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1.
Strahlenther Onkol ; 196(11): 1018-1033, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32519025

RESUMEN

BACKGROUND: In this exploratory study, the impact of local irradiation on systemic changes in stress and immune parameters was investigated in eight patients treated with intensity-modulated radiation therapy (IMRT) or stereotactic ablative body radiotherapy (SABR) for prostate adenocarcinoma to gain deeper insights into how radiotherapy (RT) modulates the immune system. PATIENTS AND METHODS: RT-qPCR, flow cytometry, metabolomics, and antibody arrays were used to monitor a panel of stress- and immune-related parameters before RT, after the first fraction (SABR) or the first week of treatment (IMRT), after the last fraction, and 3 weeks later in the blood of IMRT (N = 4) or SABR (N = 4) patients. Effect size analysis was used for comparison of results at different timepoints. RESULTS: Several parameters were found to be differentially modulated in IMRT and SABR patients: the expression of TGFB1, IL1B, and CCL3 genes; the expression of HLA-DR on circulating monocytes; the abundance and ratio of phosphatidylcholine and lysophosphatidylcholine metabolites in plasma. More immune modulators in plasma were modulated during IMRT than SABR, with only two common proteins, namely GDF-15 and Tim­3. CONCLUSION: Locally delivered RT induces systemic modulation of the immune system in prostate adenocarcinoma patients. IMRT and SABR appear to specifically affect distinct immune components.


Asunto(s)
Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Sistema Inmunológico/efectos de la radiación , Metaboloma/efectos de la radiación , Proteínas de Neoplasias/sangre , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Proteoma/efectos de la radiación , Radiocirugia/métodos , Radioterapia de Intensidad Modulada/métodos , Estrés Fisiológico/efectos de la radiación , Adenocarcinoma/inmunología , Adenocarcinoma/fisiopatología , Anciano , Anciano de 80 o más Años , Biomarcadores , Citocinas/sangre , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Antígenos HLA/sangre , Humanos , Mediadores de Inflamación/sangre , Lisofosfatidilcolinas/sangre , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Fosfatidilcolinas/sangre , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/fisiopatología
2.
Diabet Med ; 36(10): 1209-1216, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30889281

RESUMEN

AIMS: To assess the number of people with diabetes in Poland using combined national sources and to evaluate the usefulness of data from an insurance system for epidemiological purposes. METHODS: The data were collected from four sources: 1) 2013 all-billing records of the national insurance system comprising people of all age groups undergoing procedures or receiving services in primary healthcare, specialist practices and hospitals and also those receiving drugs; 2) an epidemiological study, NATPOL, that involved the assessment of people with undiagnosed diabetes; 3) the RECEPTOmetr Sequence study on prescriptions; and 4) regional child diabetes registries. RESULTS: In 2013, 1.76 million people (0.98 million women and 0.79 million men) had medical consultations (coded E10-E14) and 2.13 million people (1.19 million women and 0.94 million men) purchased drugs or strip tests for diabetes. A total of 0.04 million people who used medical services did not buy drugs. In total, the number of people with diabetes in the insurance system was 2.16 million (1.21 million women and 0.95 million men), which corresponds to 6.1% (95% CI 6.11-6.14) of women and 5.1% (95% CI 5.12-5.14) of men. Including undiagnosed cases, the total number of people with diabetes in Poland was 2.68 million in 2013. CONCLUSION: The estimated prevalence of diabetes (diagnosed and undiagnosed cases) in Poland is 6.97%. Data from the national insurance system with full coverage of the population can be treated as a reliable source of information on diseases with well-defined diagnosis and treatment methods, combined with an assessment of the number of undiagnosed individuals.


Asunto(s)
Diabetes Mellitus/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Niño , Preescolar , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Reembolso de Seguro de Salud/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Programas Nacionales de Salud/estadística & datos numéricos , Polonia/epidemiología , Prevalencia , Adulto Joven
3.
Diabet Med ; 34(9): 1252-1258, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28257151

RESUMEN

AIMS: To present the incidence trend for Type 1 diabetes in Polish children aged 0-14 years, updated using data collected during 2005-2012, and assess the reliability of the predictive model constructed previously using the 1989-2004 database. METHODS: Children aged < 15 years with newly diagnosed Type 1 diabetes are recorded prospectively (EURODIAB criteria) in several regional registers in Poland. Age- and gender-standardized incidence rates for Type 1 diabetes were calculated per 100 000 persons/year. Incidence rates were analysed in terms of the dependency on age, gender, geographical region and population density. Incidence rate trends over time were modelled using generalized linear models. RESULTS: The mean standardized incidence for 1989-2012 was 12.72 per 100 000 persons/year [95% confidence interval (CI), 11.35 to 14.21]. Over the 24-year observation period, the incidence increased from 5.36 to 22.74 per 100 000 persons/year. The lowest incidence rate was in children aged 0-4 years (8.35, 95% CI 7.27 to 9.57 per 100 000 persons/year). There was no difference between genders, or urban and rural regions. Incidence rates were higher in northern compared with southern Poland [14.04 (95% CI 12.59 to 15.63) vs. 11.94 (95% CI 10.62 to 13.39) per 100 000 persons/year]. The new data corrected the earlier predictive model by changing the estimates of some factors related to patient age, gender and their interactions with the remaining factors. The incidence rate shows periodic 5.33-year fluctuations. The periodicity component allows for a more accurate prediction of the incidence rate over time. CONCLUSIONS: This cohort study reveals a sustained increase in Type 1 diabetes incidence in Polish children aged 0-14 years with regular, sinusoidal fluctuations and a slight levelling off in past few years. It is of concern that are the highest increases in incidence are found in children aged 0-4 years.


Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Distribución por Edad , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Polonia/epidemiología , Crecimiento Demográfico
4.
Atherosclerosis ; 237(1): 129-34, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25238220

RESUMEN

OBJECTIVE: Being the earliest step on the way to atherosclerosis, endothelial dysfunction is particularly escalated in diabetes. This study aimed at assessing endothelial dysfunction and blood pressure disturbances in young patients with type 1 diabetes mellitus (T1DM) and defining their interrelations. METHODS: The study group comprised 52 children and adolescents aged 14.07 ± 3.03 years, with T1DM duration 5.13 ± 2.18 years. 20 healthy controls with similar age and sex distribution were included. Chosen serum biochemical markers of endothelial damage: intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), sE-selectin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) as well as ambulatory blood pressure monitoring (ABPM) were performed in all subjects. RESULTS: Patients with T1DM displayed significantly higher concentrations of chosen markers of endothelial dysfunction compared to controls (sVCAM-1 (ng/ml): 951.56 ± 330.68 vs. 710.35 ± 162.12, TNF-α (pg/ml): 16.63 ± 8.32 vs. 9.41 ± 4.23, IL-6 (pg/ml): 3.38 ± 1.31 vs. 2.45 ± 0.81; p < 0.05). Within the study group subjects with an abnormal ABPM reading had significantly higher concentrations of sE-selectin compared with subjects with normal ABPM (in ng/ml: 45.71 ± 15.63 vs. 32.42 ± 11.95; p < 0.01). The study revealed a significant positive correlation between sE-selectin and systolic as well as diastolic pressure loads during the day period (respectively: r = 0.46, r = 0.60; p < 0.01). CONCLUSIONS: Endothelium dysfunction may be present early in the course of T1DM in children and adolescents. It seems to be related with blood pressure disturbances which highlights the need to intensify treatment in this group of patients.


Asunto(s)
Presión Sanguínea , Diabetes Mellitus Tipo 1/sangre , Endotelio Vascular/patología , Adolescente , Monitoreo Ambulatorio de la Presión Arterial , Estudios de Casos y Controles , Niño , Complicaciones de la Diabetes/diagnóstico , Selectina E/sangre , Femenino , Humanos , Hipertensión/complicaciones , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Masculino , Análisis de Regresión , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/sangre , Molécula 1 de Adhesión Celular Vascular/sangre
5.
Clin Exp Immunol ; 177(3): 598-602, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24773566

RESUMEN

Persistent presence of ATP4A autoantibodies (ATP4AA) directed towards parietal cells is typical for atrophic body gastritis (ABG), an autoimmune disease associated with type 1 diabetes. We assessed whether Helicobacter pylori (Hp) infection might be associated with positivity for ATP4AA in children with type 1 diabetes. Sera were collected from 70 (38♀) type 1 diabetes children [aged 13·2 ± 4·5 years, age at diagnosis 8·8 ± 4·3 years, diabetes duration 4·5 ± 3·8 years, mean HbA1c 7·8 ± 1·6% (62 ± 17·5 mmol/mol)] seen at the regional diabetes clinic in Katowice, Poland. Patients were tested concurrently for Hp infection by means of a 13C urea breath test. ATP4AA were measured using a novel radioimmunoprecipitation assay developed at the Barbara Davies Center for Childhood Diabetes, University of Colorado. ATP4AA were present in 21 [30%, 95% confidence interval (CI) = 19-41%] and Hp infection was detected in 23 (33%, 95% CI = 22-44%) children. There was no statistically significant association between ATP4AA presence and Hp status. ATP4AA presence was not associated with current age, age at type 1 diabetes diagnosis, diabetes duration or current HbA1c. ATP4AA were more prevalent in females [42% (26-58%)] than males [16% (3-28%)], P = 0·016. ATP4A are found in nearly one-third of children with type 1 diabetes and more common among females. In this cross-sectional analysis, Hp infection was not associated with autoimmunity against parietal cells.


Asunto(s)
Autoinmunidad , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/microbiología , ATPasa Intercambiadora de Hidrógeno-Potásio/inmunología , Infecciones por Helicobacter/microbiología , Helicobacter pylori , Adolescente , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/microbiología , Niño , Preescolar , Estudios Transversales , Femenino , ATPasa Intercambiadora de Hidrógeno-Potásio/sangre , Infecciones por Helicobacter/inmunología , Humanos , Masculino , Factores Sexuales , Adulto Joven
6.
Acta Diabetol ; 51(4): 633-40, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24562335

RESUMEN

The aim of our study was to characterize the association of clinical and genetic risk factors such as: ACE genotype (rs17997552, rs1800764, rs4459609) and RGS2 (rs2746071) with the development of hypertension (HT) and non-dipping phenomenon in patients with type 1 diabetes mellitus (T1DM). A total of 238 adolescents and young adults with T1DM-103 females and 135 males, aged 8-30 years (mean 17.35 ± 5.2) with diabetes duration 1-26 years (mean 7.72 ± 6.2), with mean HbA1c (IFCC) 58 ± 15 mmol/mmol-were subjected to 24-h ambulatory blood pressure measurements (ABPM). The results of the ABPM were analyzed in association with the polymorphisms of ACE and RGS2 genes and clinical data of patients. HT was recognized in 65 (27 %) and non-dipping in 111 (46.63 %) patients. In the multivariate analysis of factors predisposing to HT, the variables that remained significant were the following: male sex (OR 1.62; 95 % CI 1.171-2.250), non-dipping (OR 1.40; 95 % CI 1.03-1.90) and total cholesterol level (OR 1.01; 95 % CI 1.005-1.021). The only factor influencing non-dipping was the duration of diabetes-OR 1.09 (95 % CI 1.04-1.14). The patients displaying non-dipping have a twice increased risk of development of HT (OR 2.17; 95 % CI 1.21-3.89). There was no association between disturbances of blood pressure (BP) and genotypes of ACE: rs17997552, rs1800764, rs4459609 and RGS2: rs2746071. Clinical rather than genetic risk factors seem to be connected with BP disturbances in young patients with T1DM. Although we have identified representative groups of HT versus non-HT and dipping versus non-dipping subjects, the effect of genetic predisposition to the development of higher BP is too weak to be statistically significant.


Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Variación Genética , Hipertensión/etiología , Peptidil-Dipeptidasa A/genética , Proteínas RGS/genética , Adolescente , Adulto , Presión Sanguínea , Niño , Diabetes Mellitus Tipo 1/enzimología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Humanos , Hipertensión/enzimología , Hipertensión/genética , Hipertensión/fisiopatología , Masculino , Peptidil-Dipeptidasa A/metabolismo , Polimorfismo de Nucleótido Simple , Proteínas RGS/metabolismo , Adulto Joven
7.
Int J Clin Pract ; 66(4): 374-7, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22248162

RESUMEN

BACKGROUND: Metalloproteinases of the external matrix play an important role in ethiopatogenesis of diabetic complications especially in microangiopathy and also in fibrosing processes with occurrence the cheiroarthropathy, but clinical data are insufficient. AIMS: The aim of the study was to assess the influence of metalloproteinases such as gelatinase A (MMP2) and gelatinase B (MMP9), and their tissue inhibitors (TIMP2, TIMP9) in ethiopathogenesis of cheiroatrhopathy in children with diabetes type 1. MATERIALS AND METHODS: Forty one children were observed in average age of 14.98 years (±3.03 years), with the average duration of diabetes 6.78 years (±3.21 years), and with average HbA1c within all diabetes duration time 7.1% (6.47-7.5%). In all patients, the occurrence of cheiroarthropathy was checked, and concentration of metalloproteinase's and their inhibitors in serum were measured using ELISA method. Probe was divided into two groups because of presence of cheiroarthropathy. The comparing analysis of these two groups was conducted, and the correlation between metalloproteinase's concentration and their tissue inhibitors with selected parameters was done. RESULTS: When comparing group with cheiroarthropathy (n = 19) with the group without cheiroarthropathy (n = 22), the statistically significant elevated levels of metalloproteinase's were proved such as: MMP2 - 202 ng/ml (193-207) vs. 138 ng/ml (130-158), p < 0.001; MMP9 - 462 ng/ml (426-505) vs. 288 ng/ml (251-313), 0.001; TIMP2 - 182 ng/ml (177-190) vs. 104 ng/ml (88-165), p < 0.001); TIMP9 - 85 ng/ml (68-95) vs. 55 ng/ml (50-60), p < 0.001. There was no correlation between occurrence of cheiroarthropathy and age of the diabetes onset, duration of diabetes, grade of metabolic compensation, insulin dosages, weight and height. CONCLUSION: In children with long-term diabetes, although relatively metabolic compensation, the cheiroarthropathy has been occurred accompanying by elevated concentrations of metalloproteinase's and their tissue inhibitors. The presence of cheiroarthropathy could be treated as a simple test to identification the patients endangered to develop chronic vascular complication.


Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Artropatías/etiología , Metaloproteinasas de la Matriz/fisiología , Inhibidores Tisulares de Metaloproteinasas/fisiología , Adolescente , Niño , Diabetes Mellitus Tipo 1/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Artropatías/metabolismo , Masculino , Metaloproteinasas de la Matriz/metabolismo , Proyectos Piloto , Síndrome , Inhibidores Tisulares de Metaloproteinasas/metabolismo
8.
Diabetologia ; 54(3): 508-15, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21165594

RESUMEN

AIMS/HYPOTHESIS: We analysed the temporal changes in the incidence of childhood type 1 diabetes and its demographic determinants in Poland from 1989 to 2004, validating the model with data from 1970 to 1989. We also estimated a predictive model of the trends in childhood diabetes incidence for the near future. METHODS: Children under 15 years with newly diagnosed type 1 diabetes mellitus and drawn from seven regional registries in Poland were ascertained prospectively using the Epidemiology and Prevention of Diabetes study (EURODIAB) criteria. The type 1 diabetes incidence rates (IRs) were analysed in dependency of age, sex, seasonality, geographical region and population density. Time trends in IR were modelled using several approaches. RESULTS: The average incidence, standardised by age and sex, for 1989 to 2004 was 10.2 per 100,000 persons per year and increased from 5.4 to 17.7. No difference was found between boys and girls, or between urban and rural regions. In children above 4 years, IR was significantly higher in the population of northern Poland than in that of the country's southern part, as well as in the autumn-winter season, this finding being independent of child sex. Based on the trend model obtained, almost 1,600 Polish children aged 0 to 14 years are expected to develop type 1 diabetes in 2010, rising to more than 4,800 in 2025. The estimates suggest at least a fourfold increase of IR between 2005 and 2025, with the highest dynamics of this increment in younger children. CONCLUSIONS/INTERPRETATION: These estimates show that Poland will have to face a twofold higher increase in childhood type 1 diabetes than predicted for the whole European population. The dramatic increase could have real downstream effects on Poland's healthcare system.


Asunto(s)
Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Distribución por Edad , Niño , Preescolar , Femenino , Humanos , Incidencia , Masculino , Polonia/epidemiología , Distribución por Sexo
9.
Neoplasma ; 57(6): 537-44, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20845992

RESUMEN

Mass spectrometry-based analysis of the serum proteome allows identifying multi-peptide patterns/signatures specific for blood of cancer patients, thus having high potential value for cancer diagnostics. However, because of problems with optimization and standardization of experimental and computational design, none of identified proteome patterns/signatures was approved for diagnostics in clinical practice as yet. Here we compared two methods of serum sample preparation for mass spectrometry-based proteome pattern analysis aimed to identify biomarkers that could be used in early detection of breast cancer patients. Blood samples were collected in a group of 92 patients diagnosed at early (I and II) stages of the disease before the start of therapy, and in a group of age-matched healthy controls (104 women). Serum specimens were purified and analyzed using MALDI-ToF spectrometry, either directly or after membrane filtration (50 kDa cut-off) to remove albumin and other large serum proteins. Mass spectra of the low-molecular-weight fraction (2-10 kDa) of the serum proteome were resolved using the Gaussian mixture decomposition, and identified spectral components were used to build classifiers that differentiated samples from breast cancer patients and healthy persons. Mass spectra of complete serum and membrane-filtered albumin-depleted samples have apparently different structure and peaks specific for both types of samples could be identified. The optimal classifier built for the complete serum specimens consisted of 8 spectral components, and had 81% specificity and 72% sensitivity, while that built for the membrane-filtered samples consisted of 4 components, and had 80% specificity and 81% sensitivity. We concluded that pre-processing of samples to remove albumin might be recommended before MALDI-ToF mass spectrometric analysis of the low-molecular-weight components of human serum Keywords: albumin removal; breast cancer; clinical proteomics; mass spectrometry; pattern analysis; serum proteome.


Asunto(s)
Proteínas Sanguíneas/análisis , Neoplasias de la Mama/diagnóstico , Proteoma , Albúmina Sérica/aislamiento & purificación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Adulto , Anciano , Neoplasias de la Mama/sangre , Neoplasias de la Mama/clasificación , Femenino , Humanos , Persona de Mediana Edad , Peso Molecular , Sensibilidad y Especificidad
10.
Diabetologia ; 53(8): 1754-60, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20454951

RESUMEN

AIMS: The aim of the study was to investigate the potential negative impact of type 1 diabetes on bone status of adolescents. Bone status in adolescents with type 1 diabetes was assessed by means of quantitative ultrasound (QUS) and the influence of metabolic control and other disease-related and growth variables was analysed. METHODS: Group I consisted of 99 pubertal (Tanner > or = 2) adolescents (49 female), aged 14.3 +/- 2.5 years, diabetes duration 4.6 +/- 2.3 years. Controls (group II) were 297 children, matched by sex and age, from a healthy population. The influence of glycated haemoglobin (current: HbA(1c)D; last year's mean: HbA(1c)Y; whole duration mean: HbA(1c)T), diabetes duration, percentage of life with disease and daily insulin requirement (DIR) on amplitude dependent speed of sound (Ad-SoS) at distal phalanges was studied. RESULTS: In comparison to the control group, adolescents with type 1 diabetes presented significantly higher BMI SDS (0.82 [95% CI 0.54, 1.10] vs -0.06 [95% CI -0.16, 0.04] p < 0.001) and lower Ad-SoS SDS (-0.34 [95% CI -0.57, -0.11] vs -0.03 [95% CI -0.15, 0.08], p < 0.05). No correlation between Ad-SoS SDS and sex, DIR or diabetes duration was observed. The lower Ad-SoS SDS reflects reduced bone status, and the reduction was significantly more marked in those patients whose HbA(1c)T was higher than 7.0% when compared with those whose HbA(1c)T was lower. CONCLUSIONS: Bone status of adolescents with type 1 diabetes mellitus assessed with QUS differs from that of healthy peers and is dependent on long-term metabolic control.


Asunto(s)
Huesos/diagnóstico por imagen , Diabetes Mellitus Tipo 1/diagnóstico por imagen , Pubertad/metabolismo , Adolescente , Análisis de Varianza , Glucemia/metabolismo , Huesos/metabolismo , Niño , Cromatografía Líquida de Alta Presión , Diabetes Mellitus Tipo 1/metabolismo , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Selección de Paciente , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Ultrasonografía
11.
J Appl Genet ; 51(2): 169-83, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20453304

RESUMEN

In light of the high incidence of mammary cancer in dogs and completion of the canine genome sequencing, the new possibilities of gene profiling by using DNA microarrays give hope to veterinary oncology. The cell lines isolated from mammary tumors are a valuable tool in developing and testing new pathway-specific cancer therapeutics. Differential cytometric analysis of 6 canine mammary cancer cell lines was performed. We divided cell lines into 3 groups based on their phenotype: 2 lines with high proliferative potential, 2 lines with high antiapoptotic potential, and 2 lines with high metastatic potential. DNA microarray analysis revealed common genes for cell lines of each group. We found that genes encoding the receptors for growth hormone and ghrelin are related to high proliferation rate, while ABR (active BCR-related) and TMD1 (TM2 domain containing 1) genes are related to a high antiapoptotic potential of the cancer cells. Metastatic properties of mammary cancer cells seem to be associated with elevated expression of PGP (P glycoprotein), SEMA3B (semaphorin 3B), and STIM1 (stromal interaction molecule 1).


Asunto(s)
Enfermedades de los Perros/genética , Perfilación de la Expresión Génica , Neoplasias Mamarias Animales/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/veterinaria , Animales , División Celular , Línea Celular Tumoral , ADN de Neoplasias/genética , Perros , Femenino , Cinética , Neoplasias Mamarias Animales/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Ploidias
12.
J Appl Genet ; 51(1): 37-50, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20145299

RESUMEN

Metastasis is a final step in the progression of mammary gland cancer, usually leading to death. Potentially, a molecular signature of metastasis can be defined via comparison of primary tumors with their metastases. Currently, there is no data in the literature regarding the molecular portrait of metastases in dogs and only few reports regarding human cancer. This is the first report describing the transcriptomic signature of canine cancer metastatic cells. Two adenocarcinoma cell lines isolated from the canine mammary gland (CMT-W1 and CMT-W2) were compared with cell lines isolated from their lung metastases (CMT-W1M and CMT-W2M) with regards to the following cytometric parameters: cell cycle, ploidy, Bcl-2 expression, susceptibility to induced apoptosis, and transcriptomic profile. Cytometric analyses revealed significant differences in cell cycle and antiapoptotic potential between the examined cells. Using oligonucleotide microarrays, we found 104 up-regulated genes in the metastatic cell line CMT-W1M and 21 up-regulated genes in the primary CMT-W1 cell line. We also found 83 up-regulated genes in the CMT-W2M cell line and only 21 up-regulated genes in the CMT-W2 cell line. Among the up-regulated genes in both metastatic cell lines, we found 15 common genes. These differently expressed genes are involved mainly in signal transduction, cell structure and motility, nucleic acid metabolism, developmental processing, and apoptosis (GHSR, RASSF1, ARF1GAP, WDR74, SMOC2, SFRP4, DIAPH1, FSCN1, ALX4, SNX15, PLD2, WNT7B, POU6F2, NKG7, and POLR2F). Seven of them are involved in a cellular pathway dependent on ghrelin via growth hormone secretagogue receptor (GHSR). Our results suggest that this pathway may be essential for mammary cancer cells to have a metastatic potential.


Asunto(s)
Adenocarcinoma/genética , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Neoplasias Pulmonares/genética , Neoplasias Mamarias Animales/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Apoptosis , Biomarcadores de Tumor/metabolismo , Western Blotting , Perros , Femenino , Técnica del Anticuerpo Fluorescente , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Neoplasias Mamarias Animales/metabolismo , Neoplasias Mamarias Animales/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Ploidias , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas
13.
Diabetologia ; 53(4): 641-51, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20063147

RESUMEN

AIMS/HYPOTHESIS: We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. METHODS: Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders.Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. RESULTS: Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p=0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p=0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p=0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. CONCLUSIONS/INTERPRETATION: Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.


Asunto(s)
Peso al Nacer , Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Edad de Inicio , Orden de Nacimiento , Niño , Preescolar , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Edad Materna , Embarazo , Factores de Riesgo
14.
Int J Radiat Biol ; 84(8): 635-42, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18608641

RESUMEN

PURPOSE: To study the relationship between lymphocyte radiosensitivity measured in vitro and acute reactions to radiotherapy in patients with head and neck cancer. MATERIALS AND METHODS: Acute reactions were measured in 34 patients using the Dische scale. Lymphocyte radiosensitivity was measured using the alkaline comet assay, the micronucleus assay, the nuclear division index and morphological assessment of apoptosis. RESULTS: There was a weak, statistically significant correlation between in vitro radiosensitivity measured as the rate of DNA damage repair and the cumulative radiation dose exerting the maximum acute reaction scored (r = -0.366, p = 0.039, n = 34). Subgroup analyses showed that for patients with a low level of radiation-induced DNA damage there was a statistically significant relationship between lymphocyte radiosensitivity measured as inhibition of proliferation and acute toxicity (r = -0.621, p = 0.007, n = 18). For patients with a high level of residual DNA damage, there was a relationship between lymphocyte radiosensitivity measured using the micronucleus assay and acute toxicity (r = -0.597, p = 0.023, n = 14). CONCLUSIONS: Combining two measures of radiosensitivity improves the ability to correlate in vitro lymphocyte radiosensitivity and acute radiotherapy toxicity data.


Asunto(s)
Daño del ADN/efectos de la radiación , Reparación del ADN/efectos de la radiación , Neoplasias de Cabeza y Cuello/radioterapia , Linfocitos/efectos de la radiación , Ensayo Cometa , Roturas del ADN de Cadena Simple/efectos de la radiación , Neoplasias de Cabeza y Cuello/genética , Humanos , Linfocitos/ultraestructura , Pruebas de Micronúcleos , Tolerancia a Radiación , Radioterapia/efectos adversos
15.
Acta Diabetol ; 45(1): 37-40, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17932620

RESUMEN

The aim of this study was to evaluate the prevalence of thyroid autoantibodies and clinical significance of thyroid autoimmunity in children with the diagnosis of diabetes mellitus type 1. The study group comprised 222 children all with newly diagnosed diabetes mellitus type 1 (122 boys) with a mean age 9.92 +/- 4.5 years, who were admitted to a regional diabetes division in 2000-2004. Assessment of ATA and ATG were performed and two emerging groups-ATA/ATG (+) and ATA/ATG (-) were compared, including anthropometric data, HbA1C, plasma lipids, TSH, fT4. Positive antibodies titre was found in 27 (12.16%) of the children. Apart from older age in the antibody positive group (11.67 vs. 9.67 years, p < 0.05), there were no significant differences among these groups regarding other clinical and laboratory characteristics. Concluding, the presence of thyroid autoantibodies in 12.16% of subjects with newly diagnosed diabetes confirms the necessity of screening of all children, especially adolescents from the time of diagnosis of diabetes mellitus type 1 onwards. No association between existence of autoantibodies and the clinical status of a child at the presentation of diabetes was demonstrated by this study.


Asunto(s)
Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/inmunología , Yoduro Peroxidasa/inmunología , Tiroglobulina/inmunología , Adolescente , Estatura , Peso Corporal , Niño , Preescolar , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/inmunología , Hemoglobina Glucada/metabolismo , Humanos , Lípidos/sangre , Polonia/epidemiología , Tiroglobulina/sangre , Glándula Tiroides
16.
Exp Clin Endocrinol Diabetes ; 115(10): 662-8, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18058601

RESUMEN

BACKGROUND: To evaluate the changes in the glycemic profile and metabolic control after introducing glargine in children with DMT1 in a one-year follow up. METHODS: 70 children (36 boys) at the average age of 12.03+/-2.50 with the mean diabetes duration of 3.35+/-2.19 years were observed. Glargine was substituted for NPH in children treated with multiple daily injections. RESULTS: The analysis showed the differences in the dynamics of changes in mean glycemia based on home blood glucose monitoring and HbA1c between prepubertal children (Group 1) and teenagers (Group 2). A significant reduction in mean glycemia from baseline to 12 months was observed at all chosen points in Group 2: fasting glycemia (125+/-27 mg/dl vs 117+/-17 mg/dl,p<0.05), bedtime glycemia (128+/-24 mg/dl vs. 117+/-20 mg/dl,p=0.001) and 3 a.m. glycemia (143+/-47 mg/dl vs. 90+/-25 mg/dl,p<0.001). A significant decrease in mean glycemia in Group 1 was observed from the beginning of treatment only at bedtime (0-12 months:129+/-27 mg/dl vs. 112+/-25 mg/dl,p=0.001) and at 3 am with the delay (6-12 months:122+/-36 mg/dl vs. 90+/-22 mg/dl,p<0.05). A significant improvement in HbA1c between baseline and 12 months was observed in both groups but with different dynamics of changes: 6.91+/-0.77% vs. 6.59+/-0.65% (p<0.05) and 7.44+/-1.26% vs. 7.18+/-1.58% (p=0.001) respectively in the groups. A trend towards decreasing the number of hypoglycemic episodes and no changes in BMI and insulin requirement were noted. CONCLUSIONS: Introduction of glargine provides diabetic children with a better stabilization of the daily glycemic profile even in the cases of baseline good metabolic control. The rate of reaching the target in a long-term observation depends on age. A slower reduction of glycemia observed in smaller subjects suggests a great individuality in the regimen of diabetic children.


Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/análisis , Insulina/análogos & derivados , Pubertad/sangre , Adolescente , Glucemia/análisis , Índice de Masa Corporal , Niño , Preescolar , Ayuno/sangre , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/sangre , Hipoglucemia/tratamiento farmacológico , Insulina/administración & dosificación , Insulina Glargina , Insulina de Acción Prolongada , Masculino
17.
Exp Clin Endocrinol Diabetes ; 115(3): 179-81, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17427107

RESUMEN

UNLABELLED: The often CSII treatment complication is local skin infection. The aim of the study was to analyze chosen factors predisposing to this complication. MATERIAL AND METHODS: We observed 40 children aged 1.9-15.6, suffering from diabetes for 0.1-12 and treated by CSII for 0.01-4.4 years in whom HbA1c, BMI, injection site and catheter insertion duration, catheter colonization, skin flora and Staphylococcus aureus carrier state were analyzed. The catheter cultures were prepared with Maki method. The skin and nasal vestibule swab were taken to detect local flora. RESULTS: In the culture of 43 catheters (Maki method) a positive growth (>10 cfu) was detected in 9 (21%), homogeny culture of coagulase-negative staphylococci in 7 and mixed culture (both S.epidermidis and S.aureus) in two cases. Skin inflammation of the injection site was observed in a total of 10 children (25%), in two of whom catheter culture was positive. A statistically significant relation between the presence of bacteria in the catheter and on the skin around the injection site was found. Among the examined parameters, the relation between the catheter colonization and HbA1c, female sex and BMI were observed. CONCLUSIONS: Metabolic control, female sex and BMI influence the development of a skin inflammatory state in patients treated with CSII. S.aureus carrier state has no impact either on catheter colonization or the development of an infection. However, bacteria skin occurrences can predispose to catheter colonization by the strain as well as to developing an inflammation.


Asunto(s)
Infecciones Bacterianas/clasificación , Infecciones Bacterianas/etiología , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Inflamación/etiología , Sistemas de Infusión de Insulina/efectos adversos , Enfermedades de la Piel/microbiología , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Inflamación/epidemiología , Masculino , Polonia , Enfermedades de la Piel/etiología
18.
Przegl Lek ; 58(10): 908-14, 2001.
Artículo en Polaco | MEDLINE | ID: mdl-11957817

RESUMEN

Obesity in adults is associated with multiple disorders of glucose, insulin and lipid homeostasis. Children with early onset of obesity appear to be an interesting group for study of early alterations in human obesity. However only few such studies have been performed. In this group, many data show that obesity in childhood and adolescents is associated with the development of risk factors for cardiovascular and metabolic diseases. The objective of this study was to determine contribution of obesity to the development of impaired glucose tolerance, dyslipidaemia and hormonal imbalance. Body mass index (BMI) greater than 25 kg/m2 has recommended as the cutoff value respectively for overweight. In obese patients insulin secretion, glucose and lipid metabolism was impaired.


Asunto(s)
Obesidad , Adolescente , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Niño , Preescolar , Femenino , Intolerancia a la Glucosa/etiología , Prueba de Tolerancia a la Glucosa , Humanos , Hiperlipidemias/etiología , Insulina/sangre , Lípidos/sangre , Masculino , Obesidad/sangre , Obesidad/complicaciones , Obesidad/epidemiología , Obesidad/fisiopatología , Polonia/epidemiología , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Estadísticas no Paramétricas
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