective (AR) characteristics through the combination of a layer-by-layer (LbL) assembly technique and biomineralization. LbL assembled decanoyl-modified poly(l-lysine)/poly(l-glutamic acid) (PLL-g-Dec/PLGA) multilayer films were used as templates for silica mineralization, followed by calcination. The specific deposition of silica onto the LbL polypeptide assemblies through amine-catalyzed polycondensation resulted in silica coatings that exhibited the transcription of the nano-/microstructured polypeptide films and their film thickness and porosity can be tuned by varying the number of bilayers, degree of substitution, and PLL molecular weight. AR silica coatings exhibiting more than 6% increase in transmittance in the near UV/visible spectral range can be obtained at an optimized refractive index, thickness, and surface roughness. The abrasion test showed that the silica coatings exhibited sufficient structural durability due to continuous silica nanostructures and low surface roughness. This study demonstrated that nanostructured thin films can be synthesized for AR coatings using the synergy between the LbL assembly technique and biomineralization.


Assuntos
Materiais Revestidos Biocompatíveis/química , Membranas Artificiais , Ácido Poliglutâmico/química , Polilisina/química , Dióxido de Silício/química
18.
Chronobiol Int ; 33(2): 210-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26818960

RESUMO

This retrospective study tested the hypothesis that disease control and treatment-related toxicity in patients undergoing high-dose radiotherapy (HDRT) for prostate cancer varies in a circadian manner. Patients with localized prostate adenocarcinoma receiving HDRT (median 78 Gy) to the prostate and involved seminal vesicle(s) without elective pelvic irradiation were divided into a daytime treatment (before 5 PM) group (n = 267) and evening treatment (after 5 PM) group (n = 142). Biochemical failure (Phoenix definition), acute and late gastrointestinal (GI) and genitourinary toxicities (Common Terminology Criteria for Adverse Events version 4), biochemical failure-free survival (BFFS) and freedom from late toxicity were assessed. Analyses were performed by binary logistic regression and Cox proportional hazard regression. The median follow-up was 68 months, and 75% of patients were ≥70 years old. Evening HDRT was significantly associated with worse freedom from ≥grade 2 late GI complications (hazard ratio = 2.96; p < 0.001). The detrimental effect of evening HDRT was significant in patients older than 70 years old (p < 0.001) but not in younger patients (p = 0.63). In a subgroup of propensity score-matched cohort with T2b-T3 disease (n = 154), the 5-year BFFS was worse in the evening group than the daytime group (72% vs. 85%, hazard ratio = 1.95, p = 0.05). Our study indicates that evening HDRT may lead to more GI complications, especially in older patients, and worse BFFS in patients with T2b-T3 disease.


Assuntos
Adenocarcinoma/radioterapia , Ritmo Circadiano/fisiologia , Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Adenocarcinoma/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
Int J Radiat Oncol Biol Phys ; 93(5): 1023-31, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26475065

RESUMO

PURPOSE: Our aim was to investigate the association of clinical factors, dosimetric parameters, and biomarkers with postoperative pulmonary complications (PPCs) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated by neoadjuvant concurrent chemoradiation therapy (CCRT) under strict pulmonary dose constraints and esophagectomy. METHODS AND MATERIALS: We prospectively enrolled 112 patients undergoing trimodality treatment (including radiation therapy [40 Gy], concurrent taxane-/5-fluorouracil-based regimens, and radical esophagectomy) for ESCC. A PPC was defined as pneumonia or acute respiratory distress syndrome within 30 days after surgery. Serum samples were collected before and within 1 month after CCRT. The association of serum biomarkers with PPCs was detected by proximity ligation assay (PLA) and verified by enzyme-linked immunosorbent assay. Associations of clinical factors, lung dosimetric parameters, and biomarkers with PPC were tested statistically. RESULTS: Thirty-three patients (29.5%) had PPCs. None of the dosimetric parameters was associated with PPCs. Preoperative functional vital capacity (FVC) was significantly associated with PPCs (P=.004). Of the 15 PLA-screened biomarkers, posttreatment transforming growth factor-ß1 (TGF-ß1) was borderline significantly associated with PPCs (P=.087). Patients with PPCs had significantly larger pre-CCRT to post-CCRT decrease in serum TGF-ß1 concentration (-11,310 vs -5332 pg/mL, P=.005) and higher pre-CCRT to post-CCRT percent decline in serum TGF-ß1 concentration (-37.4% vs -25.0%, P=.009) than patients without PPCs. On multivariate analysis, preoperative FVC (P=.003) and decrease in TGF-ß1 >7040 pg/mL (P=.014) were independent factors associated with PPCs. CONCLUSIONS: Preoperative FVC and decrease in serum TGF-ß1 level after dose-limited CCRT to the lung are associated with the development of PPCs.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/terapia , Terapia Neoadjuvante/métodos , Fator de Crescimento Transformador beta1/sangue , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia/efeitos adversos , Ensaio de Imunoadsorção Enzimática , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante/efeitos adversos , Pneumonia/etiologia , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Adulto/etiologia , Taxoides/administração & dosagem
20.
J Thorac Oncol ; 10(10): 1481-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26313683

RESUMO

INTRODUCTION: To determine whether the postchemoradiotherapy (post-CRT) pathologic stage predicts the outcomes of patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing preoperative CRT followed by surgery. METHODS: From three phase II trials of preoperative CRT for locally advanced ESCC, 140 patients were included. Preoperative CRT comprised twice weekly paclitaxel and cisplatin-based regimens and 40-Gy radiotherapy in 20 fractions. The post-CRT pathologic stage was classified according to the American Joint Committee on Cancer, 7th edition staging system. The prognostic effects of clinicopathologic factors were analyzed using Cox regression. RESULTS: With a median follow-up of 61.9 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort were 24.5 and 30.9 months, respectively. The post-CRT pathologic stage was 0 in 34.5%, I in 12.9%, II in 29.3%, III in 13.6%, and ypT0N1-2 in 6.4% of the patients. The median PFS was 47.2, 25.9, 16.0, 9.4, and 15.1 months, and the median OS was 57.4, 34.1, 26.2, 14.1, and 17.6 months for patients with post-CRT pathologic stage 0, I, II, III, and ypT0N1-2, respectively. In multivariate analysis, performance status (p < 0.001), tumor location (p = 0.016), and extranodal extension (p = 0.024) were independent prognostic factors for PFS, whereas performance status (p < 0.001) and post-CRT pathologic stage (p = 0.027) were independent prognostic factors for OS. CONCLUSIONS: The post-CRT pathologic stage classified by American Joint Committee on Cancer, 7th edition staging system predicted the survival of locally advanced ESCC patients who underwent preoperative paclitaxel and cisplatin-based CRT followed by esophagectomy.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Adulto , Idoso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimiorradioterapia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estados Unidos , Organização Mundial da Saúde
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