Dolphin CONTINUE: a multi-center randomized controlled trial to assess the effect of a nutritional intervention on brain development and long-term outcome in infants born before 30 weeks of gestation.

BACKGROUND: Preterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm. METHODS: This is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children's Abilities - Revised (PARCA-R)). DISCUSSION: The investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care. TRIAL REGISTRATION: WHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).

Probing and perturbing riboswitch folding using a fluorescent base analogue.

Riboswitches are mRNA segments that regulate gene expression in response to ligand binding. The Class I preQ1 riboswitch consists of a stem-loop and an adenine-rich single-stranded tail ("L3"), which adopt a pseudoknot structure upon binding of the ligand preQ1 . We inserted 2-aminopurine (2-AP), a fluorescent analogue of adenine (A), into the riboswitch at six different positions within L3. Here, 2-AP functions both as a spectroscopic probe and as a "mutation" that reveals how alteration of specific A residues impacts the riboswitch. Using fluorescence and circular dichroism spectroscopy, we found that 2-AP decreases the affinity of the riboswitch for preQ1 at all labeling positions tested, although modified and unmodified variants undergo the same global conformational changes at sufficiently high preQ1 concentration. 2-AP substitution is most detrimental to ligand binding at sites proximal to the ligand-binding pocket, while distal labeling sites exhibit the largest impacts on the stability of the L3 domain in the absence of ligand. Insertion of multiple 2-AP residues does not induce significant additional disruptions. Our results show that interactions involving the A residues in L3 play a critical role in ligand recognition by the preQ1 riboswitch and that 2-AP substitution exerts complex and varied impacts on this riboswitch.

Base-Stacking Heterogeneity in RNA Resolved by Fluorescence-Detected Circular Dichroism Spectroscopy.

RNA plays a critical role in many biological processes, and the structures it adopts are intimately linked to those functions. Among many factors that contribute to RNA folding, van der Waals interactions between adjacent nucleobases stabilize structures in which the bases are stacked on top of one another. Here, we utilize fluorescence-detected circular dichroism spectroscopy (FDCD) to investigate base-stacking heterogeneity in RNA labeled with the fluorescent adenine analogue 2-aminopurine (2-AP). Comparison of standard (transmission-detected) CD and FDCD spectra reveals that in dinucleotides, 2-AP fluorescence is emitted almost exclusively by unstacked molecules. In a trinucleotide, some fluorescence is emitted by a population of stacked and highly quenched molecules, but more than half originates from a minor ∼10% population of unstacked molecules. The combination of FDCD and standard CD measurements reveals the prevalence of stacked and unstacked conformational subpopulations as well as their relative fluorescence quantum yields.

Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas.

BACKGROUND: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce. The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC. METHODS: 32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 > 20%) and with intended curative resection/RFA of liver metastases, were identified among 840 patients from two Nordic GEP-NEC registries. Tumor morphology (well vs poor differentiation) was reassessed. Overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier analyses for the entire cohort and for subgroups. RESULTS: Median OS after resection/RFA of liver metastases was 35.9 months (95%-CI: 20.6-51.3) with a five-year OS of 43%. The median PFS was 8.4 months (95%-CI: 3.9-13). Four patients (13%) were disease-free after 5 years. Two patients had well-differentiated morphology (NET G3) and 20 patients (63%) had Ki-67 ≥ 55%. A Ki-67 < 55% and receiving adjuvant chemotherapy were statistically significant factors of improved OS after liver resection/RFA. CONCLUSION: This study shows a long median and long term survival after liver surgery/RFA for these selected metastatic GEP-NEC patients, particularly for the group with a Ki-67 in the relatively lower G3 range. Our findings indicate a possible role for surgical treatment of liver metastases in the management of this patient population.

Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study.

BACKGROUND: As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. PATIENTS AND METHODS: Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals. RESULTS: The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-67<55% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-67<55% had a lower response rate (15% versus 42%, P<0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P<0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels. CONCLUSIONS: Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

Postmating isolation and genetically variable host use in ecologically divergent host forms of Neochlamisus bebbianae leaf beetles.

Ecological speciation studies have more thoroughly addressed premating than postmating reproductive isolation. This study examines multiple postmating barriers between host forms of Neochlamisus bebbianae leaf beetles that specialize on Acer and Salix trees. We demonstrate cryptic isolation and reduced hybrid fitness via controlled matings of these host forms. These findings reveal host-associated postmating isolation, although a nonecological, 'intrinsic' basis for these patterns cannot be ruled out. Host preference and performance results among cross types further suggest sex-linked maternal effects on these traits, whereas family effects indicate their genetic basis and associated variation. Genes of major effect appear to influence these traits. Together with previous findings of premating isolation and adaptive differentiation in sympatry, our results meet many assumptions of 'speciation with gene flow' models. Here, such gene flow is likely asymmetric, with consequences for the dynamics of future ecological divergence and potential ecological speciation of these host forms.

A double hit implicates DIAPH3 as an autism risk gene.

Recent studies have shown that more than 10% of autism cases are caused by de novo structural genomic rearrangements. Given that some heritable copy number variants (CNVs) have been observed in patients as well as in healthy controls, to date little attention has been paid to the potential function of these non-de novo CNVs in causing autism. A normally intelligent patient with autism, with non-affected parents, was identified with a maternally inherited 10 Mb deletion at 13q21.2. Sequencing of the genes within the deletion identified a paternally inherited nonsynonymous amino-acid substitution at position 614 of diaphanous homolog 3 (DIAPH3) (proline to threonine; Pro614Thr). This variant, present in a highly conserved domain, was not found in 328 healthy subjects. Experiments showed a transient expression of Diaph3 in the developing murine cerebral cortex, indicating it has a function in brain development. Transfection of Pro614Thr in murine fibroblasts showed a significant reduction in the number of induced filopodia in comparison to the wild-type gene. DIAPH3 is involved in cell migration, axon guidance and neuritogenesis, and is suggested to function downstream of SHANK3. Our findings strongly suggest DIAPH3 as a novel autism susceptibility gene. Moreover, this report of a 'double-hit' compound heterozygote for a large, maternally inherited, genomic deletion and a paternally inherited rare missense mutation shows that not only de novo genomic variants in patients should be taken seriously in further study but that inherited CNVs may also provide valuable information.

Symbiont-mediated phenotypic variation without co-evolution in an insect-fungus association.

Recent studies have shown that symbionts can be a source of adaptive phenotypic variation for their hosts. It is assumed that co-evolution between hosts and symbionts underlies these ecologically significant phenotypic traits. We tested this assumption in the ectosymbiotic fungal associate of the gall midge Asteromyia carbonifera. Phylogenetic analysis placed the fungal symbiont within a monophyletic clade formed by Botryosphaeria dothidea, a typically free-living (i.e. not associated with an insect host) plant pathogen. Symbiont isolates from four divergent midge lineages demonstrated none of the patterns common to heritable microbial symbioses, including parallel diversification with their hosts, substitution rate acceleration, or A+T nucleotide bias. Amplified fragment length polymorphism genotyping of the symbiont revealed that within-lineage genetic diversity was not clustered along host population lines. Culture-based experiments demonstrated that the symbiont-mediated variation in gall phenotype is not borne out in the absence of the midge. This study shows that symbionts can be important players in phenotypic variation for their hosts, even in the absence of a co-evolutionary association.

Effect of 3D-microstructure of bioabsorbable PGA:TMC scaffolds on the growth of chondrogenic cells.

Various biomaterial scaffolds have been investigated for cartilage tissue engineering, although little attention has been paid to the effect of scaffold microstructure on tissue growth. Non-woven, fibrous, bioabsorbable scaffolds constructed from a copolymer of glycolide and trimethylene carbonate with varying levels of porosity and pore size were seeded with mesenchymal stroma cells with a chondrogenic lineage. Scaffolds and media were evaluated for both cell and extracellular matrix organization and content after up to 28 days of culture in a spinner flask. Analysis of DNA and glycosaminoglycan contents showed that the most porous of the three scaffold types, with a porosity of 81% and a porometry determined mean flow pore diameter of 54 microm, supported the most rapid proliferation of cells and accumulation of extracellular matrix. Analysis of the high porosity scaffold system, using Western Blot and immunohistochemistry confirmed the presence of collagen type II and absence of collagen type I, and demonstrated cells with a chondrocyte morphology with aggrecan and collagen II accumulation attached to the scaffolds. It was concluded that the 3D-microstructural characteristics of the scaffold (interconnecting porosity and pore size) play an important role in proliferation and phenotype of chondrogenic cells and accumulation of extracellular matrix molecules.

Anemia in patients with midgut carcinoid, treated with alpha interferon: effects by erythropoietin treatment on the perceived quality of life.

One important side effect from alpha interferon is depression of bone marrow function and studies have shown that patients with carcinoid tumours treated with alpha interferon suffers from fatigue and impaired physical functions. The aim of this pilot study was to investigate if treatment with erythropoietin (EPO) could have a positive effect on self-rated quality of life (QoL). Eighteen patients with midgut carcinoid treated with alpha interferon were included in the study. There were statistical significant increases in haemoglobin (Hb) levels between baseline and 4 months, between baseline and 8 months as well as between baseline and 2-year follow-up. No EPO related side effects were reported. There were improvements of more than 10 points in self-rated QoL-issues related to anaemia. Even though the analysis did not reveal any statistically significant relation between the observed increase in Hb levels and self-rated QoL, this pilot study has increased the knowledge about benefits, doses and frequency of EPO treatment in patients with midgut carcinoid suffering from interferon related anaemia.

Liver embolization with trisacryl gelatin microspheres (embosphere) in patients with neuroendocrine tumors.

PURPOSE: To report our experience of liver embolization with trisacryl gelatin microspheres (Embospheretrade mark) in patients with metastatic neuroendocrine tumors. MATERIAL AND METHODS: Fifteen patients underwent selective embolization of the right or left hepatic artery with Embosphere. One lobe was embolized in seven patients and both lobes, on separate occasions, in eight patients. Seven patients had midgut carcinoids, two had lung carcinoids, one suffered from a thymic carcinoid, and five had endocrine pancreatic tumors. Eight patients suffered from endocrine symptoms, seven of whom had carcinoid syndrome and one WDHA (watery diarrhea, hypokalemia, achlorhydria) syndrome. RESULTS: Partial radiological response was seen after eight embolizations (in six different patients), stable disease was observed after 13 embolizations (after three of these, necroses occurred), while radiological progression was noted after only two embolizations. Only two patients experienced a biochemical response. Clinical improvement of carcinoid syndrome was observed after five embolizations. There were no major complications. Fever >38 degrees C was seen after all but four embolizations, and urinary tract infections were diagnosed after eight embolizations. CONCLUSION: Selective hepatic artery embolization with Embosphere particles is a safe treatment for patients with metastatic neuroendocrine tumors and may lead to partial radiological response as well as symptomatic improvement of disabling endocrine symptoms.

Regulation of insulin and glucagon secretion from rat pancreatic islets in vitro by somatostatin analogues.

Somatostatin is an inhibitor of hormone secretion through specific receptors (sst1-5). The aim of this study was to investigate the putative regulatory role of somatostatin analogues on the secretion of insulin and glucagon by rat pancreatic islets. After 48 h exposure only the non-selective agonists (somatostatin, octreotide and SOM-230) inhibited insulin accumulation. The inhibition of insulin secretion was accompanied by increased islet insulin contents. None of the analogues showed a consistent effect on the glucagon accumulation in the medium after 48 h. Since we observed a difference in the regulatory effect between the non-selective and selective analogues, combinations of selective analogues were studied. Combination of sst2+sst5 agonists inhibited the medium insulin accumulation, while combination of sst1+sst2 analogues caused a decrease in glucagon accumulation. After removal of somatostatin a rebound effect with increased insulin secretion were observed. This effect was reversed after 6 h. For SOM-230 insulin secretion continued to be suppressed even after the analogue was removed and returned to control values after 3 h. As for glucagon secretion there was an initial decline after culture with octreotide, while the other substances failed to induce any changes. In summary, non-selective somatostatin analogues or combinations of receptor selective analogues may cause inhibition of hormone secretion from rat pancreatic islets. For insulin and glucagon, combinations of sst2+sst5 and sst1+sst2, respectively may exert this effects. Thus, our data suggest that more than one sst must be involved to down-regulate islet glucagon and insulin secretion.

Expression of somatostatin receptor subtypes 1-5 in pancreatic islets of normoglycaemic and diabetic NOD mice.

OBJECTIVE: Somatostatin acts on five specific receptors (sst1-5) to elicit different biological functions. The non-obese diabetic (NOD) mouse is an experimental model of type 1 diabetes. The aim of this study was to investigate whether the islet expression of sst1-5 is affected during the development of diabetes in NOD mice, with insulitis accompanied by spontaneous hyperglycaemia. METHODS: By immunostaining for sst1-5 the expression and co-expression together with the four major islet hormones in pancreatic islets were investigated in female and male NOD mice at different stages of disease. The NOD related non-diabetic ICR mouse was also examined. RESULTS: The islet cells of diabetic NOD mice showed an increased islet cell expression of sst2-5 compared with normoglycaemic female NOD mice. This correlated to increasing age and extent of insulitis. Major findings from the co-expression investigations were that sst2 was expressed in a majority of beta-cells in the normoglycaemic NOD mice, but absent in the beta-cells in the diabetic NOD mice. A majority of the alpha-cells expressed sst2 and 5 in normoglycaemic and diabetic NOD mice. About 60% of delta-cells showed co-expression of sst4 and 5 in both normoglycaemic and diabetic NOD mice. 60% of pancreatic polypeptide (PP)-cells expressed sst4 in both groups. Insulitis was found to be accompanied by a down-regulation of sst in normoglycaemic animals. CONCLUSIONS: The difference in sst expression in the islets cells of diabetic mice may suggest either a contributing factor in the process leading to diabetes, or a defence response against ongoing beta-cell destruction.

Somatostatin analogs in the treatment of neuroendocrine gastroenteropancreatic and intrathoracic tumors.

Somatostatin is a peptide hormone that posses several biological functions of which inhibition of hormone secretion from endocrine cells is one. Neuroendocrine tumors usually express somatostatin receptors (SSTRs), although the subtypes and number of SSTRs expressed in a certain tumor is very variable. The primary goal of somatostatin analog treatment is to decrease hormone production and secretion, resulting in control of hormone induced symptoms, while the ability of somatostatin analogs to retard tumor growth is less well documented. All patients considered for somatostatin analog treatment should undergo SSTR scintigraphy (111In-pentetreotide) to establish SSTR status, since the expression is usually correlated to therapeutic response. By this approach, it is possible to select patients suitable for treatment. Among patients with functioning neuroendocrine tumors expressing SSTR, more than 80% respond with symptomatic relief during somatostatin analog treatment, while treatment of non-functioning tumors still remains somewhat controversial.

A comparison between three commercial kits for chromogranin A measurements.

Chromogranin (CgA) has been shown to be an excellent marker for neuroendocrine tumours. There are now three commercial assays on the market. We wanted to compare the usefulness of the different kits in a clinical situation. We have thus measured CgA in 77 patients and compared the results from the different methods. CgA was measured with three different commercial kits according to the recommendations from the manufacturers (CGA-RIA CT; CIS bio international, Gif-sur-Yvette cedex, France, DAKO Chromogranin A ELISA kit; DAKO A/S, Glostrup, Denmark and CgA; EuroDiagnostica, Malmö, Sweden). The sensitivity and specificity differed between the different kits. The CIS kit showed a sensitivity of 67% and a specificity of 96%. The sensitivity and specificity were both 85% for the DAKO kit and 93% and 88% respectively for the EuroDiagnostica assay. We have concluded that CgA is an important tumour marker for all neuroendocrine tumours. However, different analytical properties of the respective kits give different performances, a fact that must be taken into consideration when comparing results from different clinical studies. A recognised international standard for CgA would be a step on the way to harmonisation, but antibody selection and construction of the assays will probably still influence the results.

Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs.

Somatostatin analogs and alpha-interferon induce good responses as single drugs in the treatment of endocrine pancreatic tumors. We examined the efficacy and tolerability of the combination of alpha-interferon and somatostatin analogs in 16 patients with metastatic endocrine pancreatic tumors. All patients except one had received prior treatment and were in a progressive state. Doses of alpha-interferon and somatostatin analogs were individually titrated. The alpha-interferon doses varied between 9 and 25 million units per week and were combined with 100-1500 microg of octreotide or 6000 microg of lanreotide daily. Radiological response was seen in 3 of 16 (19%) patients (median duration 23 mo). Biochemical response was seen in 10 of 16 (62.5%) patients (median duration 22 mo). All three patients previously progressing on both alpha-interferon and somatostatin analog as single drugs achieved a stabilization of the disease when treated with the combination (median duration 10 mo). Seven of eight (88%) patients previously progressing on alpha-interferon treatment benefited from the combination with biochemical partial response or stabilization. All six patients previously progressing during somatostatin analog treatment achieved biochemical partial response or stabilization. More than 80% of patients who progressed during previous treatment with either drug benefited from the combined treatment, which also was well tolerated. Thus, a combination of alpha-interferon and somatostatin analogs may be considered for patients previously progressing on treatment with alpha-interferon or somatostatin analogs. However, in this study, the value of sequential treatment has not been evaluated.

Treatment with cisplatin and etoposide in patients with neuroendocrine tumors.

BACKGROUND: Patients with malignant endocrine pancreatic tumors (EPTs) are responsive to combinations of chemotherapy with streptozotocin and 5-fluorouracil/doxorubicin, whereas patients with malignant carcinoids are not. For both categories of patients, alpha-interferon and/or somatostatin analogs can produce long-lasting responses. Cisplatin in combination with etoposide has been suggested to be effective in patients with malignant neuroendocrine carcinomas. The authors used this therapy as second-line or third-line treatment in patients with poorly differentiated and/or rapidly progressing disease. METHODS: Thirty-six patients with histopathologically verified malignant neuroendocrine tumors were included: Eighteen tumors were of foregut origin, of which 5 were atypical, and 15 tumors were EPTs, of which 4 were poorly differentiated endocrine carcinomas. Three tumors were of midgut origin. The median patient age was 47.5 years. The median duration of disease from the time of diagnosis was 12 months. All patients had metastatic disease. Thirty of 36 patients had received previous treatment. Etoposide was given at a dose of 100 mg/m(2) per day for 3 days, and cisplatin was given at a dose of 45 mg/m(2) on Days 2 and 3 as a continuous intravenous infusion that was repeated every 4 weeks. RESULTS: Ten of 18 patients with foregut carcinoids (56%) responded radiologically and/or biochemically, with a median duration of 9 months; and 7 of 14 patients with EPTs (50%) responded radiologically and/or biochemically, with a median duration of 9 months. No difference in response was seen between patients with atypical or typical foregut carcinoids or between patients with well differentiated or poorly differentiated endocrine pancreatic carcinoma. Nineteen of 36 patients (53%) experienced World Health Organization (WHO) Grade 1-2 nephrotoxicity, and 23 patients (64%) suffered from WHO Grade 3-4 neutropenia. CONCLUSIONS: The combination of cisplatin and etoposide can produce significant responses in patients with heavily pretreated and poorly differentiated/rapidly progressing neuroendocrine tumors. The toxicity is considerable, and nephrotoxicity is the dose limiting factor.

Novel long-acting somatostatin analog with endocrine selectivity: potent suppression of growth hormone but not of insulin.

Somatostatin, also known as somatotropin release-inhibiting factor (SRIF), is a natural cyclic peptide inhibitor of pituitary, pancreatic, and gastrointestinal secretion. Its long-acting analogs are in clinical use for treatment of various endocrine syndromes and gastrointestinal anomalies. These analogs are more potent inhibitors of the endocrine release of GH, glucagon, and insulin than the native SRIF; hence, they do not display considerable physiological selectivity. Our goal was to design effective and physiologically selective SRIF analogs with potential therapeutic value. We employed an integrated approach consisting of screening of backbone cyclic peptide libraries constructed on the basis of molecular modeling of known SRIF agonists and of high throughput receptor binding assays with each of the five cloned human SRIF receptors (hsst1-5). By using this approach, we identified a novel, high affinity, enzymatically stable, and long-acting SRIF analog, PTR-3173, which binds with nanomolar affinity to human SRIF receptors hsst2, hsst4, and hsst5. The hsst5 and the rat sst5 (rsst5) forms have the same nanomolar affinity for this analog. In the human carcinoid-derived cell line BON-1, PTR-3173 inhibits forskolin-stimulated cAMP accumulation as efficiently as the drug octreotide, indicating its agonistic effect in this human cell system. In hormone secretion studies with rats, we found that PTR-3173 is 1000-fold and more than 10,000-fold more potent in inhibiting GH release than glucagon and insulin release, respectively. These results suggest that PTR-3173 is the first highly selective somatostatinergic analog for the in vivo inhibition of GH secretion, with minimal or no effect on glucagon and insulin release, respectively.

Levels of angiogenic peptides in sera from patients with carcinoid tumours during alpha-interferon treatment.

BACKGROUND: Alpha-interferon, a known inhibitor of angiogenesis and cell proliferation, is used in the standard treatment of patients with carcinoid tumors. We studied the levels of two angiogenic peptides (bFGF and VEGF) in sera from patients with carcinoid tumours before and during treatment with alpha-interferon. The aim was to investigate if the antitumoral effect of alpha-interferon in these patients could be at least in part explained by a reduction in the measured angiogenetic peptides. PATIENTS AND METHODS: Sera from 29 patients with carcinoid tumours were collected before and during alpha-interferon treatment and analyzed using commercially available ELISA-kits. RESULTS: Interferon alpha treatment did not cause reduction of bFGF and VEGF levels in serum from patients with carcinoid tumours. In fact there was no correlation between changes in bFGF or VEGF levels and treatment effect. CONCLUSION: The action of alpha-interferon does not seem to be mediated by bFGF or VEGF in patients with carcinoid tumours. If alpha-interferon has an anti-angiogenic effect in this patient group, it is probably mediated by angiogenic peptides other than bFGF and VEGF.