Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 102
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Prostate ; 84(6): 584-598, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38311868

RESUMEN

BACKGROUND: Teverelix drug product (DP) is a novel injectable gonadotropin-releasing hormone antagonist. METHODS: An adaptive phase 2, open-label, multicenter trial was conducted in patients with advanced prostate cancer to evaluate the efficacy and safety of a combined subcutaneous (SC) and intramuscular (IM) loading dose regimen of teverelix DP of 120 mg SC + 120 mg IM (Group 1; N = 9) or 180 mg SC + 180 mg IM (Group 2; N = 41) administered at a single visit, followed by 6-weekly SC maintenance doses of 120 mg (Group 1) or 180 mg (Group 2), up to Day 168. The primary endpoint was the proportion of patients achieving castration levels with serum testosterone <0.5 ng/mL at Day 28 with a target castration rate of 90%. Injection sites were inspected by the investigator at every visit and reactions (ISRs) were proactively recorded. RESULTS: The target castration rate was reached in Group 2 (97.5%) but not in Group 1 (62.5%). The castration rates were not maintained to Day 42 (Group 2: 82.5%; Group 1: 50.0%). Suppression of testosterone to castrate levels occurred rapidly (median time: 2 days for both groups). Suppression of testosterone, prostate-specific antigen, follicle-stimulating hormone, and luteinizing hormone was sustained throughout the treatment period, being more prominent with the higher dose. The adverse event (AE) profile was similar between groups. The most common AEs were injection-site induration (n = 40: 80.0%), injection-site erythema (n = 35: 70.0%), and hot flush (n = 21: 42.0%). Most ISRs were Grade 1. CONCLUSION: Overall, the teverelix DP doses were generally well-tolerated but did not adequately maintain castration levels.


Asunto(s)
Neoplasias de la Próstata , Humanos , Masculino , Hormona Liberadora de Gonadotropina , Oligopéptidos , Antígeno Prostático Específico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Testosterona/sangre
2.
Medicina (Kaunas) ; 59(4)2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-37109639

RESUMEN

Background and objectives: Teverelix drug product (DP) is a gonadotropin-releasing hormone antagonist in development for the treatment of patients with prostate cancer in whom androgen deprivation therapy is indicated. The aim of this paper is to present the results of five Phase 2 studies that assessed the pharmacokinetics, pharmacodynamics, efficacy and safety of different loading dose regimens of teverelix DP. Methods: Five single-arm, uncontrolled clinical trials were conducted in patients with advanced prostate cancer. The five different loading dose regimens of teverelix DP tested were (a) a single 90 mg subcutaneous (SC) injection of teverelix DP given on 3 consecutive days (Days 0, 1 and 2); (b) a single 90 mg intramuscular (IM) injection of teverelix DP given 7 days apart (Days 0 and 7); (c) a single 120 mg SC injection of teverelix DP given on 2 consecutive days (Days 0 and 1); (d) 2 × 60 mg SC injections of teverelix DP given on 3 consecutive days (Days 0, 1 and 2), and (e) 2 × 90 mg SC injections of teverelix DP given on 3 consecutive days (Days 0, 1 and 2). The primary efficacy parameter was the duration of action of an initial loading dose regimen in terms of suppression of testosterone to below the castration level (0.5 ng/mL). Results: Eighty-two patients were treated with teverelix DP. Two regimens (90 mg and 180 mg SC on 3 consecutive days) had a mean duration of castration of 55.32 days and 68.95 days with >90% of patients having testosterone levels < 0.5 ng/mL at Day 28. The mean onset of castration for the SC regimens ranged from 1.10 to 1.77 days, while it was slower (2.4 days) with IM administration. The most common adverse event (AE) was injection site reaction. No AEs of severe intensity were reported. Conclusions: Teverelix DP is safe and well tolerated. Castrate levels of testosterone can be rapidly achieved following the subcutaneous injection of teverelix DP on 3 consecutive days. Streamlining of the administration of the loading dose and identifying a suitable maintenance dose will be investigated in future trials.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Hormona Liberadora de Gonadotropina/uso terapéutico , Leuprolida/efectos adversos , Antagonistas de Andrógenos/uso terapéutico , Testosterona/uso terapéutico
3.
J Hepatol ; 77(4): 1047-1058, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35750139

RESUMEN

BACKGROUND & AIMS: Late diagnosis is a critical factor undermining clinical management of patients with biliary tract cancer (BTC). While biliary tumours display extensive inter-patient heterogeneity, the host immune response may be comparatively homogenous, providing diagnostic opportunities. Herein, we investigated whether cancer-associated systemic reprogramming could be detected non-invasively to improve diagnosis of BTC. METHODS: In this prospective Danish study, whole blood (WB) microRNA (miRNA) profiling was performed in samples from 218 patients with BTC, 99 healthy participants, and 69 patients with differential diagnoses split into discovery (small RNA-sequencing) and validation (RT-qPCR) cohorts. miRNA expression and activity were further investigated in 119 and 660 BTC tissues, respectively. RESULTS: Four WB miRNAs (let-7a-3p, miR-92b-5p, miR-145-3p, miR-582-3p) were identified and validated as diagnostic of BTC on univariable analysis. Two diagnostic miRNA indexes were subsequently identified that were elevated in patients with BTC and in patients with differential diagnoses, compared to healthy participants. The combination of these miRNA indexes with serum CA 19-9 significantly improved the diagnostic performance of CA 19-9 alone, consistently achieving superior AUC values irrespective of clinical setting (minimum AUC >0.84) or tumour location (minimum AUC >0.87). The diagnostic information captured by miRNA indexes was not recapitulated by routine clinical measurements. Index miRNA expression in BTC tissues was associated with distinct pathobiological and immune features. CONCLUSIONS: WB miRNA profiles are altered in patients with BTC. Quantification of miRNA indexes in combination with serum CA 19-9 has the potential to improve early diagnosis of BTC, pending further validation. LAY SUMMARY: Surgery is currently the only curative intervention for patients with biliary tract cancer (BTC). However, resection is not possible for most patients who are diagnosed with late-stage disease. With the aim of identifying new early diagnostic opportunities, we analysed circulating microRNAs (small non-coding RNAs whose role in cancer is being increasingly recognised) in whole blood samples. We identified a microRNA signature that could distinguish patients with BTC from healthy participants. These miRNAs significantly improved the diagnostic potential of the routinely measured biomarker, CA 19-9, and were implicated in distinct immune processes in tumour tissues.


Asunto(s)
Neoplasias del Sistema Biliar , MicroARN Circulante , MicroARNs , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/genética , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica , Humanos , MicroARNs/genética , Estudios Prospectivos
4.
Oncologist ; 27(1): 67-78, 2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-34498352

RESUMEN

BACKGROUND: Older patients with cancer are at risk of physical decline and impaired quality of life during oncological treatment. Exercise training has the potential to reduce these challenges. The study aim was to investigate the feasibility and effect of a multimodal exercise intervention in older patients with advanced cancer (stages III/IV). PATIENTS AND METHODS: Eighty-four older adults (≥65 years) with advanced pancreatic, biliary tract, or non-small cell lung cancer who received systemic oncological treatment were randomized 1:1 to an intervention group or a control group. The intervention was a 12-week multimodal exercise-based program including supervised exercise twice weekly followed by a protein supplement, a home-based walking program, and nurse-led support and counseling. The primary endpoint was change in physical function (30-second chair stand test) at 13 weeks. RESULTS: Median age of the participants was 72 years (interquartile range [IQR] 68-75). Median adherence to the exercise sessions was 69% (IQR 21-88) and 75% (IQR 33-100) for the walking program. At 13 weeks, there was a significant difference in change scores of 2.4 repetitions in the chair stand test, favoring the intervention group (p < .0001). Furthermore, significant beneficial effects were seen for physical endurance (6-minute walk test), hand grip strength, physical activity, symptom burden, symptoms of depression and anxiety, global health status (quality of life), and lean body mass. No effects were seen for dose intensity, hospitalizations, or survival. CONCLUSION: A 12-week multimodal exercise intervention with targeted support proved effective in improving physical function in older patients with advanced cancer during oncological treatment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Terapia por Ejercicio , Fuerza de la Mano , Humanos , Neoplasias Pulmonares/terapia , Calidad de Vida
5.
Glob Chang Biol ; 28(8): 2657-2677, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35106859

RESUMEN

Global warming is affecting the population dynamics and trophic interactions across a wide range of ecosystems and habitats. Translating these real-time effects into their long-term consequences remains a challenge. The rapid and extreme warming period that occurred after the Last Glacial Maximum (LGM) during the Pleistocene-Holocene transition (7-12 thousand years ago) provides an opportunity to gain insights into the long-term responses of natural populations to periods with global warming. The effects of this post-LGM warming period have been assessed in many terrestrial taxa, whereas insights into the impacts of rapid global warming on marine taxa remain limited, especially for megafauna. In order to understand how large-scale climate fluctuations during the post-LGM affected baleen whales and their prey, we conducted an extensive, large-scale analysis of the long-term effects of the post-LGM warming on abundance and inter-ocean connectivity in eight baleen whale and seven prey (fish and invertebrates) species across the Southern and the North Atlantic Ocean; two ocean basins that differ in key oceanographic features. The analysis was based upon 7032 mitochondrial DNA sequences as well as genome-wide DNA sequence variation in 100 individuals. The estimated temporal changes in genetic diversity during the last 30,000 years indicated that most baleen whale populations underwent post-LGM expansions in both ocean basins. The increase in baleen whale abundance during the Holocene was associated with simultaneous changes in their prey and climate. Highly correlated, synchronized and exponential increases in abundance in both baleen whales and their prey in the Southern Ocean were indicative of a dramatic increase in ocean productivity. In contrast, the demographic fluctuations observed in baleen whales and their prey in the North Atlantic Ocean were subtle, varying across taxa and time. Perhaps most important was the observation that the ocean-wide expansions and decreases in abundance that were initiated by the post-LGM global warming, continued for millennia after global temperatures stabilized, reflecting persistent, long-lasting impacts of global warming on marine fauna.


Asunto(s)
Ecosistema , Calentamiento Global , Animales , Océano Atlántico , Dinámica Poblacional , Ballenas/fisiología
6.
Chemistry ; 28(13): e202104151, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35072296

RESUMEN

Phase transitions in molecular crystals are often determined by intermolecular interactions. The cage complex of [Co(C12 H30 N8 )]3+ ⋅ 3 NO3 - is reported to undergo a disorder-order phase transition at Tc1 ≈133 K upon cooling. Temperature-dependent neutron and synchrotron diffraction experiments revealed satellite reflections in addition to main reflections in the diffraction patterns below Tc1 . The modulation wave vector varies as function of temperature and locks in at Tc3 ≈98 K. Here, we demonstrate that the crystal symmetry lowers from hexagonal to monoclinic in the incommensurately modulated phases in Tc1

7.
Scand J Public Health ; 50(7): 914-918, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35548941

RESUMEN

Denmark has a 35-year history of monitoring health status in the general population through health surveys. In this commentary, we outline the development of health surveys in Denmark from the beginning in 1987 to the present time. We describe how the current systematic framework for the Danish National Health Survey (DNHS) developed. We discuss the methodological basis for the DNHS and describe its application in public health practice and research. Over the years, the DNHS has become an important part of the Danish public health environment. Challenges for the DNHS in the future are to adapt to new trends in public health and at the same time to be able to monitor important changes consistently over time.


Asunto(s)
Estado de Salud , Práctica de Salud Pública , Dinamarca/epidemiología , Encuestas Epidemiológicas , Humanos , Encuestas y Cuestionarios
8.
Int J Cancer ; 148(10): 2542-2556, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33336394

RESUMEN

Metastatic colorectal cancer (mCRC) is treated with cetuximab 250 mg/m2 administered weekly over 1 hour or biweekly (q2w) over 3.5 hours when combined with irinotecan. This prospective study investigated cetuximab 500 mg/m2 plus irinotecan 180 mg/m2 administered q2w over 1.5 hours independent of RAS or BRAF mutation status in mCRC patients in a third-line setting. The intention-to-treat population included 181 patients. No patients had complete response, 18% had partial responses (PR) and 48% stable disease (SD). For cetuximab, a relative dose intensity of ≥90% was reached in 78% and for irinotecan in 67% of the patients. Grade 3 to 4 toxicities were pain (17%), fatigue (9%), neutropenia (8%), diarrhea (8%), rash (8%), infection (7%) and hypersensitivity (3%). No deaths occurred. Next-generation sequencing in 96.7% of the patients revealed that 50.3% had RAS and BRAFV600E wild type (WT), with a mutation type (MT) in 45.1% of the RAS and 4.4% of the BRAFV600E genes. In patients with RAS-WT and RAS-MT tumors, a PR was obtained in 32% and 4% (P = .000003) and an SD in 43% and 53%, respectively, with a superior PFS (6.2 vs 3.7 months; hazard ratio [HR] 2.12, P = .00001) and OS (12.9 vs 8.8 months; HR 1.71, P = .0008). Treatment efficacy was poor in 7.4% of patients with an RAS mutation outside KRAS exon 2 and in 38% of patients with KRAS exon 2 mutations. Administration of cetuximab and irinotecan q2w, shortening treatment time from 3.5 to 1.5 hours, is recommended as standard therapy.

9.
Br J Cancer ; 125(2): 240-246, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33837301

RESUMEN

BACKGROUND: In colorectal cancer, the inflamed tumour microenvironment with its angiogenic activities is immune- tolerant and incites progression to liver metastasis. We hypothesised that angiogenic and inflammatory factors in serum samples from patients with non-metastatic rectal cancer could inform on liver metastasis risk. METHODS: We measured 84 angiogenic and inflammatory markers in serum sampled at the time of diagnosis within the population-based cohort of 122 stage I-III patients. In a stepwise manner, the statistically strongest proteins associated with time to development of liver metastasis were analysed in the corresponding serum samples from 273 stage II-III rectal cancer patients in three independent cohorts. RESULTS: We identified the soluble form of the costimulatory immune checkpoint receptor cluster of differentiation molecule 40 (sCD40) as a marker of liver metastasis risk across all patient cohorts-the higher the sCD40 level, the shorter time to liver metastasis. In patients receiving neoadjuvant treatment, the sCD40 value remained an independent variable associated with progression to liver metastasis along with the local treatment response. Of note, serum sCD40 was not associated with progression to lung metastasis. CONCLUSIONS: Circulating sCD40 is a marker of liver metastasis risk in rectal cancer and may be developed for use in clinical practice.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígenos CD40/sangre , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Neoplasias del Recto/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/inmunología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias del Recto/sangre , Neoplasias del Recto/patología , Microambiente Tumoral
10.
Scand J Public Health ; 49(8): 821-832, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32122260

RESUMEN

Aims: This study aimed to compare health-related quality of life (HRQOL) among cancer survivors and controls in the Danish population, with special attention given to the impact of low educational attainment. Comparisons were made at population level and for subgroups stratified by education. Furthermore, comparisons were made for all cancer diagnoses combined and for the 14 most prevalent cancer sites and 'other cancer sites'. Finally, the importance of time since initial diagnosis was examined. Methods: HRQOL was measured using the physical component score (PCS) and mental component score (MCS) of the 12-item Short-Form Health Survey version 2 in a population-based survey. By linking data with the Danish Cancer Registry, 11,166 cancer survivors and 151,117 individuals with no history of cancer were identified. Results: HRQOL was reduced in cancer survivors for all cancers combined and most cancer sites. Differences were found at population level and stratified by educational attainment. PCS was reduced to a similar extent in the three educational groups, whereas MCS was reduced slightly more in the low than in the high educational attainment group. HRQOL increased with time since initial diagnosis during the first years. Conclusions: Cancer survivors had lower HRQOL than controls, and HRQOL was lower in the low than in the high educational attainment group. However, low educational attainment did not widen the gap in HRQOL following a cancer diagnosis. Despite this, the combined effect of low educational attainment and a cancer diagnosis markedly reduced HRQOL in some cancer survivors. The study identified groups of cancer survivors with low HRQOL who may have unmet rehabilitation needs.


Asunto(s)
Supervivientes de Cáncer , Neoplasias , Escolaridad , Encuestas Epidemiológicas , Humanos , Calidad de Vida , Encuestas y Cuestionarios
11.
BMC Public Health ; 21(1): 543, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33740936

RESUMEN

BACKGROUND: High levels of perceived stress have a negative bearing on health and well-being, and stress is a major public health issue. According to the Stress Process Model, stressors are socially patterned and combine to produce strain. Despite this, most studies on stress have focused on work-related stressors leaving non-work determinants under-investigated. The aim of the present study was to determine the relative importance of work-related and non-work-related stressors and perceived social support for the overall perceived stress level. METHODS: Self-reported data were drawn from the 2017 population-based health survey "How are you?" conducted in the Central Denmark Region (N = 32,417). Data were linked with data drawn from national administrative registers. Work- and non-work-related stressors assessed included major life events, chronic stressors and daily hassles. Perceived social support was assessed using a single question. Overall perceived stress was assessed by the 10-item Perceived Stress Scale. We conducted dominance analyses based on a multiple linear regression model to determine the most important explanatory variables of overall perceived stress. Analyses were weighted and adjusted. RESULTS: Work- and non-work-related stressors along with perceived social support explained 42.5% of the total variance (R2) in overall perceived stress. The most important explanatory variables were disease, perceived social support and work situation. The stratified analyses produced slightly varying results ("dominance profiles") of perceived stress between subgroups. Work situation was the most important explanatory variable in the employed group. However, adding non-work-related explanatory variables to the analysis tripled the explained variance. CONCLUSIONS: The overall level of perceived stress can be statistically explained by a combination of work- and non-work-related stressors and perceived social support both at population level and in subgroups. The most important explanatory variables of overall perceived stress are disease, perceived social support and work situation. Results indicate that public health strategies aiming to reduce stress should take a comprehensive approach and address a variety of stressor domains rather than focus on a single domain. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (r. no. 2012-58-0006) and registered in the Central Denmark Region (r. no. 1-16-02-593-16).


Asunto(s)
Apoyo Social , Estrés Psicológico , Estudios Transversales , Humanos , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios
12.
Int J Cancer ; 146(7): 2019-2026, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-31872440

RESUMEN

In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Inmunidad/efectos de los fármacos , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/secundario , Oxaliplatino/administración & dosificación , Adulto , Anciano , Biomarcadores , Ablación por Catéter , Neoplasias Colorrectales/metabolismo , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/terapia , Masculino , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Resultado del Tratamiento
13.
Eur J Cancer Care (Engl) ; 29(4): e13228, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31999396

RESUMEN

OBJECTIVES: To study whether educational attainment had less impact on work disability in cancer survivors than in individuals without cancer. To study whether comorbidity had a higher impact on work disability in low-educated cancer survivors than in high-educated and whether this impact differed when compared with individuals without cancer. METHODS: Linkage of population-based public health survey data and the Danish Cancer Registry formed two groups: cancer survivors (n = 3,514) and cancer-free individuals (n = 171,262). In logistic regression models, the risk of experiencing an 8-week sick leave spell and the granting of disability pension within a 3-year follow-up period was studied in three educational levels and whether these associations were modified by history of cancer and comorbidity. Odds ratios (OR) with 95% confidence intervals (CI) are reported. RESULTS: Non-stratified adjusted risk of experiencing an 8-week sick leave spell (OR: 1.41, 95% CI (1.33-1.49)) or being granted a disability pension (OR: 1.61, 95% CI (1.31-1.97)) was significantly higher in low-educated than in high-educated respondents. Cancer or comorbidity did not significantly interact with education on the risk of work disability. CONCLUSIONS: A moderate impact of low education on future work disability was found for all respondents, neither history of cancer nor comorbidity modified this association.


Asunto(s)
Supervivientes de Cáncer , Personas con Discapacidad , Escolaridad , Empleo , Neoplasias/fisiopatología , Ausencia por Enfermedad/estadística & datos numéricos , Seguridad Social/estadística & datos numéricos , Adulto , Estudios de Casos y Controles , Comorbilidad , Dinamarca , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pensiones , Factores de Riesgo , Factores de Tiempo
14.
Mol Phylogenet Evol ; 135: 86-97, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30771513

RESUMEN

The advent of massive parallel sequencing technologies has resulted in an increase of studies based upon complete mitochondrial genome DNA sequences that revisit the taxonomic status within and among species. Spatially distinct monophyly in such mitogenomic genealogies, i.e., the sharing of a recent common ancestor among con-specific samples collected in the same region has been viewed as evidence for subspecies. Several recent studies in cetaceans have employed this criterion to suggest subsequent intraspecific taxonomic revisions. We reason that employing intra-specific, spatially distinct monophyly at non-recombining, clonally inherited genomes is an unsatisfactory criterion for defining subspecies based upon theoretical (genetic drift) and practical (sampling effort) arguments. This point was illustrated by a re-analysis of a global mitogenomic assessment of fin whales, Balaenoptera physalus spp., published by Archer et al. (2013), which proposed to further subdivide the Northern Hemisphere fin whale subspecies, B. p. physalus. The proposed revision was based upon the detection of spatially distinct monophyly among North Atlantic and North Pacific fin whales in a genealogy based upon complete mitochondrial genome DNA sequences. The extended analysis conducted in this study (1676 mitochondrial control region, 162 complete mitochondrial genome DNA sequences and 20 microsatellite loci genotyped in 380 samples) revealed that the apparent monophyly among North Atlantic fin whales reported by Archer et al. (2013) to be due to low sample sizes. In conclusion, defining sub-species from monophyly (i.e., the absence of para- or polyphyly) can lead to erroneous conclusions due to relatively "trivial" aspects, such as sampling. Basic population genetic processes (i.e., genetic drift and migration) also affect the time to the most recent common ancestor and hence the probability that individuals in a sample are monophyletic.


Asunto(s)
Ballena de Aleta/clasificación , Ballena de Aleta/genética , Genoma Mitocondrial , Filogenia , Animales , Secuencia de Bases , Teorema de Bayes , ADN Mitocondrial/genética , Variación Genética , Genotipo , Geografía , Repeticiones de Microsatélite/genética
15.
Oncology ; 96(6): 299-308, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30999314

RESUMEN

BACKGROUND: In case of response to chemotherapy, unresectable liver metastases from colorectal cancer can be converted to resectable and thereby obtain a chance of cure. The primary aim of this trial was to evaluate the response rate with intrahepatic oxaliplatin in combination with systemic 5-FU +/- cetuximab. Secondary aims were to evaluate the conversion rate from unresectable to resectable liver metastases, median progression-free survival, median overall survival, and toxicity. METHODS: Forty-five chemo-naïve patients with liver metastases from colorectal cancer were treated in a prospective phase II trial. Calcium folinate and 5-FU were delivered systemically while oxaliplatin was delivered alternating between systemic and intrahepatic administration. When oxaliplatin was delivered intrahepatic-ally, infusion time was reduced to 10 min followed by embolic material. In patients with KRAS wild-type tumors, cetuximab was added. RESULTS: The treatment was well tolerated and only pain in the liver and a mild increase in liver enzymes were observed after intrahepatic oxaliplatin. The patients obtained a response rate of 82%. Further, 58% converted from having unresectable to resectable liver metastases. The median overall survival and progression-free survival were 38.7 months (95% confidence interval [CI] 33.0-44.3) and 12.9 months (95% CI 10.2-15.6), respectively. CONCLUSIONS: Intrahepatic infusion of oxaliplatin in 10 min with systemic 5-FU to patients with chemo-naïve colorectal cancer is feasible and with low toxicity. A high response rate and long median overall survival were obtained.


Asunto(s)
Cetuximab/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Oxaliplatino/administración & dosificación , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Colorrectales/genética , Esquema de Medicación , Femenino , Fluorouracilo/uso terapéutico , Humanos , Infusiones Intraarteriales , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Oxaliplatino/uso terapéutico , Supervivencia sin Progresión , Estudios Prospectivos , Proteínas Proto-Oncogénicas p21(ras)/genética , Resultado del Tratamiento
16.
Scand J Prim Health Care ; 37(2): 182-190, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31122102

RESUMEN

Objective: There is strong evidence that medication adherence and lifestyle changes are essential in patients undergoing secondary cardiovascular disease prevention. Cardiac rehabilitation (CR) increases medication adherence and improves lifestyle changes. Patients with cardiac diseases and a low educational level and patients with little social support are less responsive to improve medication adherence and to adapt lifestyle changes. The aim of the present study was to investigate the long-term effects of a socially differentiated CR intervention on medication adherence as well as changes in biological and lifestyle risk factors at two- five- and ten-year follow-up. Design: A prospective cohort study. Setting: The cardiac ward at Aarhus University Hospital, Denmark. Intervention: A socially differentiated CR intervention in addition to the standard CR program. Subjects: Patients admitted with first-episode myocardial infarction between 2000 and 2004, N = 379. Patients were defined as socially vulnerable or non-socially vulnerable according to their educational level and extent of social network. Main outcome measures: Primary outcome was medication adherence to antithrombotics, beta-blockers, statins and angiotensin-converting enzyme inhibitors. Secondary outcomes were biological and lifestyle risk factors defined as; total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glycated hemoglobin, blood pressure and smoking status. Results: No significant long-term effect of the intervention was found. Conclusions: The results indicate a non-significant effect of the intervention. However, it was found that equality in health was improved in the study population except concerning smoking. General practitioners manage to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status. Key points The socially differentiated intervention did not significantly improve medication adherence or biological and lifestyle risk factors. Despite the non-significant effect of the intervention, equality in health was improved except concerning smoking. General practitioners managed to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status.


Asunto(s)
Rehabilitación Cardiaca , Enfermedades Cardiovasculares , Estilo de Vida , Cumplimiento de la Medicación , Infarto del Miocardio/rehabilitación , Prevención Secundaria , Anciano , Biomarcadores/sangre , Presión Sanguínea , Fármacos Cardiovasculares/uso terapéutico , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Colesterol/sangre , Dinamarca , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Equidad en Salud , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Fumar , Apoyo Social , Factores Socioeconómicos
17.
Br J Cancer ; 118(10): 1322-1328, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29695770

RESUMEN

BACKGROUND: Systemic failure remains a challenge in rectal cancer. We investigated the possible systemic anti-tumour immune activity invoked within oxaliplatin-based neoadjuvant therapy. METHODS: In two high-risk patient cohorts, we assessed the circulating levels of the fms-like tyrosine kinase 3 ligand (Flt3L), a factor reflecting both therapy-induced myelosuppression and activation of tumour antigen-presenting dendritic cells, at baseline and following induction chemotherapy and sequential chemoradiotherapy, both modalities containing oxaliplatin. The primary end point was progression-free survival (PFS). RESULTS: In both cohorts, the median Flt3L level was significantly higher at completion of each sequential modality than at baseline. The 5-year PFS (most events being metastatic progression) was 68% and 71% in the two cohorts consisting of 33% and 52% T4 cases. In the principal cohort, a high Flt3L level following the induction chemotherapy was associated with low risk for a PFS event (HR: 0.15; P < 0.01). These patients also had available dose scheduling and toxicity data, revealing that oxaliplatin dose reduction during chemoradiotherapy, undertaken to maintain compliance to the radiotherapy protocol, was associated with advantageous PFS (HR: 0.47; P = 0.046). CONCLUSION: In high-risk rectal cancer, oxaliplatin-containing neoadjuvant therapy may promote an immune response that favours survival without metastatic progression.


Asunto(s)
Proteínas de la Membrana/sangre , Terapia Neoadyuvante/efectos adversos , Neoplasias del Recto/sangre , Neoplasias del Recto/tratamiento farmacológico , Adulto , Anciano , Quimioradioterapia/efectos adversos , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Metástasis de la Neoplasia , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Supervivencia sin Progresión , Neoplasias del Recto/inmunología , Neoplasias del Recto/radioterapia , Factores de Riesgo
18.
Oncology ; 94(1): 19-24, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28930749

RESUMEN

OBJECTIVE: Since 2010, gemcitabine and cisplatin have been considered standard first-line treatment in patients with advanced biliary tract cancer. Many centers have replaced cisplatin with oxaliplatin, which seems to obtain similar results. While first-line treatment has been well established, there are no phase III trials supporting second-line treatment, and the phase II trials with chemotherapy do not show any clear benefit. In this study, we investigated the effect of adding bevacizumab to chemotherapy in second-line treatment. METHODS: From November 2013 to January 2016, 50 patients with advanced biliary tract cancer were enrolled in this prospective phase II trial. All patients had received a gemcitabine-platinum combination as first-line treatment. The patients received capecitabine, irinotecan, gemcitabine, and bevacizumab in a 2-week schedule as second-line treatment. RESULTS: The combination was well tolerated with a median progression-free survival of 3.6 months, a median overall survival of 6.4 months, and a response rate of 6%. CONCLUSION: The combination of capecitabine, irinotecan, gemcitabine, and bevacizumab as a second-line treatment for advanced biliary tract cancer is well tolerated but with a modest, if any, benefit.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Biliar/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Capecitabina/administración & dosificación , Capecitabina/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Estudios Prospectivos , Gemcitabina
19.
BMC Cancer ; 18(1): 934, 2018 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-30261853

RESUMEN

BACKGROUND: Several intervention studies have demonstrated that exercise training has beneficial effects among cancer patients. However, older cancer patients are underrepresented in clinical trials, and only few exercise-based studies have focused specifically on older patients with cancer. In particular, research investigating the effects of exercise training among older patients with advanced cancer is lacking. The purpose of the current study is to investigate the effect of a 12-week multimodal and exercise-based intervention among older patients (≥65 years) with advanced pancreatic, biliary tract or lung cancer, who are treated with first-line palliative chemotherapy, immunotherapy or targeted therapy. METHODS: PACE-Mobil-PBL is a two-armed randomized controlled trial. Participants will be randomized 1:1 to an intervention group (N = 50) or a control group (N = 50). Participants in the intervention group will receive standard oncological treatment and a 12-week multimodal intervention, comprised of: (I) supervised exercise training, twice weekly in the hospital setting, (II) home-based walking with step counts and goal-setting, (III) supportive and motivational nurse-led counseling, and (IV) protein supplement after each supervised training session. Participants in the control group will receive standard oncological treatment. The primary outcome is physical function measured by the 30-s chair stand test. Secondary outcomes include measures of feasibility, activity level, physical capacity and strength, symptom burden, quality of life, toxicity to treatment, dose reductions, inflammatory biomarkers, body weight and composition, hospitalizations and survival. Assessments will be conducted at baseline, and after 6, 12 and 16 weeks. DISCUSSION: The current study is one of the first to investigate the effect of an exercise-based intervention specifically targeting older patients with advanced cancer. PACE-Mobil-PBL supports the development of health promoting guidelines for older patients with cancer, and the study results will provide new and valuable knowledge in this understudied field. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov on January 26, 2018 (ID: NCT03411200 ).


Asunto(s)
Neoplasias del Sistema Biliar/terapia , Consejo Dirigido/métodos , Terapia por Ejercicio/métodos , Neoplasias Pulmonares/terapia , Neoplasias Pancreáticas/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Masculino , Cuidados Paliativos , Calidad de Vida , Resultado del Tratamiento
20.
Acta Oncol ; 57(8): 1057-1062, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29380640

RESUMEN

BACKGROUND: Several studies have investigated correlations between metastatic pattern and mutation status in patients with colorectal cancer (CRC). However, most of the studies were small and heterogeneously designed and further research is needed to confirm previous results. In this study, we investigated the association between RAS (KRAS or NRAS), BRAF, PIK3CA mutations and metastatic pattern in patients with metastatic (m) CRC. MATERIAL AND METHODS: This study reviewed Danish biobank and database of patients with mCRC who received cetuximab and irinotecan, independent of RAS mutation status, after fluoropyrimidine, oxaliplatin and irinotecan treatment failure. The database contained information regarding tumor mutation status of KRAS, NRAS, BRAF and PIK3CA genes. RESULTS: Totally, 448 patients were included. On multivariate analyses, RAS mutations were significantly associated with increased odds of having lung metastases at diagnosis of mCRC (odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.32-3.17), and PIK3CA mutations with decreased odds of peritoneal metastases at diagnosis of mCRC (OR = 0.10; 95%CI = 0.01-0.79). On multivariate analyses of the hazard of developing metastases at any time during follow-up, RAS mutations were significantly associated with increased hazard of lung (hazard ratio (HR) = 1.34; 95%CI = 1.04-1.72) and ovarian metastases (HR = 3.12; 95%CI = 1.05-9.24), BRAF V600E mutation was associated with increased hazard of skin metastases (HR = 6.82; 95%CI = 1.86-25.02) and PIK3CA mutations with decreased hazard of peritoneal metastases (HR = 0.31; 95%CI = 0.11-0.86). CONCLUSIONS: This study indicated that in patients with mCRC, RAS mutations are associated with increased risk of lung and ovary metastases. BRAF V600E is associated with increased risk of skin metastases, and PIK3CA mutation with decreased risk of peritoneal metastases.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/genética , Neoplasias Colorrectales/patología , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/genética , Neoplasias Ováricas/secundario , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/secundario , Estudios Retrospectivos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/secundario
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA