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1.
Br J Surg ; 107(2): e170-e178, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31903598

RESUMO

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.


ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Paraganglioma/cirurgia , Assistência Perioperatória/métodos , Feocromocitoma/cirurgia , Padrões de Prática Médica/estatística & dados numéricos , Adrenalectomia/métodos , Adrenalectomia/mortalidade , Antagonistas Adrenérgicos alfa/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/mortalidade , Resultado do Tratamento
2.
Dis Esophagus ; 32(6)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30462194

RESUMO

Long-term pharyngeal dysphagia is a common complication following head and neck cancer (HNC) therapies. High-level evidence for pharyngoesophageal junction (POJ) dilatation as a treatment in this population is lacking. We aimed to evaluate the safety and efficacy of POJ dilatation in dysphagic HNC survivors. This single-center, single-blind, placebo-controlled trial (St George Hospital, Sydney, Australia) randomly assigned (1:1) HNC survivors with long-term dysphagia (≥12 months postcompleted HNC therapies) to receive either graded endoscopic dilatations or sham dilatation (placebo). Patients were blinded to intervention types. Two strata were used for permuted randomization: (1) HNC therapies (total laryngectomy vs. chemoradiation alone); (2) Prior POJ dilatation (nil vs. previous dilatation). The primary endpoint was a short-term clinical response in swallowing function (3 months), defined as (1) a decrease in Sydney Swallow Questionnaire score by ≥200 or a score ≤ ULN; and (2) satisfactory global clinical assessment. The secondary endpoints were dysphagia relapse and serious adverse events. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000707369). Between 13 January 2013 and 16 January 2017, 41 patients were randomly assigned to endoscopic dilatation (n = 21) or placebo (n = 20). The short-term response rate in the endoscopic dilatation group was 76% (n = 16), compared with 5% (n = 1) in the placebo group (P < 0.001). There were no serious adverse events. The finding of a mucosal tear postdilatation was associated strongly with clinical response (OR 13.4, 95% CI [2.4, 74.9], P = 0.003). Kaplan-Meier estimate of dysphagia relapse is 50% by 9.6 months (95% CI [6.0, 19.2]) from completion of dilatation. Endoscopic dilatation of the POJ is a safe and efficacious therapy for the treatment of long-term dysphagia in HNC survivors. Close follow-up and repeat dilatation are necessary given the high dysphagia relapse rate.


Assuntos
Transtornos de Deglutição/terapia , Deglutição , Dilatação/métodos , Neoplasias de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia/efeitos adversos , Doença Crônica , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Dilatação/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Feminino , Humanos , Lacerações/etiologia , Laringectomia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mucosa/lesões , Estudos Prospectivos , Recidiva , Método Simples-Cego , Inquéritos e Questionários , Fatores de Tempo
3.
Br J Cancer ; 105(2): 272-80, 2011 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-21712826

RESUMO

BACKGROUND: The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER+) breast cancer after breast-conserving therapy (BCT). In all, 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC. METHODS: The ER+ tumours were classified as 'luminal A' (LA): ER+ and/or PR+, Ki-67 low, p53-, HER2- or 'luminal B' (LB): ER+ and/or PR+and/or Ki-67 high and/or p53+ and/or HER2+. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS). RESULTS: In all, 73 patients previously LA were re-classified as LB: a greater than four-fold increase (4.6-19.3%) compared with ER, PR, HER2 alone. In multivariate analysis, the LB signature independently predicted LRR (hazard ratio (HR) 3.612, 95% CI 1.555-8.340, P=0.003), DMFS (HR 3.023, 95% CI 1.501-6.087, P=0.002) and BCSS (HR 3.617, 95% CI 1.629-8.031, P=0.002) but not IBTR. CONCLUSION: The prognostic evaluation of ER+ breast cancer is improved using a marker panel, which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma/diagnóstico , Antígeno Ki-67/metabolismo , Receptores de Estrogênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/fisiologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma/metabolismo , Carcinoma/patologia , Carcinoma/terapia , Terapia Combinada , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/análise , Antígeno Ki-67/fisiologia , Mastectomia Segmentar , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Radioterapia Conformacional , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/fisiologia
4.
Clin Oncol (R Coll Radiol) ; 18(1): 70-6, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16477923

RESUMO

AIM: To test the viability of a full-scale randomised comparison of two steroid doses given with radiotherapy for malignant spinal-cord compression (MSCC), to test Internet randomisation and to compare different functional outcome measures. MATERIALS AND METHODS: A log of screened patients at eight recruiting centres was maintained. Patients were randomised via the Superdex website to either 96 mg or 16 mg daily of dexamethasone. Radiotherapy treatment was 30 Gy in 10 fractions. Outcomes assessed used ambulation, Barthel Index ambulation, Functional Independence Measure (FIM) ambulation and Functional Improvement Score (FIS) at 1 month. RESULTS: One hundred and thirty-one patients were screened. Ninety-three (71%) were ineligible, 65% of these were because duration of prior steroid use was greater than 12 h, failure to meet strict definition of magnetic resonance imaging, defined MSCC, multi-level disease or previous spinal-cord compression treatment. Twenty of the 38 eligible patients were randomised, including seven outside standard office hours. There was a high rate of serious adverse events (n = 9), but only one was considered likely to be related to study medication. At baseline, 75% were ambulant, 70% had FIM ambulation scores greater than 5 and 50% had Barthel Index ambulation scores greater than 2. At day 28, including all randomised patients (by scoring four dead patients as non-ambulant), ambulation scores by the various definitions were 60%, 45% and 40%, respectively. For the 16 patients evaluable at day 28, the mean FIS was -1.4. Median survival was 69 days and 1-year survival 13%. CONCLUSION: Web randomisation was successful; however, the high ineligibility rate precludes a full-scale dexamethasone dose trial in Australia. Choice of measure of ambulation has potentially significant effects on outcomes and implications for the design of any future MSCC trials. Referral delays are of concern.


Assuntos
Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Neoplasias/complicações , Compressão da Medula Espinal/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/efeitos adversos , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Projetos Piloto , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/radioterapia , Taxa de Sobrevida , Resultado do Tratamento , Caminhada
5.
J Clin Oncol ; 21(12): 2372-6, 2003 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-12805340

RESUMO

PURPOSE: To determine whether the inhalation of aromatherapy during radiotherapy reduces anxiety. PATIENTS AND METHODS: Three hundred thirteen patients undergoing radiotherapy were randomly assigned to receive either carrier oil with fractionated oils, carrier oil only, or pure essential oils of lavender, bergamot, and cedarwood administered by inhalation concurrently with radiation treatment. Patients underwent assessment by the Hospital Anxiety and Depression Scale (HADS) and the Somatic and Psychological Health Report (SPHERE) at baseline and at treatment completion. RESULTS: There were no significant differences in HADS depression or SPHERE scores between the randomly assigned groups. However, HADS anxiety scores were significantly lower at treatment completion in the carrier oil only group compared with either of the fragrant arms (P =.04). CONCLUSION: Aromatherapy, as administered in this study, is not beneficial.


Assuntos
Aromaterapia , Neoplasias/radioterapia , Óleos Voláteis/uso terapêutico , Radioterapia/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Ansiedade/prevenção & controle , Depressão/etiologia , Depressão/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Lavandula , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Placebos , Óleos de Plantas , Resultado do Tratamento
6.
Int J Radiat Oncol Biol Phys ; 31(2): 261-6, 1995 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-7836078

RESUMO

PURPOSE: To evaluate the results of a departmental treatment policy in a consecutive series of patients with nonsmall cell carcinoma of the lung. A second purpose was to estimate the survival of patients treated with radical intent. A third purpose was to estimate the impact of comorbidity on the selection of patients for treatment and on its outcome. METHODS AND MATERIALS: The records of 720 consecutive patients referred to a single Department of Radiation Oncology between 1979 and 1985 were reviewed. One hundred fifty patients with early stage (Stage I and II disease) were studied in detail and the results are presented for the outcome of 103 patients treated by radical radiotherapy. All patients were followed for a minimum period of five years or until death. RESULTS: Patients referred for radiation therapy were elderly and usually had squamous cell carcinoma of the lung. Comorbidity was significant as was weight loss which occurred in a third of patients. The overall survival of patients treated with radical intent was 13%. In a small subgroup of patients with T1 tumors without weight loss and aged under 70 survival reached 50% at 5 years with no treatment-related mortality and with insignificant treatment-related morbidity. CONCLUSION: Highly selected subsets of patients suitable for treatment with radiotherapy can be defined equally as well as highly selected subsets of patients can be selected for surgery. Treatment outcome can be surprisingly good in these subsets indicating that the treatment of nonsmall cell lung cancer, particularly in older patients without comorbidity should not automatically be by a surgical approach.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Doenças Cardiovasculares/epidemiologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Morbidade , Estadiamento de Neoplasias , Radioterapia/efeitos adversos , Radioterapia/mortalidade , Análise de Regressão , Doenças Respiratórias/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Redução de Peso
7.
Breast ; 11(1): 66-71, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14965648

RESUMO

This study aimed to assess exposure to flying in breast cancer survivors and assess the relationship of flying to lymphoedema. A total of 293 relapse-free breast cancer survivors with known pathology and treatment details and prospectively measured arm circumferences were surveyed for their flight exposure and precautions history. Of these, 287 responded, with a mean follow-up of 31.6 (4-111) months. A total of 50.5% had flown, and of these, 27% had travelled overseas. The mean number of flights was 5.3 (1-100); 24% had taken lymphoedema precautions, 90% of which utilized compression techniques. There was no significant difference in lymphoedema rates for fliers (11.2%) and non-fliers (8.3%). No woman reported permanent (new or increased) swelling after flying. Of the nine reporting temporary swelling, six reported 1-3 concurrent potential risk factors. On regression modelling for both measured and self-reported swelling endpoints the use of precautions (OR 5.6 for lymphoedema and 3.7 for flight-related temporary swelling) were statistically significant. For patient-reported swelling, the number of positive nodes (OR 1.2) and the number of overseas flights (OR 1.4) was also significant, whereas for clinical lymphoedema age (OR 1.07) was significant. We conclude that domestic air travel (<4.5 h) is low risk and that compression devices are possibly counterproductive.

8.
Syst Appl Microbiol ; 22(3): 378-86, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10553290

RESUMO

Twenty-two rhizobial strains isolated from the root nodules of two Chinese peanut cultivars (Arachis hypogaea L. Tianfu no. 3 and a local cultivar) growing at four different sites in the Sichuan province, Southwest China, were characterized by growth rate, rep-PCR, PCR-RFLP of 16S rDNA, partial sequencing of ribosomal genes, and fatty acid-methyl ester analysis (FAME), and compared with strains representing Bradyrhizobium japanicum, B. elkanii and other unclassified Bradyrhizobium sp. All peanut isolates from Sichuan were bradyrhizobia. Dendrograms constructed using the rep-PCR fingerprints grouped the strains mainly according to their geographic and cultivar origin. Based on PCR-RFLP and partial sequence analysis of 16S rDNA it appears that peanut bradyrhizobial strains from Sichuan are similar to peanut strains from Africa and Israel, and closely related to B. japonicum. In contrast, analysis of FAME data using two-dimensional principal component analysis indicated that Bradyrhizobium sp. (Arachis) were similar to, but slightly different from other bradyrhizobia. The presence and level of fatty acid 16:1 w5c was the distinguishing feature. The results of PCR-RFLP of the 16S rRNA gene, the partial sequence analysis of 16S rDNA, and FAME were in good agreement.


Assuntos
Arachis/microbiologia , Bradyrhizobium/classificação , Sequência de Bases , Bradyrhizobium/química , Bradyrhizobium/fisiologia , China , Impressões Digitais de DNA , Ácidos Graxos/análise , Dados de Sequência Molecular , Filogenia , Raízes de Plantas/microbiologia , RNA Bacteriano/análise , RNA Ribossômico 16S/análise
9.
Clin Oncol (R Coll Radiol) ; 26(11): 697-703, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25239671

RESUMO

AIMS: Dysphagia is a well-recognised acute complication after radiotherapy. However, knowledge about the long-term prevalence and effect remains limited. The aims of this study were to determine the prevalence, severity, morbidity, time course and reporting patterns of dysphagia symptoms after head and neck radiotherapy. MATERIALS AND METHODS: An observational cross-sectional study was conducted in a large consecutive series of head and neck cancer patients. All patients in the St George Hospital Cancer Care database who had received head and neck radiotherapy with curative intent 0.5-8 years previously and recorded as being alive were surveyed using the Sydney Swallow Questionnaire (SSQ). Case notes were reviewed to determine the level of awareness of swallowing dysfunction in all patients, as well as the causes of mortality in the 83 deceased patients. RESULTS: The mean follow-up at the time of survey was 3 years after radiotherapy (range 0.5-8 years). Of the 116 patients surveyed by questionnaire, the response rate was 72% (83). Impaired swallowing (SSQ score > 234) was reported by 59% of patients. Dysphagia severity was not predicted by tumour site or stage, nor by the time since therapy, age, gender or adjuvant chemotherapy. Review of the hospital medical records and cancer database revealed that cancer accounted for 55% of deaths and aspiration pneumonia was responsible for 19% of non-cancer-related deaths. Of those with abnormal SSQ scores, only 47% reported dysphagia during follow-up clinic visits. CONCLUSIONS: Persistent dysphagia is a prevalent, under-recognised and under-reported long-term complication of head and neck radiotherapy which currently cannot be predicted on the basis of patient, tumour or treatment characteristics. Aspiration pneumonia is an important contributor to non-cancer-related mortality in these patients. These data highlight the need for closer monitoring of swallow dysfunction and its sequelae in this population.


Assuntos
Transtornos de Deglutição/mortalidade , Deglutição , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/radioterapia , Lesões por Radiação/mortalidade , Radioterapia de Intensidade Modulada/efeitos adversos , Estudos Transversais , Transtornos de Deglutição/etiologia , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida
10.
Cell Death Dis ; 5: e1437, 2014 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-25275598

RESUMO

The PI3K/Akt/mTOR pathway has a central role in cancer metastasis and radiotherapy. To develop effective therapeutics to improve radiosensitivity, understanding the possible pathways of radioresistance involved and the effects of a combination of the PI3K/Akt/mTOR inhibitors with radiotherapy on prostate cancer (CaP) radioresistant cells is needed. We found that compared with parent CaP cells, CaP-radioresistant cells demonstrated G0/G1 and S phase arrest, activation of cell cycle check point, autophagy and DNA repair pathway proteins, and inactivation of apoptotic proteins. We also demonstrated that compared with combination of single PI3K or mTOR inhibitors (BKM120 or Rapamycin) and radiation, low-dose of dual PI3K/mTOR inhibitors (BEZ235 or PI103) combined with radiation greatly improved treatment efficacy by repressing colony formation, inducing more apoptosis, leading to the arrest of the G2/M phase, increased double-strand break levels and less inactivation of cell cycle check point, autophagy and non-homologous end joining (NHEJ)/homologous recombination (HR) repair pathway proteins in CaP-radioresistant cells. This study describes the possible pathways associated with CaP radioresistance and demonstrates the putative mechanisms of the radiosensitization effect in CaP-resistant cells in the combination treatment. The findings from this study suggest that the combination of dual PI3K/Akt/mTOR inhibitors (BEZ235 or PI103) with radiotherapy is a promising modality for the treatment of CaP to overcome radioresistance.


Assuntos
Autofagia , Reparo do DNA por Junção de Extremidades , Inibidores Enzimáticos/farmacologia , Recombinação Homóloga , Inibidores de Fosfoinositídeo-3 Quinase , Neoplasias da Próstata/fisiopatologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Reparo do DNA por Junção de Extremidades/efeitos dos fármacos , Reparo do DNA por Junção de Extremidades/efeitos da radiação , Recombinação Homóloga/efeitos dos fármacos , Recombinação Homóloga/efeitos da radiação , Humanos , Masculino , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
11.
Cell Death Dis ; 4: e875, 2013 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-24157869

RESUMO

Radioresistance is a major challenge in prostate cancer (CaP) radiotherapy (RT). In this study, we investigated the role and association of epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and the PI3K/Akt/mTOR signaling pathway in CaP radioresistance. We developed three novel CaP radioresistant (RR) cell lines (PC-3RR, DU145RR and LNCaPRR) by radiation treatment and confirmed their radioresistance using a clonogenic survival assay. Compared with untreated CaP-control cells, the CaP-RR cells had increased colony formation, invasion ability and spheroid formation capability (P<0.05). In addition, enhanced EMT/CSC phenotypes and activation of the checkpoint proteins (Chk1 and Chk2) and the PI3K/Akt/mTOR signaling pathway proteins were also found in CaP-RR cells using immunofluorescence, western blotting and quantitative real-time PCR (qRT-PCR). Furthermore, combination of a dual PI3K/mTOR inhibitor (BEZ235) with RT effectively increased radiosensitivity and induced more apoptosis in CaP-RR cells, concomitantly correlated with the reduced expression of EMT/CSC markers and the PI3K/Akt/mTOR signaling pathway proteins compared with RT alone. Our findings indicate that CaP radioresistance is associated with EMT and enhanced CSC phenotypes via activation of the PI3K/Akt/mTOR signaling pathway, and that the combination of BEZ235 with RT is a promising modality to overcome radioresistance in the treatment of CaP. This combination approach warrants future in vivo animal study and clinical trials.


Assuntos
Transição Epitelial-Mesenquimal , Células-Tronco Neoplásicas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tolerância a Radiação , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/efeitos da radiação , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos da radiação , Humanos , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Masculino , Modelos Biológicos , Invasividade Neoplásica , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/enzimologia , Fenótipo , Inibidores de Fosfoinositídeo-3 Quinase , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/radioterapia , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/efeitos da radiação , Reprodutibilidade dos Testes , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia , Esferoides Celulares/efeitos da radiação , Serina-Treonina Quinases TOR/antagonistas & inibidores
12.
Int J Radiat Oncol Biol Phys ; 77(3): 648-54, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-19836153

RESUMO

PURPOSE: The present study compared the intracranial control rate and quality of life for two radiation fractionation schemes for cerebral metastases. METHODS AND MATERIALS: A total of 113 patients with a Eastern Cooperative Oncology Group performance status <3; and stable (>2 months), absent, or concurrent presentation of extracranial disease were randomized to 40 Gy in 20 twice-daily fractions (Arm A) or 20 Gy in four daily fractions (Arm B), stratified by resection status. The European Organization for Research and Treatment of Cancer Quality of Life 30-item questionnaire was administered monthly during Year 1, bimonthly during Year 2, and then every 6 months to Year 5. RESULTS: The patient age range was 28-83 years (mean 62). Of the 113 patients, 41 had undergone surgical resection, and 74 patients had extracranial disease (31 concurrent and 43 stable). The median survival time was 6.1 months in Arm A and 6.6 months in Arm B, and the overall 5-year survival rate was 3.5%. Intracranial progression occurred in 44% of Arm A and 64% of Arm B patients (p = .03). Salvage surgery or radiotherapy was used in 4% of Arm A patients and 21% of Arm B patients (p = .004). Death was attributed to central nervous system progression in 32% of patients in Arm A and 52% of patients in Arm B (p = .03). The toxicity was minimal, with a minor increase in short-term cutaneous reactions in Arm A. The patients' quality of life was not impaired by the more intense treatment in Arm A. CONCLUSION: Intracranial disease control was improved and the quality of life was maintained with 40 Gy in 20 twice-daily fractions. This schema should be considered for better prognosis subgroups of patients with cerebral metastases.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Irradiação Craniana/mortalidade , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Inquéritos e Questionários , Taxa de Sobrevida
13.
J Med Imaging Radiat Oncol ; 53(6): 569-73, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20002290

RESUMO

Proscription of antiperspirant or deodorant use during adjuvant breast radiotherapy is common. The investigators were seeking an information base to facilitate design of an appropriate controlled trial of the use of deodorants during radiotherapy. The first component consisted of a survey of women after adjuvant breast radiotherapy seeking information about routine deodorant use and potential concern if deodorants were not permitted during radiotherapy. The second component comprised a literature search for any existing controlled evidence regarding harm from deodorant use during radiotherapy. Four hundred fourteen women completed surveys. Two hundred eighty recalled advice against deodorants. Two hundred ninety-nine women routinely used deodorants, 70% of whom used roll-on products. Forty-five continued deodorant use during radiation, 20 of these despite recalling advice not to wear a deodorant. Of the 233 women who routinely wore a deodorant but abstained during radiotherapy, 19% expressed a lot of concern about body odour and 45% were slightly concerned. Three controlled studies totalling 310 patients report specific deodorants versus no deodorant use which did not show statistically significantly increased skin reactions, but had only a small subset with axillary irradiation. The proscription of deodorant use during radiotherapy is of unproven benefit and causes body odour concern to the majority of women who are usual deodorant users. The next most appropriate trial would compare use of the usual deodorant versus no deodorant, would encompass a significant number of women with radiotherapy to the axilla or application of deodorant to irradiated skin areas, and include endpoints other than skin reaction alone.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/radioterapia , Desodorantes , Toxidermias/epidemiologia , Cooperação do Paciente/estatística & dados numéricos , Radiodermite/epidemiologia , Radioterapia Adjuvante/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Comorbidade , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência
14.
J Med Imaging Radiat Oncol ; 53(2): 234-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19527373

RESUMO

Malignant myoepithelioma of the breast (MMB) is a rare and often aggressive disease with poor prognosis. Little is known regarding its optimal treatment and progression. We describe the clinical history of a woman following excision of a benign adenomyoepithelioma which recurred years later as a radioresistant malignant myoepithelioma with high levels of ataxia telangiectasia mutated protein and mutant p53 (Cys135Phe). MMB requires close follow-up and aggressive treatment. If adjuvant radiotherapy is adopted to improve local control, minimal postoperative delay and higher doses than for standard post-mastectomy radiation are recommended.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/radioterapia , Proteínas de Ciclo Celular/análise , Proteínas de Ligação a DNA/análise , Mioepitelioma/radioterapia , Proteínas Serina-Treonina Quinases/análise , Proteínas Supressoras de Tumor/análise , Proteínas Mutadas de Ataxia Telangiectasia , Feminino , Humanos , Pessoa de Meia-Idade , Falha de Tratamento
15.
Can J Microbiol ; 53(3): 351-63, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17538644

RESUMO

The increase in human population and the spread of agriculture over the past 150 years have transformed the landscape in west-central Minnesota into a mosaic of agricultural fields and urban land, leaving only remnants of the once dominant prairie ecosystem. Limited natural habitat in this fragmented landscape threatens the diversity and abundance of native legumes and could impact the size and function of associated belowground microbial populations. In this study, BOXA1R PCR and 16S rRNA gene sequence analyses were used to assess the genetic diversity of rhizobia associated with Dalea purpurea (Vent.) in nine prairie remnants ranging in size from 0.04 to 3.5 ha. The variation in soil properties was also determined. While 53 different genotypes of rhizobia were identified, four of these accounted for 84% of the 1029 rhizobia characterized using BOXA1R PCR. Representatives from three of the four dominant genotypes had a 16S rRNA gene sequence similar to that of Rhizobium gallicum, with two of these genotypes recovered at all sites. The fourth genotype was similar to that of Rhizobium etli and occurred with frequency at only two sites. Rhizobium genotype richness and site area were positively correlated. The implications of these results are discussed.


Assuntos
Ecossistema , Fabaceae/microbiologia , Variação Genética , Rhizobium/classificação , Rhizobium/genética , DNA Bacteriano/análise , DNA Ribossômico/análise , Fabaceae/crescimento & desenvolvimento , Genes de RNAr , Genótipo , Minnesota , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase/métodos , RNA Ribossômico 16S/genética , Rhizobium/isolamento & purificação , Rhizobium etli/classificação , Rhizobium etli/genética , Rhizobium etli/isolamento & purificação , Análise de Sequência de DNA , Solo/análise
16.
Australas Radiol ; 50(4): 342-8, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16884421

RESUMO

The aim of this study was to audit the results of a high-dose, combined-modality prospective protocol for non-small-cell lung cancer in terms of survival, disease-specific survival and toxicity. One hundred and twenty-one patients with non-small-cell lung cancer were treated with a concurrent, end-phase, boost, high-dose radiotherapy protocol with 65 Gy in 35 fractions for more than 5 weeks. Sixty-six patients received radiotherapy alone (group 1), 29 received concurrent chemoradiation (group 2) and 26 received neoadjuvant and concurrent chemotherapy (group 3). Thirty-four patients had stage I disease, six had stage II and 81 had stage III. Overall median survival was 23 months: 75% at 1 year and 23% at 5 years. Median survivals for patients with stage I and stages II and III disease were 43 and 19 months, respectively. For stages II and III patients by groups 1-3, median survivals were 18, 25 and 18 months, respectively, and 2-year survivals were 36, 52 and 38%, respectively. Toxicity was acceptable. Overall, 9% had symptomatic pneumonitis and 7% had grades 3 and 4 oesophagitis. For those who had the mediastinum included in the volume, grade > or = 3 oesophagitis occurred in 0, 11 and 22% (n = 110, P = 0.001), respectively, for treatment groups 1-3. Overall treatment-related mortality was 3%, consisting of two septic deaths, one pneumonitis and possibly one late cardiac event, all occurring in patients who had chemotherapy (7% of 55 patients). Treatment-related mortality declined over the study period. Accelerated radiotherapy was well tolerated, with only moderate increased acute toxicity when combined with concurrent platinum chemotherapy. Toxicity was enhanced by induction chemotherapy. Overall survival outcomes were excellent for this condition. Continued use of this radiotherapy schedule is recommended as the platform for assessment of other chemotherapy schedules.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Distribuição de Qui-Quadrado , Cisplatino/uso terapêutico , Terapia Combinada , Fracionamento da Dose de Radiação , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Pneumonite por Radiação/epidemiologia , Dosagem Radioterapêutica , Taxa de Sobrevida , Resultado do Tratamento
17.
Can J Microbiol ; 51(1): 15-23, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15782230

RESUMO

Habitat fragmentation affects the biodiversity and function of aboveground organisms in natural ecosystems but has not been studied for effects on belowground species. In this paper, we consider the diversity of the rhizobia associated with the indigenous legume Dalea purpurea in 3 residual prairie areas in Minnesota and Iowa. Using Dalea purpurea as a trap host, 218 rhizobia were recovered from these soils then characterized using BOXA1R PCR. Three major and 13 minor groups were distinguished based on a similarity of greater than 75% in fingerprint patterns. Each major group consisted almost exclusively of rhizobia from a single prairie, with the diversity of Dalea rhizobia recovered from the Hayden Prairie less than that obtained with rhizobia from the other prairies. Based on 16S rRNA gene sequence analysis, isolates from the Hayden, Ordway, and Kellogg-Weaver Dunes prairies were most similar to Rhizobium etli and Rhizobium leguminosarum, Rhizobium gallicum, and Mesorhizobium amorphae and Mesorhizobium huakuii, respectively. This variation in the dominant microsymbiont species across the 3 prairies studied was unexpected but could have been influenced by the limited number of samples that we were allowed to take, by unanticipated cross-nodulation between native legumes, and by variation in the range of legume species present in each residual prairie area. While some of the rhizobia from Dalea nodulated Phaseolus vulgaris, Macroptilium atropurpureum, Leucaena leucocephala, and Onobrychis viciifolia in addition to the Dalea species tested, others nodulated Astragalus canadensis or Amorpha canescens.


Assuntos
Fabaceae/microbiologia , Rhizobium/classificação , Microbiologia do Solo , DNA Bacteriano/análise , DNA Ribossômico/análise , Ecossistema , Fabaceae/crescimento & desenvolvimento , Genes de RNAr , Variação Genética , Iowa , Minnesota , Fixação de Nitrogênio , Filogenia , Reação em Cadeia da Polimerase/métodos , RNA Ribossômico 16S/genética , Rhizobium/genética , Rhizobium/isolamento & purificação , Rhizobium/metabolismo , Especificidade da Espécie , Simbiose
18.
Med J Aust ; 160(10): 625-7, 1994 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-8177108

RESUMO

OBJECTIVE: To investigate how much information a specialist oncologist receives at the time of initial assessment of referred patients. PATIENTS AND METHOD: Prospective audit of 103 new patients referred to the Department of Radiation Oncology, Westmead Hospital--based on referral letters; availability of blood, radiology and histopathology investigations; and the use of interpreters. RESULTS: Eighty of 103 patients had a referral letter; a positive correlation was found between the provision of a letter and the availability of the result of a critical investigation. Results were not available at the time of assessment for a third of the investigations. Interpreter use was inadequate. CONCLUSION: The communication of information to specialists can be improved, and will help optimise the delivery of specialist services.


Assuntos
Comunicação , Relações Interprofissionais , Encaminhamento e Consulta , Austrália , Humanos , Ambulatório Hospitalar
19.
Appl Microbiol ; 17(5): 769-70, 1969 May.
Artigo em Inglês | MEDLINE | ID: mdl-5785965

RESUMO

A new medium has been developed for selectively isolating strains of Rhizobium from soil.


Assuntos
Meios de Cultura , Rhizobium/isolamento & purificação , Microbiologia do Solo
20.
Can J Microbiol ; 42(8): 844-50, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22049998

RESUMO

Common bean (Phaseolus vulgaris L.) is a traditional crop in much of Latin America, where it is often planted into soils containing numerous, sometimes ineffective, indigenous rhizobia. The presence of these indigenous organisms can limit response to inoculation. Because of this, we have sought bean cultivars that will nodulate preferentially with the inoculant strain, and have previously reported on the preference between the bean cultivar RAB39 and strains of Rhizobium tropici. We have detailed this interaction using the inoculant-quality strain UMR1899. In the present study the root tip marking (RTM) technique was used to demonstrate that this preference in nodulation was evident, even when inoculation with UMR1899 was delayed up to 8 relative to that with Rhizobium etli UMR1632. In contrast to studies with other legumes, roots of RAB39 were not predisposed to nodulate with UMR1632, even though preexposed to this strain for considerable periods of time. The presence of UMR1899 actually reduced nodulation by UMR1632 substantially, even when inoculation with UMR1899 was significantly delayed. When UMR1899 and UMR1632 were applied to separate halves of a split-root system, the number of nodules on the side receiving UMR1632 was less than for the half root inoculated with UMR1899, but the differences were not significant. This suggests that the preference response is not systemic but requires proximity between the strains involved. UMR1899 produced more than 50% of the nodules even when the ratio of UMR1632:UMR1899 in the inoculant was 10:1. The results are further evidence of a stable and marked preference of RAB39 for UMR1899, which warrants a more detailed study at the field level.Key words: Phaseolus vulgaris L., common bean, delayed inoculation, strain preference, cell proportions.

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