Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The medullary thyroid carcinoma was characterized as clinicopathological entity by Hazard, Hawk and Crile as early as 1959. As reported in literature the incidence of these tumors ranges from 3.5 to 11.9% of the thyroid carcinomas. In the study presented the morphological, histochemical and electron microscopical investigations in 8 cases of medullary thyroid carcinoma are reported. Different methods are used to demonstrate polysaccharides, proteins, especially polypeptide hormones, and amyloid. Furthermore several silver impregnation techniques for differentiation of argentaffin and argyrophilic cells were performed. The age of the 8 patients ranged from 30 to 65 years, 5 patients were females, the sex ratio of females to males runs to 1.7:1. In 4 cases metastases in regional lymph nodes were found. The tumor tissue preponderately showed a solid-travecular pattern. The tumor cells were seen in cord-like and nest-like arrangement. In places also a typical endocrine structure was present revealing an orientation of cells around capillaries here and there. A differentiation of light and dark cells was possible. Electron microscopically these light microscopical observations could be confirmed: dark cells possessed more organeles than light cells. Infiltrations of blood vessels did not occur, but infiltrations of lymph vessels were the rule. The tumors contained variable amounts of amyloid which could be seen by fluorescence and polarization microscopical methods in fine fiber-like structures or in coarse deposits. At the ultrastructural level typical secretory granules varying in electron density and having a diameter of 220-560 nm were visible. Some light tumor cells exhibited 50-120 A thick fibrils which could not be distinguished from extracellular amyloid fibrils. The histochemical findings evidenced moderately abundant proteins in the cytoplasm of tumor cells. Histochemically the amyloid corresponds to the so-called apudamyloid. A great deal of the proteins is orderly arranged in amyloid whereas this is not the case in the tumor cell cytoplasm as proved by the coupled tetrazonium reaction which was evaluated polarization microscopically. In amyloid tryptophan was absent. The medullary thyroid carcinoma has a low-grade malignancy and, in accordance to other authors, it is to be stated that this tumor is histogenetically related to the parafollicular cells (C-cells). Its distinction from other thyroid tumors is warranted basing on morphological and pathophysiological features. Structural patterns common with those of other endocrine tumors are demonstrable. The findings point to a relationship of medullary thyroid carcinoma with the APUD series or Feyrter's Helle-Zellen-System. Considering the possible simultaneous occurrence of pheochromocytomas and adenomas of the parathyroid gland it must be assumed that the medullary thyroid carcinoma is one of the dysplasias of the neural ectoderm.
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PMID:[Morphology and histochemistry of medullary thyroid carcinomas (author's transl)]. 446 14

The concentration of adenosine 3':5'-cyclic monophosphate in the spinal fluid of ten patients with liver dysfunction was analyzed. Ages of the patients ranged from 31 to 75 years. The state of consciousness varied between normality and stupor. After a liver biopsy the diagnoses were as follows: cirrhosis in six cases, porphyria cutanea tarda in one case, hepatic metastases in two cases and Wilson's disease in one case. Mean values in these patients (22.91 +/- 4.18 pM/ml) have been significantly greater (p less than 0.0005) than those in ten control individuals (15.55n control individuals (15.44 +/- 3.66 pM/ml). Values corresponding to two patients in coma were still higher (52.62 and 36.50 pM/ml respectively). A previous lumbar puncture carried out in one of these patients when he was conscious showed a figure of 23 pM/ml. These results suggest a progressive rise of cyclic adenosine monophosphate in the spinal fluid in relation to clinical impairment, and may indicate a similar behaviour for this nucleotide to that of tryptophan, as reported by other authors. These findings point toward the role of the alteration of neurotransmitters in the pathogenesis of hepatic coma.
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PMID:[Cyclic adenosine monophosphate in the cerebrospinal fluid of patients with liver disease (author's transl)]. 737 36

Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who received the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.
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PMID:Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors. 768 63

Steady state and time-resolved fluorescence spectroscopy were employed to study the fluorescence from non-metastatic, metastatic and non-tumorigenic cell lines from different species. Excitations at 310 nm and 350 nm were used to monitor tryptophan and reduced nicotinamide adenine dinucleotide (NADH) fluorescence respectively. Subtle and consistent differences were observed between different categories of cell lines. It was found that the tryptophan to NADH fluorescence intensity ratio is higher in metastatic cell lines than in non-metastatic and normal cell lines. The fluorescence decay of the tryptophan residue in different cell lines was best described by triple exponential kinetics, whereas the NADH fluorescence decay was best described by mainly double and, in some cases, triple exponential kinetics. The average fluorescence lifetimes for tryptophan were in the range 2.5-3.7 ns. The average lifetime of NADH was lower (by a factor of approximately three) in metastatic cells than in non-metastatic cells and this finding is consistent for cell lines from different origins (rat or human). Correcting the fluorescence intensity for the average fluorescence lifetime of each species and for the volume of each cell line, it was shown that the concentrations of tryptophan and NADH are consistently higher in malignant metastatic cancer cells than in non-metastatic cells.
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PMID:Steady state and time-resolved fluorescence properties of metastatic and non-metastatic malignant cells from different species. 858 78

With metastatic disease at diagnosis for 70% of patients, ovarian cancer represents the most lethal gynecological malignancy. Ovarian carcinomas are aggressive malignancies that can evade immune surveillance and frequently develop into metastases. The tumor microenvironment is decisive for preventing immune attack but, in the case of ovarian carcinoma, the mechanisms are unclear. We recently isolated a novel type of stromal cell from the ascitis of patients with ovarian carcinoma that interacts with epithelial ovarian cancers conferring them chemoresistance. These cells, called Hospicells, have the cell surface markers CD9, CD10, CD29, CD146 and CD166. Here, we investigated whether Hospicells also have immunomodulatory functions that might interfere with immunity to cancer. We report that Hospicells inhibit the proliferation of human CD4(+), CD8(+) and Vgamma9Vdelta2 T cells in vitro and the production of cytokines by these immune cells. The immunosuppression of CD4(+) T cells is independent of direct contact with the Hospicells and is mainly due to nitric oxide produced by the inducible nitric oxide synthase and to products of the tryptophan degradation by indoleamine 2,3-dioxygenase. We proposed that Hospicells in the microenvironment of the tumor mediate immunosuppression of T cells and thus allow ovarian cancers to evade immune surveillance. Targeting of Hospicells could be an alternative to strong chemotherapy through the recovery of immune responses against tumor cells.
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PMID:Hospicells derived from ovarian cancer stroma inhibit T-cell immune responses. 1973 80

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. Some reports have noted a clinical correlation between IDO expression and outcome in some malignant tumors. This study aimed to investigate IDO expression as related to prognosis in osteosarcoma. IDO expression was immunohistochemically scored as five grades. IDO was expressed in most of the cases. Univariate analysis revealed no significant correlation between IDO staining intensity and various variables including sex, age, anatomical site, chemotherapy regimen, necrosis after chemotherapy, and surgical stage. Patients with high IDO expression had significantly lower metastasis-free survival (P = 0.016) and overall survival (P = 0.005). On univariate analysis, age over 20 years and high IDO expression were found to be independent risk factors of lower overall survival and metastasis-free survival. On multivariate analysis, there was no significant correlation between high IDO expression and metastasis-free survival (P = 0.070) and overall survival (P = 0.066). The immune tolerance mediated through IDO may have an important role in the tumorigenesis of osteosarcoma and may exert an impact on the clinical outcome, and thus may lend itself as a therapeutic target of immunotherapy for osteosarcoma.
Clin Exp Metastasis 2009
PMID:Prognostic value of indoleamine 2,3-dioxygenase expression in high grade osteosarcoma. 1980 33

Many neuroendocrine tumors (NET) are small and may escape localization by conventional imaging techniques. In such cases, 11C-5-hydroxy-tryptophan (11C-5-HTP) positron emission tomography (PET) has been tested as an additional diagnostic tool. Nine patients with clinically, biochemically and/or histologically confirmed NET and negative computerized tomography (CT) or magnetic resonance imaging (MRI), and 111In-pentetreotide (Octreoscan) scintigraphy underwent imaging with 11C-5-HTP-PET/CT in order to: 1) detect the primary tumor lesion in three patients; 2) detect residual disease in two patients with appendiceal carcinoid, one with rectal carcinoid, one with midgut carcinoid, and one with ectopic ACTH secretion (EAS) due to residual pulmonary carcinoid; and 3) restage a patient with medullary thyroid carcinoma (MTC) and hepatic metastases. 11C-5-HTP-PET/CT detected lesions in the mediastinum in a patient with EAS due to a pulmonary carcinoid, further hepatic metastases in a patient with carcinoid syndrome (CS) from a NET of unknown primary, further hepatic metastases in the patient with MTC, and hepatic metastases in the patient with midgut carcinoid. The 11C-5-HTP-PET/CT findings contributed to radical cure of the patient with recurrent EAS, and pointed towards bilateral adrenalectomy in the patient with EAS without evident primary tumor. In addition, 11C-5- HTP-PET/CT directed towards combined surgical and medical treatment in the patient with CS and multiple rather than single hepatic metastases and in the patient with midgut carcinoid, and towards continuation of medical treatment in the patient with MTC. 11C-5-HTP-PET/CT is a useful imaging technique, providing additional information for the diagnosis, staging and decision-making regarding management of patients with NET.
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PMID:The value of 11C-5-hydroxy-tryptophan positron emission tomography in neuroendocrine tumor diagnosis and management: experience from one center. 2033 8

The spectral changes of native fluorophores among normal fibroblasts and cancer cell lines of different metastatic ability are investigated by fluorescence spectroscopy. The normal (fibroblast), moderately metastatic (DU-145), and advanced metastatic (PC-3) cell lines were each selectively excited at 300 nm, and their fluorescence emission spectra are analyzed using principal component analysis to explore the differences of the relative contents of tryptophan and reduced nicotinamide adenine dinucleotide in these cell lines. The results show that the tryptophan emission featured predominantly in the fluorescence spectra of the advanced metastatic cancer cells in comparison with the moderately metastatic cancer and normal cells.
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PMID:Native fluorescence spectroscopy reveals spectral differences among prostate cancer cell lines with different risk levels. 2391 61

We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)activity during toremifene(TOR)therapy for aromatase inhibitor(AI) / -resistant metastatic breast cancer. IDO activity can be measured using the tryptophan/kynurenine (Trp/Kyn)ratio. Trp and Kyn were measured using high performance liquid chromatography(HPLC). The response rate of TOR therapy for AI-resistant metastatic breast cancer patients was 21.9%, and the clinical benefit rate was 62.5%. The serum Trp/Kyn ratio was significantly lower in AI-resistant metastatic breast cancer patients with distant metastases than in patients who had local recurrence. During TOR therapy, IDO activity was significantly decreased in the TOR responder group compared to the TOR non-responder group. IDO activity correlated with the number of metastatic lesions treated during TOR therapy. These results suggest that the Trp/Kyn ratio is a useful measurement in evaluating the immunological metastatic status during endocrine therapy.
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PMID:[Indoleamine 2,3-dioxygenase activity during toremifene therapy for aromatase inhibitor-resistant metastatic breast cancer]. 2533 19

We evaluated the significance of indoleamine 2,3-dioxygenase(IDO)activity in breast cancer patients with local recurrence or distant metastases. IDO activity can be determined using the tryptophan/kynurenine(Trp/Kyn)ratio. Trp and Kyn were measured by high-performance liquid chromatography(HPLC). The survival rate after recurrence was higher in the local recurrence group(n=11)than in the distant metastases group(n=26). The mean Trp/Kyn ratio was lower in the distant metastases group than in the local recurrence group. The mean Trp/Kyn ratio was also lower in patients who had multiple metastases than in patients who had a single metastatic lesion. The Trp/Kyn ratio decreased during chemotherapy in all patients who received chemotherapy.
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PMID:[Indoleamine 2,3-dioxygenase activity in breast cancer patients with local recurrence or distant metastases]. 2533 25


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