RESUMEN
Acute leukemias (ALs) are the most common cancers in pediatric population. There are two types of ALs: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Some studies suggest that the Renin Angiotensin System (RAS) has a role in ALs. RAS signaling modulates, directly and indirectly, cellular activity in different cancers, affecting tumor cells and angiogenesis. Our review aimed to summarize the role of RAS in ALs and to explore future perspectives for the treatment of these hematological malignancies by modulating RAS molecules. The database including Pubmed, Scopus, Cochrane Library, and Scielo were searched to find articles about RAS molecules in ALL and in pediatric patients. The search terms were "RAS", "Acute Leukemia", "ALL", "Angiotensin-(1-7)", "Pediatric", "Cancer", "Angiotensin II", "AML". In the bone marrow, RAS has been found to play a key role in blood cell formation, affecting several processes including apoptosis, cell proliferation, mobilization, intracellular signaling, angiogenesis, fibrosis, and inflammation. Local tissue RAS modulates tumor growth and metastasis through autocrine and paracrine actions. RAS mainly acts via two molecules, Angiotensin II (Ang II) and Angiotensin (1-7) [Ang-(1-7)]. While Ang II promotes tumor cell growth and stimulates angiogenesis, Ang-(1-7) inhibits the proliferation of neoplastic cells and the angiogenesis, suggesting a potential therapeutic role of this molecule in ALL. The interaction between ALs and RAS reveals a complex network of molecules that can affect the hematopoiesis and the development of hematological cancers. Understanding these interactions could pave the way for innovative therapeutic approaches targeting RAS components.
Asunto(s)
Angiotensina II , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sistema Renina-Angiotensina , Humanos , Sistema Renina-Angiotensina/fisiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Angiotensina II/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Transducción de Señal , Angiotensina I/metabolismo , Neovascularización Patológica/metabolismo , Animales , Fragmentos de Péptidos/metabolismoRESUMEN
OBJECTIVE: To evaluate the maternal-fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort. METHODS: The prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study, RESULTS: We included 194 women with a mean age of 31 (17-45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases. CONCLUSIONS: Our findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed.
Asunto(s)
Cabergolina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Prolactinoma/patología , Aborto Espontáneo/patología , Adolescente , Adulto , Anciano , Femenino , Humanos , Hiperprolactinemia/patología , Persona de Mediana Edad , Embarazo , Complicaciones Neoplásicas del Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: The effects of GH therapy on thyroid function among previous reports have shown remarkable discrepancies, probably due to differences in hormone assay methods, degree of purification of former pituitary-derived GH preparations, dosage schedules, diagnostic criteria, patient selection, duration of treatment and study design. These considerations motivated us to investigate whether and how GH replacement therapy changes serum thyroid hormone levels, including the much less studied rT3 levels, in a group of unequivocally GH-deficient children receiving long-term recombinant human GH therapy. PATIENTS AND DESIGN: Twenty clinically and biochemically euthyroid children were studied in two therapeutic conditions: on GH replacement therapy for at least 6 months and without GH replacement, either before GH was started or after GH was withdrawn for 30-60 days. Eight patients were on thyroxine replacement treatment and thyroxine doses were kept constant during the study. Blood was collected before and after 15, 20 and 60 minutes of TRH administration in both therapeutic conditions (with GH and without GH). MEASUREMENTS: Concentrations of thyroid hormone levels were determined only in sera obtained before TRH administration. FT4, T3 and TSH were measured by immunoflourimetric assays and rT2 was measured by immunoradioassay. RESULTS: Patients were classified into two groups, according to basal TSH levels: group I (TSH > 0.4 mU/l, n = 12) and group II (on thyroxine and TSH < 0.05 mU/l, n = 8). In both groups, serum FT4 levels decreased (17. 0 +/- 1.1 vs. 14.3 +/- 0.9 mU/l, P < 0.001, and 18.0 +/- 1.7 vs. 14. 2 +/- 1.7 mU/l, P < 0.01, respectively), serum T3 levels increased (1.8 +/- 0.1 vs. 2.4 +/- 0.2 nmol/l, P < 0.001, and 1.9 +/- 0.3 vs. 2.4 +/- 0.2 nmol/l, P < 0.05, respectively), and serum rT3 levels decreased (0.35 +/- 0.03 vs. 0.25 +/- 0.03 nmol/l, P < 0.01, and 0. 48 +/- 0.06 vs. 0.34 +/- 0.06 nmol/l, P < 0.01, respectively). Basal (3.2 +/- 0.50 vs. 2.6 +/- 0.72 mU/l, P = 0.28, paired t-test), TRH-stimulated peak TSH levels (13.9 +/- 5.3 vs. 15.9 +/- 8.0 mU/l, P = 0.35, paired t-test) and TRH-stimulated TSH secretion, expressed as area under the curve (609 +/- 97 vs. 499 +/- 53 mU/l.minutes-1, P = 0.15, paired t-test), remained unchanged during GH replacement in group I patients. Low serum FT4 and high serum T3 levels were observed in only one patient each, but low serum rT3 levels were found in six patients (four in group I and two in group II) during GH replacement. CONCLUSIONS: These results show that long-term GH replacement therapy in children with unequivocal GHD significantly decreases serum FT4 and rT3 levels and increases serum T3 levels; that these changes are independent of TSH and result from increased peripheral conversion of T4 to T3 and that GH replacement therapy in GH deficient children does not induce hypothyroidism, but simply reveals previously unrecognized cases whose serum FT4 values fall in the low range during GH replacement.
Asunto(s)
Trastornos del Crecimiento/etiología , Hormona del Crecimiento/administración & dosificación , Hormona del Crecimiento/deficiencia , Terapia de Reemplazo de Hormonas , Hormonas Tiroideas/sangre , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/sangre , Trastornos del Crecimiento/tratamiento farmacológico , Humanos , Hipotiroidismo/inducido químicamente , Hipotiroidismo/diagnóstico , Masculino , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangre , Triyodotironina Inversa/sangreRESUMEN
OBJECTIVES: To compare the effect of Parlodel SRO (Sandoz, Basel, Switzerland), a long-acting oral bromocriptine, to Parlodel (Sandoz) and to study the chronic effects of Parlodel SRO. DESIGN: The study was twofold: (1) random, double-blind and (2) open. SETTING: Patients were studied in an academic environment. PATIENTS: Hyperprolactinemic patients were selected. Sixteen patients were treated during 1 month. Ten patients completed the 1-year follow-up. INTERVENTIONS: Parlodel SRO or Parlodel was administered during 1 month (first 15 days: 5 mg/d; afterwards: 10 mg/d). Parlodel SRO was given during 1 year in variable doses (maximal 20 mg/d). MAIN OUTCOME MEASURES: Prolactin (PRL) levels, clinical improvement, and side effects were evaluated. RESULTS: After 1 month, 63% of the patients in both groups had normal PRL and 43% had menses. Side effects were similar. After 1 year all patients except one had normal PRL levels, and 89% were ovulating. CONCLUSIONS: The efficacy, tolerability, and long duration of action of Parlodel SRO make it an excellent alternative for the treatment of hyperprolactinemic patients.
Asunto(s)
Bromocriptina/administración & dosificación , Hiperprolactinemia/tratamiento farmacológico , Administración Oral , Bromocriptina/efectos adversos , Bromocriptina/uso terapéutico , Femenino , Humanos , Hiperprolactinemia/complicaciones , Hiperprolactinemia/fisiopatología , Masculino , Ciclo Menstrual , Trastornos de la Menstruación/complicaciones , Trastornos de la Menstruación/fisiopatología , Ovulación , Prolactina/sangre , RadioinmunoensayoRESUMEN
A case of true precocious puberty of cerebral origin is reported in a girl with hydrocephaly, calcification of the pineal region and previous pulmonary tuberculosis