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1.
Biochem Biophys Res Commun ; 478(1): 162-167, 2016 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-27444382

RESUMEN

Ergothioneine (ET), a naturally occurring thione, can accumulate in the human body at high concentrations from diet. Following absorption via a specific transporter, OCTN1, ET may accumulate preferentially in tissues predisposed to higher levels of oxidative stress and inflammation. Given its potential cytoprotective effects, we examined how ET levels change with age. We found that whole blood ET levels in elderly individuals decline significantly beyond 60 years of age. Additionally, a subset of these subjects with mild cognitive impairment had significantly lower plasma ET levels compared with age-matched subjects. This decline suggests that deficiency in ET may be a risk factor, predisposing individuals to neurodegenerative diseases.


Asunto(s)
Envejecimiento/metabolismo , Disfunción Cognitiva/sangre , Disfunción Cognitiva/epidemiología , Ergotioneína/sangre , Enfermedades Neurodegenerativas/sangre , Enfermedades Neurodegenerativas/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Disfunción Cognitiva/diagnóstico , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Enfermedades Neurodegenerativas/diagnóstico , Reproducibilidad de los Resultados , Medición de Riesgo/métodos , Factores de Riesgo , Sensibilidad y Especificidad , Singapur/epidemiología
2.
Chem Soc Rev ; 44(3): 790-814, 2015 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-25408245

RESUMEN

Nanotechnology refers to the fabrication, characterization, and application of substances in nanometer scale dimensions for various ends. The influence of nanotechnology on the healthcare industry is substantial, particularly in the areas of disease diagnosis and treatment. Recent investigations in nanotechnology for drug delivery and tissue engineering have delivered high-impact contributions in translational research, with associated pharmaceutical products and applications. Over the past decade, the synthesis of nanofibers or nanoparticles via electrostatic spinning or spraying, respectively, has emerged as an important nanostructuring methodology. This is due to both the versatility of the electrospinning/electrospraying process and the ensuing control of nanofiber/nanoparticle surface parameters. Electrosprayed nanoparticles and electrospun nanofibers are both employed as natural or synthetic carriers for the delivery of entrapped drugs, growth factors, health supplements, vitamins, and so on. The role of nanofiber/nanoparticle carriers is substantiated by the programmed, tailored, or targeted release of their contents in the guise of tissue engineering scaffolds or medical devices for drug delivery. This review focuses on the nanoformulation of natural materials via the electrospraying or electrospinning of nanoparticles or nanofibers for tissue engineering or drug delivery/pharmaceutical purposes. Here, we classify the natural materials with respect to their animal/plant origin and macrocyclic, small molecule or herbal active constituents, and further categorize the materials according to their proteinaceous or saccharide nature.


Asunto(s)
Materiales Biocompatibles , Sistemas de Liberación de Medicamentos , Nanopartículas , Nanotecnología , Ingeniería de Tejidos , Animales , Células Cultivadas , Técnicas Electroquímicas , Humanos , Ratones , Ratas
4.
Cochrane Database Syst Rev ; (3): CD009454, 2014 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-24585087

RESUMEN

BACKGROUND: The benefits of adding upfront whole-brain radiotherapy (WBRT) to surgery or stereotactic radiosurgery (SRS) when compared to surgery or SRS alone for treatment of brain metastases are unclear. OBJECTIVES: To compare the efficacy and safety of surgery or SRS plus WBRT with that of surgery or SRS alone for treatment of brain metastases in patients with systemic cancer. SEARCH METHODS: We searched MEDLINE, EMBASE and The Cochrane Central Register of Controlled Trials (CENTRAL) up to May 2013 and annual meeting proceedings of ASCO and ASTRO up to September 2012 for relevant studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing surgery or SRS plus WBRT with surgery or SRS alone for treatment of brain metastases. DATA COLLECTION AND ANALYSIS: Two review authors undertook the quality assessment and data extraction. The primary outcome was overall survival (OS). Secondary outcomes include progression free survival (PFS), local and distant intracranial disease progression, neurocognitive function (NF), health related quality of life (HRQL) and neurological adverse events. Hazard ratios (HR), risk ratio (RR), confidence intervals (CI), P-values (P) were estimated with random effects models using Revman 5.1 MAIN RESULTS: We identified five RCTs including 663 patients with one to four brain metastases. The risk of bias associated with lack of blinding was high and impacted to a greater or lesser extent on the quality of evidence for all of the outcomes. Adding upfront WBRT decreased the relative risk of any intracranial disease progression at one year by 53% (RR 0.47, 95% CI 0.34 to 0.66, P value < 0.0001, I(2) =34%, Chi(2) P value = 0.21, low quality evidence) but there was no clear evidence of a difference in  OS (HR 1.11, 95% CI 0.83 to 1.48, P value = 0.47, I(2) = 52%, Chi(2) P value = 0.08, low quality evidence) and PFS (HR 0.76, 95% CI 0.53 to 1.10, P value = 0.14, I(2) = 16%, Chi(2) P value = 0.28, low quality evidence). Subgroup analyses showed that the effects on overall survival were similar regardless of types of focal therapy used, number of brain metastases, dose and sequence of WBRT. The evaluation of the impact of upfront WBRT on NF, HRQL and neurological adverse events was limited by the unclear and high risk of reporting, performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies. AUTHORS' CONCLUSIONS: There is low quality evidence that adding upfront WBRT to surgery or SRS decreases any intracranial disease progression at one year. There was no clear evidence of an effect on overall and progression free survival. The impact of upfront WBRT on neurocognitive function, health related quality of life and neurological adverse events was undetermined due to the high risk of performance and detection bias, and inconsistency in the instruments and methods used to measure and report results across studies.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Irradiación Craneana/métodos , Radiocirugia , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
Gynecol Oncol ; 131(1): 93-8, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23906655

RESUMEN

OBJECTIVE: To review the characteristics, outcomes and toxicities of cervical cancer patients treated with 6 fractions of brachytherapy after external beam radiotherapy (EBRT). METHODS: All patients diagnosed with cervical cancer from 2000 to 2009 who were referred for radical treatment and who received 6 fractions of brachytherapy were retrospectively reviewed. Overall survival (OS), disease free survival (DFS), local control (LC), distant control (DC) rate, acute and late toxicities were the primary endpoints. RESULTS: Thirty-two patients with mainly advanced stage squamous cell carcinoma were identified and reviewed. Patients received EBRT of 45 to 50.4 Gy in 1.8 Gy daily fractions followed by 6 sessions of 3 channel brachytherapy of 5.3 Gy prescribed to point H. Response rates to treatment were good, with no residual disease in 84% six weeks after the completion of treatment. With a median follow up time of 8.1 years, the five-year OS, DFS, LC and distant control rates were 75%, 68.5%, 92.8% and 76.9% respectively. None of the patients developed any G3-4 acute toxicity but one patient who had advanced disease developed G3-4 proctitis with a fistula formation. CONCLUSIONS: HDR brachytherapy utilizing 6 fractions of 5.3 Gy prescribed to point H with concurrent chemo-radiation is superior in terms of OS and LC to regimens that deliver a lower EQD2 dose to point A/H and is associated with very low rates of toxicities.


Asunto(s)
Adenocarcinoma/radioterapia , Braquiterapia/efectos adversos , Carcinoma de Células Escamosas/radioterapia , Neoplasias del Cuello Uterino/radioterapia , Adenocarcinoma/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Quimioterapia Adyuvante , Enfermedad Crónica , Cisplatino/uso terapéutico , Cistitis/etiología , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Gastroenteritis/etiología , Humanos , Persona de Mediana Edad , Neoplasia Residual , Proctitis/etiología , Traumatismos por Radiación/etiología , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adulto Joven
6.
Front Immunol ; 14: 1196931, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37457726

RESUMEN

Rheumatoid arthritis (RA) is a destructive inflammatory autoimmune disease that causes pain and disability. Many of the currently available drugs for treating RA patients are aimed at halting the progression of the disease and alleviating inflammation. Further, some of these treatment options have drawbacks, including disease recurrence and adverse effects due to long-term use. These inefficiencies have created a need for a different approach to treating RA. Recently, the focus has shifted to direct targeting of transcription factors (TFs), as they play a vital role in the pathogenesis of RA, activating key cytokines, chemokines, adhesion molecules, and enzymes. In light of this, synthetic drugs and natural compounds are being explored to target key TFs or their signaling pathways in RA. This review discusses the role of four key TFs in inflammation, namely NF-κB, STATs, AP-1 and IRFs, and their potential for being targeted to treat RA.


Asunto(s)
Artritis Reumatoide , Factores de Transcripción , Humanos , FN-kappa B/metabolismo , Transducción de Señal , Inflamación/tratamiento farmacológico
7.
iScience ; 26(10): 108079, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37860753

RESUMEN

Glucocorticoids (GCs) are potent anti-inflammatory agents and are broadly used in treating rheumatoid arthritis (RA) patients, albeit with adverse side effects associated with long-term usage. The negative consequences of GC therapy provide an impetus for research into gaining insights into the molecular mechanisms of GC action. We have previously reported that granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced CCL17 has a non-redundant role in inflammatory arthritis. Here, we provide molecular evidence that GCs can suppress GM-CSF-mediated upregulation of IRF4 and CCL17 expression via downregulating JMJD3 expression and activity. In mouse models of inflammatory arthritis, GC treatment inhibited CCL17 expression and ameliorated arthritic pain-like behavior and disease. Significantly, GC treatment of RA patient peripheral blood mononuclear cells ex vivo resulted in decreased CCL17 production. This delineated pathway potentially provides new therapeutic options for the treatment of many inflammatory conditions, where GCs are used as an anti-inflammatory drug but without the associated adverse side effects.

8.
Rheumatol Autoimmun ; 2(2): 92-97, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35942411

RESUMEN

Introduction: The mRNA vaccines Comirnaty (Pfizer/BioNTech) and Spikevax (Moderna) are considered safe and highly effective against SARS-COV2. However, they are also associated with a small increased risk of pericarditis and myocarditis. There is concern about an increased risk of these complications in patients with autoimmune inflammatory rheumatic diseases (AIRD). Case Report: We describe three patients with pre-existing AIRD who developed myocarditis or pericarditis shortly after receiving their first dose of the Pfizer-BioNTech vaccine. The first case is a 31-year-old female with systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APLS) who presented 7 days after receiving the Pfizer-BioNTech vaccine and was diagnosed with myopericarditis following a positive troponin and abnormal transthoracic echocardiogram (TTE). The second case is a 29-year-old man with seronegative inflammatory arthritis and APLS who presented 7 days after receiving the first dose of the Pfizer-BioNTech vaccine. His troponin and TTE were unremarkable however his ECG showed widespread ST elevation. Lastly, the third case is a 34-year-old man with Behcet's disease with a history of recurrent pericarditis. He developed a recurrence of symptoms approximately 7 days after his Pfizer-BioNTech vaccine and self-commenced prednisolone at home. He had normal laboratory and radiological findings. All patients received prednisolone resulting in a quick recovery and resolution of symptoms. Discussion: In this review we discuss the association between myocarditis, pericarditis and mRNA COVID-19 vaccines, those who are at greatest risk and current clinical considerations. We also discuss the possible increased risk in AIRD patients and the current research supporting this.

9.
Clin Rheumatol ; 40(3): 867-875, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32740672

RESUMEN

INTRODUCTION/OBJECTIVES: To evaluate the incidence rate (IR) of tuberculosis (TB) and viral hepatitis B and C (HBV/HCV) during certolizumab pegol (CZP) treatment, worldwide and in Asia-Pacific countries, across clinical trials and post-marketing reports (non-interventional studies and real-world practice). METHOD: CZP safety data were pooled across 49 clinical trials from 1998 to June 2017. Post-marketing reports were from initial commercialization until March 2015 (TB)/February 2017 (HBV/HCV). All suspected TB and HBV/HCV cases underwent centralized retrospective review by external experts. Incidence rates (IRs) were calculated per 100 patient-years (PY) of CZP exposure. RESULTS: Among 11,317 clinical trial patients (21,695 PY), 62 TB cases were confirmed (IR 0.29/100 PY) including 2 in Japan (0.10/100 PY) and 3 in other Asia-Pacific countries (0.58/100 PY). From > 238,000 PY estimated post-marketing CZP exposure, there were 31 confirmed TB cases (0.01/100 PY): 5 in Japan (0.05/100 PY), 1 in other Asia-Pacific countries (0.03/100 PY). Reported regional TB IRs were highest in eastern Europe (0.17/100 PY), central Europe (0.09/100 PY), and Mexico (0.16/100 PY). Across clinical trials, there was 1 confirmed HBV reactivation and no HCV cases. From > 420,000 PY estimated post-marketing CZP exposure, 5 HBV/HCV cases were confirmed (0.001/100 PY): 2 HCV reactivations; 1 new HCV; plus 2 HBV reactivations in Japan (0.008/100 PY). CONCLUSIONS: CZP TB risk is aligned with nationwide TB rates, being slightly higher in Asia-Pacific countries excluding Japan. Overall, TB and HBV/HCV risk with CZP treatment is currently relatively low, as risk can be minimized with patient/physician education, screening, and vigilant treatment, according to international guidelines. KEY POINTS: • TB rates were highest in eastern/central Europe, Mexico, and Asia-Pacific regions. • With the implementation of stricter TB screening and risk evaluations in 2007, especially in high TB incidence countries, there was a notable reduction TB occurrence. • Safety profile of biologics in real-world settings complements controlled studies. • TB and hepatitis (HBV/HCV) risk with certolizumab pegol (CZP) treatment is low.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Hepatitis Viral Humana , Tuberculosis , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Asia/epidemiología , Certolizumab Pegol/efectos adversos , Europa (Continente) , Europa Oriental , Hepatitis Viral Humana/tratamiento farmacológico , Humanos , Japón , México , Estudios Retrospectivos , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología
10.
J Med Imaging Radiat Oncol ; 65(4): 460-463, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34146383

RESUMEN

The Radiation Oncology Department at The National Cancer Institute, Singapore (NCIS) and the Royal Australian and New Zealand College of Radiology (RANZCR) has had a well-established relationship that began as a partnership to grow a pool of local radiation oncologists to meet a nation's demand for radiotherapy services. This journey has surpassed its initial aims and now has produced a generation of radiation oncologists leading a national cancer institute. We recount the history and progress of this partnership here, as well as the unique success of its product; the only RANZCR-accredited radiation oncology training site outside of Australia and New Zealand since 2002. We outline the mutual benefits through many years of collaboration and deliberate efforts to grow the partnership. We also outline the distinctive specialist training path that our trainees take to meet both the local accreditation body as well as the RANZCR requirements.


Asunto(s)
Internado y Residencia , Oncología por Radiación , Australia , Humanos , Nueva Zelanda , Oncólogos de Radiación , Oncología por Radiación/educación , Singapur
12.
In Vivo ; 34(2): 757-765, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32111781

RESUMEN

BACKGROUND/AIM: To report the outcomes of patients with prostate cancer treated with dose-escalated radiotherapy over a 15-year period at our Institution. PATIENTS AND METHODS: Patients with biopsy-proven cT1-4N0M0 disease who received radical external beam radiotherapy (EBRT) were reviewed. The endpoints were 5-year overall survival (OS), freedom from biochemical failure (FFBF) and late treatment toxicities. RESULTS: A total of 236 patients were eligible. Median follow-up was 70 months. Low-, intermediate- and high-risk disease was found in 9%; 29% and 62% of patients, respectively. The median radiation dose was 73.8 Gy. Overall 42% of patients had dose escalation to >74 Gy. Five-year OS and FFBF were 95.2%/81.6%/75.4% and 95.0%/98.0%/82.0% for low-/intermediate-/high-risk patients, respectively. Dose escalation to >74 Gy did not improve FFBF (hazard ratio=0.97, 95% confidence intervaI=0.43-2.19, p=0.93) and was associated with a 4.3-fold increase in the odds of grade 3 or more rectal bleeding (p<0.01). CONCLUSION: Dose escalation to >74 Gy did not improve OS or FFBF but was associated with a higher rate of grade 3 or more rectal haemorrhage.


Asunto(s)
Neoplasias de la Próstata/radioterapia , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/uso terapéutico , Relación Dosis-Respuesta en la Radiación , Hemorragia/etiología , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/tratamiento farmacológico , Radioterapia/efectos adversos , Radioterapia/métodos , Recto/patología , Recto/efectos de la radiación
13.
J Geriatr Oncol ; 10(2): 292-297, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30630748

RESUMEN

BACKGROUND: Muscle invasive bladder cancer (MIBC) is prevalent in the older patients, who are a vulnerable population with multiple co-morbidities and at increased risk of complications. Radical cystectomy is often not suitable, hence radical radiotherapy (RT) is an alternative option. We reviewed the outcomes of older patients treated with RT with or without concurrent chemotherapy (CRT) at our institution. METHODS: We retrospectively reviewed patients aged 65 years and above treated with radical RT for MIBC at our institution between March 2002 to January 2017. Data was collected from institutional medical records and RT databases. The primary outcome was 2- and 5-year overall survival (OS), recurrence free survival (RFS), and toxicities. Univariate cox proportional hazard regression models were performed to identify independent factors with significant impact on survival. RESULTS: We identified 45 patients (34 males, 11 females) with a median age of 77 years (range 65-95). All patients received maximal transurethral resection of the bladder tumour prior to RT. Median dose of total RT was 64 Gy (range 50-69.8 Gy). Twenty one patients (47%) received CRT. Planned treatment was completed in 42 (93.3%) patients. Median follow-up was 31 months (range 1-147 months). The 2- and 5-year OS was 64% and 44%, respectively. The 2- and 5-year RFS was 68% and 49%, respectively. Median RFS was 34 months (range 8-121 months). Median OS was 56 months (range 18-100 months). Univariate analysis showed that performance status (0-1 vs. 2-3; HR 2.7, 95% CI 1.07-6.8, p = 0.035) and International Society of Geriatric Oncology (SIOG) group (≤2 vs. >2; HR 3.23, 95% CI 1.12-8.64, p = 0.019) were significantly associated with increased hazard for death. One patient (2%) had grade 3 cystitis. CONCLUSION: Radical RT is well tolerated in older patients with MIBC. We report outcomes similar to published data. Older patients should be considered for curative treatment despite their age. However, careful selection is warranted as frail patients (PS ≥2; SIOG >2) may benefit less.


Asunto(s)
Carcinoma de Células Transicionales/terapia , Quimioradioterapia Adyuvante/métodos , Cistoscopía , Músculo Liso/patología , Radioterapia Adyuvante/métodos , Neoplasias de la Vejiga Urinaria/terapia , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma de Células Transicionales/epidemiología , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/fisiopatología , Cistitis/epidemiología , Diarrea/epidemiología , Supervivencia sin Enfermedad , Femenino , Fragilidad/epidemiología , Humanos , Síntomas del Sistema Urinario Inferior/epidemiología , Masculino , Náusea/epidemiología , Invasividad Neoplásica , Estadificación de Neoplasias , Selección de Paciente , Modelos de Riesgos Proporcionales , Traumatismos por Radiación/epidemiología , Radiodermatitis/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/fisiopatología
14.
Am J Clin Pathol ; 151(3): 241-254, 2019 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-30551183

RESUMEN

Objectives: The list of tumors involving the pituitary gland has been expanded to include a variety of neuronal and paraneuronal tumors in the 2017 World Health Organization tumor classification of endocrine organs. All the entities included in this category are distinctly rare, with limited case reports in the literature. Methods: We illustrate two extraordinary sellar tumors with neuronal differentiation: a sellar paraganglioma and a sellar neurocytoma, with thorough literature review and comparison of the clinicopathologic features of these entities. Results: Both entities are exceptionally rare and tend to be misdiagnosed as pituitary adenoma preoperatively. Both entities demonstrate frequent clinical recurrence compared with pituitary adenoma, as well as the rare occurrence of metastatic disease. Conclusions: In evaluating a sellar tumor with an uncommon morphology and neuroendocrine differentiation, an increased awareness of the unusual entities that may involve the sellar region and a judicious panel of immunohistochemical studies should improve the diagnosis.


Asunto(s)
Adenoma/patología , Tumores Neuroendocrinos/patología , Paraganglioma/patología , Neoplasias Hipofisarias/patología , Adenoma/clasificación , Adenoma/diagnóstico por imagen , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tumores Neuroendocrinos/clasificación , Tumores Neuroendocrinos/diagnóstico por imagen , Paraganglioma/clasificación , Paraganglioma/diagnóstico por imagen , Neoplasias Hipofisarias/clasificación , Neoplasias Hipofisarias/diagnóstico por imagen , Silla Turca/diagnóstico por imagen , Silla Turca/patología , Organización Mundial de la Salud
15.
Asia Pac J Clin Oncol ; 15(6): 323-330, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31332959

RESUMEN

BACKGROUND: To report outcomes of localized prostate cancer treated with radical external beam radiation therapy (EBRT) in our institution over a 14-year period, and to determine the impact of dose escalation of prostate cancer outcomes. METHODS: Patients with T1-T4 N0 M0 prostate cancer who received radical EBRT between January 2002 and December 2015 were reviewed retrospectively. Clinical data were obtained via the institutional electronic medical records. The primary endpoint was 5-year overall survival (OS). The secondary endpoints were 5-year freedom from biochemical failure (FFBF) and treatment toxicities. RESULTS: A total of 200 eligible patients were identified. Median follow-up duration was 48 months. 13%, 36% and 51% of patients had low-, intermediate- and high-risk disease. Median dose was 79.2 Gy. The 5-year OS were 90%, 87% and 78% and FFBF were 94%, 100% and 81% for low-, intermediate- and high-risk patients, respectively. Multivariable analysis showed that Eastern Cooperate Oncology Group performance status 2 and Gleason grade group 5 were independent predictors of worse OS. The incidence of grade ≥2 proctitis was 24.5%. Dose escalation was significantly associated with increased incidence of grade ≥2 proctitis (odd ratio, 4.42; 95% confidence interval, 1.95-10.08; P < 0.01). CONCLUSION: Men with localized prostate cancer treated with EBRT in our population had excellent 5-year OS and biochemical outcomes. Dose escalation did not significantly improve these outcomes but was associated with significantly increased risk of grade ≥2 proctitis in our population. Future studies should be performed to identify patients who will benefit the most from dose-escalated EBRT.


Asunto(s)
Neoplasias de la Próstata/radioterapia , Radioterapia/métodos , Anciano , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/mortalidad , Traumatismos por Radiación/epidemiología , Radioterapia/efectos adversos , Radioterapia/mortalidad , Dosificación Radioterapéutica , Estudios Retrospectivos
16.
Cancer Med ; 8(4): 1447-1458, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30790469

RESUMEN

To evaluate the response and quality of life of palliative gastric radiotherapy in patients with symptomatic locally advanced gastric cancer. Patients with bleeding, pain or obstruction and were treated with palliative gastric radiotherapy to a dose of 36 Gy in 12 daily fractions. The primary outcomes were symptom response rates. Secondary outcomes included overall survival, adverse events and proportion of patients with ≥10-point absolute improvement in the fatigue, nausea/vomiting and pain subscales in the EORTC Qualify of Life Questionnaire C30 (EORTC QLQ-C30) and dysphagia/pain subscales in the gastric specific module (STO22) at the end of RT and 1 month after the completion of radiotherapy. Fifty patients were accrued. Median survival duration was 85 days. 40/50 patients (80%) with bleeding, 2/2 (100%) patients with obstruction and 1/1 (100%) patient with pain responded to radiotherapy. Improvements fatigue, nausea/vomiting and pain subscales of the EORTC QLQ-C30 was seen in 50%, 28% and 44% of patients at the end of RT and in 63%, 31% and 50% of patients 1 month after RT. Improvements in dysphagia/pain subscales of the STO22 was seen in 42% and 28% of patients at then end of RT and 44% and 19% of patients 1 month after RT. Two patients (5%) had grade 3 anorexia and gastritis. Palliative gastric radiotherapy was effective, well tolerated and resulted in improvement in fatigue, dysphagia and pain at the end of radiotherapy and 1 month after the completion of radiotherapy in a significant proportion of patients.


Asunto(s)
Calidad de Vida/psicología , Neoplasias Gástricas/radioterapia , Anciano , Anciano de 80 o más Años , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Radioterapia/efectos adversos , Neoplasias Gástricas/psicología , Análisis de Supervivencia , Resultado del Tratamiento
17.
FEBS Lett ; 593(16): 2139-2150, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31211853

RESUMEN

The abnormal accumulation of ß-amyloid peptide (Aß) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aß-mediated neurotoxicity remain elusive, Aß has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione-derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors. This study investigates ET's potential to counteract Aß-toxicity in transgenic Caenorhabditis elegans overexpressing a human Aß peptide. The accumulation of Aß in this model leads to paralysis and premature death. We show that ET dose-dependently reduces Aß-oligomerization and extends the lifespan and healthspan of the nematodes.


Asunto(s)
Péptidos beta-Amiloides/toxicidad , Antioxidantes/administración & dosificación , Caenorhabditis elegans/genética , Ergotioneína/administración & dosificación , Parálisis/prevención & control , Péptidos beta-Amiloides/genética , Animales , Animales Modificados Genéticamente , Antioxidantes/farmacología , Caenorhabditis elegans/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ergotioneína/farmacología , Humanos , Estrés Oxidativo/efectos de los fármacos , Parálisis/genética , Resultado del Tratamiento
18.
Med Decis Making ; 28(1): 127-37, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18083993

RESUMEN

BACKGROUND: The manner of presentation of research results may affect how clinicians interpret research and make clinical decisions. The authors evaluate whether the use of confidence levels improve research interpretation and decision making compared with P values and 95% confidence intervals. METHODS: The 2 Presentation and Interpretation of Medical Research (PRIMER) studies were 3-arm randomized trials. PRIMER 1 presented results of 5 fictitious scenarios with P values (P), P plus 95% confidence intervals (P + CI), or P, CI, and confidence levels (P + CI + CL); PRIMER 2 compared P + CI + CL, P + CI, and P + CL. Clinicians were asked to identify the correct interpretation of scenarios in terms of statistical and clinical significance and then indicate the intended decision making in terms of treatment recommendation. RESULTS: Seventy-five and 246 clinicians participated in PRIMER 1 and PRIMER 2, respectively. In PRIMER 1, P+CI+CL was superior to P + CI and P (P < 0.05); the latter 2 arms did not differ significantly. Decision making was not significantly different between arms. In PRIMER 2, P+CI+CL resulted in better interpretation than P + CI (P = 0.03), with no difference between P + CI and P + CL. In combined analysis, the odds of correct interpretation were higher for P+CI+CL than P+CI (odds ratio = 1.73, P=0.005, 95% CI= 1.19--2.52). Decision making was better for P + CI+ CL (P = 0.03). On multivariate analysis, the P + CI+ CL arm and clinicians with statistics training, not in private practice, or participating in PRIMER 1 had better interpretation. The P + CI+ CL arm was the only factor improving decision making. CONCLUSIONS: Presenting research with a combination of P values, confidence intervals, and confidence levels leads to better interpretation and decision making by clinicians.


Asunto(s)
Interpretación Estadística de Datos , Toma de Decisiones , Difusión de la Información/métodos , Investigación , Adulto , Intervalos de Confianza , Femenino , Humanos , Masculino , Nueva Gales del Sur , Ensayos Clínicos Controlados Aleatorios como Asunto , Investigación/estadística & datos numéricos , Encuestas y Cuestionarios
19.
Asia Pac J Clin Oncol ; 14(5): e386-e391, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29171166

RESUMEN

AIM: External beam radiotherapy (EBRT) followed by high dose rate (HDR) brachytherapy boost has demonstrated minimal toxicities and improved disease control rate compared with EBRT alone in observational and randomized studies with predominantly Caucasian patients. This study aims to report the outcomes of patients treated with this approach in our predominantly Asian population. METHODS: Medical records for patients with localized prostate cancer who received combined EBRT delivered via intensity modulated radiotherapy (IMRT) technique followed by HDR brachytherapy boost were retrospectively reviewed. Outcomes evaluated included 5-year biochemical recurrence-free survival (per Phoenix definition), overall survival and treatment toxicities. RESULTS: From June 2009 to March 2015, 75 patients were treated with IMRT followed by HDR brachytherapy boost. Twenty patients (27%) had intermediate risk, 55 (74%) had high-risk disease. Median follow up was 64 months. All patients received IMRT to a median dose of 45 Gy to the pelvis followed by HDR brachytherapy boost. Sixty, 10 and 5 patients received boost of 21 Gy in two fractions, 19 Gy in two fractions and 15 Gy in a single fraction, respectively. All patients met the planning criteria adapted from RTOG 0815. The 5-year prostate-specific antigen (PSA) control was 85.2% (80.3% and 100% for high-risk and intermediate-risk group, respectively). Cancer-specific survival and overall survival are 97.3% and 92.0%, respectively. Eleven (15%) patients developed biochemical failure, six of which had distant metastasis. Three (4%) developed grade 3 genitourinary toxicity (urethral stricture and/or cystitis) and none developed grade 3 radiation proctitis. CONCLUSION: Our outcomes are comparable to internationally published data and demonstrate reproducibility of this approach in our population.


Asunto(s)
Pueblo Asiatico/estadística & datos numéricos , Braquiterapia/mortalidad , Neoplasias de la Próstata/mortalidad , Radioterapia de Intensidad Modulada/mortalidad , Anciano , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Estudios Retrospectivos
20.
Singapore Med J ; 58(1): 41-45, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26915391

RESUMEN

INTRODUCTION: Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. Although the survival rate for GBM has improved with recent advancements in treatment, the prognosis remains generally poor. METHODS: We conducted a retrospective review of GBM patients seen in National University Hospital, Singapore, and Tan Tock Seng Hospital, Singapore, from January 2002 to December 2011. Data on disease and treatment factors was collected and correlated with survival. RESULTS: Data on a total of 107 GBM patients was analysed. Their median survival time was 15.1 months and the two-year survival rate was 23.5%, which is comparable with data published in other series. The factors associated with improved median survival time were radiotherapy dose > 50 Gy (16.1 months vs. 8.7 months, p = 0.01) and adjuvant concurrent chemotherapy (16.4 months vs. 9.2 months, p = 0.003). CONCLUSION: GBM confers a poor prognosis. Adjuvant radiotherapy and chemotherapy are associated with improved survival. Ethnicity may be a contributing factor to differences in GBM incidence and prognosis.


Asunto(s)
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Adulto , Anciano , Neoplasias Encefálicas/etnología , Femenino , Glioblastoma/etnología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Singapur , Análisis de Supervivencia , Resultado del Tratamiento
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