Kjell E Oberg

..None of these can cure a patient with malignant disease. In future, therapy will be custom-made and based on current knowledge of tumour biology and molecular genetics...

..Genome-wide screening of different types of NETs can now be performed for a reasonable price and is likely to generate new insights into the tumor biology and carcinogenesis in various subtypes of NETs...

..At the same time new targeted agents have been developed for treatment of GEP-NETs and it is important discuss these new agents in relation to the classification and staging system...

..Peptide receptor radiotherapy with [90]yttrium-DOTATOC or [177]lutetium-DOTATE is also a new interesting treatment option for NETs...

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..Neuroendocrine tumors of the gastrointestinal tract represent a small area within oncology, but many new data have been reported during the past year. This paper updates the recent findings...

..Part I of these guidelines discusses the principles of histopathology, biochemical and radiological diagnosis as well as therapeutic options...

..Tumor-targeted radioactive treatment based on somatostatin analogues is now under clinical evaluation. Preliminary data indicate interesting clinical potentials...

..177)Lutetium may be more effective for smaller tumours whereas (90)yttrium may be more effective for larger tumours...

..We compare the efficacy of octreotide and lanreotide in reducing diarrhea and flushing. Side-effects are described and we provide practical information on somatostatin analog treatment...

..We have, however, tried to give more updated information about the epidemiology and histopathology, which is essential for the clinical management of these tumours...

..It might also be possible to give higher doses of alpha interferon with hopefully improved clinical efficacy...

..However, the WHO classification introduced in clinical practice will give more insight into genetic and molecular changes related to tumor subtypes...

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..In the future, treatment will be based on tumor biology and molecular genetics with the aim of so-called personalized medicine...

..Molecular imaging will increase in importance in the near future. There is still an unmet need for more sensitive biomarkers for diagnosis and follow-up...

..The quality of life has been significantly improved by using the long-acting formulations...

..Treatment with combined streptozotocin and liposomal doxorubicin is safe and efficient in patients with endocrine pancreatic tumors (EPTs). No cardiac toxicity was reported...

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..This might be a new tumor entity of the stomach, and it is suggested that patients with malignant gastric neuroendocrine tumors should be investigated for ghrelin production...

..We also found that an increase in AI during high-dose somatostatin analog treatment was correlated with the biochemical response, but not with the tumor size as detected by CT in patients or with the tumor mass in the experimental model...

..By utilizing data from PET scanning with both tracers, we could quantify the decarboxylation rate and tissue accumulation of [11C]-serotonin and hence the enzymatic action of aromatic amino acid decarboxylase...

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..In conclusion, there are at least three effective therapies for malignant EPT and by combining them simultaneously or consecutively, a median survival of more than four years can be obtained...

..Thus, these antibodies may be used to determine the presence of sst2 in carcinoid tumors and to select patients suitable for somatostatin analogue treatment. The method is easily applicable in clinical practice...

..Thus, the antitumor effect, in vivo and in vitro, in IFN-alpha-treated carcinoid tumors seems to be mediated via upregulation of Stat proteins and enhancement of phosphorylation of these proteins...

..We believe that high-dose treatment with somatostatin analogues can be an important addition to the therapeutic arsenal for patients with advanced progressive midgut carcinoid tumours...

..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...

..However, the importance of the number of somatostatin receptors and subtypes expressed will have to be further studied...

..However, in this study, the value of sequential treatment has not been evaluated...

..Differential expression of these genes may contribute to the PLCB3-induced tumor suppression of neuroendocrine tumor cell lines...

..To report our experience of liver embolization with trisacryl gelatin microspheres (Embospheretrade mark) in patients with metastatic neuroendocrine tumors...

..Tumor-targeted therapy with (111)In and (90)Y coupled to somatostatin analogs show promising results but await further studies...

..This study also shows that WB-(11)C-HTP-PET is sensitive in imaging small NET lesions, such as primary tumors, and can in a majority of cases image significantly more tumor lesions than SRS and CT...

..g., inhibition of exocytosis, antiproliferative effects and induction of apoptosis during treatment will help to optimize treatment and provide new insights into mechanisms of action of somatostatin analogs...

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..Alpha-interferon and octreotide offer efficient symptomatic relief, but stabilizes tumor growth in merely 15% of the cases. Plasma chromogranin A is the most frequently elevated tumor marker...

..The aim of this study was to investigate some of the monoamine processing pathways of neuroendocrine GEP-tumors and try to find a new tracer substance for in vivo characterization and visualization by Positron Emission Tomography (PET)...

..Development of new PET radiopharmaceuticals may in the future allow in vivo detection of tumour biological properties, such as malignant potential and responsiveness to treatment...

..The somatostatin analogue has proved to be particularly useful in the treatment of patients with severe hormone-related clinical symptoms and in the perioperative period.(ABSTRACT TRUNCATED AT 400 WORDS)..

..Two of these lesions represented previously undetectable primary tumours. It is concluded that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]-octreotide has a future role in the staging of patients with carcinoid disease...

..Our results also indicate that the combination of octreotide and alpha-interferon might be of beneficial value for long-term management of this disease...

..Our data indicate that combination treatment with streptozocin and 5-fluorouracil is of little value for patients with malignant carcinoid tumors...

..Recent findings might indicate that CA-50 could be an indicator of malignant disease and possibly also correlate with survival...

..Chromogranin A serum or plasma levels reflect tumor load, and it may be an independent marker of prognosis in patients with midgut carcinoids...

..It detects more lesions in the liver and lymph nodes than other methods and furthermore, it can be used to monitor treatment effects...

..Also in immunocytochemical stainings, our polyclonal antiserum detecting both chromogranin A and B showed a greater sensitivity than other available antisera against chromogranin A, B and C...

..It is therefore concluded that the inhibitory effect of somatostatin in forskolin-stimulated cells is not dependent on cell contraction...

..Furthermore, while VMAT1 can take up serotonin, VMAT1Delta15 cannot, indicating different functions for the two forms of VMAT1...

..This observation correlated to positive immunostaining to chromogranin A and synaptophysin. Different growth factors might stimulate different fractions of tumor cells to retain the endocrine characteristics...

..1 versus 5.8 years). Patients who received interferon after failing chemotherapy had a significantly better survival than those given chemotherapy alone (5-year survival 65 and 50% respectively)...

..Other adverse reactions were skin lesions and myalgia. The combination therapy demonstrated subjective improvement in half of the patients, but lacked antitumoral effects...

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..Moreover, CD44, nm23, and Ki-67 may give valuable prognostic information and help identify the patients at risk of disease-related death...

..We conclude that treatment with [(111)In-DTPA-D-Phe1]-octreotide can be used in patients with neuroendocrine tumors but blood parameters have to be carefully monitored to avoid severe side effects...

..The observation of PLC-beta3 nuclear localization suggests that PLC-beta3 may have intranuclear functions...

..However, positive staining for CD44s, v7-8 and v9 seems to be associated with a more favorable outcome, and may be taken into consideration in prognostic evaluation...

..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...

..The adverse reactions are dose-dependent and manageable. The anti-tumor effects of alpha interferons are pleiotropic and include several direct effects on tumor cells but also immunomodulation...

..A change from diploid to aneuploid records was also seen in 7/23 (30%) carcinoid tumors after treatment. The DNA patterns before and after treatment did not show any correlation with survival or treatment response...

..We have examined the expression of molecular targets in patients with malignant endocrine pancreatic tumors, which is necessary to justify additional studies investigating the potential benefit from such treatment...

..Our results indicate an inhibitory role of bcl-2 in development and progression of ovarian tumours...

..The animal model was probably unsuitable for demonstration of IFN effects...

..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...

..These new somatostatin receptor subtype specific analogues will soon be tested in clinical trials. In this review article the development of new analogues and new preparations of old analogues and their use in the clinic is discussed...

..We also showed that mouse PLCbeta3 is expressed in unfertilized eggs, 3-cell and egg cylinder stages of embryos. In conclusion, these results indicate that PLCbeta3 expression is essential for early mouse embryonic development...

..Thus, deterioration of physical function was not accompanied by a deterioration of emotional function, and levels of tumour markers were not related to patients' HRQoL...

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..The somatostatin analogue SMS 201-995 has a beneficial effect in the treatment of patients with the carcinoid syndrome. However, the precise role of the drug in the long-term management of these patients has to be further investigated...

..This would result in loss of repression of menin/JunD target genes, as well as non-target genes through indirect mechanisms, deregulation of cellular growth control and endocrine tumorigenesis...

..Although it still remains to be established whether early intervention will have an impact on mortality, our long-term experience with 20 MEN 1 kindreds suggests a reduced morbidity as a result of thorough biochemical screening...

..This is in agreement with the comparative mapping of the MEN1 flanking markers in mouse...

..The causative medical treatment of patients with malignant endocrine pancreatic tumors and the MEN-1 trait include chemotherapy (streptozotocin plus 5-fluorouracil), interferons and the somatostatin analogue SMS 201-995...

..IL-8R mRNA containing cells were predominately found in the mantle zone of the germinal center. These cells were identified as B lymphocytes using the OX-33 monoclonal antibody...

..Little is known about the health-related-quality of life (HRQoL) of patients with endocrine gastrointestinal tumours. In this study, HRQoL was investigated in long-term survivors of endocrine GI tumours...

..Also a comprehensive review of the literature about chemotherapy in NETs is presented...

..If pheochromocytoma is ruled out, yet symptoms and biochemical markers for catecholamine excess are present, then carcinoid and other amine-precursor-uptake decarboxylation (APUD) tumors must remain in the differential diagnosis...

..A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors...

..In patients with metastatic gastrinomas not suitable for chemotherapy, interferon or targeted radiotherapy, single therapy with somatostatin analogs may be an alternative...

..Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics...

..We therefore constructed Ad[CgA-E1A], a novel replication-selective oncolytic adenovirus, where the chromogranin A (CgA) promoter controls expression of the adenoviral E1A gene...

..In an attempt to assess the efficacy of diagnostic and therapeutic measures in patients with glucagonoma, a retrospective study was performed using the archives of a tertiary care center...

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..All other tumour types were consistently GRP-negative (p?<?0.0001). We conclude that immunostaining for GRP may aid in defining the origin of the tumour, and that GRP-immunoreactivity increases the suspicion of a lung carcinoid...

..We were interested in estimating the efficacy of octreoscan for detection of the primary tumour and metastases in patients with bronchial carcinoids...

..Several CgA-related peptides have been identified in tissue, and many of the biological effects attributed to CgA seem to be mediated by these peptides...

..These differences indicate the importance of determining each tumor s subset of receptors before treatment with receptor-subtype-specific analogs is initiated. The importance of sst expression in intratumoral vessels is not yet known...

..CONCLUSION: IFN-alpha confers its antitumor activity, at least in part, by its antiangiogenic activity, which results from Sp1- and/or Sp3-mediated inhibition of VEGF gene transcription...

..However, patients with tumor cells being LDR to at least one drug ex vivo lived significantly longer than those with no such drug...

..In addition, adrenocortical cancer shows high uptake, suggesting that this PET tracer can be used for staging purposes...

..Based on these results, we conclude that IFN-alpha exerts antitumor effects by increased p21 expression in neuroendocrine tumors...

..Liver metastases and significant preoperative weight loss are identified as major negative prognostic factors for survival...

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