Showing papers in "Annales D Endocrinologie in 2013"
TL;DR: Before the real impact of BPA on human health can be clearly assessed, prospective longitudinal epidemiological studies are needed as well as characterization of selective biomarkers to verify long-term exposure and selective imprinting.
Abstract: Bisphenol A (BPA), initially designed, like diethylstilbestrol, as a synthetic estrogen, has been rapidly and widely used for its cross-linking properties in the manufacture of polycarbonate plastics and epoxy resins. Because of incomplete polymerization and degradation of the polymers by exposure to higher than usual temperatures, BPA leaches out from food and beverage containers, as well as from dental sealants. In humans, free active unconjugated BPA is metabolized by rapid glucurono- or sulfo-conjugation and eliminated via renal clearance. However, exposure to environmental nanomolar concentrations of BPA is ubiquitous and continuous via different routes: oral, air, skin. In rodents, fetal and perinatal exposure to such environmentally relevant doses of BPA has been shown to affect the brain, liver, gut, adipose tissue, endocrine pancreas, mammary gland and reproductive tract and function. Similar concentrations are also able in vitro to impact human malignant breast, prostate, male germ or adipocyte cell lines (with a promoting effect and by interfering with chemotherapy drugs), or to stimulate pancreatic β cell insulin secretion. High levels of BPA have recently been correlated with obesity, diabetes, cardiovascular diseases, polycystic ovarian disease or low sperm count. However, before the real impact of BPA on human health can be clearly assessed, prospective longitudinal epidemiological studies are needed as well as characterization of selective biomarkers to verify long-term exposure and selective imprinting.
193 citations
TL;DR: The potential mechanisms involved in the remodeling of the AT vascular network are considered in this paper, and the physiological and pathological consequences of AT vascular remodeling are discussed. But, the role of the vascular network appears to play an important role in AT plasticity and functions.
Abstract: The first major role of adipose tissue (AT) is the storage and release of lipids depending on the energy balance. In addition to its key role in maintaining body energy homeostasis the AT is now recognized as an endocrine organ. Both metabolic and secretory functions require constant interactions between the blood compartment and adipocytes highlighting the importance of the AT vascular network. Ignored for a long time, the functionality and integrity of the AT vascular network appears to play an important role in the AT plasticity and functions. This chapter describes the literature data on the AT vascular network and its role in controlling the metabolic and secretory activities of AT in relation to blood flow. The potential mechanisms involved in the remodeling of AT vascular network are considered. The physiological and pathological consequences of AT vascular remodeling are discussed.
89 citations
TL;DR: Recent evidence showed that metformin-induced inhibition of hepatic glucose output is mediated by reducing cellular energy charge rather than direct inhibition of gluconeogenic gene expression, and a novel mechanism of action is supported involving antagonism of glucagon signaling pathways by inducing the accumulation of AMP, which inhibits adenylate cyclase and reduced levels of cAMP.
Abstract: Although considerable efforts have been made since the 1950s to better understand the action of metformin, the first line therapeutic for type 2 diabetes, its mechanisms of action has not been fully elucidated. The main antidiabetic effect of this drug is to decrease hepatic glucose production. A plausible molecular mechanism of action now emerges from recent breakthroughs that place metformin at the control of energy homeostasis. Metformin was shown to induce a mild and transient inhibition of the mitochondrial respiratory chain complex 1. The resulting decrease in hepatic energy state activates the AMP-activated protein kinase (AMPK), a cellular metabolic sensor, and provided a generally accepted mechanism for metformin action on hepatic gluconeogenic program. However, the role of AMPK activation in metformin action has recently been challenged by loss-of-function experiments. Recent evidence showed that metformin-induced inhibition of hepatic glucose output is mediated by reducing cellular energy charge rather than direct inhibition of gluconeogenic gene expression. Furthermore, recent data support a novel mechanism of action for metformin involving antagonism of glucagon signaling pathways by inducing the accumulation of AMP, which inhibits adenylate cyclase and reduced levels of cAMP.
67 citations
TL;DR: The objective was to establish an experimental procedure and show clear results that unequivocally can be assigned as a surrogate for human papillomavirus infection and confirm the presence of the virus in the immune system.
Abstract: Annales d'Endocrinologie - In Press.Proof corrected by the author Available online since lundi 2 septembre 2013
45 citations
TL;DR: Data indicate moderate-resistance training would lead to gains in maximal strength, muscle circumference and increases anabolic hormone secretion for M men and consequently promoting of health, improve daily life and delay negative effects with aging.
Abstract: Objectives To examine the response of the endocrine system, strength development and muscle circumference to moderate-resistance training in younger and middle-aged men. Material and methods Two groups of men of similar activity background, but differing in age (Y: 21.2 ± 2.2 years and M: 49.7 ± 2.1 years) participated in an 8-week moderate-resistance training program. Blood sampling was obtained at rest before and after training for analysis of serum testosterone, growth hormone, cortisol and ACTH concentrations. One repetition maximum for the bench press (1RM BP ) and squat (1RM S ); thigh (TC) and arm circumference (AC) were also measured. Both groups underwent a 1-h standardized moderate-resistance training session (three series of 8 to 15 RM; nine exercises with 1–3 min rest between sets) three times a week for 8 weeks. Results Both the Y and M groups gained significant improvements in 1RM BP , 1RM S , TC and AC ( P Conclusion These data indicate moderate-resistance training would lead to gains in maximal strength, muscle circumference and increases anabolic hormone secretion for M men and consequently promoting of health, improve daily life and delay negative effects with aging.
28 citations
TL;DR: Giptins may represent a valuable alternative to a sulfonylurea or a glitazone after failure of monotherapy with metformin while GLP-1 receptor agonists may be considered as a good alternative to insulin (especially in obese patients) after Failure of a dual oral therapy.
Abstract: Pharmacological treatment of type 2 diabetes has been enriched during recent years, with the launch of incretin therapies targeting glucagon-like peptide-1 (GLP-1). Such medications comprise either GLP-1 receptor agonists, with short (one or two daily injections: exenatide, liraglutide, lixisenatide) or long duration (one injection once weekly: extended-released exenatide, albiglutide, dulaglutide, taspoglutide); or oral compounds inhibiting dipeptidyl peptidase-4 (DPP-4), the enzyme that inactives GLP-1, also called gliptins (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin). Although both pharmacological approaches target GLP-1, important differences exist concerning the mode of administration (subcutaneous injection versus oral ingestion), the efficacy (better with GLP-1 agonists), the effects on body weight and systolic blood pressure (diminution with agonists versus neutrality with gliptins), the tolerance profile (nausea and possibly vomiting with agonists) and the cost (higher with GLP-1 receptor agonists). Both agents may exert favourable cardiovascular effects. Gliptins may represent a valuable alternative to a sulfonylurea or a glitazone after failure of monotherapy with metformin while GLP-1 receptor agonists may be considered as a good alternative to insulin (especially in obese patients) after failure of a dual oral therapy. However, this scheme is probably too restrictive and modalities of using incretins are numerous, in almost all stages of type 2 diabetes. Physicians may guide the pharmacological choice based on clinical characteristics, therapeutic goals and patient's preference.
27 citations
TL;DR: Tumour cell secretions are able to modify tumour-surrounding adipocytes to an activated state that is named Cancer-Associated Adipocytes (CAAs), and the role of CAAs in breast cancer progression, as well as the potential amplification of this negative effect in obesity conditions will be discussed.
Abstract: Accumulating recent evidence highlights the tumour-surrounding adipose tissue as a key component of breast cancer progression. We have recently demonstrated that a bidirectional crosstalk is established with breast cancer cells and tumour-surrounding adipocytes. Tumour cell secretions are able to modify tumour-surrounding adipocytes to an activated state that we have named Cancer-Associated Adipocytes (CAAs). The role of CAAs in breast cancer progression, as well as the potential amplification of this negative effect in obesity conditions will be discussed.
26 citations
TL;DR: In this article, the authors highlight some of the HIF-1-induced gene products, such as carbonic anhydrases IX and XII (CAs) and monocarboxylate transporters (MCTs), which regulate the intracellular pH by controlling export of metabolically-generated acids (carbonic and lactic acids).
Abstract: The transcription factor hypoxia-inducible factor-1 (HIF-1) facilitates the induction of enzymes necessary for regulation of biological processes required for cell survival and the acquisition of an aggressive and invasive phenotype, such as regulation of the intracellular pH (pHi), anaerobic glycolysis, angiogenesis, migration/invasion... In this presentation, we will highlight some of the HIF-1-induced gene products – carbonic anhydrases IX and XII (CAs) and monocarboxylate transporters (MCTs) – which regulate the pHi by controlling export of metabolically-generated acids (carbonic and lactic acids). We reported that targeting these pHi-regulated processes through inhibition of either HIF-1-induced CAIX/CAXII or HIF-1-induced MCT4, MCT1 or Basigin/EMMPRIN/CD147 chaperone of MCTs, severely restricts glycolysis-generated ATP levels and tumor growth. In addition, we demonstrated that the Myc/HIF-1-targeted glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzing a key step producing the NADH cofactor, activates the Akt pathway, thereby upregulating expression of the anti-apoptotic Bcl-xL. As a consequence, high expression of GAPDH contributes to tumor aggressiveness, in particular in the context Myc- driven B lymphomas. We propose that membrane-bound carbonic anhydrases (CAIX, CAXII), monocarboxylate transporters/chaperon Basigin (Myc-induced MCT1 and HIF-induced-MCT4) and GAPDH that are associated with exacerbated tumor metabolism, represent new potential targets for anticancer therapy.
24 citations
19 citations
TL;DR: Clinicians must be aware of possible false-positive findings to avoid misinterpretations of the I-131 WBS, which could lead to inappropriate treatments.
Abstract: Background Iodine-131 (I-131) whole-body scan (WBS) plays an important role in the management of patients with differentiated thyroid carcinoma (DTC), to detect normal thyroid remnants and recurrent or metastatic disease. A focus of I-131 accumulation outside the thyroid bed and the areas of physiological uptake is strongly suggestive of a distant functioning metastasis. However, many false-positive I-131 WBS findings have been reported in the literature. Patient findings We describe a series of 11 personal cases of patients with DTC, collected from 1992 to 2011, in whom diagnostic or post-treatment WBS showed false-positive retention of I-131 in various locations. Summary False-positive accumulations of I-131 on WBS may be classified according to the underlying pathophysiological mechanisms: external and internal contaminations by body secretions, ectopic normal thyroid and gastric tissues, inflammatory and infectious diseases, benign and malignant tumors, cysts and effusions of serous cavities, thymic uptake, and other non classified causes. Conclusions Clinicians must be aware of possible false-positive findings to avoid misinterpretations of the I-131 WBS, which could lead to inappropriate treatments.
17 citations
TL;DR: An invasive macroadenoma in young women requires: the preoperative determination of plasma GH and IGF-1, the immunohistochemical detection in the tumor of GH, PRL, somatostatin receptor expression and the evaluation of the proliferation (mitoses count, Ki-67 and p53 indexes).
Abstract: Silent GH pituitary tumors are characterized by the absence of clinical features of acromegaly, normal to slightly elevated GH and/or IGF-1 levels, as well as immunohistochemical expression of GH. The diagnostic and the therapeutic challenges of these "silent" GH tumors are illustrated in this case report, supported by a literature review. A 20-year-old woman presented with visual disturbances related to an invasive macroadenoma but without clinical and biological signs of GH hypersecretion. After two surgeries, a residual tumor remained in the right cavernous sinus. According to the recent classifications, the histopathological diagnosis was a sparsely GH-PRL atypical adenoma or invasive and proliferative (Ki-67 index: 4%) and p53 positive (1%) grade 2b tumor, with high expression (>75% of the cells) of somatostatin receptors type 2A and 5. From this case and the review of the literature, an invasive macroadenoma in young women requires: the preoperative determination of plasma GH and IGF-1, the immunohistochemical detection in the tumor of GH, PRL, somatostatin receptor expression and the evaluation of the proliferation (mitoses count, Ki-67 and p53 indexes). The suspicion of an aggressive behavior needs a particular follow-up. In the case of tumor remnant, a postoperative treatment such as radiotherapy and/or somatostatin analogs must be considered.
TL;DR: The results confirmed the predominance of the EMTs in relation to the hôpital Haut-Lévêque and the CHU de Bordeaux in terms of the number of admissions and the quality of the treatment provided for these patients.
Abstract: Arnaud Agin b, Anne Charrie c, Karim Chikh c, Antoine Tabarin d, Delphine Vezzosi a,∗ a Service d’endocrinologie, maladies métaboliques et nutrition, centre hospitalier universitaire Rangueil-Larrey, université Paul Sabatier et Inserm U1037 Toulouse, 31059 Toulouse cedex 09, France b Unité mixte de recherche 7004, centre national de la recherche scientifique, institut de physique biologique, faculté de médecine, université Louis-Pasteur, 67000 Strasbourg, France c Laboratoire de technique nucléaire et biophysiques, centre hospitalier Lyon-Sud, 69495 Pierre-Bénite, France d Service d’endocrinologie-diabétologie et maladies métaboliques, hôpital Haut-Lévêque, GH Sud, CHU de Bordeaux, 33604 Pessac cedex, France
TL;DR: This paper shows participation of the E2F1-CDK4 axis in the modulation of oxidative metabolism, in the positive regulation of lipid synthesis, and the regulation glycolysis, which are crucial factors for cancer cell survival.
Abstract: An important hallmark of cancer cells is a profound change in metabolism. Indeed, most tumor cells are characterized by higher rates of glycolysis, lactate production, and biosynthesis of lipids and other macromolecules. Our group, among others, has previously demonstrated a close relationship between metabolic responses and proliferative stimuli, showing that cell cycle regulators have a major role in the control of metabolism. Changes in this coordinated response might lead to abnormal metabolic changes during tumor development and cancer progression. In this paper we review the dual role of cell cycle regulators in the control of both proliferation and metabolism in normal and in cancer cells. We show participation of the E2F1-CDK4 axis in the modulation of oxidative metabolism, in the positive regulation of lipid synthesis, and the regulation glycolysis. These three metabolic pathways are, interestingly fundamental in providing synthetic processes, energy production and cell signaling events, which are crucial factors for cancer cell survival.
TL;DR: HIV infection is associated with adrenal disorders, which must not be underestimated, and the impact of HIV infection on the other adrenocortical functions has been less reported in the literature although several studies show low levels of adrenal androgens, especially dehydroepiandrostenedione (DHEA).
Abstract: Human Immunodeficiency Virus (HIV) infection is associated with adrenal disorders, which must not be underestimated. Adrenal morphologic changes are primarily related to opportunistic infections, mostly by cytomegalovirus and mycobacteria, and malignant tumours such as non-Hodgkin's lymphoma and Kaposi's sarcoma. The most frequent biological alteration reported to date is the increases in cortisol concentrations which results from a decrease in cortisol metabolism and hyperactivity of the hypothalamo-pituitary-adrenal axis commonly referred to as pseudo-Cushing's syndrome. These modifications can be a consequence of antiretroviral therapy and do not require any investigation or specific treatment. Conversely, adrenal insufficiency, either iatrogenic or secondary to glandular infiltration by neoplasms or infections, needs long-term substitution with hydrocortisone, but at present occurs more rarely and usually at late stages of disease progression. The impact of HIV infection on the other adrenocortical functions has been less reported in the literature although several studies show low levels of adrenal androgens, especially dehydroepiandrostenedione (DHEA). Impairment in mineralocorticoid function appears occasional and remains a subject of debate.
TL;DR: Dans ce contexte, la leptine semble etre un facteur majeur de the cancerogenese mammaire susceptible of contribuer a la reaction inflammatoire locale and a l’angiogenese, notamment chez les patientes obeses pour lesquelles une augmentation du potentiel metastatique et du risque de mortalite est decrite.
Abstract: Resume Plus d’un million de nouveaux cas de cancer du sein sont diagnostiques chaque annee dans le monde et plus de 400 000 deces sont enregistres suite a cette pathologie. L’obesite est un facteur de risque du cancer du sein en post-menopause et la place tenue par le tissu adipeux et les secretions adipocytaires (i.e. adipokines) commence a etre reconnue. En effet, d’une part, l’impregnation plasmatique en adipokines, modulee en situation d’obesite, pourrait avoir des effets « a distance » sur la cancerogenese mammaire et, d’autre part, les cellules mammaires sont au contact direct du microenvironnement adipocytaire, probablement plus developpe en situation d’obesite. Dans ce contexte, la leptine semble etre un facteur majeur de la cancerogenese mammaire susceptible de contribuer a la reaction inflammatoire locale et a l’angiogenese, notamment chez les patientes obeses pour lesquelles une augmentation du potentiel metastatique et du risque de mortalite est decrite.
TL;DR: Recent results concerning the antitumor action of metformin are reviewed in epidemiological, metabolic, cellular and molecular levels to help better understand the mechanisms of action and determine whether the drug can be used in the treatment of cancer.
Abstract: Cancer and type II diabetes are two diseases that appear to be associated In fact, diabetes increases the incidence of several cancers (colon, endometrium, rectum and breast) Retrospective epidemiological studies show that metformin, a drug commonly used in type II diabetes, has antitumor properties Therefore, many experimental studies (in vivo and in vitro) have been initiated in recent years to understand the cellular and molecular mechanisms that may explain the protective effects of metformin against cancer Two main mode of action have been proposed The first, indirect, involves the decrease of insulinemia The second, via a direct action on cells, results in the regulation of the activated AMPK kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway, which plays a central role in many cellular processes such as energy metabolism, protein synthesis, autophagy and apoptosis Here, we review recent results concerning the antitumor action of metformin: epidemiological, metabolic, cellular and molecular levels Ongoing experimental and clinical trials should help us better understand the mechanisms of action of metformin and allow us to determine whether the drug can be used in the treatment of cancer
TL;DR: It is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting.
Abstract: Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting.
TL;DR: Treatment: Symptomatic treatment of hypoglycaemia Traitement symptomatique d’une hypoglycémie.
Abstract: Treatment: Symptomatic treatment of hypoglycaemia Traitement symptomatique d’une hypoglycémie♦ Antoine Tabarin a,∗, Bernard Goichot b a Service d’endocrinologie-diabétologie et maladies métaboliques, hôpital Haut-Lévêque, groupe hospitalier Sud, CHU de Bordeaux, 33604 Pessac cedex, France b Pôle médecine interne, rhumatologie, nutrition, endocrino-diabetologie (MIRNED), CHRU de Strasbourg, 67000 Strasbourg, France
TL;DR: In this paper, an in vivo molecular "dissection" that allows to delineate in mouse the role of the main "subfunctions" of the estrogen receptor was presented.
Abstract: Given this widespread role for estrogen in human physiology, it is not surprising that estrogen influence the pathophysiology of numerous diseases, including cancer (of the reproductive tract as breast, endometrial but also colorectal, prostate…), as well as neurodegenerative, inflammatory-immune, cardiovascular and metabolic diseases, and osteoporosis. These actions are mediated by the activation of estrogen receptors (ER) alpha (ERα) and beta (ERβ), which regulate target gene transcription (genomic action) through two independent activation functions (AF)-1 and AF-2, but can also elicit rapid membrane initiated steroid signals (MISS). Targeted ER gene inactivation has shown that although ERβ plays an important role in the central nervous system and in the heart, ERα appears to play a prominent role in most of the other tissues. Pharmacological activation or inhibition of ERα and/or ERβ provides already the basis for many therapeutic interventions, from contraception or hormone replacement at menopause to prevention of the recurrence of breast cancer. However, the use of these estrogens or selective estrogen receptors modulators (SERMs) have also induced undesired effects. Thus, an important challenge consists now to uncouple the beneficial actions from other deleterious ones. We summarize here an in vivo molecular "dissection" that allows to delineate in mouse the role of the main "subfunctions" of the receptor. This could pave the way to an optimization of the ER modulation.
TL;DR: The team is focused on the role of mammalian Target of Rapamycin (mTOR) in two pathophysiological conditions that modulate liver growth: liver regeneration after partial hepatectomy, and steatosis-associated tumorigenesis.
Abstract: It is established that overnutrition is a risk factor for hepatocellular carcinoma. Il has been proposed that hepatic steatosis leads to a subinflammatory response and to the production of mitogenic cytokines. Our team is focused on the role of mammalian Target of Rapamycin (mTOR) in two pathophysiological conditions that modulate liver growth: liver regeneration after partial hepatectomy, and steatosis-associated tumorigenesis. Target kinases of mTOR seem more specifically involved in these processes: while S6K1 contributes to liver regeneration following hepatectomy, Akt2 is implicated in steatosis-associated tumorigenesis. In addition, recent data indicate that the transcription factor PPARγ, through an activation of glycolytic enzymes, could promote liver steatosis, hypertrophy and hyperplasia.
TL;DR: Overt hypothyroidism may be related to impairment of LV longitudinal myocardial function, and 2D-STE is useful for the detection of early impairment, and Successful treatment of overt hyp Timothyroidism has a beneficial effect on cardiac functions.
Abstract: Objective Our aim was to evaluate cardiac function and myocardial contractility in patients with overt hypothyroidism using two-dimensional speckle tracking echocardiography (2D-STE) strain imaging and real-time three-dimensional echocardiography (RT3DE) and compare the changes at one month after starting the treatment. We also compared the P wave dispersion (Pdis) in patients with and without hypothyroidism. Subjects and methods Forty-one patients with overt hypothyroidism and forty age- and body mass index-matched healthy subjects underwent conventional echocardiography, RT3DE and 2D-STE for assessment of resting LV function. Electrocardiography (ECG) recordings were obtained and the P wave parameters were calculated. Measurements of RT3DE volumes and ejection fraction (EF) were performed. Global longitudinal strain (GLS) was calculated from 3 standard apical views using 2D-STE. Results Patients with overt hypothyroidism had significantly longer isovolumic contraction time (P Conclusions Overt hypothyroidism may be related to impairment of LV longitudinal myocardial function, and 2D-STE is useful for the detection of early impairment. Successful treatment of overt hypothyroidism has a beneficial effect on cardiac functions. In addition, overt hypothyroidism has increased risk for atrial arrhythmias due to high Pdis value.
TL;DR: (131)I therapy is a feasible and effective treatment for DTC lung metastases and a better prognosis would be accomplished in those who had low level of preablation stimulated Tg in DTC patient with lung metastase.
Abstract: Objective Our objective was to investigate the clinical efficacy of 131 I therapy for lung metastases from differentiated thyroid cancer (DTC) and assess whether the preablation stimulated thyroglobulin (Tg) could have predictive value for the outcome. Methods and materials Fifty-two DTC patients (mean 44.5 ± 19.2 years; 33 females and 19 males) with lung metastases treated with 131 I were retrospectively analysed. The therapeutic efficacy was evaluated based on the change in serum Tg. Fifty patients’ preablation stimulated Tg were collected with negative Tg antibody levels and estimated using the t -test method. Results After 131 I therapy, a significant decrease in serum Tg was seen in 30 patients (effective rate, 57.6%), and changes in serum Tg that indicated stabilization and ineffectiveness were both seen in 11 patients (21.2%). Only patients with age under 45 years were more likely to respond to serum Tg changes ( P = 0.046). But binary logistic regression revealed that none of the six factors (age, patient gender, pathological type, local lymph node involvement, size of metastases, and 131 I uptake by metastases) had statistically significant impacts on the efficacy analysis (all P > 0.05). For analysing with the preablation stimulated Tg, the “Fine miliaric” and 131 I uptake positive with great prognosis group was much lower than any other group (all the P Conclusion 131 I therapy is a feasible and effective treatment for DTC lung metastases. A better prognosis would be accomplished in those who had low level of preablation stimulated Tg in DTC patient with lung metastases.
TL;DR: Several meta-analyses recently confirmed that metformin therapy reduces the incidence of cancers and cancer-related mortality and was more evident in observational cohort studies than in case-control studies.
Abstract: With the better management of cardiovascular risk factors, cancer plays an increasing role in the causes of death among patients with type 2 diabetes. Numerous epidemiological cohort and case-control studies showed that type 2 diabetes is a risk factor for cancer and that metformin therapy is associated with a significant reduction in the incidence of cancer and cancer-related death when compared to other glucose-lowering agents (sulfonylureas, insulin). Such beneficial effect is observed almost whatever the type of cancer, but seems to be more prominent in case of gastrointestinal and breast cancers. Several studies showed a significant relationship between the amplitude of the protection against cancer, on the one hand, and the daily dose of metformin and the duration of exposure, on the other hand. In general, the protective effect was more evident in observational cohort studies (however, more exposed to bias due to confounding factors) than in case-control studies. Several meta-analyses recently confirmed that metformin therapy reduces the incidence of cancers and cancer-related mortality. However, the results of the rather rare controlled clinical trials available are not conclusive, but none of them was performed with the objective to specifically assess cancer risk. Considering all promising clinical information in patients with type 2 diabetes, further clinical trials are currently ongoing with the aim of assessing the role of metformin in oncology, independently of the presence of diabetes.
TL;DR: The patient developed allergy to human regular insulin and insulin analogs (insulin aspart and insulin glargine), which was resolved by subcutaneous insulin desensitization.
Abstract: Insulin allergy is a rare clinical situation. We report a 51-year-old patient with type 2 diabetes who required multiple daily insulin injections. The patient developed allergy to human regular insulin and insulin analogs (insulin aspart and insulin glargine), which was resolved by subcutaneous insulin desensitization.
TL;DR: Two populations of human white adipose tissue (WAT) progenitors cooperate in breast cancer angiogenesis, growth and metastatic progression, which raises the issue of lipotransfer in patients undergoing plastic or reconstructive surgery.
Abstract: Obesity, an excess accumulation of adipose tissue occurring in mammalians when caloric intake exceeds energy expenditure, is associated with an increased frequency and progression of several types of neoplastic diseases including postmenopausal breast cancer. Recent studies have suggested that obesity-related disruption of the energy homeostasis results in inflammation and alterations of adipokine signalling that may foster cancer initiation and progression. Moreover, two populations of human white adipose tissue (WAT) progenitors cooperate in breast cancer angiogenesis, growth and metastatic progression. This raises the issue of lipotransfer in patients undergoing plastic or reconstructive surgery.
TL;DR: In this article, the authors suggest that Activin A (ActA) and Myostatin (Mstn), two members of the TGFβ superfamily, could contribute to skeletal muscle atrophy observed in some cancers.
Abstract: Recent works suggest that Activin A (ActA) and Myostatin (Mstn), two members of the TGFβ superfamily, could contribute to skeletal muscle atrophy observed in some cancers. It is known that several human tumoral cell lines synthesize and secrete ActA and Mstn. In addition, systemic treatment with ActA and Mstn in mice induce muscle atrophy. Likewise, Inhibin-α knock-out mice, which are characterized by elevated circulating levels of ActA, exhibit muscle atrophy and die of cachexia. Finally, administration of ActA and Mstn antagonists prevents muscular atrophy and mortality induced by some animal tumors. Collectively, these findings suggest that ActA or Mstn production by several cancers could contribute to cachexia and thus to mortality associated with some cancers in human. This hypothesis is very interesting since new molecules that are able to inhibit ActA and Mstn, in particularly the sActRIIB, are under development.
TL;DR: Topographic diagnosis: Respective roles of morphological and functional imaging Diagnostic topographique : rôles respectifs de l’imagerie morphologique and fonctionnelle.
Abstract: Topographic diagnosis: Respective roles of morphological and functional imaging Diagnostic topographique : rôles respectifs de l’imagerie morphologique et fonctionnelle♦ David Taieb a,∗, Paul Legmann b, Frederic Prat c, Patrick Chevallier d, Florence Tenenbaum e a Department of Nuclear Medicine, La Timone University Hospital, CERIMED, 264, rue Saint-Pierre, 13385 Marseille cedex 5, France b Department of Radiology, Cochin Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France c Department of Gastroenterology, Cochin Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France d Département d’imagerie médicale, hôpital de l’Archet, 151, route de Saint-Antoine de Ginestière, 06200 Nice, France Assistance Publique des Hôpitaux de Paris, Paris, France
TL;DR: The case of a 56-year-old man with malignant insulinoma, which was misdiagnosed as epilepsy, is reported, showing that timely diagnosis of this disease is of paramount importance to prevent neurologic sequelae of hypoglycemia.
Abstract: Pancreatic neuroendocrine tumors (PNET) are extremely rare, and although insulinomas are the commonest, less than 10% of insulinomas are malignant. Most patients with insulinomas present neuroglycopenic symptoms. Because of the rarity of the condition, we report the case of a 56-year-old man with malignant insulinoma, which was misdiagnosed as epilepsy. Timely diagnosis of this disease is of paramount importance to prevent neurologic sequelae of hypoglycemia. Insulinomas should be regarded from the beginning as potentially malignant, although the majority of malignant insulinomas progresses slowly.
TL;DR: Insulinome de cause genetique a,∗ b c d Francoise Borson-Chazot, Catherine Cardot-Bauters, Eric Mirallie, Francois Pattou, Department of endocrinology, hospices civils de Lyon, groupement hospitalier Est, Lille university hospital, 59000 Lille, France.
Abstract: Insulinome de cause genetique a,∗ b c d Francoise Borson-Chazot , Catherine Cardot-Bauters , Eric Mirallie , Francois Pattou a Department of endocrinology, hospices civils de Lyon, groupement hospitalier Est, aile A, 59, boulevard Pinel 1, 69677 Bron cedex, France b Endocrinology and metabolism department, Lille university hospital, 59000 Lille, France c Clinique de chirurgie digestive et endocrinienne, IMAD, 44000 Nantes, France d Inserm U859, endocrine surgery department, Lille university hospital, 59000 Lille, France