RÉSUMÉ
BACKGROUND: Patients with a neuroendocrine tumour (NET) frequently have physical and psychosocial complaints. Aim of this study is to determine whether a web-based, personalised information and support system (WINS) reduces distress and/or improves patients' perception of and satisfaction with information received. METHODS: Patients with NET, stratified for those newly diagnosed (< 6 months, n = 28) and with a longer history of disease (n = 74), were randomised between standard care (n = 49) and intervention, consisting of access to WINS (n = 53). Primary outcome was change of distress and satisfaction with perceived information measured with the distress thermometer and problem list and the QoL questionnaire (QLQ)-INFO25. The intervention group also completed a questionnaire based on the technical acceptance model (TAM). RESULTS: We observed no difference in distress slope and slope of median global score on perceived information and satisfaction between the intervention and control group. Interestingly, 55% of patients wished to receive more information at baseline. CONCLUSIONS: In a population of NET patients, access to WINS did not improve indicators for distress, perception of information and satisfaction with information received, more than standard care only. Despite the need for more information, the WINS does not have added value to the information and care provided by health care professionals. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02472678 ). Registered 6th Jan 2015. Retrospectively registered 1st May 2017.
Sujet(s)
Diffusion de l'information/méthodes , Internet , Tumeurs neuroendocrines/psychologie , Médecine de précision/méthodes , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Tumeurs neuroendocrines/thérapie , Projets pilotes , Médecine de précision/normes , Systèmes de soutien psychosocial , Enquêtes et questionnaires , Résultat thérapeutiqueSujet(s)
Compléments alimentaires , Tumeurs neuroendocrines/diétothérapie , Vitamines/usage thérapeutique , Sujet âgé , Régime alimentaire , Femelle , Humains , Mâle , Adulte d'âge moyen , Tumeurs neuroendocrines/sang , Tumeurs neuroendocrines/traitement médicamenteux , Qualité de vie , Somatostatine/analogues et dérivés , Somatostatine/usage thérapeutique , Vitamines/sangRÉSUMÉ
OBJECTIVE: Exercise interventions benefit cancer patients. However, only low numbers of patients adhere to these interventions. This review aimed to identify predictors of exercise intervention adherence in patients with cancer, during and after multimodality cancer treatment. METHODS: A literature search was performed using electronic databases (PubMed, Embase, and Cochrane) to identify relevant papers published before February 1, 2017. Papers reporting randomized controlled trials, conducted in adult cancer patients who participated in an exercise intervention during and/or after multimodality cancer treatment, and providing outcome of factors predicting exercise adherence were included. Papers were assessed for methodological quality by using the Physiotherapy Evidence Database scale. RESULTS: The search identified 720 potentially relevant papers, of which 15 fulfilled the eligibility criteria. In these 15 studies, 2279 patients were included and 1383 of these patients were randomized to an exercise intervention. During cancer treatment, the factors predicting exercise adherence were as follows: location of the rehabilitation center, extensive exercise history, high motivation for exercise, and fewer exercise limitations. After cancer treatment, factors that predicted adherence were as follows: less extensive surgery, low alcohol consumption, high previous exercise adherence, family support, feedback by trainers, and knowledge and skills of exercise. Methodological quality of the included papers was rated "high". CONCLUSIONS: The most prominent predictors of adherence to exercise interventions were location of the rehabilitation center, extensive exercise history, high motivation for exercise, and fewer exercise limitations. To increase the number of cancer patients who will benefit, these results should be considered into the development and implementation of future exercise interventions.
Sujet(s)
Survivants du cancer/psychologie , Traitement par les exercices physiques/psychologie , Comportement en matière de santé , Tumeurs/rééducation et réadaptation , Observance par le patient/psychologie , Adulte , Survivants du cancer/statistiques et données numériques , Association thérapeutique , Exercice physique , Traitement par les exercices physiques/statistiques et données numériques , Femelle , Humains , Mâle , Adulte d'âge moyen , Observance par le patient/statistiques et données numériques , Essais contrôlés randomisés comme sujetRÉSUMÉ
Background: Assessment of clinical benefit of systemic treatments of rare diseases including gastroenteropancreatic neuroendocrine tumours (GEP-NET) is challenging. Recently several tools have been developed to grade the clinical benefit of cancer drugs. The European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). The American Society of Clinical Oncology (ASCO) has developed and revised the ASCO framework consisting of the Net Health Benefit (NHB) score juxtaposed against the costs of the treatment. In this review, we graded systemic treatments for GEP-NET patients with both frameworks. Methods: The electronic databases (PubMed and EMBASE) were searched for papers reporting comparative trials, conducted in adult GEP-NET patients in the English language. Papers were assessed according to the ESMO-MCBS and the NHB part of the ASCO revised Framework (NHB-ASCO-F) by four independent assessors, and discrepancies were discussed. Results: The search yielded 32 trials of which 6 were eligible for grading with the ESMO-MCBS resulting in scores of 2 or 3. Eight trials were eligible for grading with the NHB-ASCO-F, resulting in scores between 37.6 and 57.4. Trials that were not primary assessable by the tools were analysed separately. Consensus between assessors was reached in 68% of trials with the ESMO-MCBS and in 23% of trials with the NHB-ASCO-F. Conclusion: The currently used systemic treatments for GEP-NET patients had low scores according to the NHB-ASCO-F and none could be graded as meaningful clinical beneficial according to the ESMO-MCBS. Despite the low incidence, the heterogeneous patient population and relatively long natural course of NET, future studies on new treatment modalities should aim for high clinical benefit outcomes.
Sujet(s)
Tumeurs gastro-intestinales/traitement médicamenteux , Tumeurs de l'intestin/traitement médicamenteux , Tumeurs neuroendocrines/traitement médicamenteux , Tumeurs du pancréas/traitement médicamenteux , Tumeurs de l'estomac/traitement médicamenteux , Bases de données factuelles , Humains , Essais contrôlés randomisés comme sujetRÉSUMÉ
Increasing numbers of long-term cancer survivors face important treatment related adverse effects. Cancer treatment induced metabolic syndrome (CTIMetS) is an especially prevalent and harmful condition. The aetiology of CTIMetS likely differs from metabolic syndrome in the general population, but effective treatment and prevention methods are probably similar. In this review, we summarize the potential mechanisms leading to the development of CTIMetS after various types of cancer treatment. Furthermore, we propose a safe and accessible method to treat or prevent CTIMetS through lifestyle change. In particular, we suggest that a lifestyle intervention and optimization of energy balance can prevent or mitigate the development of CTIMetS, which may contribute to optimal survivorship care.
Sujet(s)
Syndrome métabolique X/étiologie , Tumeurs/thérapie , Animaux , Humains , Mode de vie , Syndrome métabolique X/épidémiologie , Prévalence , Résultat thérapeutiqueRÉSUMÉ
Due to differences in anatomy, primary rectal and colon cancer require different staging procedures, different neo-adjuvant treatment and different surgical approaches. For example, neoadjuvant radiotherapy or chemoradiotherapy is administered solely for rectal cancer. Neoadjuvant therapy and total mesorectal excision for rectal cancer might be responsible in part for the differing effect of adjuvant systemic treatment on overall survival, which is more evident in colon cancer than in rectal cancer. Apart from anatomic divergences, rectal and colon cancer also differ in their embryological origin and metastatic patterns. Moreover, they harbor a different composition of drug targets, such as v-raf murine sarcoma viral oncogene homolog B (BRAF), which is preferentially mutated in proximal colon cancers, and the epidermal growth factor receptor (EGFR), which is prevalently amplified or overexpressed in distal colorectal cancers. Despite their differences in metastatic pattern, composition of drug targets and earlier local treatment, metastatic rectal and colon cancer are, however, commonly regarded as one entity and are treated alike. In this review, we focused on rectal cancer and its biological and clinical differences and similarities relative to colon cancer. These aspects are crucial because they influence the current staging and treatment of these cancers, and might influence the design of future trials with targeted drugs.
Sujet(s)
Chimioradiothérapie adjuvante/méthodes , Tumeurs du côlon , Procédures de chirurgie digestive/méthodes , Récepteurs ErbB/génétique , Protéines proto-oncogènes B-raf/génétique , Tumeurs du rectum , Tumeurs du côlon/épidémiologie , Tumeurs du côlon/génétique , Tumeurs du côlon/anatomopathologie , Tumeurs du côlon/thérapie , Prise en charge de la maladie , Humains , Métastase tumorale , Stadification tumorale , Tumeurs du rectum/épidémiologie , Tumeurs du rectum/génétique , Tumeurs du rectum/anatomopathologie , Tumeurs du rectum/thérapie , Analyse de survieRÉSUMÉ
BACKGROUND: Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma. METHODS: In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated. RESULTS: The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log10CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log10CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated with OS. CONCLUSION: CEC numbers increased during treatment with bevacizumab plus lomustine but not during treatment with either agent alone, suggesting that this combination induced the greatest vascular damage. Although the absolute number of CECs was not associated with OS in patients treated with bevacizumab either alone or in combination, they could serve as a marker in glioblastoma patients receiving lomustine single agent.
Sujet(s)
Anticorps monoclonaux humanisés/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Tumeurs du cerveau/traitement médicamenteux , Cellules endothéliales/physiologie , Glioblastome/traitement médicamenteux , Lomustine/usage thérapeutique , Récidive tumorale locale/traitement médicamenteux , Adulte , Sujet âgé , Anticorps monoclonaux humanisés/administration et posologie , Antigènes CD/analyse , Bévacizumab , Tumeurs du cerveau/mortalité , Tumeurs du cerveau/anatomopathologie , Mouvement cellulaire , Cellules endothéliales/cytologie , Femelle , Protéines liées au GPI/analyse , Glioblastome/mortalité , Glioblastome/anatomopathologie , Humains , Cinétique , Lomustine/administration et posologie , Mâle , Adulte d'âge moyen , Protéines tumorales/analyse , Récidive tumorale locale/mortalité , Récidive tumorale locale/anatomopathologie , Pronostic , Modèles des risques proportionnels , Études prospectivesRÉSUMÉ
Formyl peptide receptor 1 (FPR1) activity in U87 glioblastoma (GBM) cells contributes to tumor cell motility. The present study aimed to evaluate the FPR1 expression in human GBM, the possibility to elicit agonist induced FPR1 activation of GBM cells and inhibit this activation with chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Immunohistochemistry was used to assess FPR1 expression in GBM patient samples, which was present in all 178 samples. Also FPR1 mRNA levels measured with quantitative PCR, could be detected in all 25 GBM patient samples tested. Activation of FPR1 in U87 cells, as measured by human mitochondrial-derived agonists, increased calcium mobilization, AKT and ERK1/2 phosphorylation, and ligand-induced migration. Inhibition of all responses could be achieved with CHIPS. Eight early passage human Groningen Glioma (GG) cell lines, isolated from primary GBM tissue were screened for the presence of FPR1. FPR1 mRNA and protein expression as well as receptor activation could not be detected in any of these early passage GG cell lines. However FPR1 was present in ex vivo tumors formed by the same GG cell lines after being implanted in mouse brains. FPR1 is highly expressed in human GBM specimens, it can be activated by human mitochondrial-derived agonists in U87 and inhibited with CHIPS. FPR1 cannot be detected in early passage GG cell lines in vitro, however when engrafted in the mouse brain these cells show FPR1 expression. These results suggest a role of the brain microenvironment in FPR1 expression in GBM.
Sujet(s)
Marqueurs biologiques tumoraux/métabolisme , Tumeurs du cerveau/métabolisme , Glioblastome/métabolisme , Interleukine-2/physiologie , Récepteurs aux peptides formylés/métabolisme , Microenvironnement tumoral , Animaux , Apoptose , Marqueurs biologiques tumoraux/génétique , Technique de Western , Tumeurs du cerveau/génétique , Tumeurs du cerveau/anatomopathologie , Mouvement cellulaire , Prolifération cellulaire , Technique d'immunofluorescence , Glioblastome/génétique , Glioblastome/anatomopathologie , Humains , Techniques immunoenzymatiques , Souris , Souris de lignée NOD , Souris knockout , Souris SCID , ARN messager/génétique , Réaction de polymérisation en chaine en temps réel , Récepteurs aux peptides formylés/génétique , RT-PCR , Cellules cancéreuses en cultureRÉSUMÉ
Different molecular subtypes of glioblastoma (GBM) have been recently identified, of which the mesenchymal subtype is associated with worst prognoses. Here, we report that transforming growth factor-ß (TGF-ß) is able to induce a mesenchymal phenotype in GBM that involves activation of SMAD2 and ZEB1, a known transcriptional inducer of mesenchymal transition in epithelial cancers. TGF-ß exposure of established and newly generated GBM cell lines was associated with morphological changes, enhanced mesenchymal marker expression, migration and invasion in vitro and in an orthotopic mouse model. TGF-ß-induced mesenchymal differentiation and invasive behavior was prevented by chemical inhibition of TGF-ß signaling as well as small interfering RNA (siRNA)-dependent silencing of ZEB1. Furthermore, TGF-ß-responding and -nonresponding GBM neurospheres were identified in vitro. Interestingly, nonresponding cells displayed already high levels of pSMAD2 and ZEB1 that could not be suppressed by inhibition of TGF-ß signaling, suggesting the involvement of yet unknown mechanisms. These different GBM neurospheres formed invasive tumors in mice as well as revealed mesenchymal marker expression in immunohistochemical analyses. Moreover, we also detected distinct zones with overlapping pSMAD2, elevated ZEB1 and mesenchymal marker expression in GBM patient material, suggestive of the induction of local, microenvironment-dependent mesenchymal differentiation. Overall, our findings indicate that GBM cells can acquire mesenchymal features associated with enhanced invasive potential following stimulation by secretory cytokines, such as TGF-ß. This property of GBM contributes to heterogeneity in this tumor type and may blur the boundaries between the proposed transcriptional subtypes. Targeting TGF-ß or downstream targets like ZEB1 might be of potential benefit in reducing the invasive phenotype of GBM in a subpopulation of patients.
Sujet(s)
Transition épithélio-mésenchymateuse , Glioblastome/métabolisme , Protéines à homéodomaine/métabolisme , Facteurs de transcription/métabolisme , Facteur de croissance transformant bêta-1/métabolisme , Animaux , Lignée cellulaire tumorale , Mouvement cellulaire , Glioblastome/génétique , Glioblastome/anatomopathologie , Glioblastome/physiopathologie , Protéines à homéodomaine/génétique , Humains , Souris , Souris SCID , Invasion tumorale , Transduction du signal , Protéine Smad2/génétique , Protéine Smad2/métabolisme , Facteurs de transcription/génétique , Facteur de transcription Zeb1RÉSUMÉ
BACKGROUND: In certain cancers, expression of CXCL16 and its receptor CXCR6 associate with lymphocyte infiltration, possibly aiding anti-tumour immune response. In other cancers, CXCL16 and CXCR6 associate with pro-metastatic activity. In the current study, we aimed to characterise the role of CXCL16, sCXCL16, and CXCR6 in ovarian cancer (OC). METHODS: CXCL16/CXCR6 expression was analysed on tissue microarray containing 306 OC patient samples. Pre-treatment serum sCXCL16 was determined in 118 patients using ELISA. In vitro, (primary) OC cells were treated with an ADAM-10/ADAM-17 inhibitor (TAPI-2) and an ADAM-10-specific inhibitor (GI254023x), whereupon CXCL16 levels were evaluated on the cell membrane (immunofluorescent analysis, western blots) and in culture supernatants (ELISA). In addition, cell migration was assessed using scratch assays. RESULTS: sCXCL16 independently predicted for poor survival (hazard ratio=2.28, 95% confidence interval=1.29-4.02, P=0.005), whereas neither CXCL16 nor CXCR6 expression correlated with survival. Further, CXCL16/CXCR6 expression and serum sCXCL16 levels did not associate with lymphocyte infiltration. In vitro inhibition of both ADAM-17 and ADAM-10, but especially the latter, decreased CXCL16 membrane shedding and strongly reduced cell migration of A2780 and cultured primary OC-derived malignant cells. CONCLUSIONS: High serum sCXCL16 is a prognostic marker for poor survival of OC patients, possibly reflecting ADAM-10 and ADAM-17 pro-metastatic activity. Therefore, serum sCXCL16 levels may be a pseudomarker that identifies patients with highly metastatic tumours.
Sujet(s)
Protéines ADAM/métabolisme , Amyloid precursor protein secretases/métabolisme , Chimiokines CXC/sang , Protéines membranaires/métabolisme , Tumeurs de l'ovaire/sang , Récepteurs éboueurs/sang , Protéine ADAM10 , Protéine ADAM17 , Chimiokine CXCL16 , Chimiokines CXC/biosynthèse , Femelle , Humains , Immunohistochimie , Métastase tumorale , Tumeurs de l'ovaire/enzymologie , Tumeurs de l'ovaire/anatomopathologie , Pronostic , Études prospectives , Récepteurs CXCR6 , Récepteurs aux chimiokines/biosynthèse , Récepteurs aux chimiokines/sang , Récepteurs éboueurs/biosynthèse , Récepteurs viraux/biosynthèse , Récepteurs viraux/sang , Analyse de survie , Analyse sur puce à tissusRÉSUMÉ
BACKGROUND: High-grade astrocytomas are malignant brain tumours that infiltrate the surrounding brain tissue and have a poor prognosis. Activation of formyl peptide receptor (FPR1) on the human astrocytoma cell line U87 promotes cell motility, growth and angiogenesis. We therefore investigated the FPR1 inhibitor, Chemotaxis Inhibitory Protein of S. aureus (CHIPS), as a potential anti-astrocytoma drug. METHODS AND RESULTS: FPR1 expression was studied immunohistochemically in astrocytomas WHO grades I-IV. With intracellular calcium mobilisation and migration assays, human ligands were tested for their ability to activate FPR1 on U87 cells and on a cell line derived from primary astrocytoma grade IV patient material. Thereafter, we selectively inhibited these ligand-induced responses of FPR1 with an anti-inflammatory compound called Chemotaxis Inhibitory Protein of S. aureus (CHIPS). U87 xenografts in NOD-SCID mice served to investigate the effects of CHIPS in vivo. FPR1 was expressed in 29 out of 32 (90%) of all grades of astrocytomas. Two human mitochondrial-derived formylated peptides, formyl-methionil-leucine-lysine-isoleucine-valine (fMLKLIV) and formyl-methionil-methionil-tyrosine-alanine-leucine-phenylalanine (fMMYALF), were potent activators of FPR1 on tumour cells. Ligand-induced responses of FPR1-expressing tumour cells could be inhibited with FPR1 inhibitor CHIPS. Treatment of tumour-bearing mice with CHIPS slightly reduced tumour growth and improved survival as compared to non-treated animals (P=0.0019). CONCLUSION: Targeting FPR1 with CHIPS reduces cell motility and tumour cell activation, and prolongs the survival of tumour-bearing mice. This strategy could be explored in future research to improve treatment results for astrocytoma patients.
Sujet(s)
Astrocytome/anatomopathologie , Astrocytome/prévention et contrôle , Protéines bactériennes/pharmacologie , Tumeurs du cerveau/prévention et contrôle , Chimiotaxie/effets des médicaments et des substances chimiques , Fragments peptidiques/pharmacologie , Récepteurs aux peptides formylés/antagonistes et inhibiteurs , Animaux , Astrocytome/métabolisme , Technique de Western , Tumeurs du cerveau/métabolisme , Tumeurs du cerveau/anatomopathologie , Calcium/métabolisme , Mouvement cellulaire/effets des médicaments et des substances chimiques , Test ELISA , Humains , Techniques immunoenzymatiques , Souris , Souris de lignée NOD , Souris SCID , Grading des tumeurs , Récepteurs aux peptides formylés/métabolisme , Cellules cancéreuses en cultureRÉSUMÉ
In AML high VEGFA protein expression correlates with poor overall and relapse-free survival (OS/RFS). To date, the relevance of the various VEGFA isoforms is unclear. We determined VEGF121, VEGF145, VEGF148, VEGF165, VEGF183, and VEGF189 mRNA expression in pediatric AML samples and investigated the relation between VEGFA isoform expression and clinicopatholologic characteristics and outcome. A significant co-expression of VEGF121, VEGF165, VEGF183, and VEGF189 isoforms was apparent (mean rho = 0.716, P < 0.0001). This co-expression justifies measuring a single VEGFA isoform (e.g., 121, 165, 183, and 189) as representative expression of all VEGFA isoforms in future studies designed to determine the prognostic importance of VEGFA isoforms.
Sujet(s)
Leucémie aigüe myéloïde/métabolisme , ARN messager/biosynthèse , Facteur de croissance endothéliale vasculaire de type A/biosynthèse , Adolescent , Enfant , Enfant d'âge préscolaire , Survie sans rechute , Femelle , Expression des gènes , Analyse de profil d'expression de gènes , Humains , Nourrisson , Nouveau-né , Estimation de Kaplan-Meier , Leucémie aigüe myéloïde/génétique , Leucémie aigüe myéloïde/mortalité , Mâle , Pronostic , Isoformes de protéines/analyse , Isoformes de protéines/biosynthèse , ARN messager/analyse , RT-PCR , Facteur de croissance endothéliale vasculaire de type A/génétiqueRÉSUMÉ
Chemokines are small cytokines, characterised by their ability to induce directional migration of cells by binding to chemokine receptors. They are known to play a role in tumour development, angiogenesis and metastasis. Interestingly, the chemokine network also contributes to the progression of gliomas, mainly by intensifying their characteristic invasive character. The main hurdle in treatment of these tumours is their infiltration of surrounding tissues, hampering complete surgical tumour removal. Standard postsurgical treatment with radio- and chemotherapy is of limited effect. Therefore drugs that target the chemokine system in high grade gliomas might fill the gap existing in the current approach. This review presents the current knowledge of the role of chemokine network in the development of the central nervous system, in brain physiology and the involvement in brain tumour progression. Finally, current studies exploring new compounds targeting the chemokine network in cancer patient are discussed.
Sujet(s)
Antinéoplasiques/usage thérapeutique , Tumeurs du cerveau/traitement médicamenteux , Chimiokines/métabolisme , Gliome/traitement médicamenteux , Thérapie moléculaire ciblée/méthodes , Récepteurs aux chimiokines/antagonistes et inhibiteurs , Transduction du signal , Animaux , Antinéoplasiques/immunologie , Astrocytes/effets des médicaments et des substances chimiques , Astrocytes/immunologie , Astrocytes/anatomopathologie , Tumeurs du cerveau/immunologie , Tumeurs du cerveau/métabolisme , Tumeurs du cerveau/anatomopathologie , Mouvement cellulaire/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Chimiokines/immunologie , Chimiokines/pharmacologie , Évolution de la maladie , Gliome/immunologie , Gliome/métabolisme , Gliome/anatomopathologie , Humains , Souris , Souris transgéniques , Neurones/effets des médicaments et des substances chimiques , Neurones/immunologie , Neurones/anatomopathologie , Récepteurs aux chimiokines/immunologie , Récepteurs aux chimiokines/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Transduction du signal/immunologieRÉSUMÉ
BACKGROUND: Somatostatin analogues are administered to control hormone hypersecretion in acromegaly and carcinoid patients. Somatostatin analogues can increase fat in the stools, which can lead to loss of fat-soluble vitamins. The effect of long-term somatostatin analogue use on vitamin levels remains unknown. AIM: To investigate the prevalence of fat-soluble vitamin deficiencies in long-term somatostatin analogue users. METHODS: All acromegaly and carcinoid patients using somatostatin analogues for ≥ 18 months visiting the University Medical Center Groningen between December 2008 and April 2009 were eligible. Vitamin levels of fat-soluble vitamins in blood, clinical and vitamin-dependent laboratory parameters were collected. RESULTS: In all, 19 acromegaly and 35 carcinoid patients were included. Twelve patients experienced steatorrhoea; two carcinoid patients experienced night blindness. Forty-two (78%) were deficient for one or more vitamins, and 32% (n = 17) had multiple deficiencies. Deficiencies for vitamin A, D, E, K1 and E in erythrocytes occurred in 6%, 28%, 15%, 63% and 58% of the patients. Prevalence of vitamin D, E and K1 deficiencies was similar in both patient groups. Treatment duration did not influence vitamin levels. The length of intestinal resection and age correlated negatively with vitamin A levels. CONCLUSIONS: Fat-soluble vitamin deficiencies are frequent during long-term somatostatin analogue treatment. Therefore, fat-soluble vitamins should be monitored in these patients.
Sujet(s)
Acromégalie/traitement médicamenteux , Avitaminoses/induit chimiquement , Tumeur carcinoïde/traitement médicamenteux , Somatostatine/analogues et dérivés , Vitamines/sang , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Femelle , Humains , Mâle , Adulte d'âge moyen , Somatostatine/effets indésirables , Facteurs tempsRÉSUMÉ
The natural occurring tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis following binding to the two TRAIL death receptors (DRs). Its recombinant form and monoclonal antibodies against the TRAIL DRs induce cell death in a wide variety of tumor cell lines and xenografts without causing toxicity to normal cells and are therefore potential attractive anticancer agents. These agents are currently in early clinical development. The phase 1 and 2 studies showed until now limited toxicity and tumor responses have been observed. Ongoing studies focus especially on combination of these agents with other targeted therapies or cytotoxic therapies. In this review, we summarize current knowledge on these agents and highlight their potential role in the intrinsically chemotherapy-resistant glioblastomas. In addition, we discuss the mechanisms to sensitize tumors cells to rhTRAIL by combination with the proteasome inhibitor bortezomib.
Sujet(s)
Antinéoplasiques/pharmacologie , Tumeurs/traitement médicamenteux , Récepteurs à domaine de mort/effets des médicaments et des substances chimiques , Récepteurs de TRAIL/effets des médicaments et des substances chimiques , Animaux , Anticorps monoclonaux/pharmacologie , Anticorps monoclonaux/usage thérapeutique , Antinéoplasiques/usage thérapeutique , Acides boroniques/usage thérapeutique , Bortézomib , Tumeurs du cerveau/traitement médicamenteux , Tumeurs du cerveau/anatomopathologie , Gliome/traitement médicamenteux , Gliome/anatomopathologie , Antigène HLA-DR4/effets des médicaments et des substances chimiques , Antigène HLA-DR5/effets des médicaments et des substances chimiques , Humains , Pyrazines/usage thérapeutiqueRÉSUMÉ
Cryptococcal capsular Ags induce the production of proinflammatory cytokines in patients with cryptococcal meningitis. Despite this, their cerebrospinal fluid typically contains few neutrophils. Capsular glucuronoxylomannan is generally considered to mediate the inhibition of neutrophil extravasation. In the current study, culture supernatant harvested from the nonglucuronoxylomannan-producing strain CAP67 was found to be as potent as supernatant from wild-type strains in preventing migration. We identified capsular mannoprotein (MP)-4 as the causative agent. Purified MP-4 inhibited migration of neutrophils toward platelet-activating factor, IL-8, and fMLP, probably via a mechanism involving chemoattractant receptor cross-desensitization, as suggested by its direct chemotactic activity. Supporting this hypothesis, MP-4 elicited Ca(2+) transients that were inhibited by preincubation with either fMLP, IL-8, or C5a, but not platelet-activating factor, and vice versa. Moreover, MP-4 strongly decreased the neutrophil surface expression of L-selectin and induced shedding of TNF receptors p55/p75, whereas CD11b/18 increased. Finally, MP-4 was clearly detectable in both serum and cerebrospinal fluid of patients suffering from cryptococcal meningitis. These findings identify MP-4 as a novel capsular Ag prematurely activating neutrophils and desensitizing them toward a chemoattractant challenge.
Sujet(s)
Antigènes bactériens/pharmacologie , Chimiotaxie des leucocytes/effets des médicaments et des substances chimiques , Cryptococcus/pathogénicité , Glycoprotéines membranaires/pharmacologie , Granulocytes neutrophiles/effets des médicaments et des substances chimiques , Antigènes bactériens/sang , Antigènes CD18/métabolisme , Calcium/métabolisme , Cellules cultivées , Facteurs chimiotactiques/pharmacologie , Cryptococcose/sang , Cryptococcus/immunologie , Relation dose-effet des médicaments , Antagonisme des médicaments , Humains , Sélectine L/métabolisme , Antigène macrophage 1/métabolisme , Glycoprotéines membranaires/sang , Méningite bactérienne/sang , Granulocytes neutrophiles/immunologie , Récepteurs immunologiques/métabolisme , Récepteurs aux facteurs de nécrose tumorale/métabolismeSujet(s)
Agents antiVIH/usage thérapeutique , Thérapie antirétrovirale hautement active , Cryptococcose/complications , Cryptococcose/épidémiologie , Infections à VIH/complications , Infections à VIH/traitement médicamenteux , Infections opportunistes liées au SIDA/complications , Infections opportunistes liées au SIDA/épidémiologie , Infections opportunistes liées au SIDA/microbiologie , Études de cohortes , Cryptococcose/microbiologie , Bases de données comme sujet , Infections à VIH/épidémiologie , Infections à VIH/microbiologie , Humains , Immunosuppresseurs/effets indésirables , Incidence , Pays-Bas/épidémiologie , Études rétrospectives , Transplantation/effets indésirablesRÉSUMÉ
Macrophages and monocytes are adherent phagocytic cells which play an important role in host defence against the yeast-like fungus Cryptococcus neoformans. Before, phagocytosis by adherent phagocytes could only be measured by means of microscopy or by a radioactive assay, which both have obvious disadvantages. We have developed a new, rapid and objective method to measure phagocytosis of C. neoformans by adherent phagocytes (e.g. alveolar macrophages) using a fluorescence multi-well plate reader. This method allows us to discriminate accurately between adherence and internalisation of C. neoformans by macrophages during long term incubation. In addition, the method was used to study the role of the mannose receptor in phagocytosis of the acapsular yeast in the absence of serum by human monocyte-derived macrophages (MDM).