RESUMEN
p53 pathway is important in tumorigenesis. However, no study has been performed to specifically investigate the role of p53 pathway genes in bladder cancer (BLCA). In this study, transcriptomics data of muscle invasive bladder cancer patients (n = 411) from The Cancer Genome Atlas (TCGA) were investigated. Using the hallmark p53 pathway gene set, the Non-Negative Matrix factorization (NMF) analysis identified two subtypes (C1 and C2). Clinical, survival, and immunological analysis were done to validate distinct characteristics of the subtypes. Pathway enrichment analysis showed the subtype C1 with poor prognosis having enrichment in genes of the immunity related pathways, where C2 subtype with better prognosis being enriched in genes of the steroid synthesis and drug metabolism pathways. A signature gene set consisting of MDGA2, GNLY, GGT2, UGT2B4, DLX1, and DSC1 was created followed by a risk model. Their expressions were analyzed in RNA extracted from the blood and matched tumor tissues of BLCA patients (n = 10). DSC1 had significant difference of expression (p = 0.005) between the blood and tumor tissues in our BLCA samples. Contrary to the usual normal bladder tissue to blood ratio, DLX1 expression was lower (p = 0.02734) in tumor tissues than in blood. Being the first research of p53 pathway related signature gene set in bladder cancer, this study potentially has a substantial impact on the development of biomarkers for BLCA.
RESUMEN
The neurotransmitter histamine exists in two isomeric forms and could be an interesting ligand due to three nitrogen atoms with the possibility of binding to metals in different ways besides its crucial role in biological systems. However, no metal-histamine interaction is known in the literature. Therefore, two histamine-bound magnesium porphyrins [MgT(4-Cl)PP(hist)2] 1 and [MgT(4-Br)PP(hist)] 2 have been synthesized and structurally characterized. Interestingly, 1 is a hexa-coordinated magnesium porphyrin due to the axial coordination of two histamine molecules via the nitrogen of the aliphatic amino group with the Mg-Nhistamine distance of 2.300 Å, while 2 is penta-coordinated due to the axial coordination of one histamine molecule through the imidazole nitrogen atom with the Mg-Nhistamine distance of 2.145 Å. The diverse coordination modes of this unique ligand are explored for the first time. Theoretical studies at the level of DFT supported the binding of histamine via imidazole nitrogen atoms for complex 2. Histamine-bound magnesium porphyrins are found to be stable against the photodegradation of magnesium porphyrin in the presence of light and oxygen. Freshly isolated chlorophyll a from spinach showed similar resistivity against photodegradation. Moreover, the histamine-bound complexes showed higher antioxidant activity for 1 (92.45%) compared to the free base porphyrin (73.11%) and MgT(4-Cl)PP (75.89%).
Asunto(s)
Fotólisis , Histamina/química , Magnesio/química , Porfirinas/química , Antioxidantes/química , Clorofila A/química , Modelos Moleculares , Técnicas ElectroquímicasRESUMEN
A core 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridine-4-one scaffold is elaborated at C-3(Me) by base-mediated aldol condensation to give new 3-alkenyl-4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridine-4-ones, which are masked forms related to the acylpyridone natural products.
RESUMEN
This study was performed to develop a simple scoring system to aid in the early clinical management of patients suspected of heparin-induced thrombocytopenia (HIT) with regard to decisions for continued heparin therapy. The system was designed to arrive at low (0) or possible (1) probability scores without knowledge of laboratory test results (except platelet counts) to avoid delays. As the safest clinical approach is to discontinue heparin, intermediate and high scores were combined. Critically ill VA hospital patients (n = 100) with a ≥30% fall in platelet count were assessed by platelet aggregation (PA), (14)C-serotonin release assay ((14)C-SRA), and GTI ELISA. In this population, 53% were scored 1 and of these 43% were positive by laboratory test. Emphasizing the decision to discontinue heparin, the clinical signs of HIT were paramount for the immediate determination of a diagnosis of HIT without dependence on a positive laboratory test.
Asunto(s)
Anticoagulantes/efectos adversos , Heparina/efectos adversos , Monitoreo Fisiológico/métodos , Trombocitopenia , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Ensayo de Inmunoadsorción Enzimática , Femenino , Heparina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria , Recuento de Plaquetas , Serotonina/sangre , Trombocitopenia/sangre , Trombocitopenia/inducido químicamente , Trombocitopenia/diagnóstico , Factores de TiempoRESUMEN
BACKGROUND: This phase I study was designed to determine the maximum tolerated dose (MTD) and preliminary efficacy of docetaxel with concurrent radiotherapy (RT), in high-risk squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Eligible patients had resected squamous cell carcinoma of the head and neck, histologically involved lymph nodes, and/or extranodal disease, and/or involved surgical margins and performance status 0 to 1. Treatment included weekly docetaxel with concurrent RT in a dose-finding study; a subsequent small cohort of patients was treated using the MTD of docetaxel. RESULTS: Twenty patients were enrolled. Planned accrual was 25, but the study was closed prematurely because of slow accrual. The MTD was 15 mg/m2. Dose-limiting toxicity was oral stomatitis. Therapy was well tolerated. Five patients experienced locoregional relapse at a median follow-up of 32 months. CONCLUSION: Docetaxel with concurrent RT has acceptable toxicity. This approach warrants further investigation in a phase II trial.
Asunto(s)
Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Traumatismos por Radiación/prevención & control , Radioterapia de Intensidad Modulada/métodos , Taxoides/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/mortalidad , Terapia Combinada , Intervalos de Confianza , Docetaxel , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/patología , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Probabilidad , Pronóstico , Estudios Prospectivos , Dosificación Radioterapéutica , Radioterapia Adyuvante , Medición de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Hemolytic anemia is uncommon in the general population; however, drug-induced hemolysis is not rare in hospitalized patients. We report a case of unrecognized subacute hemolytic anemia due to ceftriaxone in a geriatric patient requiring multiple blood transfusions before a correct diagnosis could be established.
Asunto(s)
Anemia Hemolítica/inducido químicamente , Ceftriaxona/efectos adversos , Anciano , Ceftriaxona/administración & dosificación , Ceftriaxona/sangre , Ceftriaxona/uso terapéutico , Humanos , Masculino , Atención Perioperativa , Cirugía TorácicaRESUMEN
This article presents the status of rural Bangladeshi adolescent girls' awareness about reproductive health. Analysis of data revealed that a sizable proportion of adolescent girls had incorrect knowledge or misconceptions about the fertile period, reproduction, sexually transmitted diseases, and HIV/AIDS. Age, education either of adolescents or their mothers, residence, and exposure to mass media were the significant predictors of adolescent girls' knowledge about reproductive health. Strong efforts are needed to improve awareness and to clarify misconceptions about reproductive health. Improved access to mass media and education could improve rural Bangladeshi adolescent girls' awareness about reproductive health.
Asunto(s)
Educación en Salud/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Reproducción , Enfermedades de Transmisión Sexual , Adolescente , Bangladesh , Niño , Estudios Transversales , Escolaridad , Femenino , Infecciones por VIH , Humanos , Entrevistas como Asunto , Modelos Logísticos , Madres/educación , Análisis Multivariante , Psicología del Adolescente , Salud Rural , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Anemia is a well-recognized complication of concurrent chemoradiation therapy for head and neck carcinoma. It impairs quality of life and many studies also have reported an association between anemia and increased tumor recurrence and decreased long-term survival. In the current study, the authors attempted to identify the severity, risk factors, and physician practices in the management of anemia. METHODS: Medical records of those patients receiving concurrent chemoradiation for head and neck carcinoma between 1999-2003 were reviewed. The average weekly nadir hemoglobin level (AWNH) was defined as the mean value of the lowest hemoglobin concentration in each week. Independent predictors for an AWNH < 11 g/dL were identified using multivariable logistic regression analyses. RESULTS: Seventy-two patients were included in the current study, 66.7% of whom had unresectable disease. The overall median survival was 402 days. At baseline, 76.4% (95% confidence interval [95% CI], 66.3-86.4%) of patients already had a hemoglobin level < 13.5 g/dL. The hemoglobin level dropped 2.5 +/- 1.9 g/dL during concurrent chemoradiation, resulting in 95.8% of patients having a hemoglobin level < 13.5 g/dL at the end of the observation period. Blood was transfused to 24 patients (33.3%); erythropoietin or darbepoietin was administered to 2 patients (2.7%). The mean lowest hemoglobin threshold of transfusion was 7.3 +/- 1.0 g/dL. The cumulative percentage of patients who received a transfusion reached 50% when the mean nadir hemoglobin level was 7.4 g/dL. Independent predictors of an AWNH < 11.0 g/dL were low baseline hemoglobin and receiving multiple concurrent chemotherapeutic agents, with relative risks of 13.6 and 1.8, respectively (95% CI,1.9-93.9 and 1.1-3.1, respectively). CONCLUSIONS: Anemia is prevalent in patients undergoing treatment for head and neck carcinoma and can be severe with concurrent chemoradiation therapy. However, the intensity of anemia management is low. A low baseline hemoglobin level and the reception of multiple concurrent chemotherapeutic agents are considered to be the main risk factors of anemia. Cancer 2006.
Asunto(s)
Anemia/etiología , Anemia/terapia , Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Anciano , Anemia/clasificación , Anemia/patología , Terapia Combinada , Femenino , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND: Statins are effective in reducing events from coronary heart disease and can prolong survival. However, this benefit is controversial when other concurrent serious health problems greatly limit the patient's longevity. METHODS: We conducted a retrospective chart review of patients with advanced lung cancer who were receiving statins and had lived for at least one month since diagnosis. FINDINGS: Forty-seven patients with median age of 71 years were included. Discontinuation of statins occurred in 25 patients (53.2%) before the date of death. Median survival was 370 days. Statins were discontinued at a median of 244 days after cancer diagnosis. Discontinuations were more prevalent in patients who received chemotherapy or had a history of cerebrovascular diseases. Lipid monitoring was observed in 25 patients (53.2%). INTERPRETATION: About half of patients with advanced lung cancer who were prescribed statins did not have this drug discontinued until the time of death. Lipid monitoring was suboptimal and, when it occurred, indicated the lipid goal was rarely achieved.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Neoplasias Pulmonares/complicaciones , Pautas de la Práctica en Medicina/estadística & datos numéricos , Privación de Tratamiento/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Células Pequeñas/complicaciones , Monitoreo de Drogas/estadística & datos numéricos , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Hospitales de Veteranos , Humanos , Hipercolesterolemia/complicaciones , Hipercolesterolemia/diagnóstico , Illinois/epidemiología , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Auditoría Médica , Persona de Mediana Edad , Estadificación de Neoplasias , Selección de Paciente , Sistema de Registros , Estudios RetrospectivosAsunto(s)
Antagonistas de Andrógenos/efectos adversos , Flutamida/efectos adversos , Goserelina/efectos adversos , Encefalopatía Hepática/inducido químicamente , Síndrome de Lisis Tumoral/etiología , Anciano , Quimioterapia Combinada , Resultado Fatal , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológicoRESUMEN
OBJECTIVE: To describe severe hypocalcemia and acute renal failure associated with zoledronic acid and interferon alfa in a patient with metastatic carcinoid tumors. CASE SUMMARY: A 39-year-old white man with metastatic carcinoid tumor tolerated treatment with subcutaneous long-acting octreotide monthly and interferon alfa 6 million units 3 times weekly for 6 months. Due to multiple bony metastases, zoledronic acid was prescribed as a monthly 4-mg intravenous infusion over 30 minutes to prevent skeletal-related events. Although the first infusion went well, the patient developed severe hypocalcemia and acute renal failure after the second zoledronic infusion. DISCUSSION: Bisphosphonates may infrequently cause symptomatic hypocalcemia, especially among patients who have vitamin D deficiency or hypoparathyroidism or receive treatment with an aminoglycoside. Our literature review suggests that zoledronic acid and interferon alfa may exert additive effects on the inhibition of osteoclasts, thus potentially precipitating hypocalcemia. Renal dysfunction may not be a direct consequence of interferon alfa. However, altered mental function due to hypocalcemia may lead to dehydration and further exacerbate renal dysfunction, a known adverse effect of zoledronic acid. Since therapeutic indications of both interferon alfa and zoledronic acid continue to expand, clinicians should be aware of these serious adverse reactions and potential interaction. Supportive treatment with hydration, calcium supplement, and oral calcitriol resulted in resolution of hypocalcemia, but only partial improvement of azotemia. CONCLUSIONS: In our patient with metastatic carcinoid tumor, treatment with zoledronic acid and interferon alfa was associated with symptomatic hypocalcemia and acute renal failure.