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1.
J Therm Biol ; 115: 103619, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37437370

RESUMO

INTRODUCTION: Irreversible electroporation (IRE) is an ablation modality that applies short, high-voltage electric pulses to unresectable cancers. Although considered a non-thermal technique, temperatures do increase during IRE. This temperature rise sensitizes tumor cells for electroporation as well as inducing partial direct thermal ablation. AIM: To evaluate the extent to which mild and moderate hyperthermia enhance electroporation effects, and to establish and validate in a pilot study cell viability models (CVM) as function of both electroporation parameters and temperature in a relevant pancreatic cancer cell line. METHODS: Several IRE-protocols were applied at different well-controlled temperature levels (37 °C ≤ T ≤ 46 °C) to evaluate temperature dependent cell viability at enhanced temperatures in comparison to cell viability at T = 37 °C. A realistic sigmoid CVM function was used based on thermal damage probability with Arrhenius Equation and cumulative equivalent minutes at 43 °C (CEM43°C) as arguments, and fitted to the experimental data using "Non-linear-least-squares"-analysis. RESULTS: Mild (40 °C) and moderate (46 °C) hyperthermic temperatures boosted cell ablation with up to 30% and 95%, respectively, mainly around the IRE threshold Eth,50% electric-field strength that results in 50% cell viability. The CVM was successfully fitted to the experimental data. CONCLUSION: Both mild- and moderate hyperthermia significantly boost the electroporation effect at electric-field strengths neighboring Eth,50%. Inclusion of temperature in the newly developed CVM correctly predicted both temperature-dependent cell viability and thermal ablation for pancreatic cancer cells exposed to a relevant range of electric-field strengths/pulse parameters and mild moderate hyperthermic temperatures.


Assuntos
Hipertermia Induzida , Neoplasias Pancreáticas , Humanos , Projetos Piloto , Eletroporação/métodos , Temperatura , Neoplasias Pancreáticas/terapia
2.
Sci Rep ; 12(1): 7017, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488115

RESUMO

Hyperthermic intravesical chemotherapy (HIVEC)-whereby the bladder is heated to ± 43 °C during a chemotherapy instillation-can improve outcomes of non-muscle invasive bladder cancer (NMIBC) treatments. Experiments in animal models are required to explore new hyperthermia based treatments. Existing HIVEC devices are not suitable for rodents or large-scale animal trials. We present a HIVEC setup compatible with orthotopic rat models. An externally heated chemotherapeutic solution is circulated in the bladder through a double-lumen catheter with flow rates controlled using a peristaltic pump. Temperature sensors in the inflow channel, bladder and outflow channel allow temperature monitoring and adjustments in real-time. At a constant flow rate of 2.5 mL/min the system rapidly reaches the desired bladder temperature of 42-43 °C with minimal variability throughout a one-hour treatment in a rat bladder phantom, as well as in euthanised and live rats. Mean intraluminal bladder temperatures were 42.92 °C (SD = 0.15 °C), 42.45 °C (SD = 0.37 °C) and 42.52 °C (SD = 0.09 °C) in the bladder phantom, euthanised, and live rats respectively. Thermal camera measurements showed homogenous heat distributions over the bladder wall. The setup provides well-controlled thermal dose and the upscaling needed for performing large scale HIVEC experiments in rats.


Assuntos
Hipertermia Induzida , Neoplasias da Bexiga Urinária , Administração Intravesical , Animais , Feminino , Temperatura Alta , Humanos , Masculino , Ratos , Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico
3.
Adv Drug Deliv Rev ; 163-164: 84-97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31982475

RESUMO

Mild hyperthermia, local heating of the tumour up to temperatures <43 °C, has been clinically applied for almost four decades and has been proven to substantially enhance the effectiveness of both radiotherapy and chemotherapy in treatment of primary and recurrent tumours. Clinical results and mechanisms of action are discussed in this review, including the molecular and biological rationale of hyperthermia as radio- and chemosensitizer as established in in vitro and in vivo experiments. Proven mechanisms include inhibition of different DNA repair processes, (in)direct reduction of the hypoxic tumour cell fraction, enhanced drug uptake, increased perfusion and oxygen levels. All mechanisms show different dose effect relationships and different optimal scheduling with radiotherapy and chemotherapy. Therefore, obtaining the ideal multi-modality treatment still requires elucidation of more detailed data on dose, sequence, duration, and possible synergisms between modalities. A multidisciplinary approach with different modalities including hyperthermia might further increase anti-tumour effects and diminish normal tissue damage.


Assuntos
Antineoplásicos/urina , Hipertermia Induzida/métodos , Neoplasias/terapia , Radioterapia/métodos , Animais , Antineoplásicos/administração & dosagem , Terapia Combinada , Dano ao DNA/fisiologia , Humanos , Hipertermia/fisiopatologia , Fatores de Tempo , Microambiente Tumoral/fisiologia
4.
BMC Pregnancy Childbirth ; 19(1): 85, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832681

RESUMO

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.


Assuntos
Cesárea/métodos , Metrorragia/etiologia , Técnicas de Sutura/efeitos adversos , Útero/cirurgia , Cicatriz/diagnóstico por imagem , Cicatriz/etiologia , Método Duplo-Cego , Dismenorreia/etiologia , Endossonografia , Feminino , Fertilidade , Humanos , Menstruação , Complicações do Trabalho de Parto/etiologia , Gravidez , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sexualidade , Útero/diagnóstico por imagem
5.
Radiat Oncol ; 13(1): 96, 2018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769103

RESUMO

BACKGROUND: Prediction of radiobiological response is a major challenge in radiotherapy. Of several radiobiological models, the linear-quadratic (LQ) model has been best validated by experimental and clinical data. Clinically, the LQ model is mainly used to estimate equivalent radiotherapy schedules (e.g. calculate the equivalent dose in 2 Gy fractions, EQD2), but increasingly also to predict tumour control probability (TCP) and normal tissue complication probability (NTCP) using logistic models. The selection of accurate LQ parameters α, ß and α/ß is pivotal for a reliable estimate of radiation response. The aim of this review is to provide an overview of published values for the LQ parameters of human tumours as a guideline for radiation oncologists and radiation researchers to select appropriate radiobiological parameter values for LQ modelling in clinical radiotherapy. METHODS AND MATERIALS: We performed a systematic literature search and found sixty-four clinical studies reporting α, ß and α/ß for tumours. Tumour site, histology, stage, number of patients, type of LQ model, radiation type, TCP model, clinical endpoint and radiobiological parameter estimates were extracted. Next, we stratified by tumour site and by tumour histology. Study heterogeneity was expressed by the I2 statistic, i.e. the percentage of variance in reported values not explained by chance. RESULTS: A large heterogeneity in LQ parameters was found within and between studies (I2 > 75%). For the same tumour site, differences in histology partially explain differences in the LQ parameters: epithelial tumours have higher α/ß values than adenocarcinomas. For tumour sites with different histologies, such as in oesophageal cancer, the α/ß estimates correlate well with histology. However, many other factors contribute to the study heterogeneity of LQ parameters, e.g. tumour stage, type of LQ model, TCP model and clinical endpoint (i.e. survival, tumour control and biochemical control). CONCLUSIONS: The value of LQ parameters for tumours as published in clinical radiotherapy studies depends on many clinical and methodological factors. Therefore, for clinical use of the LQ model, LQ parameters for tumour should be selected carefully, based on tumour site, histology and the applied LQ model. To account for uncertainties in LQ parameter estimates, exploring a range of values is recommended.


Assuntos
Fracionamento da Dose de Radiação , Modelos Estatísticos , Neoplasias/classificação , Neoplasias/radioterapia , Humanos , Modelos Lineares
6.
Int J Hyperthermia ; 34(7): 901-909, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29749270

RESUMO

PURPOSE: Thermoradiotherapy is an effective treatment for locally advanced cervical cancer. However, the optimal time interval between radiotherapy and hyperthermia, resulting in the highest therapeutic gain, remains unclear. This study aims to evaluate the effect of time interval on the therapeutic gain using biological treatment planning. METHODS: Radiotherapy and hyperthermia treatment plans were created for 15 cervical cancer patients. Biological modeling was used to calculate the equivalent radiation dose, that is, the radiation dose that results in the same biological effect as the thermoradiotherapy treatment, for different time intervals ranging from 0-4 h. Subsequently, the thermal enhancement ratio (TER, i.e. the ratio of the dose for the thermoradiotherapy and the radiotherapy-only plan) was calculated for the gross tumor volume (GTV) and the organs at risk (OARs: bladder, rectum, bowel), for each time interval. Finally, the therapeutic gain factor (TGF, i.e. TERGTV/TEROAR) was calculated for each OAR. RESULTS: The median TERGTV ranged from 1.05 to 1.16 for 4 h and 0 h time interval, respectively. Similarly, for bladder, rectum and bowel, TEROARs ranged from 1-1.03, 1-1.04 and 1-1.03, respectively. Radiosensitization in the OARs was much less than in the GTV, because temperatures were lower, fractionation sensitivity was higher (lower α/ß) and direct cytotoxicity was assumed negligible in normal tissue. TGFs for the three OARs were similar, and were highest (around 1.12) at 0 h time interval. CONCLUSION: This planning study indicates that the largest therapeutic gain for thermoradiotherapy in cervical cancer patients can be obtained when hyperthermia is delivered immediately before or after radiotherapy.


Assuntos
Dosagem Radioterapêutica/normas , Neoplasias do Colo do Útero/radioterapia , Fracionamento da Dose de Radiação , Feminino , Humanos , Hipertermia Induzida/métodos , Doses de Radiação
7.
Int J Hyperthermia ; 34(1): 30-38, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28540813

RESUMO

PURPOSE: Biological modelling of thermoradiotherapy may further improve patient selection and treatment plan optimisation, but requires a model that describes the biological effect as a function of variables that affect treatment outcome (e.g. temperature, radiation dose). This study aimed to establish such a model and its parameters. Additionally, a clinical example was presented to illustrate the application. METHODS: Cell survival assays were performed at various combinations of radiation dose (0-8 Gy), temperature (37-42 °C), time interval (0-4 h) and treatment sequence (radiotherapy before/after hyperthermia) for two cervical cancer cell lines (SiHa and HeLa). An extended linear-quadratic model was fitted to the data using maximum likelihood estimation. As an example application, a thermoradiotherapy plan (23 × 2 Gy + weekly hyperthermia) was compared with a radiotherapy-only plan (23 × 2 Gy) for a cervical cancer patient. The equivalent uniform radiation dose (EUD) in the tumour, including confidence intervals, was estimated using the SiHa parameters. Additionally, the difference in tumour control probability (TCP) was estimated. RESULTS: Our model described the dependency of cell survival on dose, temperature and time interval well for both SiHa and HeLa data (R2=0.90 and R2=0.91, respectively), making it suitable for biological modelling. In the patient example, the thermoradiotherapy plan showed an increase in EUD of 9.8 Gy that was robust (95% CI: 7.7-14.3 Gy) against propagation of the uncertainty in radiobiological parameters. This corresponded to a 20% (95% CI: 15-29%) increase in TCP. CONCLUSIONS: This study presents a model that describes the cell survival as a function of radiation dose, temperature and time interval, which is essential for biological modelling of thermoradiotherapy treatments.


Assuntos
Radioterapia/métodos , Linhagem Celular Tumoral , Sobrevivência Celular , Feminino , Humanos , Dosagem Radioterapêutica , Temperatura , Fatores de Tempo
8.
Int J Hyperthermia ; 33(4): 419-427, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28100096

RESUMO

Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells (CSCs), is considered to be of particular significance for tumour initiation, progression and metastasis. CSCs are considered in particular to be therapy-resistant and may drive disease recurrence, which positions CSCs in the focus of anti-cancer research, but successful CSC-targeting therapies are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising radiation and chemotherapy are least effective. Second, hyperthermia can modify factors that are essential for tumour survival and growth, such as the microenvironment, immune responses, vascularisation and oxygen supply. Third, hyperthermia targets multiple DNA repair pathways, which are generally upregulated in CSCs and protect them from DNA-damaging agents. Addition of hyperthermia to the therapeutic armamentarium of oncologists may thus be a promising strategy to eliminate therapy-escaping and -resistant CSCs.

9.
Clin Microbiol Infect ; 23(7): 480-484, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28110053

RESUMO

OBJECTIVES: Borrelia miyamotoi has been shown to infect humans in Eurasia and North America causing hard tick-borne relapsing fever (HTBRF). In vitro cultivation of B. miyamotoi was described recently; but clinical isolation of relapsing fever Borrelia is cumbersome. Our aim was to develop a straightforward protocol enabling B. miyamotoi isolation directly from the blood of patients. METHODS: Modified Kelly-Pettenkorfer (MKP-F) medium, with or without anticoagulants, or blood from healthy human volunteers, was spiked with B. miyamotoi spirochaetes in vitro. Subsequently, either media or plasma was used for cultivation directly, or after an additional centrifugation step. This isolation protocol was tested in a clinical setting on patients suspected of HTBRF. RESULTS: Dipotassium-EDTA, trisodium citrate and lithium heparin inhibited growth of B. miyamotoi at concentrations ≥250 µg/mL, 2.5 mM and 1 IU/mL, respectively. However, when plasma originating from human blood containing B. miyamotoi spirochaetes was subjected to an additional centrifugation step at 8000 g, suspended and inoculated into fresh MKP-F media, positive cultures were observed within 2 weeks. Of importance, this straightforward protocol allowed for isolation of B. miyamotoi from six out of nine patients with confirmed HTBRF. CONCLUSIONS: Direct culture from K2-EDTA, trisodium citrate and lithium heparin plasma containing B. miyamotoi is hampered due to anticoagulants. Using a simple centrifugation protocol we were able to circumvent this detrimental effect, allowing for the first clinical isolation of B. miyamotoi. This will be of value for future research on the pathogenesis, genetics, diagnosis, therapy and epidemiology of HTBRF and other tick-borne relapsing fevers.


Assuntos
Técnicas Bacteriológicas/métodos , Sangue/microbiologia , Borrelia/isolamento & purificação , Febre Recorrente/microbiologia , Manejo de Espécimes/métodos , Centrifugação/métodos , Meios de Cultura/química , Humanos
10.
Int J Hyperthermia ; 33(2): 160-169, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27744728

RESUMO

PURPOSE: Currently, clinical decisions regarding thermoradiotherapy treatments are based on clinical experience. Quantification of the radiosensitising effect of hyperthermia allows comparison of different treatment strategies, and can support clinical decision-making regarding the optimal treatment. The software presented here enables biological evaluation of thermoradiotherapy plans through calculation of equivalent 3D dose distributions. METHODS: Our in-house developed software (X-Term) uses an extended version of the linear-quadratic model to calculate equivalent radiation dose, i.e. the radiation dose yielding the same effect as the thermoradiotherapy treatment. Separate sets of model parameters can be assigned to each delineated structure, allowing tissue specific modelling of hyperthermic radiosensitisation. After calculation, the equivalent radiation dose can be evaluated according to conventional radiotherapy planning criteria. The procedure is illustrated using two realistic examples. First, for a previously irradiated patient, normal tissue dose for a radiotherapy and thermoradiotherapy plan (with equal predicted tumour control) is compared. Second, tumour control probability (TCP) is assessed for two (otherwise identical) thermoradiotherapy schedules with different time intervals between radiotherapy and hyperthermia. RESULTS: The examples demonstrate that our software can be used for individualised treatment decisions (first example) and treatment optimisation (second example) in thermoradiotherapy. In the first example, clinically acceptable doses to the bowel were exceeded for the conventional plan, and a substantial reduction of this excess was predicted for the thermoradiotherapy plan. In the second example, the thermoradiotherapy schedule with long time interval was shown to result in a substantially lower TCP. CONCLUSIONS: Using biological modelling, our software can facilitate the evaluation of thermoradiotherapy plans and support individualised treatment decisions.

12.
Radiat Oncol ; 11: 14, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26831185

RESUMO

BACKGROUND: Locoregional hyperthermia combined with radiotherapy significantly improves locoregional control and overall survival for cervical tumors compared to radiotherapy alone. In this study biological modelling is applied to quantify the effect of radiosensitization for three cervical cancer patients to evaluate the improvement in equivalent dose for the combination treatment with radiotherapy and hyperthermia. METHODS: The Linear-Quadratic (LQ) model extended with temperature-dependent LQ-parameters α and ß was used to model radiosensitization by hyperthermia and to calculate the conventional radiation dose that is equivalent in biological effect to the combined radiotherapy and hyperthermia treatment. External beam radiotherapy planning was performed based on a prescription dose of 46Gy in 23 fractions of 2Gy. Hyperthermia treatment using the AMC-4 system was simulated based on the actual optimized system settings used during treatment. RESULTS: The simulated hyperthermia treatments for the 3 patients yielded a T50 of 40.1 °C, 40.5 °C, 41.1 °C and a T90 of 39.2 °C, 39.7 °C, 40.4 °C, respectively. The combined radiotherapy and hyperthermia treatment resulted in a D95 of 52.5Gy, 55.5Gy, 56.9Gy in the GTV, a dose escalation of 7.3-11.9Gy compared to radiotherapy alone (D95 = 45.0-45.5Gy). CONCLUSIONS: This study applied biological modelling to evaluate radiosensitization by hyperthermia as a radiation-dose escalation for cervical cancer patients. This model is very useful to compare the effectiveness of different treatment schedules for combined radiotherapy and hyperthermia treatments and to guide the design of clinical studies on dose escalation using hyperthermia in a multi-modality setting.


Assuntos
Relação Dose-Resposta à Radiação , Hipertermia Induzida/métodos , Radioterapia/métodos , Neoplasias do Colo do Útero/radioterapia , Ensaios Clínicos como Assunto , Feminino , Humanos , Modelos Lineares , Radiossensibilizantes/química , Interpretação de Imagem Radiográfica Assistida por Computador , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Temperatura , Tomografia Computadorizada por Raios X
13.
Gene Ther ; 21(12): 1051-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25273355

RESUMO

Borrelia afzelii is the predominant Borrelia species causing Lyme borreliosis in Europe. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines against Borrelia burgdorferi sensu stricto. DNA tattooing is a novel vaccination method that can be applied in a rapid vaccination schedule. We vaccinated C3H/HeN mice with B. afzelii strain PKo OspC (outer-surface protein C) using a codon-optimized DNA vaccine tattoo and compared this with recombinant protein vaccination in a 0-2-4 week vaccination schedule. We also assessed protection by DNA tattoo in a 0-3-6 day schedule. DNA tattoo and recombinant OspC vaccination induced comparable total IgG responses, with a lower IgG1/IgG2a ratio after DNA tattoo. Two weeks after syringe-challenge with 5 × 10(5) B. afzelii spirochetes most vaccinated mice had negative B. afzelii tissue DNA loads and all were culture negative. Furthermore, DNA tattoo vaccination in a 0-3-6 day regimen also resulted in negative Borrelia loads and cultures after challenge. To conclude, DNA vaccination by tattoo was fully protective against B. afzelii challenge in mice in a rapid vaccination protocol, and induces a favorable humoral immunity compared to recombinant protein vaccination. Rapid DNA tattoo is a promising vaccination strategy against spirochetes.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Grupo Borrelia Burgdorferi , Doença de Lyme/prevenção & controle , Vacinação/métodos , Vacinas de DNA/imunologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Vacinas Bacterianas/genética , DNA Bacteriano/genética , Doença de Lyme/imunologia , Camundongos , Camundongos Endogâmicos C3H , Vacinas de DNA/genética
14.
Br J Cancer ; 110(6): 1673-80, 2014 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-24434428

RESUMO

BACKGROUND: Host germline variations and their potential prognostic importance is an emerging area of interest in paediatric ALL. METHODS: We investigated the associations between 20 germline variations and various clinical end points in 463 children with ALL. RESULTS: After adjusting for known prognostic factors, variants in two genes were found to be independently associated with poorer EFS: ABCB1 T/T at either 2677 (rs2032582) or 3435 (rs1045642) position (P=0.003) and IL15 67276493G/G (rs17015014; P=0.022). These variants showed a strong additive effect affecting outcome (P<0.001), whereby patients with both risk genotypes had the worst EFS (P=0.001), even after adjusting for MRD levels at the end of remission induction. The adverse effect of ABCB1 T/T genotypes was most pronounced in patients with favourable cytogenetics (P=0.011) while the IL15 67276493G/G genotype mainly affected patients without common chromosomal abnormalities (P=0.022). In both cytogenetic subgroups, increasing number of such risk genotypes still predicted worsening outcome (P<0.001 and=0.009, respectively). CONCLUSION: These results point to the prognostic importance of host genetic variants, although the specific mechanisms remain unclarified. Inclusion of ABCB1 and IL15 variants may help improve risk assignment strategies in paediatric ALL.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Interleucina-15/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Resultado do Tratamento
15.
Int J Biol Markers ; 22(3): 167-71, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17922458

RESUMO

The aim of this study was to develop and validate ELISAs for quantification of HAMA-IgM and HAMA-IgG in serum of patients with ovarian cancer who enrolled in a large international randomized phase III trial of intraperitoneal Yttrium-90-labeled HMFG1 murine monoclonal antibody therapy. The capture antibody of these 2 assays was the murine antibody HMFG1, while mouse anti-human IgM-HRP or mouse anti-human IgG(Fc)-HRP served as tracer antibodies. A pool of HAMA-positive serum samples was used to prepare a series of assay standards and another pool served as reference preparation. The analytical sensitivity of the HAMA-IgM assay was 2.5 arbitrary units per mL (AU/mL) and 4.7 AU/mL for the HAMA-IgG ELISA. Diluted serum samples showed good parallelism with the HAMA-IgM and HAMA-IgG standard dose-response curves. Within-assay coefficient of variation was 7.5% for HAMA-IgM and 6.5% for HAMA-IgG. Between-assay variation was 14.2% for HAMA-IgM and 15.3% for HAMA-IgG. The developed HAMA-IgM and HAMA-IgG ELISAs show satisfactory reliability criteria (sensitivity, parallelism and precision) and are suitable for monitoring of HAMA-IgM and HAMA-IgG responses in ovarian cancer patients. These ELISAs will be used to monitor the development of HAMAs in patients who received radioimmunotherapy with murine HMFG1.


Assuntos
Anticorpos Monoclonais/imunologia , Biomarcadores Tumorais/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Imunotoxinas/uso terapêutico , Neoplasias Ovarianas/imunologia , Animais , Anticorpos Anti-Idiotípicos/imunologia , Feminino , Humanos , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Imunotoxinas/imunologia , Injeções Intraperitoneais , Camundongos , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/terapia , Radioimunoterapia/métodos , Sensibilidade e Especificidade , Radioisótopos de Ítrio/uso terapêutico
16.
Diagn Cytopathol ; 35(4): 227-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17351934

RESUMO

Cytomegalovirus (CMV) infected cells in cervical smears are a rare finding but may have severe consequences. We describe the presence of characteristic "owl eye" cells in a conventional cervical smear. Medical history revealed a liver transplantation from a CMV seropositive donor 1 yr earlier. The patient experienced a delayed primary CMV infection 6 mo after transplantation. The current CMV infection was considered to be either a persisting manifestation of that primary infection or a reactivation. Since the patient experienced no clinical symptoms, it was decided to "wait and see". Infections with cytomegalovirus in immunocompromised patients may present with aspecific symptoms, but may lead to severe organ-threatening disease such as acute or chronic transplantation loss in transplant recipients. Although in the present case no serious consequences occurred, we stress that it is important to recognize these cells and report this finding promptly to the referring physician to prevent possible severe morbidity.


Assuntos
Colo do Útero/patologia , Colo do Útero/virologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , Hospedeiro Imunocomprometido , Transplante de Fígado/efeitos adversos , Infecções por Citomegalovirus/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Esfregaço Vaginal
17.
Br J Cancer ; 94(6): 814-9, 2006 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-16495917

RESUMO

To determine the effectiveness of annual gynaecological screening (pelvic examination, transvaginal ultrasound, and CA-125), a prospective cohort study of women at high risk for hereditary ovarian cancer was conducted. Women were offered DNA analysis followed by either annual screening or prophylactic bilateral salpingo-oophorectomy (BSO). Study population consisted of 512 high-risk women (median follow-up 2.07 years, range 0-9.4 years): 265 women (52%) had a BRCA mutation. Persisting abnormalities indicated diagnostic surgery in 24 women resulting in one primary ovarian cancer FIGO stage IIIc was found. The effectiveness of screening was studied by calculating the probability of finding ovarian cancers in the BRCA-1 and BRCA-2 carrier group and comparing this to the identified number of ovarian cancers. The number of ovarian cancer patients found at surveillance was in accordance with the predicted number of ovarian cancers. A total number of 169 women underwent prophylactic BSO: one ovarian cancer stage IIb was found. In conclusion, the surveillance programme for hereditary ovarian cancer does identify patients with ovarian cancer but is very inefficient considering the high number of surveillance visits and the advanced stage of ovarian cancer in the identified patient. For prevention of advanced stage ovarian cancer, prophylactic BSO from age 35-40 years is a more efficient alternative.


Assuntos
Predisposição Genética para Doença , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Adulto , Fatores Etários , Idoso , Antígeno Ca-125/análise , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Pessoa de Meia-Idade , Linhagem , Pelve , Exame Físico , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Ultrassonografia , Vagina/diagnóstico por imagem
18.
Eur Radiol ; 11(10): 1952-5, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11702127

RESUMO

We describe a rare case of a pancreatic VIPoma diagnosed in a patient presenting with watery diarrhea, hypokalemia, and achlorhydria, the so-called WDHA or Verner-Morrison syndrome. Emphasis is placed on the dynamic gadolinium-enhanced MR profile of the tumor, characteristics which have not been illustrated previously, to the best of our knowledge.


Assuntos
Meios de Contraste , Imageamento por Ressonância Magnética , Meglumina , Compostos Organometálicos , Neoplasias Pancreáticas/patologia , Vipoma/patologia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos
19.
Eur Radiol ; 11(6): 1076-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11419157

RESUMO

A rare case of idiopathic midline destructive disease is presented, which is an entity of the so-called midline granuloma syndrome. Differentiation from other granulomas, especially from Wegener's granulomatosis, is important. This report shows the MR findings in a patient with atypical clinical presentation of histopathologically proven idiopathic midline destructive disease.


Assuntos
Granuloma Letal da Linha Média/diagnóstico , Imageamento por Ressonância Magnética , Base do Crânio/patologia , Idoso , Biópsia , Diagnóstico Diferencial , Granuloma Letal da Linha Média/patologia , Humanos , Masculino
20.
JBR-BTR ; 84(5): 197-200, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11757675

RESUMO

Rhombencephalosynapsis is a rare condition in which most cases are found in newborns and infants. Morphological findings are predominantly characterized by fusion of the cerebellar hemispheres and absence of the vermis with often associated supratentorial anomalies. We review the literature with emphasis on diagnostic imaging of this condition and present a case of a 2-year-old girl.


Assuntos
Cerebelo/anormalidades , Ventrículos Cerebrais/anormalidades , Ecoencefalografia , Hidrocefalia/diagnóstico , Septo Pelúcido/anormalidades , Tomografia Computadorizada por Raios X , Cerebelo/patologia , Ventrículos Cerebrais/patologia , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Feminino , Seguimentos , Fórnice/anormalidades , Fórnice/patologia , Humanos , Lactente , Recém-Nascido , Exame Neurológico , Gravidez , Septo Pelúcido/patologia
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