RESUMEN
We aimed to examine the nucleoside triphosphate diphosphohydrolases (NTPDase) in lymphocytes; adenosine deaminase (ADA) and butyrylcholinesterase (BChE) in serum; and acetylcholinesterase (AChE), superoxide dismutase (SOD), and catalase (CAT) activity in whole blood; since these enzymes are involved in inflammation responses as well as in oxidative stress conditions. We also checked the levels of total thiols (T-SH), non-protein thiols (NPSH), and thiobarbituric acid reactive substances (TBARS) in serum of patients with lung cancer. We collected blood samples from patients (n = 31) previously treated for lung cancer with chemotherapy. Patients were classified as stage IIIb and IV according to the Union for International Cancer Control (UICC). The results showed a significant increase in the hydrolysis of ATP, ADP, and adenosine in patients when compared with the control group. The activity of AChE, SOD, and CAT as well as the T-SH and NPSH levels were higher in patients group and TBARS levels were lower in patients compared with the control group. These findings demonstrated that the enzymes activity involved in the control of inflammatory and immune processes as well as the oxidative stress parameters are altered in patients with lung cancer.
Asunto(s)
Biomarcadores de Tumor/sangre , Colinesterasas/sangre , Inflamación/enzimología , Neoplasias Pulmonares/metabolismo , Estrés Oxidativo , Acetilcolinesterasa/sangre , Adenosina Desaminasa/sangre , Anciano , Antineoplásicos/uso terapéutico , Butirilcolinesterasa/sangre , Catalasa/sangre , Colinesterasas/metabolismo , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/enzimología , Linfocitos/enzimología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nucleósido-Trifosfatasa/metabolismo , Fumar/sangre , Compuestos de Sulfhidrilo/sangre , Superóxido Dismutasa/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , GemcitabinaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The Asháninkas, indigenous people of Peru, use cat's claw (Uncaria tomentosa) to restore health. Uncaria tomentosa has antioxidant activity and works as an agent to repair DNA damage. It causes different effects on cell proliferation depending on the cell type involved; specifically, it can stimulate the proliferation of myeloid progenitors and cause apoptosis of neoplastic cells. Neutropenia is the most common collateral effect of chemotherapy. For patients undergoing cancer treatment, the administration of a drug that stimulates the proliferation of healthy hematopoietic tissue cells is very desirable. It is important to assess the acute effects of Uncaria tomentosa on granulocyte-macrophage colony-forming cells (CFU-GM) and in the recovery of neutrophils after chemotherapy-induced neutropenia, by establishing the correlation with filgrastim (rhG-CSF) treatment to evaluate its possible use in clinical oncology. MATERIALS AND METHODS: The in vivo assay was performed in ifosfamide-treated mice receiving oral doses of 5 and 15 mg of Uncaria tomentosa and intraperitoneal doses of 3 and 9 µg of filgrastim, respectively, for four days. Colony-forming cell (CFC) assays were performed with human hematopoietic stem/precursor cells (hHSPCs) obtained from umbilical cord blood (UCB). RESULTS: Bioassays showed that treatment with Uncaria tomentosa significantly increased the neutrophil count, and a potency of 85.2% was calculated in relation to filgrastim at the corresponding doses tested. An in vitro CFC assay showed an increase in CFU-GM size and mixed colonies (CFU-GEMM) size at the final concentrations of 100 and 200 µg extract/mL. CONCLUSIONS: At the tested doses, Uncaria tomentosa had a positive effect on myeloid progenitor number and is promising for use with chemotherapy to minimize the adverse effects of this treatment. These results support the belief of the Asháninkas, who have classified Uncaria tomentosa as a 'powerful plant'.
Asunto(s)
Uña de Gato , Proliferación Celular/efectos de los fármacos , Células Progenitoras Mieloides/efectos de los fármacos , Neutropenia/tratamiento farmacológico , Neutrófilos/efectos de los fármacos , Extractos Vegetales/farmacología , Administración Oral , Animales , Uña de Gato/química , Células Cultivadas , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Sangre Fetal/citología , Filgrastim , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Células Progenitoras de Granulocitos y Macrófagos/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Ifosfamida , Inyecciones Intraperitoneales , Masculino , Medicina Tradicional , Ratones , Ratones Endogámicos BALB C , Células Progenitoras Mieloides/metabolismo , Células Progenitoras Mieloides/patología , Neutropenia/inducido químicamente , Neutropenia/metabolismo , Neutropenia/patología , Neutrófilos/metabolismo , Neutrófilos/patología , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes/administración & dosificaciónRESUMEN
BACKGROUND: Acute lymphoblastic leukemia (ALL) is a type of cancer that affects lymphocytes and it is the most common form of cancer in children. Acetylcholinesterase (AChE) is well known as having non-cholinergic functions and has been detected in the blood and plasma of humans including in lymphocytes. Thus, we investigated whole blood and lymphocyte AChE activity in patients with ALL. METHODS: This study was performed on 72 children with ALL divided into 4 groups: newly diagnosed, remission induction, remission maintenance and out-of-treatment and one control group of 50 healthy subjects. We determined AChE activity in whole blood and lymphocytes of these patients. RESULTS: Results demonstrated that whole blood AChE activity was enhanced in the newly diagnosed group and reduced in the remission induction and remission maintenance groups in relation to the control group. For lymphocyte AChE activity we found an increase in the newly diagnosed group and a decrease in the remission induction group in relation to the control. CONCLUSIONS: These results suggest that AChE activity was altered in ALL patients. This fact may be related with the essential role played by AChE in the development of hematological disease and its contribution to the regulation of immune function.
Asunto(s)
Acetilcolinesterasa/sangre , Linfocitos/enzimología , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimología , Acetilcolinesterasa/metabolismo , Adolescente , Antineoplásicos/farmacología , Niño , Preescolar , Citarabina/farmacología , Femenino , Humanos , Linfocitos/efectos de los fármacos , Masculino , Metotrexato/farmacología , Adulto JovenRESUMEN
The activities of NTPDase (EC 3.6.1.5, apyrase, CD39) and 5'-nucleotidase (EC 3.1.3.5, CD73) enzymes were analyzed in platelets from breast cancer patients. Initially, patients were compared in terms of length (years) of tamoxifen use. The following groups were studied: breast cancer patients who did not use tamoxifen, patients using tamoxifen for 1-48 months, patients using tamoxifen for 49-84 months, and controls (healthy subjects). Results demonstrated that adenosine triphosphate (ATP) hydrolysis was enhanced (F(3,114)=8.53; P<0.001) and adenosine diphosphate (ADP) hydrolysis was reduced (F(3,106)=5.09, P=0.002) as a function of tamoxifen use, while adenosine monophosphate (AMP) hydrolysis was unchanged. Next, patients were compared statistically according to disease stage, determined by the tumor-node-metastasis (TNM) staging system for classifying breast tumor. ATP hydrolysis was significantly elevated in patients with stage I and II breast cancer (F(4,113)=4.35; P=0.003), but was normal in patients with stage III and IV cancer. ADP hydrolysis was reduced in stages II to IV (F(4,105)=3.88, P=0.006) and AMP hydrolysis was elevated in stage II (F(4,105)=3.45 P=0.01), but was normal in stages III and IV. Platelet aggregation time was similar in all patients regardless of tamoxifen use or disease stage. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were also within the normal range and similar among all groups. Similarly, fibrinogen and fibrin degradation product (FDP) were unchanged in all groups. In conclusion, our study demonstrated for the first time that hydrolysis of adenine nucleotides is modified in platelets from breast cancer patients taking tamoxifen.