Search Results
You are looking at 21 - 30 of 86 items for
- Abstract: Birth defect x
- Abstract: Drugs x
- Abstract: endocrine disrupters x
Department of Health Sciences, University of Florence, Florence, Italy
Search for other papers by Alessandro Barbato in
Google Scholar
PubMed
Search for other papers by Giulia Gori in
Google Scholar
PubMed
Search for other papers by Michele Sacchini in
Google Scholar
PubMed
Search for other papers by Francesca Pochiero in
Google Scholar
PubMed
Search for other papers by Sara Bargiacchi in
Google Scholar
PubMed
Search for other papers by Giovanna Traficante in
Google Scholar
PubMed
Search for other papers by Viviana Palazzo in
Google Scholar
PubMed
Search for other papers by Lucia Tiberi in
Google Scholar
PubMed
Search for other papers by Claudia Bianchini in
Google Scholar
PubMed
Search for other papers by Davide Mei in
Google Scholar
PubMed
Search for other papers by Elena Parrini in
Google Scholar
PubMed
Search for other papers by Tiziana Pisano in
Google Scholar
PubMed
Search for other papers by Elena Procopio in
Google Scholar
PubMed
NEUROFARBA Department, University of Florence, Florence, Italy
Search for other papers by Renzo Guerrini in
Google Scholar
PubMed
Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy
Search for other papers by Angela Peron in
Google Scholar
PubMed
Department of Health Sciences, University of Florence, Florence, Italy
Search for other papers by Stefano Stagi in
Google Scholar
PubMed
Context
Cytochrome C oxidase (COX) is the fourth component of the respiratory chain and is located within the internal membrane of mitochondria. COX deficiency causes an inherited mitochondrial disease with significant genetic and phenotypic heterogeneity. Four clinical subtypes have been identified, each with distinct phenotypes and genetic variants. Mitochondrial complex IV deficiency nuclear type 4 (MC4DN4) is a form of COX deficiency associated with pathogenic variants in the SCO1 gene.
Case description
We describe three patients with MC4DN4 with developmental and epileptic encephalopathy (DEE), hypopituitarism, and SCO1 pathogenic variants. These patients’ phenotypes considerably differ from previously reported MC4DN4 phenotypes as they associate DEE with progressive hypopituitarism and survival beyond the first months after birth. Pituitary deficiency in these patients progressively worsened and mainly involved growth hormone secretion and thyroid function.
Conclusions
Our findings expand knowledge of phenotypic variability in MC4DN4 and suggest that SCO1 is a candidate gene for genetic hypopituitarism and DEE.
Significance statement
Our paper describes three patients affected by MC4DN4 with hypopituitarism and developmental and epileptic encephalopathy (DEE), two features that have never been associated with this condition. In addition, we reviewed the clinical features of all previous cases of MC4DN4 to give the other clinicians a wide picture of the clinical phenotype of this genetic disease. We hope that the publication of our data may help others to identify this disease and consider the chance to analyze the SCO1 gene in cases of DEE associated with pituitary dysfunction. Our article contributes to expanding the spectrum of genetic hypopituitarism and proposes a model to explain an association between this condition, mitochondrial anomalies, and neurodevelopmental defects.
Search for other papers by Nassim Ghaffari-Tabrizi-Wizsy in
Google Scholar
PubMed
Search for other papers by Christina Angelika Passegger in
Google Scholar
PubMed
Search for other papers by Laura Nebel in
Google Scholar
PubMed
Search for other papers by Fabian Krismer in
Google Scholar
PubMed
Search for other papers by Gudrun Herzer-Schneidhofer in
Google Scholar
PubMed
Search for other papers by Gert Schwach in
Google Scholar
PubMed
Search for other papers by Roswitha Pfragner in
Google Scholar
PubMed
Preclinical trials of medullary thyroid cancer (MTC) therapeutics require both in vitro and in vivo analyses. Human tumour xenografted rodent models, which are considered the ‘gold standard’ to study and validate the efficacy and toxicity of lead compounds before translation to clinical trials, are very expensive, subject to organismal variability and ethical controversies. The avian chorioallantoic membrane (CAM) assay provides an alternative versatile, cost-effective and ethically less objectionable short-term, in vivo model for reliable screening of drugs. In this work, we grafted two MTC cell lines and patient-derived MTC tumour samples onto the avian CAM and characterised the resulted tumours histologically and immunohistochemically. Our findings provide the evidence that the CAM assay is a suitable model for studying the pathophysiology of MTC and can even be used as in vivo system for drug testing.
Search for other papers by Ruixin Hu in
Google Scholar
PubMed
Search for other papers by Yanting Yuan in
Google Scholar
PubMed
Search for other papers by Chaolong Liu in
Google Scholar
PubMed
Search for other papers by Ji Zhou in
Google Scholar
PubMed
Search for other papers by Lixia Ji in
Google Scholar
PubMed
Search for other papers by Guohui Jiang in
Google Scholar
PubMed
In patients with type 2 diabetes mellitus (T2DM), the intestinal flora is out of balance and accompanied by leaky gut. The flora is characterized by an increase in mucus-degrading bacteria and a decrease in fiber-degrading bacteria. Short-chain fatty acids (SCFAs), as the major fiber-degrading bacteria fermentation, not only ameliorate the leaky gut, but also activate GPR43 to increase the mass of functional pancreatic β-cells and exert anti-inflammation effect. At present, the gut microbiota is considered as the potential target for anti-diabetes drugs, and how to reverse the imbalance of gut microbiota has become a therapeutic strategy for T2DM. This review briefly summarizes the drugs or compounds that have direct or potential therapeutic effects on T2DM by modulating the gut microbiota, including biguanides, isoquinoline alkaloids, stilbene and C7N-aminocyclic alcohols.
Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy
Search for other papers by Maria Cristina De Martino in
Google Scholar
PubMed
Search for other papers by Richard A Feelders in
Google Scholar
PubMed
Search for other papers by Claudia Pivonello in
Google Scholar
PubMed
Search for other papers by Chiara Simeoli in
Google Scholar
PubMed
Search for other papers by Fortuna Papa in
Google Scholar
PubMed
Search for other papers by Annamaria Colao in
Google Scholar
PubMed
Search for other papers by Rosario Pivonello in
Google Scholar
PubMed
Search for other papers by Leo J Hofland in
Google Scholar
PubMed
Adrenocortical carcinomas (ACCs) are rare tumors with scant treatment options for which new treatments are required. The mTOR pathway mediates the intracellular signals of several growth factors, including the insulin-like growth factors (IGFs), and therefore represents a potential attractive pathway for the treatment of several malignancies including ACCs. Several mTOR inhibitors, including sirolimus, temsirolimus and everolimus, have been clinically developed. This review summarizes the results of the studies evaluating the expression of the mTOR pathway components in ACCs, the effects of the mTOR inhibitors alone or in combination with other drugs in preclinical models of ACCs and the early experience with the use of these compounds in the clinical setting. The mTOR pathway seems a potential target for treatment of patients with ACC, but further investigation is still required to define the potential role of mTOR inhibitors alone or in combination with other drugs in the treatment of ACC patients.
Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Search for other papers by Anne Jouinot in
Google Scholar
PubMed
Search for other papers by Bernard Royer in
Google Scholar
PubMed
Search for other papers by Etienne Chatelut in
Google Scholar
PubMed
Search for other papers by Sotheara Moeung in
Google Scholar
PubMed
Department of Endocrinology, Center for Rare Adrenal Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France
Search for other papers by Guillaume Assié in
Google Scholar
PubMed
Pharmacokinetics and Pharmacochemistry Unit, Cochin Hospital, Paris Descartes University, AP-HP, Paris, France
Search for other papers by Audrey Thomas-Schoemann in
Google Scholar
PubMed
Department of Endocrinology, Center for Rare Adrenal Diseases, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Paris, France
Search for other papers by Jérôme Bertherat in
Google Scholar
PubMed
Search for other papers by François Goldwasser in
Google Scholar
PubMed
UMR8638 CNRS, Pharmacy UFR, University of Paris Descartes, PRES sorbonne Paris Cité, Paris, France
Search for other papers by Benoit Blanchet in
Google Scholar
PubMed
Background
The combination of mitotane and platinum-etoposide chemotherapy is a front-line treatment in metastatic adrenocortical carcinoma (ACC), although this regimen shows limited efficacy. Pharmacokinetic drug–drug interaction between mitotane, a strong CYP3A4 inducer, and etoposide, which is a substrate of CYP3A4, may contribute to chemoresistance. The aim of this pilot study was to assess the pharmacokinetic interaction between mitotane and etoposide in ACC patients.
Methods
Five consecutive ACC patients treated with platinum etoposide (120–150 mg/m2 day 1–2–3 at cycle 1), with or without concomitant mitotane, were included. In the absence of limiting toxicity, a dose escalation of etoposide was proposed since cycle 2. Plasma etoposide concentrations were measured using liquid chromatography at 0, 4 and 24 h after each infusion. Clearance and area under the curve (AUC) of etoposide were determined at each cycle.
Results
Patients received two to six chemotherapy cycles, in association with mitotane (N = 4) or after mitotane discontinuation (N = 1). Etoposide clearance was two-fold higher with concomitant mitotane (4.95 L/h) than after mitotane discontinuation (2.53 L/h, P = 0.014), and 2.5-fold higher than that in reference population not treated with mitotane (1.81 L/h). Etoposide dose escalation was performed in four patients under mitotane, resulting in two minor tumor responses and one severe toxicity (febrile aplasia) at dose of 300 mg/m2/day. Tumor response was associated with higher etoposide AUC (267.3 vs 188.8 mg.h/L, P = 0.04).
Conclusion
A drug–drug interaction between mitotane and etoposide may contribute to the low efficacy of platinum-etoposide chemotherapy. This pilot study suggests further a potential benefit of increasing etoposide dose in ACC patients receiving mitotane.
Nutrition et Neurobiologie intégrée, UMR 1286, University of Bordeaux, Bordeaux, France
Groupe de Biologie Spécialisée, Société Française de Médecine Nucléaire, Paris, France
Search for other papers by Jean-Benoît Corcuff in
Google Scholar
PubMed
Search for other papers by Laurence Chardon in
Google Scholar
PubMed
Search for other papers by Ines El Hajji Ridah in
Google Scholar
PubMed
Nutrition et Neurobiologie intégrée, UMR 1286, University of Bordeaux, Bordeaux, France
Groupe de Biologie Spécialisée, Société Française de Médecine Nucléaire, Paris, France
Search for other papers by Julie Brossaud in
Google Scholar
PubMed
Context
Biogenic amines such as 5-hydroxy-indole acetic acid (5HIAA) the main metabolite of serotonin or metanephrines (catecholamines metabolites) are used as biomarkers of neuroendocrine tumours.
Objective
To re-evaluate the recommendations for urinary sampling (preservatives, diet, drugs, etc.) as many of the reported analytical interferences supporting these recommendations are related to obsolete assays.
Methods
Bibliographic analysis of old and modern assays concerning preservation, extraction, assay and interferences.
Results
5HIAA may degrade as soon as urine is excreted. Thus, acids as preservatives (hydrochloric or acetic acid) have to be immediately added. Care should be taken not to decrease the pH under 2. Urine preservative for metanephrine assays is not mandatory. Diets including serotonin-, tryptophan- and dopamine-rich foods have to be avoided depending on the biomarkers investigated (bananas, plantain, nuts, etc.). Tryptophan-rich over-the-counter formulas have to be prohibited when 5HIAA has to be assayed. Acetaminophen may interfere with electrochemical detection depending on high-pressure liquid chromatography (HPLC) parameters. No interference is known with mass spectrometric assays but with the one described for metanephrines determination. Some drugs interfere however with serotonin and catecholamines secretion and/or metabolism (monoamine oxidase inhibitors, serotonin or dopamine recapture inhibitors, etc.).
Conclusion
Revisited recommendations are provided for the diet, the drugs and the preservatives before HPLC coupled with electrochemical and mass spectrometry assays.
Search for other papers by Sarmistha Banerjee in
Google Scholar
PubMed
Search for other papers by Allison M Hayes in
Google Scholar
PubMed
Search for other papers by Bernard H Shapiro in
Google Scholar
PubMed
The sexually dimorphic expression of cytochromes P450 (CYP) drug metabolizing enzymes has been reported in all species examined. These sex differences are initially expressed during puberty and are solely regulated by sex differences in the circulating growth hormone (GH) profiles. Once established, however, the different male- and female-dependent CYP isoforms are permanent and immutable, suggesting that adult CYP expression requires imprinting. Since the hormone that regulates an adult function is likely the same hormone that imprints the function, we selectively blocked GH secretion in some newborn male rats while others also received a concurrent physiologic replacement of rat GH. Rats were subsequently challenged, peripubertally, with either a masculine-like episodic GH regimen or the GH vehicle alone. The results demonstrate that episodic GH regulation of male-specific CYP2C11 and CYP3A2, as well as female-predominant CYP2C6, are dependent on developmental GH imprinting. Moreover, the induction and/or activation of major components in the signal transduction pathway regulating the expression of the principal CYP2C11 isoform is obligatorily dependent on perinatal GH imprinting without which CYP2C11 and drug metabolism would be permanently and profoundly suppressed. Since there are additional adult metabolic functions also regulated by GH, pediatric drug therapy that is known to disrupt GH secretion could unintentionally impair adult health.
Search for other papers by Giovanni Tulipano in
Google Scholar
PubMed
A variety of endocrine and metabolic signals regulate pituitary cell function acting through the hypothalamus-pituitary neuroendocrine axes or directly at the pituitary level. The underlying intracellular transduction mechanisms in pituitary cells are still debated. AMP-activated protein kinase (AMPK) functions as a cellular sensor of low energy stores in all mammalian cells and promotes adaptive changes in response to calorie restriction. It is also regarded as a target for therapy of proliferative disorders. Various hormones and drugs can promote tissue-specific activation or inhibition of AMPK by enhancing or inhibiting AMPK phosphorylation, respectively. This review explores the preclinical studies published in the last decade that investigate the role of AMP-activated protein kinase in the intracellular transduction pathways downstream of endocrine and metabolic signals or drugs affecting pituitary cell function, and its role as a target for drug therapy of pituitary proliferative disorders. The effects of the hypoglycemic agent metformin, which is an indirect AMPK activator, are discussed. The multiple effects of metformin on cell metabolism and cell signalling and ultimately on cell function may be either dependent or independent of AMPK. The in vitro effects of metformin may also help highlighting differences in metabolic requirements between pituitary adenomatous cells and normal cells.
Search for other papers by Lijin Ji in
Google Scholar
PubMed
Search for other papers by Na Yi in
Google Scholar
PubMed
Search for other papers by Qi Zhang in
Google Scholar
PubMed
Search for other papers by Shuo Zhang in
Google Scholar
PubMed
Search for other papers by Xiaoxia Liu in
Google Scholar
PubMed
Search for other papers by Hongli Shi in
Google Scholar
PubMed
Search for other papers by Bin Lu in
Google Scholar
PubMed
Objective
To assess the current management of prolactinoma among endocrinologists in China.
Methods
An online survey of a large sample of endocrinologists was conducted in China. The questionnaire included 21 questions related to controversial issues about the management of prolactinomas. Doctors in the endocrinology department of a university-affiliated hospital or a comprehensive secondary hospital in 12 cities from East, West, South, North and Middle China were surveyed.
Results
A total of 290 valid questionnaires were collected, and the response rate was 40%. When hyperprolactinemia occurred, 97% of the respondents would test thyroid-stimulating hormone routinely. 22% of the respondents considered that prolactin levels <100 ng/mL exclude the presence of a prolactinoma. Only 9% of the respondents believed that prolactin >250 ng/mL could occur in all the following situations as macroprolactinoma, mircoprolactinoma, macroprolactinemia and drug-induced hyperprolactinemia. Surgery was not recommended by 272 (94%) endocrinologists as the first choice for treating microprolactinomas. 58% and 92% of endocrinologists would start drug treatment for microprolactinomas and macroprolactinomas at diagnosis. 70% and 40% chose to withdraw treatment after 2–3 years of prolactin normalization in microprolactinomas and macroprolactinomas. In case of pregnancy, 57% of the respondents considered bromocriptine as choice for women patients. Drug discontinuation after pregnancy was advocated in 63% and 27% for microprolactinoma and macroprolactinoma. Moreover, 44% of endocrinologists believed that breastfeeding was allowable in both micro- and macroprolactinoma.
Conclusion
This is the first study to investigate the management of prolactinomas among endocrinologists in China. We found that the current clinical treatment was not uniform. Therefore, it is necessary to strengthen the training of endocrinologists to improve clinical diagnosis and treatment practices.
Research Center for Translational Medicine, Cancer Stem Cell Institute, East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China
Search for other papers by Shan Wu in
Google Scholar
PubMed
Search for other papers by Jianjun Zhou in
Google Scholar
PubMed
Search for other papers by Jing Guo in
Google Scholar
PubMed
Search for other papers by Zhan Hua in
Google Scholar
PubMed
Search for other papers by Jianchen Li in
Google Scholar
PubMed
Search for other papers by Zai Wang in
Google Scholar
PubMed
Angiogenesis has a pivotal role in the growth and metastasis of pancreatic neuroendocrine tumors (PNETs). Apatinib inhibits angiogenesis as a highly selective KDR inhibitor and has been used to treat advanced gastric cancer and malignancies in clinical settings. However, the efficacy of apatinib in PNETs remains unclear. The aim of this study was to compare the antitumor efficacy of apatinib with that of the standard PNET drug sunitinib in our subcutaneous and liver metastasis models of insulinoma and non-functional PNET. Our results revealed that apatinib had a generally comparable or even superior antitumor effect to that of sunitinib on primary PNET, and it inhibited angiogenesis without directly causing tumor cell cytotoxicity. Apatinib inhibited the tumor in a dose-dependent manner, and the high dose was well tolerated in mice. We also found that the apatinib efficacy in liver metastasis models was cell-type (disease) selective. Although apatinib efficiently inhibited INR1G9-represented non-functional PNET liver metastasis, it led to the emergence of a hypoxic area in the INS-1-represented insulinoma and promoted liver metastasis. Our study demonstrated that apatinib has promise for clinical applications in certain malignant PNETs, and the application of anti-angiogenesis drugs to benign insulinomas may require careful consideration.
