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Primary fibroblast co-culture stimulates growth and metabolism in Sdhb-impaired mouse pheochromocytoma MTT cells.

Wed, 01/16/2019 - 11:16
Related Articles

Primary fibroblast co-culture stimulates growth and metabolism in Sdhb-impaired mouse pheochromocytoma MTT cells.

Cell Tissue Res. 2018 Dec;374(3):473-485

Authors: Richter S, D'Antongiovanni V, Martinelli S, Bechmann N, Riverso M, Poitz DM, Pacak K, Eisenhofer G, Mannelli M, Rapizzi E

Abstract
Pheochromocytomas and paragangliomas (PGLs) due to mutations of succinate dehydrogenase (SDH) B, a subunit of the SDH complex with a role in the Krebs cycle and the respiratory chain, tend to be larger at diagnosis and more prone to metastatic disease than other tumors. This presentation contrasts with the behavior of some cell line models of SDHB impairment, which show reduced growth compared to wild type. We hypothesize that reduced growth of SDHB-impaired monolayer culture models might reflect lack of support from sources within the tumor microenvironment. The present study therefore investigates how the microenvironment, modeled here by fibroblast co-culture, modulates cell metabolism, growth and invasion in an Sdhb-impaired mouse pheochromocytoma cell line. We employed two different constructs of short hairpin RNA to knockdown Sdhb and compared growth in a monolayer with and without fibroblast co-culture. Sdhb-silenced cells showed functional impairment of SDH with elevated succinate to fumarate ratio and decreased oxidative capacity. Cell growth was delayed with an increase in doubling time of 2 h or 20 h. Clonogenic cell survival and viability, on the other hand, were either unchanged or increased compared to control. In standard monolayer culture, no differences in pro-metastatic features were present. Co-culture with primary mouse fibroblast reversed the difference of proliferation between control and Sdhb knockdown but was unable to significantly influence invasiveness under these culture conditions. Metabolic studies identified that lactate secreted by fibroblasts was taken up preferentially by Sdhb-silenced cells. In summary, the present study identified a potential role for the tumor microenvironment in influencing phenotypic features of SDHB-mutated PGLs, providing a basis for the use of therapies targeted towards the tumor microenvironment.

PMID: 30159755 [PubMed - indexed for MEDLINE]

18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in Human Pheochromocytomas.

Wed, 01/16/2019 - 11:16
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18F-FDOPA PET/CT Uptake Parameters Correlate with Catecholamine Secretion in Human Pheochromocytomas.

Neuroendocrinology. 2018;107(3):228-236

Authors: Moog S, Houy S, Chevalier E, Ory S, Weryha G, Rame M, Klein M, Brunaud L, Gasman S, Cuny T

Abstract
BACKGROUND: 18F-FDOPA positron emission tomography/computed tomography (PET/CT) is a sensitive nuclear imaging technology for the diagnosis of pheochromocytomas (PHEO). However, its utility in determining predictive factors for the secretion of catecholamines remains poorly studied.
METHODS: Thirty-nine histologically confirmed PHEO were included in this retrospective single-center study. Patients underwent 18F-FDOPA PET/CT before surgery, with an evaluation of several uptake parameters (standardized uptake values [SUVmax and SUVmean] and the metabolic burden [MB] calculated as follows: MB = SUVmean × tumor volume) and measurement of plasma and/or urinary metanephrine (MN), normetanephrine (NM), and chromogranin A. Thirty-five patients were screened for germline mutations in the RET, SDHx, and VHL genes. Once resected, primary cultures of 5 PHEO were used for real-time measurement of catecholamine release by carbon fiber amperometry.
RESULTS: The MB of the PHEO positively correlated with 24-h urinary excretion of NM (r = 0.64, p < 0.0001), MN (r = 0.49, p = 0.002), combined MN and NM (r = 0.75, p < 0.0001), and eventually plasma free levels of NM (r = 0.55, p = 0.006). In the mutated patients (3 SDHD, 2 SDHB, 3 NF1, 1 VHL, and 3 RET), a similar correlation was observed between MB and 24-h urinary combined MN and NM (r = 0.86, p = 0.0012). For the first time, we demonstrate a positive correlation between the PHEO-to-liver SUVmax ratio and the mean number of secretory granule fusion events of the corresponding PHEO cells revealed by amperometric spikes (p = 0.01).
CONCLUSION: While the 18F-FDOPA PET/CT MB of PHEO strongly correlates with the concentration of MN, amperometric recordings suggest that 18F-FDOPA uptake could be enhanced by overactivity of catecholamine exocytosis.

PMID: 29949805 [PubMed - indexed for MEDLINE]

Occurrence of Endocrine and Thyroid Cancers Among Alaska Native People, 1969-2013.

Wed, 01/16/2019 - 11:16
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Occurrence of Endocrine and Thyroid Cancers Among Alaska Native People, 1969-2013.

Thyroid. 2018 04;28(4):481-487

Authors: Nash SH, Lanier AP, Southworth MB

Abstract
BACKGROUND: Nationwide, the incidence of thyroid cancer is lower among American Indian/Alaska Native (AI/AN) people than among U.S. whites (USW). However, little is known about the incidence of thyroid or other endocrine cancers specifically among Alaska Native (AN) people.
METHODS: Data were examined from the National Cancer Institute's Surveillance, Epidemiology, and End Results Alaska Native Tumor Registry on endocrine cancers diagnosed among AN people from 1969-2013, with a specific focus on thyroid cancers. Frequencies of endocrine cancers by site and also of thyroid cancers by histology, size, and stage at diagnosis were evaluated. Distributions were compared to USW (Surveillance, Epidemiology, and End Results 9 Registries) using the chi-square test. Five-year average annual age-adjusted incidence rates of thyroid cancers were calculated, stratified by histology, age, and five-year period of diagnosis, and compared to those observed among USW. Five-year cause-specific survival was evaluated using cause of death data from the National Death Index Plus from the National Center for Health Statistics.
RESULTS: During the 45-year period (1969-2013), 224 endocrine cancers were diagnosed among AN people, of which 210 (94%) were thyroid cancers. Compared to USW, AN people were diagnosed at a slightly younger age, had a higher proportion of thyroid cancers diagnosed with a size of 20-40 mm, and a larger proportion of patients with regional metastases. More than 85% of AN thyroid cancers were of papillary histology. The incidence of thyroid cancers was similar between AN people and USW, and appeared to increase among AN people over the period of surveillance. Finally, five-year cause-specific survival rate was 100% for papillary carcinoma patients and 86.3% [confidence interval 54.7-96.5] for follicular thyroid cancer patients.
CONCLUSIONS: This study is the first report of endocrine cancers and the first detailed examination of thyroid cancer among AN people. The incidence of thyroid cancer was similar among AN people and USW. However, compared to USW, AN people appear to be at risk for diagnosis at a younger age, larger size, and higher stage. Further research is needed to explore the causes of these differences.

PMID: 29439613 [PubMed - indexed for MEDLINE]

Anesthesia Case of the Month.

Wed, 01/16/2019 - 11:16
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Anesthesia Case of the Month.

J Am Vet Med Assoc. 2018 Feb 01;252(3):286-288

Authors: Katzman SA, Perez-Noguez M, Pypendop BH, Alex CE, Affolter VK

PMID: 29346057 [PubMed - indexed for MEDLINE]

Clinical effects of prophylactic use of phentolamine in patients undergoing pheochromocytoma surgery.

Wed, 01/16/2019 - 11:16
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Clinical effects of prophylactic use of phentolamine in patients undergoing pheochromocytoma surgery.

J Clin Anesth. 2018 02;44:119

Authors: Yu M, Han C, Zhou Q, Liu C, Ding Z

PMID: 29195099 [PubMed - indexed for MEDLINE]

The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH).

Wed, 01/16/2019 - 11:16
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The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH).

Mol Cell Endocrinol. 2018 01 15;460:36-46

Authors: Cavalcante IP, Nishi M, Zerbini MCN, Almeida MQ, Brondani VB, Botelho MLAA, Tanno FY, Srougi V, Chambo JL, Mendonca BB, Bertherat J, Lotfi CFP, Fragoso MCBV

Abstract
The participation of aberrant receptors and intra-adrenal ACTH in hyperplastic tissue are considered mechanisms that regulate hypercortisolism in PMAH. Additionally, germline ARMC5 mutations have been described as the most frequent genetic abnormality found in patients diagnosed with PMAH. Previous functional studies analyzed ARMC5 role using H295R cells. Therefore, we investigated the role of ARMC5 in cell cultures obtained from PMAH nodules containing steroidogenic cells, aberrant receptors and intra-adrenal ACTH. ARMC5 silencing in non-mutated PMAH cell cultures decreased steroidogenesis-related genes and increased CCNE1 mRNA expression and proliferative capacity without affecting cell viability. Additionally, ARMC5 overexpression induced cell death in PMAH mutated cell cultures, thereby decreasing cell viability. We confirmed the role of ARMC5 as an important pro-apoptotic protein involved in PMAH-related steroidogenesis. We also report for the first time the involvement of ARMC5 in controlling proliferation and regulating cell cycle in PMAH cell cultures; these effects need to be explored further.

PMID: 28676429 [PubMed - indexed for MEDLINE]

[Catecholamine Cardiomyopathy Presenting Inverted-takotsubo Pattern Asynergy].

Wed, 01/16/2019 - 11:16
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[Catecholamine Cardiomyopathy Presenting Inverted-takotsubo Pattern Asynergy].

Masui. 2017 Apr;66(4):401-404

Authors: Okuno T, Hino M, Kiyama R, Shindo K

Abstract
Pheochromocytoma is complicated with catecholamine cardiomyopathy, and preoperative care becomes considerably more difficult We report anesthetic management for an 48-year-old man brought to our hospital by ambulance and immediately hospitalized due to pheochromocytoma crisis complicated with catechol- amine cardiomyopathy presenting inverted-takotsubo pattern asynergy. Before surgery, α and β blocking drugs were used to control hypertension and tachycardia, and continuous hemodiafiltration was initiated and the patient was intubated for severe pulmonary edema. Seven days later, he underwent laparoscopic adrenalectomy. Total intravenous anesthesia was achieved with propofol, remifentanil, fentanyl, and rocuronium. During the operation, continuous infusion of landiolol, phentolamine, and nitroglycerin, and addi- tional bolus injections of landiolol were given to control hypertension. After severing the right adrenal vein, noradrenaline (0.15 μg · kg⁻¹ · min⁻¹), and dopamine (4μg · kg⁻¹ · min⁻¹) were started and the patient was placed in the intensive care unit Inverted-takotsubo pattern asynergy is not very common, and treatment consists of supportive care, as in the usual takotsubo. Preoperative CHDF (continuous hemodiafiltration) may be useful when it is difficult to control hypertension or tachycardia with medications.

PMID: 30382641 [PubMed - indexed for MEDLINE]

adrenal tumor; +21 new citations

Wed, 01/09/2019 - 10:46

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

adrenal tumor

These pubmed results were generated on 2019/01/09

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Pheochromocytoma in Dogs Undergoing Adrenalectomy.

Wed, 01/02/2019 - 10:09
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Pheochromocytoma in Dogs Undergoing Adrenalectomy.

Vet Pathol. 2018 Dec 30;:300985818819174

Authors: Zini E, Nolli S, Ferri F, Massari F, Gerardi G, Nicoli S, Romanelli G, Montinaro V, Trez D, Cavicchioli L, Ferro S

Abstract
Pheochromocytoma is frequent in dogs and carries a guarded prognosis. Current histological criteria may not predict malignant behavior in dogs, similar to humans. In humans, characterization of tumors has been refined using the pheochromocytoma of the adrenal gland scaled score (PASS) and by immunohistochemistry. The study aim was to investigate PASS and immunohistochemical markers used in humans in 24 dogs with pheochromocytoma that underwent adrenalectomy. Dogs with pheochromocytomas were reviewed and tumors collected. Histological sections were evaluated to apply the PASS and were single-labeled for chromogranin A, Ki-67, COX-2, p53, BCL-2, c-erbB-2, vascular endothelial growth factor, and S100. Survival, age, and vascular and capsular invasion were compared for PASS and immunohistochemical markers; results of PASS were also compared for each marker. Associations between markers were tested. PASS and immunohistochemical markers did not differ for survival, age, and vascular and capsular invasion. Tumors showing BCL-2 expression in >50% cells had lower PASS than those with lower expression (PASS: 7 ± 2 vs 9 ± 2; P = .011). Tumors positive for S100 had higher PASS than those that were negative (PASS: 10 ± 2 vs 7 ± 2; P = .001). Results of the different markers were not associated. In conclusion, in the context of canine pheochromocytoma, PASS and the selected immunohistochemical markers are not associated with survival, age, or vascular or capsular invasion. The higher PASS in S100-positive tumors may indicate that pheochromocytomas developing morphologic changes acquire S100 expression. The significance of lower PASS in tumors with elevated BCL-2 expression is uncertain. Overall, the use of PASS and the present immunohistochemical markers may not be useful in dogs with pheochromocytoma.

PMID: 30595108 [PubMed - as supplied by publisher]

Twist1 Correlates With Epithelial-Mesenchymal Transition Markers Fibronectin and Vimentin in Adrenocortical Tumors.

Wed, 01/02/2019 - 10:09
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Twist1 Correlates With Epithelial-Mesenchymal Transition Markers Fibronectin and Vimentin in Adrenocortical Tumors.

Anticancer Res. 2019 Jan;39(1):173-175

Authors: Bulzico D, Pires BRB, DE Faria PAS, Neto LV, Abdelhay E

Abstract
BACKGROUND/AIM: Although the knowledge regarding adrenocortical carcinomas (ACC) tumorigenesis has significantly improved during the last decade, it still remains to be completely determined. Epithelial-mesenchymal transition (EMT) is a well described transcription factor induced process, postulated as an essential step toward cancer progression and metastasis development. In this context, Twist1 has been described as the EMT master-regulator. The aim of this study was to assess the association among Twist1, fibronectin, vimentin and E-cadherin gene expression in adrenocortical tumor samples.
MATERIALS AND METHODS: Twist1, fibronectin, vimentin and E-cadherin gene expression in 18 adrenal adenomas, 18 ACC, and 24 childhood onset adrenocortical tumors were assessed in formalin-fixed paraffin-embedded tissues. The fold expression was calculated according to the 2ΔCt method.
RESULTS: A significant correlation between mRNA levels of Twist1, fibronectin and vimentin was evident. Although their expression was inversely proportional, no association was observed between Twist1 and E-cadherin expression.
CONCLUSION: The expression of Twist1, the major regulator of EMT, is directly correlated to the expression of mesenchymal markers fibronectin and vimentin in ACC samples.

PMID: 30591455 [PubMed - in process]

De Novo Testicular Extranodal NK/T-Cell Lymphoma: A Clinicopathologic Study of 21 Cases With Review of Additional 18 Cases in the Literature.

Wed, 01/02/2019 - 10:09
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De Novo Testicular Extranodal NK/T-Cell Lymphoma: A Clinicopathologic Study of 21 Cases With Review of Additional 18 Cases in the Literature.

Am J Surg Pathol. 2018 Dec 26;:

Authors: Huang Y, Shi X, Zhong P, Wang Y, Xiao H, Zhou X, Yun J

Abstract
Although the testis is not uncommonly involved during the course of disease in both nasal and non-nasal extranodal NK/T-cell lymphoma (ENKTCL), only a few cases presenting initially with a testicular mass have been previously reported. These have been documented as case reports, rather than as study series. Because of its rarity, the clinicopathologic features and the prognosis of de novo testicular ENKTCL have not been well characterized. Clinicopathologic features of 21 cases of de novo testicular ENKTCL from 3 institutions in China were retrospectively analyzed with review of an additional 18 cases from the literature. De novo testicular ENKTCL accounted for 0.72% (21/2906) of all ENKTCL during the study period. The median age of patients with de novo testicular ENKTCL was 45 years (range, 21 to 79 y). Most (90.9%) cases occurred in Asians. All patients initially presented with testicular swelling and most (91.9%) had unilateral testicular masses. The majority (73.0%) of patients presented at Ann Arbor stage I/II. Expression of CD56 was found in 92.1% (35/38) of the available cases. Interestingly, aberrant expression of CD20 was found in the tumor cells in 10.3% (4/39) of cases. The majority of patients with follow-up data (24/30, 80%) had extratesticular involvement during the follow-up period (median follow-up, 6 months; range, 0.5 to 87 mo). Preferential sites of extratesticular involvement included lymph nodes, skin, contralateral testis, bone marrow, spleen, adrenal gland, and central nervous system. Of the 30 patients with survival data, 70% (22/30) of patients died of the disease. The 2-year overall survival of patients with de novo testicular ENKTCL was 23%, and the median survival was 9.5 months. Patients that presented with B symptoms showed a trend toward inferior overall survival (P=0.095). No statistical significance was found between patients with stage I/II and stage III/IV (P=0.783). De novo testicular ENKTCL tends to disseminate early, shows extremely poor outcome, and should be recognized as a highly aggressive form of ENKTCL. A portion of cases show aberrant expression of CD20, and accurate diagnosis as well as timely and optimal treatment are very important.

PMID: 30589649 [PubMed - as supplied by publisher]

Long-Term Tumor-Free Survival in a Patient with Stage IV Epithelial Ovarian Cancer Undergoing High-Dose Chemotherapy and Viscum album Extract Treatment: A Case Report.

Wed, 01/02/2019 - 10:09
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Long-Term Tumor-Free Survival in a Patient with Stage IV Epithelial Ovarian Cancer Undergoing High-Dose Chemotherapy and Viscum album Extract Treatment: A Case Report.

Perm J. 2018;23:

Authors: Werthmann PG, Kempenich R, Kienle GS

Abstract
INTRODUCTION: Epithelial ovarian cancer (EOC) has a poor prognosis in advanced stages. High-dose chemotherapy (HDC) was pursued in the 1990s but was not found to improve survival of patients with EOC in larger studies. Many patients with cancer use Viscum album extracts (VAE). Also called European mistletoe, Viscum album can lead to improved quality of life and reduced chemotherapy side effects and may have synergistic cytotoxic and proliferation-inhibiting effects when used together with chemotherapy.
CASE PRESENTATION: A high-grade serous epithelial ovarian carcinoma with peritoneal, adrenal, and hepatic metastases (FIGO Stage IV) was diagnosed in a 50-year-old premenopausal woman. Tumor and metastases were surgically removed in cytoreductive surgery, and the patient received adjuvant chemotherapy, without experiencing side effects from treatment. After a second-look surgery revealed lymph node metastases, HDC and autologous hematopoietic stem cell transplantation were performed. Additionally, the patient opted for treatment with VAE, which she continuously received. The patient remained tumor-free in follow-up examinations and has enjoyed good health for 20 years after initial diagnosis.
DISCUSSION: Treatment with VAE in this case might have contributed to the reduction of side effects from HDC and may have acted synergistically with HDC in tumor control. Cases of VAE in EOC should be carefully documented and reported to further illustrate the influence of VAE on this cancer presentation.

PMID: 30589407 [PubMed - in process]

Perforation of small intestine secondary to metastatic lung adenocarcinoma: A case report.

Wed, 01/02/2019 - 10:09
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Perforation of small intestine secondary to metastatic lung adenocarcinoma: A case report.

Medicine (Baltimore). 2018 Dec;97(49):e13469

Authors: Wang J, Chen Y, Zhang S, Chen Q

Abstract
RATIONALE: About 50% of patients with a diagnosis of nonsmall cell lung carcinoma exhibit metastatic disease at the time of diagnosis. The preferential sites of extrapulmonary spread are the lymph nodes, liver, brain, adrenal glands, and bones; gastrointestinal tract perforation secondary to metastatic lung cancer is extremely rare.
PATIENT CONCERNS: A 60-year-old male nonsmoker patient presented with a 20-day history of facial, neck, and right upper limb edema. Physical examination revealed a 3.5 cm mass in his right chest. Computed tomography (CT) revealed a 4 cm mass near the right lung hilum.
DIAGNOSIS: Biopsy of the right chest wall mass revealed low differentiated lung adenocarcinoma. Additionally, retroperitoneal lymphadenopathy, pericardial effusion, metastases in the mediastinum, bilateral adrenal gland, and right thoracic wall nodule, as well as multiple bone metastases were also found.
INTERVENTIONS: Since the patient was diagnosed with multiple metastatic lung cancer, chemotherapy was started. One week after chemotherapy, he experienced a sudden acute abdominal pain. Abdominal CT examination indicated the possibility of intestinal perforation. Hence, the patient underwent an emergency operation. During the surgical procedure, 2 perforations of size 1×1 cm were discovered at 110 cm and 140 cm of the jejunum from Treitz's ligament. Then, an intestinal resection and end-to-end anastomosis were performed. The pathological diagnosis of the resected specimen revealed that it was a metastatic lung adenocarcinoma of small intestine.
OUTCOMES: The patient died 10 days after operation and 19 days following the cancer diagnosis due to septic shock.
LESSONS: Gastrointestinal tract metastasis from the lung is uncommon, but the survival rate is extremely low; therefore, it should be considered as a possibility in patients who present with any of the gastrointestinal symptoms.

PMID: 30544434 [PubMed - indexed for MEDLINE]

Discovery of new susceptibility genes: proceed cautiously.

Wed, 01/02/2019 - 10:09
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Discovery of new susceptibility genes: proceed cautiously.

Genet Med. 2018 12;20(12):1512-1514

Authors: Else T, Fishbein L

Abstract

PMID: 30100611 [PubMed - indexed for MEDLINE]

Response to "The combination therapy with cytapheresis plus vedolizumab in a corticosteroid-dependent patient with ulcerative colitis and previous Anti-TNF alfa failure".

Wed, 01/02/2019 - 10:09
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Response to "The combination therapy with cytapheresis plus vedolizumab in a corticosteroid-dependent patient with ulcerative colitis and previous Anti-TNF alfa failure".

Dig Liver Dis. 2018 10;50(10):1103-1104

Authors: Scrivo B, Vitello A, Cappello M

PMID: 29871799 [PubMed - indexed for MEDLINE]

Glomuvenous malformations: dual PDL-Nd:YAG laser approach.

Wed, 01/02/2019 - 10:09
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Glomuvenous malformations: dual PDL-Nd:YAG laser approach.

Lasers Med Sci. 2018 Dec;33(9):2007-2010

Authors: Moreno-Arrones OM, Jimenez N, Alegre-Sanchez A, Fonda P, Boixeda P

Abstract
Glomuvenous malformations are uncommon simple vascular malformations that might be present at birth or appear during childhood that have been classically classified as a subtype of venous malformations. Sclerotherapy and surgery have been used in the past as treatments for this condition although with disappointing results in large glomangiomas. The treatment of these lesions has still not been standardized. We conducted a retrospective study of 17 patients treated with dual wavelength PDL-Nd:YAG. The majority of the patients experience a reduction of at least a 60% in their glomuvenous malformations. Treatment was well-tolerated, and adverse effects were rare.

PMID: 29594737 [PubMed - indexed for MEDLINE]

Metabolic implications of hypoxia and pseudohypoxia in pheochromocytoma and paraganglioma.

Wed, 01/02/2019 - 10:09
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Metabolic implications of hypoxia and pseudohypoxia in pheochromocytoma and paraganglioma.

Cell Tissue Res. 2018 05;372(2):367-378

Authors: Kluckova K, Tennant DA

Abstract
Hypoxia is a critical driver of cancer pathogenesis, directly inducing malignant phenotypes such as epithelial-mesenchymal transition, stem cell-like characteristics and metabolic transformation. However, hypoxia-associated phenotypes are often observed in cancer in the absence of hypoxia, a phenotype known as pseudohypoxia, which is very well documented in specific tumour types, including in paraganglioma/pheochromocytoma (PPGL). Approximately 40% of the PPGL tumours carry a germ line mutation in one of a number of susceptibility genes of which those that are found in succinate dehydrogenase (SDH) or in von Hippel-Lindau (VHL) genes manifest a strong pseudohypoxic phenotype. Mutations in SDH are oncogenic, forming tumours in a select subset of tissues, but the cause for this remains elusive. Although elevated succinate levels lead to increase in hypoxia-like signalling, there are other phenotypes that are being increasingly recognised in SDH-mutated PPGL, such as DNA hypermethylation. Further, recently unveiled changes in metabolic re-wiring of SDH-deficient cells might help to decipher cancer related roles of SDH in the future. In this review, we will discuss the various implications that the malfunctioning SDH can have and its impact on cancer development.

PMID: 29450727 [PubMed - indexed for MEDLINE]

Molecular imaging and theranostic approaches in pheochromocytoma and paraganglioma.

Wed, 01/02/2019 - 10:09
Related Articles

Molecular imaging and theranostic approaches in pheochromocytoma and paraganglioma.

Cell Tissue Res. 2018 05;372(2):393-401

Authors: Taïeb D, Pacak K

Abstract
Pheochromocytomas and their extra-adrenal counterpart paragangliomas (PGLs; together called PPGLs), belong to the family of neural crest-derived tumors. Given the overexpression of a wide variety of specific targets in PPGLs, it seems that these tumors are optimally suited to be imaged by specific radiopharmaceuticals. Thus, theranostics approaches with somatostatin agonists and antagonists are rapidly evolving in the setting of these tumors and may be considered as the next step in the therapeutic arsenal of metastatic PPGLs.

PMID: 29450723 [PubMed - indexed for MEDLINE]

Rodent models of pheochromocytoma, parallels in rodent and human tumorigenesis.

Wed, 01/02/2019 - 10:09
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Rodent models of pheochromocytoma, parallels in rodent and human tumorigenesis.

Cell Tissue Res. 2018 05;372(2):379-392

Authors: Lussey-Lepoutre C, Buffet A, Morin A, Goncalves J, Favier J

Abstract
Paragangliomas and pheochromocytomas are rare neuroendocrine tumors characterized by a large spectrum of hereditary predisposition. Based on gene expression profiling classification, they can be classically assigned to either a hypoxic/angiogenic cluster (cluster 1 including tumors with mutations in SDHx, VHL and FH genes) or a kinase-signaling cluster (cluster 2 consisting in tumors related to RET, NF1, TMEM127 and MAX genes mutations, as well as most of the sporadic tumors). The past 15 years have seen the emergence of an increasing number of genetically engineered and grafted models to investigate tumorigenesis and develop new therapeutic strategies. Among them, only cluster 2-related predisposed models have been successful but grafted models are however available to study cluster 1-related tumors. In this review, we present an overview of existing rodent models targeting predisposition genes involved or not in human pheochromocytoma/paraganglioma susceptibility and their contribution to the improvement of pheochromocytoma experimental research.

PMID: 29427052 [PubMed - indexed for MEDLINE]

An image-based small-molecule screen identifies vimentin as a pharmacologically relevant target of simvastatin in cancer cells.

Wed, 01/02/2019 - 10:09
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An image-based small-molecule screen identifies vimentin as a pharmacologically relevant target of simvastatin in cancer cells.

FASEB J. 2018 05;32(5):2841-2854

Authors: Trogden KP, Battaglia RA, Kabiraj P, Madden VJ, Herrmann H, Snider NT

Abstract
Vimentin is a cytoskeletal intermediate filament protein that is expressed in mesenchymal cells and cancer cells during the epithelial-mesenchymal transition. The goal of this study was to identify vimentin-targeting small molecules by using the Tocriscreen library of 1120 biochemically active compounds. We monitored vimentin filament reorganization and bundling in adrenal carcinoma SW13 vimentin-positive (SW13-vim+) cells via indirect immunofluorescence. The screen identified 18 pharmacologically diverse hits that included 2 statins-simvastatin and mevastatin. Simvastatin induced vimentin reorganization within 15-30 min and significant perinuclear bundling within 60 min (IC50 = 6.7 nM). Early filament reorganization coincided with increased vimentin solubility. Mevastatin produced similar effects at >1 µM, whereas the structurally related pravastatin and lovastatin did not affect vimentin. In vitro vimentin filament assembly assays revealed a direct targeting mechanism, as determined biochemically and by electron microscopy. In SW13-vim+ cells, simvastatin, but not pravastatin, reduced total cell numbers (IC50 = 48.1 nM) and promoted apoptosis after 24 h. In contrast, SW13-vim- cell viability was unaffected by simvastatin, unless vimentin was ectopically expressed. Simvastatin similarly targeted vimentin filaments and induced cell death in MDA-MB-231 (vim+), but lacked effect in MCF7 (vim-) breast cancer cells. In conclusion, this study identified vimentin as a direct molecular target that mediates simvastatin-induced cell death in 2 different cancer cell lines.-Trogden, K. P., Battaglia, R. A., Kabiraj, P., Madden, V. J., Herrmann, H., Snider, N. T. An image-based small-molecule screen identifies vimentin as a pharmacologically relevant target of simvastatin in cancer cells.

PMID: 29401610 [PubMed - indexed for MEDLINE]

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