| 1. |
- Abrahamsson, Gun, 1947, et al.
(author)
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Ovarian cyst formation in women of reproductive age receiving mitotane as part of the treatment of adrenocortical carcinoma: Clinical and experimental observations
- 2020
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In: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 99:10, s. 1297-1302
-
Journal article (peer-reviewed)abstract
- Introduction Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery. Material and methods Five women presented with stage III-IV adrenocortical carcinoma and ovarian cyst formation during mitotane treatment. The clinical course of the disease was followed during and after treatment. The effects of mitotane on progesterone production and cell proliferation were studied in cultured human ovarian granulosa cells. Results Computed tomography and vaginal ultrasonography during mitotane treatment repeatedly demonstrated ovarian cysts of varying size without solid intralocular structures. Two women became amenorrheic during the treatment period. After mitotane cessation, the ovarian cysts disappeared and normal menstrual cycles resumed. One woman had an uncomplicated pregnancy two years after mitotane treatment. In one woman, who underwent salpingo-oophorectomy, histological analysis demonstrated benign ovarian cysts. Mitotane impeded the synthesis of progesterone, reduced the stimulatory effect of gonadotropins on progesterone formation, and reduced labeling with [H-3]thymidine in cultured granulosa cells. Conclusions Therapeutic concentrations of mitotane are associated with the formation of benign ovarian cysts and amenorrhea. Mitotane-induced suppression of ovarian steroidogenesis and impediment of the proliferative capacity of steroid-producing cells are suggested potential pathogenetic mechanisms underlying mitotane-induced ovarian dysfunction and cyst development. Mitotane treatment does not compromise future ovarian function.
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| 2. |
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| 3. |
- Nilsson, Ola, 1957, et al.
(author)
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Comparative studies on the expression of somatostatin receptor subtypes, outcome of octreotide scintigraphy and response to octreotide treatment in patients with carcinoid tumours.
- 1998
-
In: British journal of cancer. - 0007-0920. ; 77:4, s. 632-7
-
Journal article (peer-reviewed)abstract
- We have compared the expression of somatostatin receptor (sstr) subtypes with the outcome of somatostatin receptor scintigraphy and the effect of somatostatin receptor activation in patients with disseminated carcinoid tumours. Tumour tissues from nine patients with midgut carcinoids (ileal) and three patients with foregut carcinoids (gastric, thymic) were analysed using Northern blotting. Expression of somatostatin receptors was demonstrated in all tumours (12 out of 12), with all five receptor subtypes present in 9 out of 12 tumours. Somatostatin receptor scintigraphy using [111In]DTPA-D-Phe1-octreotide visualized tumours in all patients (12 out of 12). The 111In activity concentrations in tumour tissue (T) and blood (B) were determined in three tumours 1-7 days after injection of the radionuclide. The T/B 111In activity concentration ratios ranged between 32 and 651. Clinically, treatment with the long-acting somatostatin analogue octreotide resulted in marked symptom relief accompanied by a significant reduction in tumour markers, for example urinary-5-HIAA levels (28-71% reduction). Incubation of midgut carcinoid tumours in primary culture with octreotide (10 microM) resulted in a reduction in spontaneously secreted serotonin (45-71% reduction) and 5-HIAA (41-94% reduction). The results demonstrate that carcinoid tumours possess multiple somatostatin receptor subtypes and that somatostatin analogues such as octreotide, which preferentially bind to somatostatin receptor subtype 2 and 5, can be used in the diagnosis and medical treatment of these tumours. In the future, novel somatostatin analogues with subtype specific receptor profiles may prove to be of value for individualizing the treatment of disseminated carcinoid tumour disease.
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| 4. |
- Westberg, G, et al.
(author)
-
Prediction of prognosis by echocardiography in patients with midgut carcinoid syndrome.
- 2001
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In: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 88:6, s. 865-72
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Journal article (peer-reviewed)abstract
- The association between malignant midgut carcinoid tumours and right-sided cardiac lesions is well known, but the pathogenetic link between tumour secretion and valvular disease is still obscure. The purpose of this investigation was to describe the morphological and functional changes of valvular heart disease in a large patient series and to correlate these findings with hormonal secretion and prognosis.
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| 5. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Adrenocortical carcinoma--diagnostic and therapeutical implications.
- 1993
-
In: The European journal of surgery = Acta chirurgica. - 1102-4151. ; 159:3, s. 149-58
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Journal article (peer-reviewed)abstract
- To evaluate the results of treatment of a consecutive series of patients with adrenocortical carcinoma who presented during the six year period 1985 to 1991.
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| 6. |
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| 7. |
- Ahlman, Håkan, 1947, et al.
(author)
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Aspects on diagnosis and treatment of the foregut carcinoid syndrome.
- 1992
-
In: Scandinavian journal of gastroenterology. - 0036-5521. ; 27:6, s. 459-71
-
Journal article (peer-reviewed)abstract
- Eight patients with the foregut carcinoid syndrome (two gastric and six bronchial primary tumors) are reported. The patients presented with complex clinical symptoms including ectopic production of adrenocorticotrophic hormone and growth hormone-releasing factors. The most alarming symptoms were facial flush and edema, accompanied by severe bronchoconstriction, which easily was misinterpreted as asthmatic attacks. Conventional bronchodilatory drugs may be potentially dangerous in these patients, in whom combined blockade of histamine receptors and treatment with cortisone and octreotide are recommended. Owing to the patients' age and general condition individualized long-term therapy was instituted. Surgical therapy under optimal protection by drugs can be of substantial value also in patients with advanced disease. One patient with life-threatening hormonal symptoms underwent hyperthermic perfusion of the liver with cytotoxic drugs, resulting in good palliation.
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| 8. |
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| 9. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Clinical efficacy of octreotide scintigraphy in patients with midgut carcinoid tumours and evaluation of intraoperative scintillation detection.
- 1994
-
In: The British journal of surgery. - 0007-1323. ; 81:8, s. 1144-9
-
Journal article (peer-reviewed)abstract
- 111In-diethylenetriamine penta-acetate-D-Phe1-octreotide scintigraphy was evaluated in a group of 27 patients with disseminated midgut carcinoid tumour. Additional information gained by the intraoperative use of a scintillation detector was studied in five patients with midgut carcinoid tumours and in two with endocrine pancreatic tumours. In 19 patients tumours not recognized by non-invasive radiological methods were visualized in 27 locations, most commonly in liver and para-aortic lymph nodes. Three false-negative tumour locations were noted (ovarian and peritoneal). With guidance from scintigraphic findings, nine patients underwent surgical tumour reduction, leading to complete remission in three. Clinically suspect tumour lesions were measured by the detector in situ, and ex vivo after excision. After excision the tissue:blood activity concentration ratios were calculated. In situ measurements were helpful in the localization of tumours and in the control of adequate clearance of tumour tissue. High tissue:blood activity concentration ratios at 1, 2 and 5 days in the five patients with midgut carcinoid tumour indicate a potential role for radiation therapy with radiolabelled octreotide in patients with somatostatin receptor-positive tumours.
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| 10. |
- Ahlman, Håkan, 1947, et al.
(author)
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Clinical management of gastric carcinoid tumors.
- 1994
-
In: Digestion. - 0012-2823. ; 55 Suppl 3, s. 77-85
-
Journal article (peer-reviewed)abstract
- Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.
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| 11. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Cytotoxic treatment of adrenocortical carcinoma.
- 2001
-
In: World journal of surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 25:7, s. 927-33
-
Journal article (peer-reviewed)abstract
- Adrenocortical carcinoma (ACC) is a rare, aggressive tumor that is often detected in an advanced stage. Medical treatment with the adrenotoxic drug mitotane has been used for decades, but critical prospective trials on its role in residual disease or as an adjuvant agent after surgical resection are still lacking. The concept of a critical threshold plasma level of the drug must be confirmed in controlled studies. Because individual responsiveness cannot be predicted, the use mitotane is still advised for nonresectable disease. In case of cortisol or other steroid overproduction, several drugs (e.g., ketoconazole or aminoglutethimide) may be used. Chemotherapy with single agents (e.g., doxorubicin or cisplatin) have been disappointing, with low response rates (< 30%) and a short response duration. Part of this refractoriness may be explained by the fact that ACC tumors express the multidrug-resistance gene MDR-1. Chemotherapy with multiple agents has been tested in smaller series and has resulted in significant side effects. The best results were achieved by the combination of etoposide, doxorubicin, and cisplatin associated with mitotane, achieving a response rate of 54%, including individual complete responses. To be able to make progress in treating advanced ACC disease, adjuvant multicenter trials must be encouraged. When mitotane-based therapies are used, monitored drug levels are mandatory.
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| 12. |
- Ahlman, Håkan, 1947, et al.
(author)
-
En "ny" tumörmarkör.
- 1996
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In: Klinisk Kemi i Norden, 8.. - Göteborg. ; , s. 45-52
-
Book chapter (other academic/artistic)
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| 13. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Growth regulation in carcinoid tumors.
- 1993
-
In: Endocrinology and metabolism clinics of North America. - 0889-8529. ; 22:4, s. 889-915
-
Research review (peer-reviewed)abstract
- In hormone-producing tumors such as the carcinoids, overproduction of certain hormones may activate proto-oncogenes. Hormones, or growth factors, thus can be of importance for growth regulation. Information is presented on some growth factors and their receptors in this respect and on the involvement of gastrin and its receptor on tumor development in the experimental Mastomys model. The relevance of differential expression of cell adhesion molecules in endocrine tumors is discussed also.
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| 14. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Interventional treatment of gastrointestinal neuroendocrine tumours.
- 2000
-
In: Digestion. - 0012-2823. ; 62 Suppl 1, s. 59-68
-
Journal article (peer-reviewed)abstract
- Neuroendocrine (NE) tumours of the gastrointestinal tract (carcinoids and endocrine pancreatic tumours) are rare diseases. In the presence of liver metastases these patients may suffer from disabling symptoms due to hormone overproduction. Patients with localized disease can be resected for cure and also patients with liver metastases can undergo potentially curative tumour resection. However, long-term follow-up of the latter cases indicates frequent recurrence of tumour. Using close biochemical monitoring of tumour markers combined with newer techniques for tumour visualization, these recurrences can often be diagnosed at an early stage so that repeat surgical procedures can be performed. During the last years very active surgery has been recommended for NE tumours, many of which have a relatively slow growth. Even in patients not amenable to curative liver surgery, debulking can be considered if the main tumour burden can be safely excised. The primary aim of this type of treatment is palliation of hormonal symptoms. An important question is whether the aggressive treatment actually prolongs survival. No prospective studies have been performed. Such studies are hampered by the lack of strict surgical programs running over long periods and the relative rarity of NE tumours. Liver transplantation may be another treatment modality in selected cases.
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| 15. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Interventional treatment of the carcinoid syndrome
- 2004
-
In: Neuroendocrinology. - 0028-3835. ; 80 Suppl 1, s. 67-73
-
Journal article (peer-reviewed)abstract
- Liver metastases imply a major problem in patients with carcinoid tumours and hormone overproduction. Patients with distant metastases can undergo resection for potential cure or for symptom palliation. In patients with bilobar liver metastases other interventions are at hand, e.g. local ablation or hepatic arterial embolization. In selected cases liver transplantation can be a treatment alternative. Prior to all interventions patients with midgut carcinoids are protected with somatostatin analogues to reduce hormone secretion. Patients with foregut carcinoids may present special problems with life-threatening release of histamine during interventions.
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| 16. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Liver transplantation for treatment of metastatic neuroendocrine tumors
- 2004
-
In: Annals of the New York Academy of Sciences. - 0077-8923. ; 1014, s. 265-9
-
Journal article (peer-reviewed)abstract
- Liver transplantation can be considered a therapeutic option for patients with neuroendocrine tumors only metastatic to the liver. Important selection criteria are well-differentiated tumors and a low proliferation rate (Ki67 <10%). In this series, orthopic liver transplantation offered good relief of symptoms and long disease-free intervals with initial survival of grafts and patients as in benign disease. The experience with multivisceral transplantation is still limited.
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| 17. |
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| 18. |
- Ahlman, Håkan, 1947
(author)
-
Malignant pheochromocytoma: state of the field with future projections
- 2006
-
In: Annals of the New York Academy of Sciences. - 0077-8923. ; 1073, s. 449-64
-
Journal article (peer-reviewed)abstract
- The prevalence of malignant pheochromocytoma is about 10%, and is somewhat higher for paraganglioma. A problem for clinical follow-up is that patients with "benign" histopathologic findings may develop metastatic disease. At the first international symposium on pheochromocytoma in Bethesda (2005) experts from different disciplines and patients shared their experiences, and the present knowledge of this rare disease was updated. The discussion related to future strategies for better clinical/histopathologic diagnosis and understanding of different geno- and phenotypes. Curative surgery can only seldom be performed because of multiple metastases. The main therapeutic goal is therefore often tumor reduction and control of hypertension. To date the best adjunct to surgery is radionuclide therapy using 131I-MIBG, but the background information for optimal treatment is still incomplete. Certain patients may benefit from 131I-MIBG combined with radiotherapy via somatostatin receptors expressed by the tumor, or the combination with chemotherapy. The need for future multicenter studies was emphasized. In experimental models the work on enhanced expression of amine transporters critical for radiotherapy is continued. Ongoing microarray studies will reveal novel intracellular pathways of importance for proliferation/cell cycle control, which can be inhibited by pharmacologic tools.
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| 19. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Management of disseminated midgut carcinoid tumours.
- 1991
-
In: Digestion. - 0012-2823. ; 49:2, s. 78-96
-
Journal article (peer-reviewed)abstract
- Forty-one patients with disseminated midgut carcinoid tumours were treated over a 6-year period according to a strict programme including primary surgical treatment. In 10 patients, a total remission of the disease was obtained. Patients with bilobar hepatic disease had ischaemic treatment of their liver metastases by hepatic arterial embolisation after primary surgical and medical treatment (low dose octreotide). Thus, by combining surgical, radiological and medical treatment modalities, we wanted to offer these patients optimal palliation. This treatment programme resulted in good symptomatic relief in all patients accompanied by a marked reduction in 5-hydroxyindoleacetic acid (5-HIAA) levels. At recurrence of symptoms in combination with rising 5-HIAA levels, embolisation was repeated. Ten of the treated patients have deceased during the observation period, but only 5 from their carcinoid disease.
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| 20. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Neuroendocrine insights from the laboratory to the clinic.
- 1996
-
In: American journal of surgery. - 0002-9610. ; 172:1, s. 61-7
-
Journal article (peer-reviewed)abstract
- The interaction between adrenergic nerves and enterochromaffin (EC) cells was studied in health and disease using animal models and patients with the midgut carcinoid syndrome.
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| 21. |
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| 22. |
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| 23. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Sjukdomar i endokrina organ.
- 2003
-
In: Kirurgi för sjuksköterskor. eds:Jeppssen B, Bengmark S. - Lund, Sverige : Studentlitteratur. - 9144074050
-
Book chapter (peer-reviewed)
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| 24. |
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| 25. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Somatostatin receptors on neuroendocrine tumors--a way to intraoperative diagnosis and localization.
- 1994
-
In: The Yale journal of biology and medicine. - 0044-0086. ; 67:3-4, s. 215-21
-
Journal article (peer-reviewed)abstract
- Intraoperative radionuclide detection using 111In-DTPA-D-Phe1-octreotide was evaluated in five patients with midgut carcinoids and in three patients with recurrent medullary thyroid carcinoma. Three different time intervals (24, 48 and 120 hr) from injection of the radiopharmaceutical to surgery were used. At surgery, suspect tumors were measured by probe in situ and ex vivo after excision. All tissue specimens and blood samples withdrawn during surgery were measured for 111In activity, and tissue/blood activity concentration ratios were calculated. In situ measurements were valuable especially in neck surgery, where the probe was helpful not only in localization of tumors but also in the control of tumor clearance. Ex vivo measurements were helpful in diagnosing tumor tissue. All five patients with midgut carcinoids were somatostatin receptor-positive, while only three out of seven patients with medullary thyroid carcinoma were receptor-positive. The tissue/blood activity concentration ratios and probe measurement ratios were in general higher in patients with midgut carcinoid than in patients with medullary thyroid carcinoma. Of particular interest were the high tissue/blood concentration ratios in all receptor-positive patients at all time intervals studied. This fact suggests a potential role for radiolabelled octreotide in radiotherapy of these tumor types.
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| 26. |
- Ahlman, Håkan, 1947, et al.
(author)
-
The relevance of somatostatin receptors in thyroid neoplasia.
- 1997
-
In: The Yale journal of biology and medicine. - 0044-0086. ; 70:5-6, s. 523-33
-
Journal article (other academic/artistic)abstract
- 111In-octreotide scintigraphy in patients with persistent medullary thyroid carcinoma (MTC) visualized tumors in about half of the surgically explored sites. Tumor visualization correlated with rapid tumor growth and large tumor volume as judged from calcitonin levels. The 111In concentration ratio between tumor (T) and blood (B) in surgically excised lymph node metastases of MTC showed a large variation, with low values for microscopic and high values for macroscopic metastases in individual patients. Three cases of MTC, Hürthle cell adenoma and papillary thyroid cancer are reported with preoperative scintigraphy, T/B ratios and Northern analyses of the surgical biopsies. Visualization of tumors was possible in the absence of sstr2 (the high affinity receptor for octreotide) with the exception of microscopic tumor growth. T/B values in the patient with Hürthle cell adenoma were similar to those found in the contralateral thyroid lobe with goitre. The relatively high uptake of 111In in benign thyroid conditions probably limits the use of octreotide scintigraphy in the diagnosis of primary tumors. The technique has certain advantages over radioiodine scintigraphy after the surgical treatment of thyroid tumors: no need for withdrawal of thyroxin substitution; a possibility to diagnose metastases of tumors that do not concentrate radioiodine (MTC, Hürthle cell cancer); and complementary information about metastatic sites of non-medullary thyroid cancer (papillary and follicular tumors).
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| 27. |
- Ahlman, Håkan, 1947, et al.
(author)
-
Treatment of liver metastases of carcinoid tumors.
- 1996
-
In: World journal of surgery. - 0364-2313. ; 20:2, s. 196-202
-
Journal article (peer-reviewed)abstract
- Liver metastases imply a major problem in patients with carcinoid tumors. Patients with localized disease should always undergo resection for cure. Patients with distant metastatic disease can also undergo resection for potential cure or symptom palliation because of the slow growth rate of many carcinoid tumors. In patients with the midgut carcinoid syndrome and bilobar hepatic disease we have performed primary surgery to relieve such symptoms as intestinal obstruction and ischemia, followed by successive embolizations of the hepatic arteries to reduce functional tumor burden in the liver. For optimal palliation, all patients with residual tumor were treated by octreotide. In a consecutive series of 64 patients with the midgut carcinoid syndrome we thus attained a 5-year survival rate of 70%. Fourteen of the patients underwent intentionally curative surgery (e.g., primary surgery followed by liver surgery). Of these patients, none died from their tumor disease during the period of study. The value of adjunctive interferon therapy is currently under evaluation.
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| 28. |
- Amiri-Mosavi, A, et al.
(author)
-
Expression of cholecystokinin-B/gastrin receptors in medullary thyroid cancer.
- 1999
-
In: The European journal of surgery = Acta chirurgica. - : Oxford University Press (OUP). - 1102-4151. ; 165:7, s. 628-31
-
Journal article (peer-reviewed)abstract
- To characterise the cholecystokinin (CCK) receptor subtypes in medullary thyroid cancer by measuring the expression of CCK-A and CCK-B/gastrin receptor mRNA.
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| 29. |
- Andersson, Ellinor, et al.
(author)
-
High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids.
- 2009
-
In: Endocrine-related cancer. - 1479-6821. ; 16:3, s. 953-66
-
Journal article (peer-reviewed)abstract
- Ileal carcinoids are malignant neuroendocrine tumours of the small intestine. The aim of this study was to obtain a high-resolution genomic profile of ileal carcinoids in order to define genetic changes important for tumour initiation, progression and survival. Forty-three patients with ileal carcinoids were investigated by high-resolution array-based comparative genomic hybridization. The average number of copy number alterations (CNAs) per tumour was 7.1 (range 1-22), with losses being more common than gains (ratio 1.4). The most frequent CNA was loss of chromosome 18 (74%). Other frequent CNAs were gain of chromosome 4, 5, 14 and 20, and loss of 11q22.1-q22.2, 11q22.3-q23.1 and 11q23.3, and loss of 16q12.2-q22.1 and 16q23.2-qter. Two distinct patterns of CNAs were found; the majority of tumours was characterized by loss of chromosome 18 while a subgroup of tumours had intact chromosome 18, but gain of chromosome 14. Survival analysis, using a series of Poisson regressions including recurrent CNAs, demonstrated that gain of chromosome 14 was a strong predictor of poor survival. In conclusion, high-resolution profiling demonstrated two separate patterns of CNAs in ileal carcinoids. The majority of tumours showed loss of chromosome 18, which most likely represents a primary event in the development and pathogenesis of tumours. A different genetic pathway is operative in a subgroup of tumours; this is characterized by gain of chromosome 14 and is strongly associated with poor prognosis. Predictive fluorescence in situ hybridization analysis of chromosome 14 status in patients with ileal carcinoids is suggested.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Arne, Gabriella, et al.
(author)
-
Expression profiling of GIST: CD133 is associated with KIT exon 11 mutations, gastric location, and poor prognosis.
- 2011
-
In: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 129:5, s. 1149-1161
-
Journal article (peer-reviewed)abstract
- In gastrointestinal stromal tumors (GISTs), KIT exon 11 deletions are associated with poor prognosis. The aim of this study was to determine the gene expression profiles of GISTs carrying KIT exon 11 deletions and to identify genes associated with poor prognosis. Expression profiling was performed on 9 tumors with KIT exon 11 deletions and 7 without KIT exon 11 mutations using oligonucleotide microarrays. In addition, gene expression profiles for 35 GISTs were analyzed by meta-analysis. Expression of CD133 (prominin-1) protein was examined by tissue microarray (TMA) analysis of 204 GISTs from a population-based study in western Sweden. Survival analysis was performed on patients subjected to R0 resection (n=180) using the Cox proportional hazards model. Gene expression profiling, meta-analysis, and qPCR showed up regulation of CD133 in GISTs carrying KIT exon 11 deletions. Immunohistochemical analysis on TMA confirmed CD133 expression in 28% of all tumors. CD133 positivity was more frequent in gastric GISTs (48%) than in small intestinal GISTs (4%). CD133 positivity was also more frequent in GISTs with KIT exon 11 mutations (41%) than in tumors with mutations in KIT exon 9, PDGFRA, or wild-type tumors (0-17%). Univariate survival analysis showed a significant correlation between the presence of CD133 protein and shorter overall survival (hazard ratio=2.23, P=0.027). Multivariate analysis showed that CD133 provided additional information on patient survival compared to age, sex, NIH risk group and mutational status. CD133 is expressed in a subset of predominantly gastric GISTs with KIT exon 11 mutations and poor prognosis.
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| 34. |
- Arne, Gabriella, et al.
(author)
-
Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.
- 2013
-
In: Acta oncologica (Stockholm, Sweden). - 1651-226X .- 0284-186X. ; 52:4, s. 783-792
-
Journal article (peer-reviewed)abstract
- Background. Gastrointestinal stromal tumors (GISTs) can be effectively treated with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop drug resistance, and alternative treatment strategies are therefore needed. The aim of this study was to analyze the expression of somatostatin receptors (SSTR) in GIST as a target for peptide receptor-mediated radiotherapy (PRRT). Material and methods. Expression profiling of SSTR1-5 was performed on biopsies from 34 GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors). SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in tumor specimens was performed in seven patients. Uptake and internalization of (177)Lu- octreotate was studied in primary cell cultures from two patients. Results. Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the majority of tumors, while SSTR3-5 were expressed at low levels. Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in three of six GIST patients. Measurement of (111)In activity in excised tumor specimens from five patients gave tumor-to-blood (T/B) activity ratios of between eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST) specifically bound and internalized (177)Lu when incubated with the therapeutic compound (177)Lu-octreotate for 4-48 hours (p < 0.05). Conclusion. Peptide receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in carefully selected GIST patients with TKI-resistant tumors.
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| 35. |
- Arvidsson, Yvonne, 1960, et al.
(author)
-
Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract.
- 2008
-
In: Endocrine-related cancer. - 1351-0088. ; 15:2, s. 569-81
-
Journal article (peer-reviewed)abstract
- We have examined the global gene expression profile of small intestinal carcinoids by microarray analysis. High expression of a number of genes was found including amyloid precursor-like protein 1 (APLP1). Quantitative real-time PCR and western blot analysis demonstrated higher expression of APLP1 in carcinoid metastases relative to primary tumours indicating a role of APLP1 in tumour dissemination. Tissue microarray analysis of gastroentero-pancreatic tumours demonstrated a high frequency of APLP1 expression and a low frequency of APLP2 expression in neuroendocrine (NE) tumours when compared with non-NE tumours at the same sites. Meta-analysis of gene expression data from a large number of tumours outside the gastrointestinal tract confirmed a correlation between APLP1 expression and NE phenotype where high expression of APLP1 was accompanied by downregulation of APLP2 in NE tumours. Cellular localization of APLP1, APLP2 and amyloid precursor protein (APP) in carcinoid cells (GOT1) by confocal microscopy demonstrated partial co-localization with synaptophysin. This suggests that the APP family of proteins is transported to the cell membrane by synaptic microvesicles and that they may influence tumour cell adhesion and invasiveness. We conclude that APLP1 is differentially upregulated in gastrointestinal NE tumours and that APLP1 may be important for the dissemination of small intestinal carcinoids. Identification of APLP1 in NE tumours offers a novel target for treatment and may also serve as a tumour-specific marker.
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| 36. |
- Arvidsson, Yvonne, 1960, et al.
(author)
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Hypoxia stimulates CXCR4 signalling in ileal carcinoids.
- 2010
-
In: Endocrine-related cancer. - 1479-6821. ; 17:2, s. 303-316
-
Journal article (peer-reviewed)abstract
- Tumour hypoxia is associated with increased metastatic potential and resistance to radiotherapy and chemotherapy. Ileal carcinoids are usually metastatic at the time of diagnosis and respond poorly to chemotherapy. The aim of this study was to investigate the extent of hypoxia in ileal carcinoids and the response of tumour cells to induced hypoxia. VEGF, CA-IX, HIF-1alpha and HIF-2alpha were studied by immunohistochemistry in biopsies from 24 patients with ileal carcinoids. All hypoxic markers were shown to be highly expressed in localized areas of the tumours irrespective of tumour location or stage. However, HIF-2alpha expression was significantly higher in distant metastases compared to primary tumours in the same patient. Global gene expression profiling of GOT1 carcinoid cells revealed a marked response to hypoxia. Expression of genes related to epithelial-to-mesenchymal transition (EMT) and development was altered including increased expression of the chemokine receptor CXCR4, an important regulator of invasive growth and metastasis formation. High expression of CXCR4 was confirmed by immunohistochemistry in tumour biopsies. Stimulation of GOT1 cells by the CXCR4 ligand CXCL12 (SDF-1) activated the MAPK p42/44 signalling pathway and increased tumour cell migration. We conclude that ileal carcinoids contain hypoxic areas expressing HIF-1alpha, and HIF-2alpha and CXCR4. Signalling through the CXCL12-CXCR4 axis may contribute to the metastatic potential of ileal carcinoids. Targeting of HIFs and/or the CXCR4 signalling pathway may offer new therapeutic strategies for this carcinoid tumour disease.
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| 37. |
- Basson, M D, et al.
(author)
-
Biology and management of the midgut carcinoid.
- 1993
-
In: American journal of surgery. - 0002-9610. ; 165:2, s. 288-97
-
Research review (peer-reviewed)abstract
- Midgut carcinoid tumors derive from gut entoderm. These tumors may cause a complex of symptoms comprising the carcinoid syndrome by secreting a wide variety of bioactive agents in addition to serotonin. Such symptoms generally follow metastases to the liver but may also occur in primary ovarian or retroperitoneal tumors. After localization and biochemical characterization, the bioactivity of these tumors should be blocked by octreotide, sometimes in combination with other pharmacologic antagonists, so that primary resection may be performed safely. If curative resection is impossible, then a cytoreductive management scheme should be employed that includes surgical debulking and hepatic arterial embolization, followed by palliation with octreotide.
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| 38. |
- Benjegård, S A, et al.
(author)
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Evaluation of three gamma detectors for intraoperative detection of tumors using 111In-labeled radiopharmaceuticals.
- 1999
-
In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 0161-5505. ; 40:12, s. 2094-101
-
Journal article (peer-reviewed)abstract
- Attempts to detect tumors with intraoperative scintillation using tumor-binding radiopharmaceuticals have intensified recently. In some cases previously unknown lesions were found, but in most cases no additional lesions were detected. In this study the physical characteristics of three detector systems and their ability to detect tumors through accumulation of an 111In-labeled radiopharmaceutical were investigated. The first was a sodium iodide (NaI[TI]) detector; the second, a cesium iodide (CsI[TI]) detector; and the third, a cadmium telluride (CdTe) detector.
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| 39. |
- Benjegård, S A, et al.
(author)
-
Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector.
- 2001
-
In: European journal of nuclear medicine. - : Springer Science and Business Media LLC. - 0340-6997 .- 1619-7070 .- 1619-7089. ; 28:10, s. 1456-62
-
Journal article (peer-reviewed)abstract
- Intraoperative tumour detection has been used in many applications. The examined tumour forms have varied and different detector systems and radiopharmaceuticals have also been used. The aim of this study was to evaluate and compare the ability of an NaI(T1) scintillation detector to detect primary tumours and metastases in patients with different endocrine tumour types (e.g. carcinoid tumours, endocrine pancreatic tumours and thyroid tumours) and in patients with breast carcinoma or benign thyroid lesions, on the basis of their somatostatin receptor expression after i.v. injection of 111In-DTPA-D-Phe1-octreotide. Thirty patients were injected with 111In-DTPA-D-Phe1-octreotide intravenously. Scintigraphic images were taken 1 day after injection of the radiopharmaceutical, and surgery was performed 1-7 days post injection. An NaI(T1) scintillation detector was used for intraoperative tumour detection. Tissue samples were collected during surgery for determination of 111In activity concentration and histopathological examination. The scintigraphic images were positive in 29 out of 30 patients. Intraoperative tumour detection was successful in 43 of 66 collected biopsies: 10 out of 11 for carcinoid tumours, 7 out of 10 for medullary thyroid carcinoma (MTC) and 14 out of 22 for breast cancer. On the basis of our findings we conclude that intraoperative tumour detection with 111In-DTPA-D-Phe1-octreotide using this NaI(T1) detector can be successful especially for carcinoid tumours and endocrine pancreatic tumours, due to the relatively high activity concentrations in these tumour types, but is less successful in other forms of thyroid cancer, including MTC, and breast cancer. For successful intraoperative detection, the detector characteristics are also very important, and further improvement of the detector systems is required to increase the sensitivity and specificity.
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| 40. |
- Bernhardt, Peter, 1966, et al.
(author)
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Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice.
- 2007
-
In: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:5, s. 644-53
-
Journal article (peer-reviewed)abstract
- PURPOSE: The aim of this study was to analyze the effect therapeutic injections of (177)Lu-DOTA(0)-Tyr(3)]-octreotate (DOTATATE) had on the tumor uptake of a subsequent injection with (111)In-DOTATATE in GOT1-bearing nude mice. METHODS AND MATERIALS: Nude mice, xenografted with the human midgut carcinoid, GOT1, were first intravenously injected with a curative (30 MBq) or a suboptimal (7.5 MBq) amount of (177)Lu-DOTATATE. At various intervals thereafter (4-13 days), a second injection with (111)In-DOTATATE (0.5 MBq) was given. One (1) day after the second injection, the animals were sacrificed, tumor tissues collected, the tumor (111)In and (177)Lu activity concentration determined, and tumor regression/cell density was recorded. RESULTS: In animals given curative amounts, the uptake of (111)In was lower than in untreated animals. On the other hand, a second late injection (3-13 days) after suboptimal amounts resulted in a twofold higher tumor activity concentration versus untreated animals. When the uptake of the curative injection was corrected for tumor cell density, which decreased from 66% to 4% over 2 weeks, an enhanced uptake per tumor cell was observed. The curative and suboptimal amounts resulted in a different uptake and retention of (177)Lu in tumors. The suboptimal amount resulted in a constant activity concentration, while the curative amount resulted in an increased activity concentration over time. CONCLUSIONS: Our results, as presented in this paper, describe how the second injection in a fractionation protocol will be affected by the first therapeutic amount. This new information might be useful in the optimization of radionuclide therapy.
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| 41. |
- Bernhardt, Peter, 1966, et al.
(author)
-
Model of metastatic growth valuable for radionuclide therapy
- 2003
-
In: Medical physics. - 0094-2405. ; 30:12, s. 3227-32
-
Journal article (peer-reviewed)abstract
- The aim was to make a Monte Carlo simulation approach to estimate the distribution of tumor sizes and to study the curative potential of three candidate radionuclides for radionuclide therapy: the high-energy electron emitter 90Y, the medium-energy electron emitter 177Lu and the low-energy electron emitter 103mRh. A patient with hepatocellular carcinoma with recently published serial CT data on tumor growth in the liver was used. From these data the growth of the primary tumor, and the metastatis formation rate, were estimated. Assuming the same tumor growth of the primary and all metastases and the same metastatis formation rate from both primary and metastases the metastatic size distribution was simulated for various time points. Tumor cure of the metastatic size distribution was simulated for uniform activity distribution of three radionuclides; the high-energy electron emitter 90Y, the mean-energy electron emitter 177Lu and the low-energy electron emitter 103mRh. The simulation of a tumor cure was performed for various time points and tumor-to-normal tissue activity concentrations, TNC. It was demonstrated that it is important to start therapy as early as possible after diagnosis. It was of crucial importance to use an optimal radionuclide for therapy. These simulations demonstrated that 90Y was not suitable for systemic radionuclide therapy, due to the low absorbed fraction of the emitted electrons in small tumors (< 1 mg). If TNC was low 103mRh was slightly better than 177Lu. For high TNC values low-energy electron emitters, e.g., 103mRh was the best choice for tumor cure. However, the short half-life of 103mRh (56 min) might not be optimal for therapy. Therefore, other low-energy electron emitters, or alpha emitters, should be considered for systemic targeted therapy.
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| 42. |
- Bernhardt, Peter, 1966, et al.
(author)
-
Modelling of metastatic cure after radionuclide therapy: influence of tumor distribution, cross-irradiation, and variable activity concentration
- 2004
-
In: Medical physics. - : Wiley. - 0094-2405. ; 31:9, s. 2628-35
-
Journal article (peer-reviewed)abstract
- The objective was to study the influence of tumor number and size, cross-irradiation from normal tissue, and of variable activity concentration on metastatic cure after radionuclide therapy. A model to calculate the metastatic cure probability (MCP) was developed, in which it was assumed that the tumor response was an exponential function of the absorbed dose. All calculations were performed for monoenergetic electron emitters with different energies (10-1000 keV). The influence of tumor size and number of tumors were investigated with different log uniform distributions; the basic tumor distribution consisted of tumors with 1, 10, ..., 10(11) cells. The influence of cross-irradiation was assessed by calculating MCP for various tumor-to-normal tissue activity concentration ratios (TNC). The influence of variable activity concentration between tumors was calculated by assuming that the activity concentration in tumors was an inverse power law function of tumor mass. The required activity concentration (C0.9) and absorbed dose (D0.9) to obtain MCP=0.9 was calculated in the different models. The C0.9 and D0.9 needed to obtain MCP were very high; more than 25 MBq/g and 80 Gy, respectively. The lowest C0.9 and D0.9 for equal activity concentration in the different tumor sizes were obtained for electron energies less than 80 keV. For higher energies the low absorbed energy fraction in small tumors will increase the required C0.9 and D0.9 markedly. Cross-irradiation from normal cells surrounding the tumor will cause sterilization of the smallest tumors and decrease the required C0.9 and D0.9 for higher electron energies. Assuming that the activity concentration decreased with increased tumor mass caused a marked increase in C0.9 and D0.9 in favor of higher electron energies. With the MCP model we demonstrated significant influence of the number of tumors, their size, TNC and variable activity concentration on MCP. The results are valuable when evaluating optimal choices for radionuclides for internal-emitter therapy.
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| 43. |
- Borch, Kurt, 1944-, et al.
(author)
-
Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type
- 2005
-
In: Annals of surgery. - : Ovid Technologies (Wolters Kluwer Health). - 0003-4932 .- 1528-1140. ; 242:1, s. 64-73
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To analyze tumor biology and the outcome of differentiated treatment in relation to tumor subtype in patients with gastric carcinoid. BACKGROUND: Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated with atrophic gastritis, type 2 associated with gastrinoma, type 3 without predisposing conditions) and miscellaneous types (type 4). The biologic behavior and prognosis vary considerably in relation to type. METHODS: A total of 65 patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were included. Management recommendations were issued for newly diagnosed cases, that is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4 carcinoids. RESULTS: Infiltration beyond the submucosa occurred in 9 of 51 type 1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51 type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and 73.9% for type 1 (not different from the general population), but only 33.3% and 22.2% for type 4 carcinoids. CONCLUSION: Subtyping of gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management. Long-term survival did not differ from that of the general population regarding type 1 carcinoids but was poor regarding type 4 carcinoids.
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| 44. |
- Bümming, Per, 1965, et al.
(author)
-
Can the early reduction of tumour markers predict outcome in surgically treated sporadic medullary thyroid carcinoma?
- 2008
-
In: Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie. - : Springer Science and Business Media LLC. - 1435-2443. ; 393:5, s. 699-703
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Patients with sporadic medullary thyroid carcinoma (MTC) have a variable clinical course. Our aim was to analyse the reduction of tumour markers after thyroidectomy with meticulous dissection and relate it to clinical outcome. MATERIALS AND METHODS: Twenty consecutive patients with palpable sporadic MTC underwent thyroidectomy with central and uni- or bilateral modified radical neck dissection; three were subjected to mediastinal dissection. Basal (b-) and stimulated (s-) calcitonin (CT) and carcinoembryonic antigen (CEA)-levels were measured before and 6-8 weeks after primary surgery, and the reduction of these tumour markers was determined. RESULTS: Median CT (b- and s-) were markedly reduced after surgery (98.5% and 99.1%, respectively), and CEA decreased 11 times. CT (b-) fell >99% in seven patients after surgery; in these and four additional patients, CT (s-) showed a similar reduction. During follow-up (median 52.5 months), two patients (stages IV B and C) died of MTC; they had <95% reduction of CT. Four patients (stage IV A) are alive with verified metastases. Eight patients (one stage III, seven stage IV A) are alive with hypercalcitoninemia. Five stages I-III patients and one stage IV A patient are disease-free. CONCLUSIONS: Thyroidectomy and meticulous dissection caused a pronounced reduction of tumour markers. A postoperative reduction of CT (s-) >/=97% seems to be associated with less aggressive clinical course, while CEA had lower predictive value.
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| 45. |
- Bümming, Per, 1965, et al.
(author)
-
Gastrointestinal stromal tumors regularly express synaptic vesicle proteins: evidence of a neuroendocrine phenotype.
- 2007
-
In: Endocrine-related cancer. - 1351-0088. ; 14:3, s. 853-63
-
Journal article (peer-reviewed)abstract
- Gastrointestinal stromal tumors (GISTs) are thought to originate from the interstitial cells of Cajal, which share many properties with neurons of the gastrointestinal tract. Recently, we demonstrated expression of the hormone ghrelin in GIST. The aim of the present study was therefore to evaluate a possible neuroendocrine phenotype of GIST. Specimens from 41 GISTs were examined for the expression of 12 different synaptic vesicle proteins. Expression of synaptic-like microvesicle proteins, e.g., Synaptic vesicle protein 2 (SV2), synaptobrevin, synapsin 1, and amphiphysin was demonstrated in a majority of GISTs by immunohistochemistry, western blotting, and quantitative reversetranscriptase PCR. One-third of the tumors also expressed the large dense core vesicle protein vesicular monoamine transporter 1. Presence of microvesicles and dense core vesicles in GIST was confirmed by electron microscopy. The expression of synaptic-like microvesicle proteins in GIST was not related to risk profile or to KIT/platelet derived growth factor alpha (PDGFRA) mutational status. Thus, GISTs regularly express a subset of synaptic-like microvesicle proteins necessary for the regulated secretion of neurotransmitters and hormones. Expression of synaptic-like micro-vesicle proteins, ghrelin and peptide hormone receptors in GIST indicate a neuroendocrine phenotype and suggest novel possibilities to treat therapy-resistant GIST.
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| 46. |
- Bümming, Per, 1965, et al.
(author)
-
Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients.
- 2003
-
In: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:3, s. 460-4
-
Journal article (peer-reviewed)abstract
- Malignant gastrointestinal stromal tumours (GIST) have a poor prognosis. Since these tumours are resistant to conventional radiation and chemotherapy, surgery has been the mainstay of treatment. However, surgery is usually inadequate for the treatment of malignant GIST. Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST. In this centre-based study of 17 consecutive patients with high-risk or overtly malignant GIST, imatinib was used in three different settings - palliatively, adjuvantly, and neoadjuvantly. The treatment was found to be safe and particularly effective in tumours with activating mutations of exon 11 of the KIT gene. Clinical response to imatinib treatment correlated morphologically to tumour necrosis, hyalinisation, and reduced proliferative activity. The value of neoadjuvant imatinib treatment was illustrated in one case.
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| 47. |
- Bümming, Per, 1965, et al.
(author)
-
Population-based study of the diagnosis and treatment of gastrointestinal stromal tumours
- 2006
-
In: The British journal of surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 93:7, s. 836-43
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this retrospective population-based study, which was conducted before the introduction of imatinib, was to evaluate the role of surgery in patients with gastrointestinal stromal tumours (GISTs) and clarify which subgroups might benefit from adjuvant treatment. METHODS: Two hundred and fifty-nine patients with clinically detected GISTs were studied. Univariate and multivariate analyses were performed to identify predictors for recurrent disease and survival. RESULTS: Thirty of 48 patients with high-risk GISTs and all of those with overtly malignant tumours developed recurrent tumour after complete (R0) resection. Thirty-four of 38 first recurrences occurred within 36 months of surgery. No recurrence was observed after 72 months. R0 resection, achieved in 48 (80 per cent) of 60 patients with high-risk tumours, was significantly associated with a decreased risk of death from tumour recurrence (P = 0.008). CONCLUSION: Completeness of surgical resection is an independent prognostic factor in patients with high-risk GISTs. A period of adjuvant treatment with imatinib is recommended in patients with high-risk or overtly malignant GISTs who have undergone R0 resection and have a tumour-free interval of less than 6 years.
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| 48. |
- Bümming, Per, 1965, et al.
(author)
-
Use of 2-tracer PET to diagnose gastrointestinal stromal tumour and pheochromocytoma in patients with Carney triad and neurofibromatosis type 1
- 2006
-
In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:5, s. 626-30
-
Journal article (peer-reviewed)abstract
- There is rapid evolution in the functional imaging of tumours. In two patients with concomitant pheochromocytoma and gastrointestinal stromal tumour (GIST), previously unrecognized tumours were visualized by combined 2-tracer positron emission tomography (PET), which also provided precise information about tumour type. PET imaging led to radical resection and the diagnoses were histopathologically confirmed. GISTs from the Carney patient and the patient with neurofibromatosis type 1 (NF1) both lacked KIT mutations.
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| 49. |
- Dalmo, Johanna, et al.
(author)
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Biodistribution of 177Lu-octreotate and 111In-minigastrin in female nude mice transplanted with human medullary thyroid carcinoma GOT2.
- 2012
-
In: Oncology reports. - : Spandidos Publications. - 1791-2431 .- 1021-335X. ; 27:1, s. 174-181
-
Journal article (peer-reviewed)abstract
- To be able to evaluate new radiopharmaceuticals and optimize diagnostic and therapeutic procedures, relevant animal models are required. The aim of this study was to evaluate the medullary thyroid carcinoma GOT2 animal model by analyzing the biodistribution of 177Lu-octreotate and 111In-minigastrin (MG0). BALB/c nude mice, subcutaneously transplanted with GOT2, were intravenously injected with either 177Lu-octreotate or 111In-MG0, with or without excess of unlabeled human minigastrin simultaneously with 111In-MG0. Animals were sacrificed 1-7 days after injection in the 177Lu-octreotate study and 1h after injection of 111In-MG0. The activity concentrations in organs and tissues were determined and mean absorbed doses from 177Lu were calculated. There was a specific tumor uptake of either 177Lu-octreotate or 111In-MG0. 177Lu-octreotate samples showed high activity concentrations in tissues expressing somatostatin receptors (SSTR). For both radiopharmaceuticals the highest activity concentrations were found in the kidneys. Compared to results from similar studies in mice with another MTC cell line (TT) the biodistribution was favorable (higher tumor uptake) for the GOT2 model, while compared to other animal models expressing SSTR, the tumor uptake of 177Lu-octreotate was modest. In conclusion, the GOT2 animal model is a valuable model for evaluation and optimization of diagnostic and therapeutic procedures using radiolabeled somatostatin, CCK2 and gastrin analogues prior to clinical studies.
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| 50. |
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