RESUMO
BACKGROUND: To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN). PATIENTS AND METHODS: Patients with nonoperated stage III-IV SCC of oral cavity, oropharynx, hypopharynx, and larynx and unfit for receiving high-dose cisplatin were enrolled. Patients received once-daily RT up to 69.96 Gy in 33 fractions with weekly cetuximab (cetuximab-RT arm) or 200 mg Q3W pembrolizumab during RT (pembrolizumab-RT arm). The primary endpoint was locoregional control (LRC) rate 15 months after RT. To detect a difference between arms of 60%-80% in 15-month LRC, inclusion of 66 patients per arm was required to achieve a power of at least 0.85 at two-sided significance level of 0.20. RESULTS: Between May 2016 and October 2017, 133 patients were randomized to cetuximab-RT (n = 66) and pembrolizumab-RT (n = 67). Two patients (one in each arm) were not included in the analysis (a consent withdrawal and a progression before treatment start). The median age was 65 years (interquartile range 60-70 years), 92% were smokers, 60% were oropharynx (46% of oropharynx with p16+) and 75% were stage IV. Median follow-up was 25 months in both arms. The 15-month LRC rate was 59% with cetuximab-RT and 60% with pembrolizumab-RT ]odds ratio 1.05, 95% confidence interval (CI) 0.43-2.59; P = 0.91]. There was no significant difference between arms for progression-free survival (hazard ratio 0.85, 95% CI 0.55-1.32; P = 0.47) and for overall survival (hazard ratio 0.83, 95% CI 0.49-1.40; P = 0.49). Toxicity was lower in the pembrolizumab-RT arm than in the cetuximab-RT arm: 74% versus 92% patients with at least one grade ≥3 adverse events (P = 0.006), mainly due to mucositis, radiodermatitis, and rash. CONCLUSION: Compared with the SOC cetuximab-RT, pembrolizumab concomitant with RT did not improve the tumor control and survival but appeared less toxic in unfit patients with LA-SCCHN.
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Quimiorradioterapia , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Idoso , Humanos , Pessoa de Meia-Idade , Cetuximab/uso terapêutico , Quimiorradioterapia/efeitos adversos , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
Objective: To compare the effects of preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the long-term survival of patients with radical resection for esophageal squamous cell carcinoma. Methods: Totally 1 082 patients with stage T3-4aN0-3M0 thoracic esophageal squamous cell carcinoma were recruited in this study who underwent radical resection at Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University from January 2005 to January 2015. There were 798 males and 284 females, with a median age of 61 years (range: 37 to 86 years). There were 138 patients undergoing preoperative neoadjuvant chemotherapy, 392 patients postoperative adjuvant chemotherapy, and 552 patients surgery alone. The neoadjuvant chemotherapy group was used as the benchmark group to match the propensity score with the adjuvant chemotherapy group and the surgery-only group respectively at a ratio of 1â¶3. A total of 7 covariates including tumor location, number of positive lymph nodes, tumor invasion depth, tumor differentiation degree, surgical procedure, vascular tumor thrombus and nerve invasion were included, and the caliper value was taken as 0.1. After matching, a total of 699 patients were included for the analysis, including 128 patients in the neoadjuvant chemotherapy group, 267 patients in the adjuvant chemotherapy group, and 304 patients in the surgery alone group. The Kaplan-Meier method was used to generate the survival curves which was tested by the Log-rank method for survival analysis. Results: After matching analysis, the 5-year overall survival rate was 41.5% in the neoadjuvant chemotherapy group with a median overall survival time of 43 months (95%CI: 27 to 59 months), 57.6% in the adjuvant chemotherapy group with a median overall survival time unreached, and 24.9% in the surgery alone group with a median overall survival time of 28 months (95%CI: 25 to 31 months) (χ²=60.475, P<0.01). For overall survival after matching, the adjuvant chemotherapy group was better than the neoadjuvant chemotherapy group (χ²=11.384, P=0.001), the neoadjuvant chemotherapy group was better than the surgery alone group (χ²=8.654, P=0.003), and the adjuvant chemotherapy group was better than surgery alone group (χ²=60.234, P<0.01). Conclusion: Both preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy can improve the long-term survival of patients with locally advanced esophageal squamous cell carcinoma undergoing radical resection, and the improvement effect of postoperative adjuvant chemotherapy is more obvious.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Objective: To summarize the clinical data of elastic stable intramedullary nailing(ESIN) in the treatment of long bone fracture of children in a single medical center, and to analyze the problems occurred after the ESIN surgery and corresponding solutions. Methods: A retrospective analysis was conducted regarding the clinical data of 2 133 pediatric long bone fractures conforming to inclusion and exclusion criteria from June, 2005 to December, 2017 in Department of Orthopedics, Children's Hospital of Nanjing Medical University.There were 1 191 boys and 942 girls, aged from 23 months to 14 years with mean age of (5.7 ± 3.1)years.There were 1 866 cases treated with closed reduction with ESIN, while 267 cases were treated with small incision assisted reduction with ESIN.Postoperative problems have been statistically analyzed. Results: There were altogether 2 133 children, including 603 cases of femur, 311 cases of tibia, 8 cases of fibula, 219 cases of humerus, and 992 cases of ulna/radius.The postoperative complications mainly consist of 62 cases of needle tail irritation reaction, 21 cases of misalignments of fracture alignment, 11 cases of intramedullary nail deformity or angular deformity, 7 cases of limb shortening, 14 cases of limited joint activity, 4 cases of nerve injury, 2 cases of tendon injury, 14 cases of difficult nail removal, 4 cases of cortical cleavage, 8 cases of delayed union, 1 case of nonunion, 6 cases of varus/valgus deformity, 5 cases of epiphyseal injury, 6 cases of ESIN exposure, and 2 cases of metal debris of ESIN' end. Conclusions: The complications of treatment for children with long bone fractures by ESIN cannot be ignored.To master the important biomechanical properties, to get familiar with the local anatomy and to avoid obvious technical errors can reduce the occurrence of postoperative complications.
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Fixação Intramedular de Fraturas , Consolidação da Fratura , Fraturas Ósseas , Adolescente , Pinos Ortopédicos , Criança , Pré-Escolar , Feminino , Fraturas Ósseas/cirurgia , Humanos , Lactente , Masculino , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
In this article, we propose a consensus delineation of postoperative clinical target volumes for the primary tumour in maxillary sinus and nasal cavity cancers. These guidelines are developed based on radioanatomy and the natural history of those cancers. They require the fusion of the planning CT with preoperative imaging for accurate positioning of the initial GTV and the combined use of the geometric and anatomical concepts for the delineation of clinical target volume for the primary tumour. This article does not discuss the indications of external radiotherapy (nor concurrent systemic treatment) but focuses on target volumes when there is an indication for radiotherapy.
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Neoplasias Bucais , Neoplasias dos Seios Paranasais , Humanos , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Seio Maxilar/patologia , Cavidade Nasal/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Bucais/patologiaRESUMO
PURPOSE: Anaplastic thyroid carcinomas (ATC) are a heterogenous group of tumors of overall dismal prognosis. We designed models to identify relevant prognostic factors of survival of irradiated ATC patients including radiotherapy modalities (field size, dose). MATERIAL AND METHODS: Between 2000 and 2017, 166 ATC patients' treatments were divided into surgery and postoperative radiotherapy (poRT) or definitive radiotherapy (RT). Multiple imputation approach was used for missing data. Prognostic factors were identified using Lasso-penalized Cox modelling and predicted risk scores were built. RESULTS: Patients undergoing RT (n=70) had more adverse patient and disease characteristics than those undergoing poRT (n=96). Corresponding median survival rates were 5.4 and 12.1 months, respectively. PoRT patients undergoing poRT more likely received extended-field radiotherapy with prophylactic nodal irradiation, but rather received platinum- vs. adriamycin-based chemoradiotherapy. Radiotherapy was conventionally fractionated, delivered >60Gy in 51.9% and 61.7% and used extended fields in 88.5% and 71.2% of patients with poRT or RT. Radiotherapy interruption rates for toxicity were similar in the two groups. The best poRT-group model identified age>45yo, PS≥1, pathologic tumor stage≥pT4b,>N1 and R2 resection as poor prognostic factors. The best RT-group model (C-index of 0.72) identified PS≥3,>N1 and extended-field radiotherapy with prophylactic nodal irradiation (as opposed to tumour-bed irradiation only) as poor prognostic factors. CONCLUSION: In patients undergoing poRT, radiotherapy parameters had little influence over their survival irrespective of patient, disease characteristics, and quality of resection. In patients undergoing RT, extended-field radiotherapy improved survival in addition to PS and nodal stage.
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Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Quimiorradioterapia , Humanos , Pessoa de Meia-Idade , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Carcinoma Anaplásico da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
PURPOSE: Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). MATERIAL AND METHODS: A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. RESULTS: EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. CONCLUSIONS: Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.
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Endoscopia , Neoplasias dos Seios Paranasais , França , Humanos , Neoplasias dos Seios Paranasais/diagnóstico por imagem , Neoplasias dos Seios Paranasais/radioterapia , Neoplasias dos Seios Paranasais/cirurgia , Inquéritos e QuestionáriosRESUMO
It is proposed to delineate the anatomo-clinical target volumes of primary tumor (CTV-P) in ethmoid cancers treated with post-operative radiotherapy. This concept is based on the use of radioanatomy and the natural history of cancer. It is supported by the repositioning of the planning scanner with preoperative imaging for the replacement of the initial GTV and the creation of margins around it extended to the microscopic risk zones according to the anatomical concept. This article does not discuss the indications of external radiotherapy but specifies the volumes to be delineated if radiotherapy is considered.
Assuntos
Osso Etmoide , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Cranianas/radioterapia , Osso Etmoide/anatomia & histologia , Osso Etmoide/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Cuidados Pós-Operatórios/métodos , Neoplasias Cranianas/diagnóstico por imagem , Neoplasias Cranianas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Patients with synchronous metastatic head and neck squamous cell carcinomas often present associated locoregional symptoms and a risk of life-threatening primary tumour progression. Few data have been published about the use of radiation therapy in the management of newly diagnosed metastatic disease associated with advanced locoregional disease. In this article, we aim to determine the role of radiation therapy of the primary tumour in the overall therapeutic strategy for these diseases. We further address radiation therapy modalities (technique, volumes, and fractionation) in such a context. MATERIAL AND METHODS: We conducted a literature survey on locoregional radiotherapy for newly diagnosed metastatic head and neck squamous cell carcinomas. RESULTS: Several retrospective studies have reported that locoregional radiotherapy is associated with improved overall survival of patients with synchronous metastatic head and neck squamous cell carcinomas. However, data about modalities such as timing of radiotherapy in the overall strategy, dose, fractionation and delineation volumes are scarce. Two schematic situations can be distinguished with respect to prognosis and treatment adaptations: polymetastatic/bulky or oligometastatic disease. In polymetastic/bulky disease associated with poor prognosis, standard-of-care is systemic therapy, but locoregional radiotherapy can be discussed either upfront, mainly for symptomatic palliation, or as consolidation after downsizing obtained by systemic therapy. As for oligometastatic disease, with the rise in use of efficacious and well-tolerated local ablative treatments of metastases, aggressive curative-intent locoregional radiotherapy can be considered with or without systemic therapy. CONCLUSION: Because locoregional disease is a major cause of disease failure in patients with synchronous metastatic head and neck squamous cell carcinomas, aggressive locoregional radiation therapy to the primary tumour may be discussed in the initial management of the disease where systemic therapy alone may not induce sufficient primary tumour reduction. With recent technological advances in radiotherapy, the delivery of radiotherapy is safe and feasible even in metastatic setting. Clinical trials assessing radiotherapy use for metastatic head and neck squamous cell carcinomas are warranted.
Assuntos
Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Algoritmos , Humanos , Metástase Neoplásica/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
PURPOSE: To assess the efficacy and the tolerance of a split course hypofractionated (SCH) radiotherapy (RT) protocol in head and neck cancer (HNC) for eldery and/or unfit patients (pts). PATIENTS AND METHODS: Pts with HNC treated by SCH-RT in two institutions were included retrospectively. The main SCH RT regimen was two courses of 30 grays (Gy)/10 fractions separated by 2-4 weeks, without any systemic therapy. RESULTS: Between February 2012 and January 2019, 75 consecutive patients were analyzed. The median age was 80 years (range: 45.7-98.2) and 53 (70.7%) were men. Sixty-one (81.3%) pts had stage III/IV disease and 54 (72%) had at least two comorbidities. All of them were treated with intensity-modulated radiotherapy. Median follow-up was 10.6 months (range: 3.1-58.3). Local control at 12 and 24 months was 72.8% IC95%[62-85.5] and 51.7% IC95%[38.1-70.1] respectively. Progression free survival (PFS) at 12 and 24 months were 47.7% IC95%[37.4-60.8] and 41% IC95%[15-36.4] respectively, with a median of 11.5 months IC95%[8.9-17]. OS at 12 and 24 months were 60.4% IC95%[50-73.1] and 41% IC95%[30.6-54.9] respectively, with a median of 19.3 months IC95%[11.9-25.8]. Acute and late grade 3 or higher toxicities occurred for 6 (8%) and 3 (4%) pts. CONCLUSION: The present SCH-RT regimen seems effective, well-tolerated and could represent an alternative to palliative strategies for pts deemed unfit for standard exclusive RT.
Assuntos
Adenocarcinoma/radioterapia , Carcinoma de Células Escamosas/radioterapia , Idoso Fragilizado , Neoplasias de Cabeça e Pescoço/radioterapia , Hipofracionamento da Dose de Radiação , Radioterapia de Intensidade Modulada/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Intervalo Livre de Progressão , Radioterapia de Intensidade Modulada/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos RetrospectivosRESUMO
Objective: To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway. Methods: Experimental study was carried out in vitro. Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2. Then, the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM). Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2, c-Fos and c-Jun mRNA and protein respectively. The database was established and analyzed with SPSS statistical software (version 20.0). Results: After down-regulating Src, the cell proliferation was inhibited and cell apoptosis was induced. The proportions of G0/G1 stage of Hela and C33A cell in cell cycle increased while G2/M and S stages decreased. Meanwhile, the mRNA levels of ERK 1, ERK 2, c-Fos and c-Jun increased. And the expression levels of ERK 1/2, phosphorylated ERK 1/2 (p-ERK 1/2) and phosphorylated c-Fos (p-c-Fos) protein decreased, while c-Jun and phosphorylated c-Jun (p-c-Jun) protein expression increased. In addtion, the change level of Hela cell, p-ERK 1/2 and c-Fos protein were lower than that of C33A cell before and after the Src inhibition. Conclusions: Src, involved in regulating the expression of key factors of the ERK signal transduction pathway including p-ERK 1/2 and p-c-Fos, might be capable of promoting the proliferation of cervical cancer cells and inhibiting their apoptosis. The infection with HPV might have adjustable effect on this process.
Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Genes fos/efeitos dos fármacos , Genes jun/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Neoplasias do Colo do Útero/metabolismo , Feminino , Células HeLa/efeitos dos fármacos , Humanos , RNA Mensageiro , Transdução de Sinais , Neoplasias do Colo do Útero/patologia , Quinases da Família src/metabolismoRESUMO
Objective: To investigate the effect of ERK1/2 protein expression and HPV16 infection, as well as their interaction in the cervical carcinogenesis. Methods: A total of 176 patients, including 34 cases with normal cervix (NC), 26 cases with cervical intraepithelial neoplasm â (CIN â ), 57 cases with cervical intraepithelial neoplasm â ¡/â ¢ (CIN â ¡/â ¢) and 59 cases with cervical squamous cell carcinoma (SCC), were enrolled from Shanxi Tumor Hospital, Shanxi Maternal and Child Health Center, Jincheng Coal General Hospital from September 2013 to March 2014. The information about their demographic characteristics and risk factors associated with cervical cancer was collected with structural questionnaire, and cervical tissue samples were collected from each subject. HPV16 infection was detected by PCR, and phosphorylation of ERK1/2 (p-ERK1/2) protein expression levels were detected by immunohistochemistry. Meanwhile, cervical cancer cell lines Siha (HPV16 positive) and C33A (HPV negative) were treated with ERK inhibitor U0126 in vitro. Cell proliferation was determined by living cell count, cell cycle and apoptosis was detected by flow cytometry. Results: The HPV16 infection rate (trend χ(2)=17.99, P<0.001) and p-ERK1/2 protein high expression (trend χ(2)=10.58, P=0.001) increased gradually along with the severity of cervix lesions. There was an additive interaction between HPV16 infection and p-ERK protein expression in the CIN â , CIN â ¡/â ¢ and SCC groups. Cell experiments showed that after ERK inhibition, the proliferation of the two cells were reduced (Siha: t=6.863, P<0.001; C33A: t=7.092, P<0.001) and the apoptosis were increased (Siha: t=-5.201, P=0.006; C33A: t=-4.335, P=0.005). After ERK inhibition, the cell proliferation index of Siha (HPV16 positive) was higher than that of C33A (HPV16 negative) (t =7.066, P<0.001), but the apoptosis rate of Siha was lower than that of C33A (t=-2.431, P=0.057). Conclusions: HPV16 infection and the high expression of p-ERK1/2 could increase the risk of cervical cancer. And there might be synergistic actions between the two factors in the progression of cervical cancer. The effect of ERK1/2 activation to HPV16 infection cells might be more significant in the process of cervical cancer cell proliferation and apoptosis.
Assuntos
Carcinoma de Células Escamosas/virologia , Progressão da Doença , Papillomavirus Humano 16 , Proteína Quinase 1 Ativada por Mitógeno/genética , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Infecções por Papillomavirus , Reação em Cadeia da Polimerase , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/metabolismoRESUMO
PURPOSE: To report on patterns of relapse following implementation of intensity-modulated radiotherapy and subsequent changes in practice in a tertiary care centre. PATIENTS AND METHODS: Between 2008 and 2011, 188 consecutive patients (mean age 59 years old) received intensity-modulated radiotherapies with curative intent for squamous cell carcinomas of the oral cavity (17.5%), oropharynx (43%), hypopharynx (21%), larynx (14%), sinonasal cavities (6%), nasopharynx (1.5%) at the university hospital of Besançon. There were stage I and II 9%, III 24.5%, IV 66.5%. One hundred and thirty-eight underwent exclusive intensity-modulated radiotherapy, 50 underwent postoperative intensity-modulated radiotherapy, 174 had concurrent chemotherapy, 57 had induction chemotherapy. Dynamic intensity-modulated radiotherapy with static fields was performed for all patients using sequential irradiation in 174 patients and simultaneous integrated boost irradiation in 14 patients. RESULTS: With a median follow-up was 27.5 months, there was 79% of locoregional failures occurred in the 95% isodose. Two-year overall survival, disease-free, local failure-free and locoregional failure-free survival rates were73%, 60%, 79% and 72%, respectively. Prognostic factors for disease-free survival were stage (IV vs. I-III) with a relative risk of 1.7 [1.1-2.8] (P=0.02) and T stage with 1.6 [1.04-2.5] (P=0.03). CONCLUSION: The current series showed similar patterns of failure as in other tertiary care centres. We did not identify intensity-modulated radiotherapy specific relapse risks.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Feminino , França/epidemiologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Lesões por Radiação/epidemiologia , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
The structural and transport properties of LaTiO(3+ß/2) epitaxial thin films, grown at different oxygen pressures ranging from 6.6 × 10(-4) to 5 Pa, have been investigated. X-ray diffraction peaks of the films shift to lower angles with increasing oxygen pressure, indicative of a variation of the corresponding lattice spacing. All the films show T(2) dependence of resistivity over a large temperature range of â¼200 K, suggesting a band-filling-induced metallic Fermi-liquid behaviour. Upturns in resistivity have been revealed at low temperatures, which could be ascribed to the Anderson-localization effect caused by the cation vacancies. Furthermore, for the thin films grown at high oxygen pressures of 0.5 and 5 Pa, the dependence of resistivity on temperature shows a maximum at high temperatures. The maximum seems to support the argument that transition between t-orbital ordering and disordering plays an important role in dominating transport properties at high temperatures. Carrier density deduced from Hall coefficient increases with the decrease of oxygen content, and shows strong temperature dependence. From the experimental data, it can be asserted that in the LaTiO(3+ß/2) thin films, besides the band filling effect, localization or disorder caused by La and Ti vacancy effects controls the unique transport properties.
RESUMO
The activity of the combination of intravenous docetaxel 75 mg/m2 plus cisplatin 100 mg/m2 administered every 3 weeks for 3 cycles then every 6 weeks was investigated in 51 chemotherapy naive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The population was 92% male, with a median age of 54 years and median performance status of 1; 80% of patients had metastatic disease, including 37% with bone involvement. All patients received prophylactic premedication (ondansetron, dexamethasone plus cetirizine) and standard hyperhydration. With a median of 4 treatment cycles (range 1-9), 14 of 42 evaluable patients responded (overall response rate 33.3%, 95% CI 19.6-49.6%); the median response duration was 7.3 months, median survival 8.4 months, and 1-year survival rate 35%. The most common adverse event was neutropenia, occurring in two-thirds of patients. Neurosensory effects were cumulative but generally mild. No treatment-related deaths occurred. This combination of docetaxel/cisplatin showed activity in advanced NSCLC. While it was not clearly superior to single-agent docetaxel, due to differences in prognostic factors among the patients in open trials, a randomised study would be needed to demonstrate definitively whether cisplatin adds to the activity of docetaxel or not.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Taxoides , Adolescente , Adulto , Idoso , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/análogos & derivados , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Parthenogenetic activation is a major hurdle to be cleared for the examination of the human sperm chromosome after intracytoplasmic injection (ICSI) into golden hamster oocytes. Various factors that affect spontaneous activation of hamster oocytes were, therefore, investigated in this study. We collected cumulus-oocyte complexes (COC) from the oviducts of superovulated females and washed them thoroughly with Ca2+-containing or Ca2+-free TALP-HEPES medium (handling media). We cultured oocytes with intact cumulus or those without cumulus (removed by previous hyaluronidase treatment) in Ca2+-containing or -free m-TALP-3 for 6 or 12 h before examining for their activation. Among the oocytes recovered 17 h post-hCG, 92-94% were parthenogenetically activated by 6 h of in vitro culture. Activation rate in the oocytes collected at 13.5 h post-hCG (53%) was significantly (P < 0.05) lower than that in the oocytes collected 17 h post-hCG (92%), indicating that the spontaneous activation rate increased as the oocytes became older. Both cumulus-intact and cumulus-free oocytes had similar (P > 0.05) activation rates when cultured in vitro, suggesting that hyaluronidase treatment had no effect on the rate of oocyte activation. Omission of Ca2+ from the handling medium also had no effect on the activation of the oocytes. The rate of spontaneous activation of the oocytes cultured in calcium-free medium for 6 (9%) and 12 h (16%) was significantly (P < 0.01) lower than that (94%) of the control oocytes cultured in Ca2+-containing medium, implying a positive influence of Ca2+ on in vitro activation of hamster oocytes. When we cultured the oocytes first in calcium-free medium for 6 h, and then in calcium-containing medium for 6 h, 94% were activated, which is comparable to the rate for oocytes continuously cultured in Ca2+-containing medium. This indicates that the inhibition of hamster oocyte activation in Ca2+-free medium is reversible and can be used to control spontaneous activation of golden hamster oocytes.
Assuntos
Oócitos/fisiologia , Partenogênese , Animais , Cálcio/administração & dosagem , Células Cultivadas , Gonadotropina Coriônica/farmacologia , Cricetinae , Meios de Cultura , Feminino , Humanos , Hialuronoglucosaminidase/farmacologia , Masculino , Superovulação , Fatores de TempoRESUMO
The effect of eCG on follicular development and granulosa-cell apoptosis in sexually mature and immature gilts and on granulosa-cell apoptosis in vitro were studied. The sexually mature gilts were treated with eCG on Day 11 of the estrous cycle, and effects were analyzed at different times after treatment with untreated animals at corresponding stages of the cycle as controls. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), hematoxylin and eosin staining, and DNA ladder. The proportion of apoptotic cells in atretic follicles (39%) was significantly higher (P<0.01) than that in healthy follicles (9%). At 24h after eCG treatment in mature gilts, the total number of follicles visible on the ovarian surface (57 per ovary), the number of small (<3mm) follicles (31.5 per ovary) and the number of medium-sized (3-5mm) follicles (23 per ovary) were significantly higher (P<0.05) than those of control animals (28, 20 and 6.5 per ovary, respectively), and declined gradually thereafter to below the level of control animals. The number of large (>or=5mm) follicles began to show a marked increase at 72h after eCG (8.5 versus 2.5, P<0.05). At 24h after eCG treatment, the proportions of apoptotic cells in small (7.2%) and medium-sized follicles (7.4%) were markedly lower (P<0.01) than those in controls (21.5 and 21%, respectively) and increased gradually thereafter to approach the level in controls. The percentage of apoptotic cells in large follicles (10% at 24h post-eCG) did not change significantly. Before eCG treatment, there were markedly fewer follicles of all types on ovaries of immature gilts than of mature gilts (9 versus 25 per ovary) and the proportion of apoptotic cells in small and medium follicles was high (25 and 34%, respectively). After eCG treatment, the changes in follicle number and proportion of apoptotic cells in the immature gilts followed a similar pattern to that of the mature gilts. Equine chorion gonadotropin inhibited apoptosis of granulosa cells cultured either in vitro or in intact follicles in a dose-dependent manner. Thus, follicular atresia in the pig, as in other animals, was characterized by apoptosis of large numbers of granulosa cells, and eCG promoted follicular development by inhibition of granulosa-cell apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Atresia Folicular/efeitos dos fármacos , Gonadotropinas Equinas/farmacologia , Células da Granulosa/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Suínos/fisiologia , Animais , Células Cultivadas , Fragmentação do DNA , Relação Dose-Resposta a Droga , Feminino , Atresia Folicular/fisiologia , Células da Granulosa/fisiologia , Marcação In Situ das Extremidades Cortadas/veterinária , Folículo Ovariano/fisiologiaRESUMO
The effect of serum starvation and olomoucine treatment on the cell cycle and apoptosis of goat skin fibroblasts cultured in vitro is reported in this paper. The cells were obtained from the ear of a female goat 1.5 years of age. Analysis of cell cycle distribution by fluorescence-activated cell sorting (FACS) showed that 3.4, 60.8 and 15.1% of normally cycling cells were at G1, G0 and S phase, respectively. Serum starvation for 1, 3 and 5 days arrested 70.1, 70.2 and 83.4% cells, respectively, at G0/G1 phase. Seventy-eight percent of confluent cells were at G0/G1 stage, but in contrast to the serum starved group, this high percentage of G0/G1 cells was mainly associated with G1 cells. Of cells not deprived of serum, 73.6% were arrested at G1/G0 when treated with 100 microM olomoucine for 9 h compared to 85.5% of cells that had been starved of serum for 2 days (co-inhibition) (P<0.01). After co-inhibition, 45% of cells entered S phase when re-cultured in normal medium for 5 h, indicating that the inhibition was reversible. Under normal culture conditions, 1.2% of cells underwent apoptosis. Serum starvation for 1, 2, 3, 5 and 10 days caused apoptosis in 1.7, 3.9, 4.5, 11.7 and 90.3% of cells, respectively. Treatment with 100 microM olomoucine for 9h did not increase the number of apoptotic cells significantly (1.9%, P>0.05). When cells were co-inhibited, 4.1% of cells underwent apoptosis. In conclusion, although serum withdrawal for 5 days or more effectively arrested cells at G0/G1 stages, it increased apoptosis of cells significantly. However, co-inhibition by serum withdrawal and olomoucine treatment was found to be an appropriate treatment to obtain more healthy G0/G1 cells based on the low percentage of apoptotic cells after treatment.
Assuntos
Apoptose/fisiologia , Ciclo Celular/fisiologia , Fibroblastos/citologia , Cabras , Pele/citologia , Animais , Apoptose/efeitos dos fármacos , Bromodesoxiuridina/metabolismo , Células Cultivadas , Meios de Cultura Livres de Soro , Inibidores Enzimáticos/farmacologia , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Citometria de Fluxo/veterinária , Cinetina , Purinas/farmacologia , Pele/efeitos dos fármacos , Pele/metabolismoRESUMO
The peripheral blood samples obtained from 32 ballet students with a mean age of 17.5 years and 32 age-matched non- dancers who comprised a control group were analysed using the microdeterminations of lymphocyte blast transformation and mixture rosette forming cells. The percentage of lymphocyte blast transformation of ballet students was normal, but their percentage of E-rosette forming cells was lower than that of controls at rest. A significant increase in the percentage of zymosan-complement rosette forming cells was seen during dancing. The study suggests that a saving effect on expenditure of cellular immunofunction is exhibited in ballet students at rest and that intensive ballet-exercise induces an immediate humoral immune response change. However, the effect needs to be dynamically observed and the clinical implication of the response change remains to be proved.
Assuntos
Dança , Imunidade Inata , Esforço Físico , Linfócitos T/imunologia , Adolescente , Formação de Anticorpos , Peso Corporal , Eritrócitos , Feminino , Humanos , Masculino , Formação de RosetaRESUMO
Taking the percentage of zymosan-complement complex rosette forming cells (ZC-RFC%) and the number of zymosan-complement Complex rosette forming cells (ZC-RFC) in the peripheral blood as indices of humoral immunity, bone marrow derived lymphocytes were detected by modified Sondra B cell assay in 24 healthy aged taking part in Taichiquan (88 style) exercise and 24 age-matched normal subjects without any physical training. At rest, the ZC-RFC% of the exercise group was lower than that of the controls; immediately following a set of Taichiquan exercise, the increments of ZC-RFC% and ZC-RFC were highly significant. These findings give evidence of humoral immunity which supports the viewpoint that Taichiquan exercise can induce enhancement of cellular immunity in the aged.
Assuntos
Envelhecimento/imunologia , Linfócitos B/imunologia , Exercício Físico/fisiologia , Idoso , Contagem de Células , Feminino , Humanos , Masculino , Artes Marciais , Pessoa de Meia-Idade , Formação de Roseta , Medicina EsportivaRESUMO
Follicular dendritic cell sarcomas are a recently described entity, with biphenotypic characteristics of lymphomas and sarcomas. The treatment is hardly consensual in the literature. We report two head and neck cases, of favorable outcome after surgery and radiotherapy. Histopathology and differential diagnoses are discussed as well as the therapeutic strategies used.