RESUMO
OBJECTIVE: To investigate the effect of oral iron on postpartum red cell and iron parameters in non-anaemic women with iron deficiency. DESIGN: Randomised study of supplementation with oral iron sulphate 80 mg daily or placebo for 12 weeks starting 24-48 hours after delivery, with visits antepartum and 1, 4, 6 and 12 weeks postpartum. SETTING: Swiss university hospital obstetric unit. PARTICIPANTS: Fifty-two women with antenatal iron deficiency (serum ferritin <15 microg/L) and no antenatal or postnatal anaemia (haemoglobin >11 g/dL up to 48 hours before delivery, and >10 g/dL postpartum), divided into two groups comparable in antenatal iron status. METHODS: Supplementation was started 24-48 hours after delivery (visit 1:V1). Additional tablets were issued one week after V1 (V2), four weeks after V1 (V3) and six weeks after V1 (V4). The last visit took place 12 weeks after visit 1 and 6 weeks after visit 4 (V5). Patients were required to return blisters and boxes whether they were used and unused at each visit and compliance was assessed by counting the tablets. Blood samples for haematology and iron status testing were taken before delivery and at each visit. MAIN OUTCOME MEASURES: Iron status (serum ferritin, hypochromic red cells, iron, transferrin saturation, soluble transferrin receptor concentration); erythropoiesis (standard parameters, including reticulocyte indices); and inflammatory response (serum neopterin, C-reactive protein, white cell count) in five-datapoint profiles. RESULTS: Increased ferritin (P= 0.0004) and transferrin saturation (P= 0.03), decreased soluble transferrin receptors (P= 0.02); increased haemoglobin (P= 0.02) and decreased hypochromic red cells (P= 0.04) compared with placebo at 12 weeks, with no differences in other red cell or reticulocyte parameters. There was a positive correlation between C-reactive protein and postpartum ferritin. No correlation was observed in the puerperium between C-reactive protein and hypochromic red cells or soluble transferrin receptors. CONCLUSIONS: Haemoglobin levels and iron stores in women with term gestational iron deficiency benefit significantly from iron supplementation compared with placebo, even in an industrialised population.
Assuntos
Eritrócitos/citologia , Eritropoese/efeitos dos fármacos , Deficiências de Ferro , Ferro/administração & dosagem , Transtornos Puerperais/tratamento farmacológico , Administração Oral , Adulto , Proteína C-Reativa/metabolismo , Eritrócitos/química , Feminino , Ferritinas/metabolismo , Hemoglobinas/metabolismo , Humanos , Contagem de Leucócitos , Neopterina/sangue , Transtornos Puerperais/sangue , Comprimidos , Transferrina/metabolismoRESUMO
Fe is an essential component of haem in myoglobin and accounts for 70 % of haemoglobin. The balance of Fe, unlike that of other metals such as Na or Ca, is regulated solely by gastrointestinal absorption, which itself depends on the bioavailability of Fe in food, i.e. the chemical Fe species. Factors that maintain Fe homeostasis by modulating Fe transfer through the intestinal mucosa are found at the luminal, mucosal and systemic levels. Fe deficiency and its consequence, Fe-deficiency anaemia, form the commonest nutritional pathology in pregnant women. The current gold standard to detect Fe deficiency remains the serum ferritin value. Previously there was general consensus against parenteral Fe administration, i.e. parenteral Fe was only recommended for special conditions such as unresponsiveness to oral Fe, intolerance to oral Fe, severe anaemia, lack of time for therapy etc. However, especially in hospital settings, clinicians regularly face these conditions but are still worried about reactions that were described using Fe preparations such as Fe-dextrans. A widely used and safe alternative is the Fe-sucrose complex, which has become of major interest to prevent functional Fe deficiency after use of recombinant erythropoietin Numerous reports show the effectiveness and safety of the Fe-sucrose complex. Good tolerance to this Fe formulation is partly due to the low allergenic effect of the sucrose complex, partly due to slow release of elementary Fe from the complex. Accumulation of Fe-sucrose in parenchyma of organs is low compared with Fe-dextrans or Fe-gluconate, while incorporation into the bone marrow for erythropoiesis is considerably faster. Oral Fe is only started if haemoglobin levels are below 110 g/l. If levels fall below 100 g/l or are below 100 g/l at time of diagnosis, parenteral Fe-sucrose is used primarily. In cases of severe anaemia (haemoglobin <90 g/l) or non-response to parenteral Fe after 2 weeks, recombinant erythropoietin is considered in combination. By using parenteral Fe-sucrose in cases of severe Fe deficiency, anaemia during pregnancy is treated efficiently and safely according to our results and rate of blood transfusion could be reduced considerably to below 1 % of patients per year.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/administração & dosagem , Complicações Hematológicas na Gravidez/tratamento farmacológico , Anemia Ferropriva/diagnóstico , Feminino , Compostos Férricos/uso terapêutico , Óxido de Ferro Sacarado , Ácido Glucárico , Humanos , Infusões Parenterais , Gravidez , Complicações Hematológicas na Gravidez/diagnósticoRESUMO
BACKGROUND: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a growth factor commonly used to avoid leukopenia after chemotherapy. Endogenous G-CSF is produced by macrophages and granulocytes that infiltrate tumors. It has been reported that rhG-CSF stimulates the proliferation of several cell lines as well as bladder carcinoma cells. Conversely, in some hematopoietic cell lines such as U-937, WEHI-3B, and K-562 no effect or in some cases a differentiation pattern was found. Moreover, the role of rhG-CSF on the proliferation of solid tumors is not well understood. METHODS: In this study, 10 ovarian carcinoma biopsies were characterized for the presence of G-CSF and G-CSF receptor by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Proliferation was analyzed by ATP viability assays. RESULTS: Performing RT-PCR, these biopsies and four ovarian carcinoma cell lines were analyzed for endogenous G-CSF production, which was found in some biopsies and in all cell lines. Despite the presence of the G-CSF receptor in all biopsies and cell lines, no proliferation was found after rhG-CSF incubation of the cell lines or the tumor samples for 3 and for 6 days, respectively. CONCLUSIONS: Summarizing the authors' in vitro studies, rhG-CSF does not affect the proliferation of ovarian carcinoma cells in vitro.
Assuntos
Carcinoma/genética , Carcinoma/patologia , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos/fisiologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Receptores de Fator Estimulador de Colônias de Granulócitos/genética , Trifosfato de Adenosina/análise , Biópsia , Southern Blotting , Carcinoma/química , Divisão Celular , Fatores Estimuladores de Colônias/farmacologia , Feminino , Fator Estimulador de Colônias de Granulócitos/análise , Humanos , Imuno-Histoquímica , Neoplasias Ovarianas/química , Receptores de Fator Estimulador de Colônias de Granulócitos/análise , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
BACKGROUND: Dexamethasone-induced changes in radioresistance have previously been observed by several authors. Here, we examined effects of dexamethasone on resistance to ionizing radiation in 10 additional human cell lines and strains, and on resistance to carboplatin and paclitaxel in 13 fresh tumor samples. MATERIAL AND METHODS: Eight human carcinoma cell lines, a glioblastoma cell line and a strain of normal human diploid fibroblasts were arbitrarily chosen for these in-vitro studies. Effects on radiosensitivity were assessed using a conventional colony formation assay. Effects on resistance to the drugs were investigated prospectively (ATP cell viability assay) using 13 fresh tumor samples from consecutive patients operated for ovarian cancer within the context of a Swiss nation-wide randomized prospective clinical trial (SAKK 45/94). RESULTS: Dexamethasone promoted proliferation of 1 of the cell lines without affecting radiosensitivity, while it completely inhibited proliferation of another cell line (effects on radiosensitivity could thus not be examined). Furthermore, dexamethasone induced enhanced radioresistance in 1 of the 8 carcinoma cell lines examined. In the glioblastoma cell line, there was no effect on growth or radioresistance, nor in the fibroblasts. Treatment with dexamethasone enhanced resistance of the malignant cells to carboplatin in 4 of the 13 fresh tumor samples examined, while no enhancement in resistance to paclitaxel was observed. CONCLUSIONS: In agreement with previous reports, we found that dexamethasone may induce radioresistance in human carcinoma cells. Including the published data from the literature, dexamethasone induced enhancement in radioresistance in 4 of 12 carcinoma cell lines (33%), but not in 3 glioblastoma cell lines, nor in 3 fibroblast strains. Dexamethasone also induced enhanced resistance to carboplatin with a similar probability in fresh samples of ovarian cancer evaluated prospectively (in 4 of 13 samples; 31%). We worry that induction of resistance by corticosteroids given to patients undergoing either radiotherapy or chemotherapy with agents causing DNA damage might be associated with a reduced clinical responsiveness in a significant fraction of patients with a carcinoma.
Assuntos
Anti-Inflamatórios/efeitos adversos , Antineoplásicos/antagonistas & inibidores , Dexametasona/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Neoplasias/tratamento farmacológico , Antineoplásicos Fitogênicos/antagonistas & inibidores , Carboplatina/antagonistas & inibidores , Células Cultivadas/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Fibroblastos/efeitos da radiação , Humanos , Neoplasias/fisiopatologia , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/antagonistas & inibidores , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Células Tumorais Cultivadas/efeitos da radiaçãoRESUMO
The predictive value of the oncogene product ErbB-2 for chemosensitivity of tumors is still unclear. We therefore correlated the in vitro chemosensitivity of breast cancer specimens from 125 patients with the respective expression levels of ErbB-2. Twenty-six percent of the patients were premenopausal. Chemosensitivity was tested with the adenosine triphosphate cell viability assay and ErbB-2 content was assessed in the same specimens by ELISA. With the cut-off value used 34% of the patients had tumors with positive ErbB-2 levels. The mean ErbB-2 amount of positive tumors was 388 U/mg +/- 254 and of negative tumors 65 U/mg +/- 36. The mean survival fractions (SF) in the chemosensitivity assay at 0.25 peak plasma concentration (PPC) of a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were not significantly different for ErbB-2-positive and for ErbB-2-negative tumors (0.68 and 0.65, respectively (p = 0.6)). The median SF for positive tumors was 0.68 and for negative tumors 0.62, respectively. Similarly, at four times the PPC of CMF no significant differences in SF of ErbB-2-positive and -negative specimens were found (p = 0.8). Comparison of the median of ErbB-2-protein content of CMF-sensitive tumors with that of CMF-resistant tumors also yielded no significant difference. Taken together, no significant association between in vitro CMF-chemosensitivity and expression levels of ErbB-2 in tumors of patients with primary chemotherapy naive breast cancer could be determined.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Humanos , Metotrexato/administração & dosagem , Pessoa de Meia-IdadeRESUMO
Photodynamic therapy (PDT) uses laser light to activate a photosensitizer that has been absorbed preferentially by cancer cells after systemic administration. A phototoxic reaction ensues resulting in cell death and tissue necrosis. Some cells, however, may survive PDT. This study was performed to determine if surviving human breast cancer cells (MCF-7) can become resistant to PDT, chemotherapy or radiotherapy. The MCF-7 cells were cultured under standard conditions prior to being exposed to the photosensitizer, 5,10,15,20-meta-tetra(hydroxyphenyl)chlorin (m-THPC), for 24 h and then irradiated with laser light (652 nm). Surviving cells were allowed to regrow by allowing a 2 week interval between each additional PDT. After the third and final treatment, colony formation assays were used to evaluate the sensitivity of cultured cells to ionizing radiation and PDT and the ATP cell viability assay tested in vitro chemosensitivity. Flow cytometry was used to analyze the cell cycle. No alterations in the cell cycle were observed after three cycles of PDT with m-THPC. Similar responses to chemotherapy and ionizing radiation were seen in control and treatment groups. The m-THPC-sensitized PDT did not induce resistance to subsequent cycles of PDT, chemo- or radiotherapy. Photodynamic therapy with m-THPC may represent a novel adjunctive treatment of breast cancer that may be combined with surgery, chemotherapy or ionizing radiation.
Assuntos
Antineoplásicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Mesoporfirinas/toxicidade , Fotoquimioterapia , Fármacos Fotossensibilizantes/toxicidade , Tolerância a Radiação , Antineoplásicos/sangue , Antineoplásicos/uso terapêutico , Neoplasias da Mama , Sobrevivência Celular/efeitos da radiação , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Feminino , Humanos , Necrose , Paclitaxel/toxicidade , Radioterapia , Células Tumorais CultivadasRESUMO
Iron uptake in rabbit brush border membrane vesicles was measured in the presence of nitrilotriacetate. The complexes formed ranged from stable mononuclear species to hydrolyzed polynuclear complexes and are considered as a good model for nutritional iron compounds with respect to their chemical reactivity. Uptake includes both binding to and penetration through the membrane. A strategy was developed to localize iron in the following four compartments: outer membrane surface, membrane interior, inner membrane surface and aqueous phase within the vesicles. Both surfaces as well as the membrane interior revealed a high metal binding capacity. After an incubation for 10 min with 182 mumol/L iron and 364 mumol/L nitrilotriacetate, 35% of total vesicle iron was found to be bound to the outer membrane surface, 34% to the inner membrane surface, and 23% was not accessible to EDTA. Thus, by adsorption of polynuclear iron complexes to the outer surface, the residence time of iron may be prolonged. The remaining 8% of total iron was in the aqueous phase within the vesicles. Nitrilotriacetate enters the rabbit vesicles in a concentration-dependent manner. As a consequence, iron concentration in the aqueous phase within the vesicles will be driven to the medium equilibrium concentration.