32 research outputs found

    1-Methyl tryptophan, an indoleamine 2,3-dioxygenase inhibitor, attenuates cardiac and hepatic dysfunction in rats with biliary cirrhosis

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    Kynurenine Pathway (KP) is the dominant metabolic route of tryptophan which is catalyzed by indoleamine-2,3-dioxygenase (IDO). This pathway is upregulated in liver disease where the level of KP metabolites correlates with the severity of disease. Cirrhosis is associated with cardiac dysfunction, which manifests itself during severe physiological challenges such as liver transplantation. Cardiac dysfunction in cirrhosis is linked to systemic inflammation and impaired cardiac beta-adrenergic signaling pathways. The KP pathway is involved in modulation of cardiac signaling and is upregulated by systemic inflammation. Therefore, this study aimed to evaluate the effect of IDO inhibition on development of cardiac dysfunction in an experimental model of cirrhosis. Cirrhosis was induced by bile duct ligation (BDL). Experimental groups were given either 1-methyl tryptophan (1-MT, 1, 3, 9 mg/kg), or saline. 28 days after BDL, cardiac chronotropic response to epinephrine was assessed ex vivo. HPLC was employed to measure hepatic and cardiac levels of tryptophan, kynurenine and kynurenic acid. Cirrhosis in rats was associated with impaired cardiac chronotropic responsiveness to adrenergic stimulation. 1-MT dose-dependently improved cirrhosis-induced chronotropic dysfunction as well as elevated serum levels of CRP and IL-6 in BDL rats. Hepatic and cardiac kynurenine/tryptophan ratio were elevated in cirrhotic rats and were reduced following 1-MT administration. Chronic administration of 1-MT could also reduce hepatic inflammation, fibrosis and ductular proliferation. 1-MT attenuates cardiac dysfunction in rats with biliary cirrhosis. This protective effect is not limited to the cardiac function as liver histopathologic changes were also improved following chronic 1-MT administration

    Endocrine cancer in Iran: Based on cancer registry system

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    BACKGROUND: A population-based registry of endocrine cancer cases in four Iranian provinces, was performed for the years 1996-2000. MATERIALS AND METHODS: Patients in each province were grouped according to age, gender and tumor specifics (site, morphology, behavior) and the data was coded according to the international classification of diseases for oncology. STATISTICAL ANALYSIS USED: Person-years of population at risk were calculated and the results were presented as incidence rates by sex, age, age specific rates and age standard rate (ASR) per 100,000 person-years, using direct method of standardization to the world population. RESULTS: A total of 319 cases of primary endocrine cancer were found and registered, including 313 cases of thyroid carcinoma and 6 cases of adrenal cancer. The thyroid carcinoma group cases consisted of papillary (82.7%), follicular (8.6%), medullary (7.0%) and anaplastic (1.6%) carcinomas. The ASR for thyroid carcinoma was 1.289 (0.627 for men, 1.59 for women), with the highest incidence rate in Kerman (ASR 1.643) and the lowest incidence rate in Golestan (ASR 0.735). For the 6 cases of adrenal cancer, 4 were neuroblastoma and 2 were pheochromocytoma. CONCLUSIONS: Iran was considered as an endemic, iodine-deficient area, until fairly recently. Iodinization of salt has been started about 12 years ago, in the nation. Considering the effect of improvement in the iodine intake in previously deficient communities, which is associated with an increase in the incidence of papillary carcinoma compared to other histologic types, the frequency and distribution of histologic types of thyroid carcinoma was closer to what can be seen in iodine-rich areas

    Composite pheochromocytoma of the adrenal gland: a case series

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    Background: Composite pheochromocytoma is a rare pathological condition characterized by elements of both pheochromocytoma and neurogenic tumors. However, detailed clinical outcomes of this tumor have not been fully shown. From 2007 to 2013, we experienced three cases of adrenal composite pheochromocytoma. In this report, we investigate the clinicopathological features of these three cases of composite pheochromocytoma and compare them with previously reported cases. Case presentations: Cases 1 and 2 were a 29-year-old Japanese woman and a 59-year-old Japanese man, respectively. They underwent laparoscopic left adrenalectomy, and pathological examination revealed composite pheochromocytoma-ganglioneuroma. Case 3 was a 53-year-old Japanese man who had been receiving hemodialysis for 17 years. He underwent laparoscopic right adrenalectomy, and pathological examination revealed composite pheochromocytoma-ganglioneuroblastoma. Although the Ki67-positive rates varied from 1.0 to 6.2% among the three cases, no clinical recurrences occurred. Despite the relatively high rate of Ki67 positivity, complete tumor resection resulted in favorable clinical outcomes. Conclusion: We experienced three cases of adrenal composite pheochromocytoma. Although the clinical findings and treatment outcomes of composite pheochromocytoma were similar to those of ordinary pheochromocytoma, further studies of the biological behavior and genetic profiles of composite pheochromocytoma are necessary to achieve a better understanding of this tumor

    Pheochromocytoma multisystem crisis treated with emergency surgery: a case report and literature review

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    Background: Pheochromocytoma is a neuroendocrine tumor that predominantly presents with hypertension, palpitations, and tachycardia due to excessive catecholamine excretion. Although pheochromocytoma multisystem crisis (PMC) is relatively rare, urologists and clinicians should focus on early diagnosis as delay in initiating the appropriate treatment can lead to mortality Case presentation: A 70-year-old man developed ileus after a few days of medication for hypertension. Computed tomography incidentally revealed a left adrenal mass. This finding together with his clinical course was compatible with pheochromocytoma. An α-blocker was administered immediately, and his blood pressure was well controlled. However, his general condition and laboratory data deteriorated rapidly, and the patient was diagnosed with PMC with lethal status. Thus, emergency adrenalectomy was performed without confirmation of catecholamine levels. From the resected specimen, his tumor was judged as pheochromocytoma. On immunohistochemical analysis, the proliferation index evaluated by Ki-67 staining was 9.7 %. This case report was approved by the Human Ethics Review Committee of the Nagasaki University Hospital. Conclusion: The present case of PMC was successfully treated with emergency surgery. The benign pheochromocytoma also presented with high cell proliferation potential, which may be a cause of the extreme aggressiveness of PMC

    Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

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    Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available

    Oncometabolites as biomarkers in thyroid cancer: a systematic review

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    Fatemeh Khatami,1 Moloud Payab,2 Masoumeh Sarvari,3 Kambiz Gilany,3&ndash;5 Bagher Larijani,6 Babak Arjmand,7 Seyed Mohammad Tavangar1,8 1Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 2Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 3Metabolomics and Genomics Research Center, Endocrinology and Metabolomics Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 4Reproductive Biotechnology Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; 5Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, Acercr, Tehran, Iran; 6Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 7Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; 8Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Introduction: Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools are fine-needle aspiration (FNA) and histological examination following thyroidectomy. The metabolite profile alterations of thyroid cells (oncometabolites) can be considered for current TC diagnosis and management protocols.Methods: This systematic review focuses on metabolite alterations within the plasma, FNA specimens, and tissue of malignant TC contrary to benign, goiter, or healthy TC samples. A systematic search of MEDLINE (PubMed), Scopus, Embase, and Web of Science databases was conducted, and the final 31 studies investigating metabolite biomarkers of TC were included.Results: A total of 15 targeted studies and 16 untargeted studies revealed several potential metabolite signatures of TC such as glucose, fructose, galactose, mannose, 2-keto-d-gluconic acid and rhamnose, malonic acid and inosine, cholesterol and arachidonic acid, glycosylation (immunoglobulin G [IgG] Fc-glycosylation), outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 4 (MCT4), choline, choline derivatives, myo-/scyllo-inositol, lactate, fatty acids, several amino acids, cell membrane phospholipids, estrogen metabolites such as 16 alpha-OH E1/2-OH E1 and catechol estrogens (2-OH E1), and purine and pyrimidine metabolites, which were suggested as the TC oncometabolite.Conclusion: Citrate was suggested as the first most significant biomarker and lactate as the second one. Further research is needed to confirm these biomarkers as the TC diagnostic oncometabolite. Keywords: biomarkers, oncometabolites, thyroid cancer, TC, systematic revie

    Relationship between genetic polymorphism of <i>glutathione S-transferase-p1</i> and p53 protein accumulation in Iranian esophageal squamous cell carcinoma patients

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    Background: It has been reported that the activity of glutathione S-transferase (GST) is over-expressed in plasma and esophagus biopsies in Iranian patients suffering from esophageal squamous cell carcinoma (SCC). The aim of this study was to find out the frequency of GST-P genotypes in these patients. Moreover, the association of GST-P genotypes with p53 protein accumulation in esophageal epithelium was investigated. Materials and Methods: DNA isolated from paraffin-embedded tissue biopsies from patients suffering from esophageal SCC (n = 56) were collected. polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using Alw261 enzyme was applied to determine GST-P genotypes (Ile 105 Val). All the samples were also subjected to immunohistochemistry (IHC) for p53. Results: The frequency of GST-P genotypes in Iranian esophagus SCC patients for Ile/Ile, Ile/Val and Val/Val was 73.2, 21.5 and 5.3%. There was no association between GST-P polymorphism and p53 accumulation in esophageal epithelial cells. Conclusions: The frequency of GST-P polymorphism was not associated with p53 protein accumulation in esophagus epithelium. The frequency of polymorphic variants of GST-P, Ile/Ile, Ile/Val and Val/Val in SCC patients may suggest that Ile to Val substitution in GST-P gene dose not represent susceptibility to SCC in high-risk Iranian population
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