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Article ; Online: Gastritis Cystica Profunda: A Rare Disease, a Challenging Diagnosis, and an Uncertain Malignant Potential: A Case Report and Review of the Literature.

De Stefano, Francesca / Graziano, Giorgio M P / Viganò, Jacopo / Mauro, Aurelio / Peloso, Andrea / Peverada, Jacopo / Fellegara, Raffaele / Vanoli, Alessandro / Faillace, Giuseppe G / Ansaloni, Luca

Medicina (Kaunas, Lithuania)

2023 Volume 59, Issue 10

Abstract: Gastritis cystica profunda (GCP) has been defined as a rare submucosal benign gastric lesion with cystic gland growth. Due to its unclear etiopathogenesis, this lesion is often misdiagnosed and mistaken for other gastric masses. Currently, a standardized ...

Abstract	Gastritis cystica profunda (GCP) has been defined as a rare submucosal benign gastric lesion with cystic gland growth. Due to its unclear etiopathogenesis, this lesion is often misdiagnosed and mistaken for other gastric masses. Currently, a standardized treatment for GCP lesions is still missing. Here, we illustrate a case of a patient admitted to our general surgery department for melena and general discomfort. No history of peptic ulcer or gastric surgery was present. Upper GI endoscopy was performed, showing a distal gastric lesion with a small ulceration on the top. CT-scan and endoscopic ultrasound confirmed the presence of the lesion, compatible with a gastric stromal tumor, without showing any eventual metastasis. Surgical gastric resection was performed. Histological findings were diagnostic for GCP, with cistically ectasic submucosal glands, chronic inflammation, eosinophilic infiltration and foveal hyperplasia. GCP is a very exceptional cause of upper-GI bleeding with specific histological features. Its diagnosis as well as its therapy are challenging, resulting in several pitfalls. Even though it is a rare entity, GCP should always be considered in the differential diagnosis of gastric submucosal lesions.
MeSH term(s)	Humans ; Gastritis/etiology ; Rare Diseases/diagnosis ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/surgery ; Stomach Neoplasms/pathology ; Gastrointestinal Neoplasms/complications
Language	English
Publishing date	2023-10-04
Publishing country	Switzerland
Document type	Review ; Case Reports
ZDB-ID	2188113-3
ISSN	1648-9144 ; 1010-660X
ISSN (online)	1648-9144
ISSN	1010-660X
DOI	10.3390/medicina59101770
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Article ; Online: Thoracic Endometriosis Syndrome: Association With Pelvic Endometriosis and Fertility Status.

Ottolina, Jessica / De Stefano, Francesca / Viganò, Paola / Ciriaco, Paola / Zannini, Piero / Candiani, Massimo

Journal of minimally invasive gynecology

2017 Volume 24, Issue 3, Page(s) 461–465

Abstract: Study objective: To evaluate associations among catamenial pneumothorax, pelvic endometriosis, and fertility status.: Design: Retrospective study (Canadian Task Force classification II-2).: Setting: Departments of Thoracic Surgery and Obstetrics ... ...

Abstract	Study objective: To evaluate associations among catamenial pneumothorax, pelvic endometriosis, and fertility status. Design: Retrospective study (Canadian Task Force classification II-2). Setting: Departments of Thoracic Surgery and Obstetrics and Gynecology, San Raffaele Hospital, Milan, Italy. Patients: Sixteen females referred to the Department of Thoracic Surgery for treatment of spontaneous pneumothorax between January 2001 and January 2014 and referred to the outpatient clinic for gynecologic follow-up. Interventions: Thoracoscopy for catamenial pneumothorax and laparoscopy for pelvic endometriosis. Measurements and main results: Characteristics of the patients, the presence of endometriosis, and their fertility status were statistically analyzed. Pelvic endometriosis was diagnosed in 9 patients (56.3%), but 6 patients did not undergo a laparoscopic procedure to confirm or exclude the disease. Seven of the affected patients (77.8%) had stage III-IV endometriosis. Two-thirds of the patients with pelvic endometriosis who attempted conception conceived spontaneously, as did all of the patients without histopathological confirmation of endometriosis. Conclusion: Thoracic endometriosis syndrome, characterized mainly by catamenial pneumothorax, is a relevant condition in patients affected by endometriosis. However, few previous studies have analyzed this condition from a gynecologic standpoint, in terms of characteristics of endometriosis and fertility status of affected women. Our findings support the presence of a strong association between catamenial pneumothorax and pelvic endometriosis, as well as a minimal effect of catamenial pneumothorax on fertility status, even in the presence of pelvic endometriosis.
MeSH term(s)	Adult ; Endometriosis/complications ; Endometriosis/surgery ; Female ; Fertility ; Humans ; Italy/epidemiology ; Laparoscopy ; Middle Aged ; Pneumothorax/epidemiology ; Pneumothorax/etiology ; Pneumothorax/surgery ; Retrospective Studies ; Syndrome ; Young Adult
Language	English
Publishing date	2017-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	2186934-0
ISSN	1553-4669 ; 1553-4650
ISSN (online)	1553-4669
ISSN	1553-4650
DOI	10.1016/j.jmig.2016.12.025
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Article ; Online: Flexible CO2 laser fiber: first look at the learning curve required in gynecological laparoscopy training.

Vanni, Valeria S / Ottolina, Jessica / Candotti, Giorgio / Castellano, Laura M / Tandoi, Iacopo / DE Stefano, Francesca / Poppi, Giorgia / Ferrari, Stefano / Candiani, Massimo

Minerva ginecologica

2018 Volume 70, Issue 1, Page(s) 53–57

Abstract: Background: The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical ... ...

Abstract	Background: The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical skills required to use the flexible system. The purpose of our study is to evaluate whether flexible CO2 laser fiber is technically accessible. Methods: Fourteen residents in Obstetrics and Gynecology without surgical experience attending laparoscopic box training with both flexible CO2 laser fiber and traditional line-of-sight CO2 laser using Lumenis AcuPulse Duo CO2 laser (Lumenis, Yokne'am Illit, Israel) were prospectively enrolled. Participants were tested at sequential time points on specific surgical tasks and results obtained with the flexible CO2 laser fiber and the traditional line-of-sight CO2 laser were compared. Results were compared by means of paired t-test and a two-tailed P value <0.05 was considered significant. Results: Mean grading at the beginning of training were similar between flexible fiber and line-of-sight CO2 laser. At the end of training, significant improvement in surgical skills was obtained for both techniques, with a statistically significant higher grading for flexible fiber CO2 laser compared to line-of-sight CO2 laser. Conclusions: Our study found that residents without surgical experience show better skills with the flexible CO2 laser fiber delivery system compared to the standard line-of-sight CO2 laser system after a two-month training period with gynecological laparoscopic box. According to our results, flexible CO2 laser fiber delivery system is technically accessible and holds a potential in gynecological surgery.
MeSH term(s)	Adult ; Clinical Competence ; Educational Measurement ; Gynecologic Surgical Procedures/education ; Gynecologic Surgical Procedures/methods ; Gynecology/education ; Gynecology/methods ; Humans ; Internship and Residency ; Laparoscopy/education ; Laparoscopy/methods ; Lasers, Gas/therapeutic use ; Learning Curve ; Prospective Studies
Language	English
Publishing date	2018-02
Publishing country	Italy
Document type	Journal Article
ZDB-ID	80159-8
ISSN	1827-1650 ; 0026-4784 ; 0325-8793
ISSN (online)	1827-1650
ISSN	0026-4784 ; 0325-8793
DOI	10.23736/S0026-4784.17.04101-6
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Article: Transcriptional landscape of mouse-aged ovaries reveals a unique set of non-coding RNAs associated with physiological and environmental ovarian dysfunctions.

Cuomo, Danila / Porreca, Immacolata / Ceccarelli, Michele / Threadgill, David W / Barrington, William T / Petriella, Annacristina / D'Angelo, Fulvio / Cobellis, Gilda / De Stefano, Francesca / D'Agostino, Maria N / De Felice, Mario / Mallardo, Massimo / Ambrosino, Concetta

Cell death discovery

2018 Volume 4, Page(s) 112

Abstract: The progressive and physiological decline in ovarian function depends on the rate of follicular loss by atresia, contributing to the reduction in ovarian reserve. Genetics and environmental factors play important roles in ovarian senescence and in the ... ...

Abstract	The progressive and physiological decline in ovarian function depends on the rate of follicular loss by atresia, contributing to the reduction in ovarian reserve. Genetics and environmental factors play important roles in ovarian senescence and in the onset of ovarian dysfunctions such as diminished ovarian reserve. A better understanding of the mechanisms underlying ovarian aging and their regulation by genetic and environmental factors is needed to evaluate ovarian reserve and to predict fertility potential by identification of more accurate and less invasive markers. We report transcriptomic data (i) implicating novel (e.g. EIF2 signalling) and well-known pathways (e.g. TGFβ signalling), and (ii) defining a unique set of non-coding RNA (ncRNA), both associated with ovarian function. The latter includes miRNAs (e.g.
Language	English
Publishing date	2018-12-05
Publishing country	United States
Document type	Journal Article
ISSN	2058-7716
ISSN	2058-7716
DOI	10.1038/s41420-018-0121-y
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Article ; Online: Gastrointestinal cancers reactive for the PAb416 antibody against JCV/SV40 T-Ag lack JCV DNA sequences while showing a distinctive pathologic profile.

Chiaravalli, Anna Maria / Longhi, Erika / Vigetti, Davide / De Stefano, Francesca Isabella / Deleonibus, Sara / Capella, Carlo / Solcia, Enrico / Parravicini, Carlo

Journal of clinical pathology

2013 Volume 66, Issue 1, Page(s) 44–49

Abstract: Aim: Immunohistochemical and molecular studies have suggested an oncogenic role for JCV in gastrointestinal carcinomas, but at least in colorectal cancers, the data are far from being unambiguous.: Methods: Two large series of formalin-fixed paraffin- ...

Abstract	Aim: Immunohistochemical and molecular studies have suggested an oncogenic role for JCV in gastrointestinal carcinomas, but at least in colorectal cancers, the data are far from being unambiguous. Methods: Two large series of formalin-fixed paraffin-embedded gastric and colorectal cancers were analysed for the expression of JCV large T Antigen (T-Ag) with a panel of five antibodies, and for the presence of T-Ag DNA sequences using two PCR systems. Results: Intense nuclear staining was observed in 54/116 (46%) colorectal, and in 92/234 (39%) gastric cancers, using the PAb416 monoclonal antibody against large T-Ag. In colorectal cancers, PAb416-positivity was directly related to the presence of chromosomal instability, lymph node metastases and a more advanced tumour stage, and inversely related to proximal tumour site and the presence of microsatellite instability (MSI). In gastric cancers, the glandular histotype, the presence of lymph node metastases, a low frequency of MSI and EBV infection, and a worse prognosis were significantly associated with PAb416 immunoreactivity. Moreover, at both these sites, PAb416 expression was significantly associated with p53 nuclear accumulation. No positivity was obtained with all the other four anti-T-Ag-antibodies, and molecular analysis failed to demonstrate the presence of JCV DNA sequences in tested cases. Conclusions: Our immunohistochemical and molecular results do not support the idea that JCV T-Ag has a role in gastrointestinal carcinogenesis. It is possible that PAb416, besides binding the viral protein, may cross-react with a hitherto undefined protein whose expression is associated with a distinct pathological profile and, at least in gastric cancers, with worse prognosis.
MeSH term(s)	Adenocarcinoma/genetics ; Adenocarcinoma/secondary ; Adenocarcinoma/virology ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Antigens, Polyomavirus Transforming/immunology ; Blotting, Western ; Cell Nucleus/metabolism ; Cell Nucleus/pathology ; Cross Reactions ; DNA, Viral/analysis ; Female ; Gastrointestinal Neoplasms/genetics ; Gastrointestinal Neoplasms/pathology ; Gastrointestinal Neoplasms/virology ; Humans ; JC Virus/genetics ; JC Virus/immunology ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Molecular Diagnostic Techniques ; Polymerase Chain Reaction ; Sequence Analysis, DNA
Chemical Substances	Antibodies, Monoclonal ; Antigens, Polyomavirus Transforming ; DNA, Viral
Language	English
Publishing date	2013-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80261-x
ISSN	1472-4146 ; 0021-9746
ISSN (online)	1472-4146
ISSN	0021-9746
DOI	10.1136/jclinpath-2012-200963
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Article ; Online: Benchmarking postoperative outcomes after open liver surgery for cirrhotic patients with hepatocellular carcinoma in a national cohort.

Famularo, Simone / Russolillo, Nadia / Donadon, Matteo / Cipriani, Federica / Ardito, Francesco / Perri, Pasquale / Giani, Alessandro / De Stefano, Francesca / Lai, Quirino / Molfino, Sarah / Zanello, Matteo / Iaria, Maurizio / La Barba, Giuliano / Pinotti, Enrico / Germani, Paola / Conci, Simone / Ferrari, Cecilia / Fumagalli, Luca / Romano, Maurizio /

Antonucci, Adelmo / Zimmitti, Giuseppe / Troci, Albert / Floridi, Antonio / Ferraro, Valentina / Patauner, Stefan / Frena, Antonio / Memeo, Riccardo / Crespi, Michele / Hilal, Mohammed A / Zanus, Giacomo / Chiarelli, Marco / Percivale, Andrea / Ruzzenente, Andrea / Tarchi, Paola / Zago, Mauro / Ercolani, Giorgio / Dalla Valle, Raffaele / Jovine, Elio / Baiocchi, Gian Luca / Rossi, Massimo / Maestri, Marcello / Romano, Fabrizio / Grazi, Gian Luca / Giuliante, Felice / Aldrighetti, Luca / Ferrero, Alessandro / Torzilli, Guido

HPB : the official journal of the International Hepato Pancreato Biliary Association

2022 Volume 24, Issue 8, Page(s) 1365–1375

Abstract: Background: Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined.: Methods: Patients were identified from the Italian national registry HE.RC.O.LE.S. The Achievable Benchmark of Care ( ...

Abstract	Background: Benchmark analysis for open liver surgery for cirrhotic patients with hepatocellular carcinoma (HCC) is still undefined. Methods: Patients were identified from the Italian national registry HE.RC.O.LE.S. The Achievable Benchmark of Care (ABC) method was employed to identify the benchmarks. The outcomes assessed were the rate of complications, major comorbidities, post-operative ascites (POA), post-hepatectomy liver failure (PHLF), 90-day mortality. Benchmarking was stratified for surgical complexity (CP1, CP2 and CP3). Results: A total of 978 of 2698 patients fulfilled the inclusion criteria. 431 (44.1%) patients were treated with CP1 procedures, 239 (24.4%) with CP2 and 308 (31.5%) with CP3 procedures. Patients submitted to CP1 had a worse underlying liver function, while the tumor burden was more severe in CP3 cases. The ABC for complications (13.1%, 19.2% and 28.1% for CP1, CP2 and CP3 respectively), major complications (7.6%, 11.1%, 12.5%) and 90-day mortality (0%, 3.3%, 3.6%) increased with the surgical difficulty, but not POA (4.4%, 3.3% and 2.6% respectively) and PHLF (0% for all groups). Conclusion: We propose benchmarks for open liver resections in HCC cirrhotic patients, stratified for surgical complexity. The difference between the benchmark values and the results obtained during everyday practice reflects the room for potential growth, with the aim to encourage constant improvement among liver surgeons.
MeSH term(s)	Benchmarking ; Carcinoma, Hepatocellular ; Hepatectomy/adverse effects ; Hepatectomy/methods ; Humans ; Liver Cirrhosis/complications ; Liver Cirrhosis/pathology ; Liver Cirrhosis/surgery ; Liver Failure/etiology ; Liver Neoplasms/complications ; Liver Neoplasms/surgery ; Postoperative Complications ; Retrospective Studies
Language	English
Publishing date	2022-03-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2131251-5
ISSN	1477-2574 ; 1365-182X
ISSN (online)	1477-2574
ISSN	1365-182X
DOI	10.1016/j.hpb.2022.02.008
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Article ; Online: The p66Shc protein controls redox signaling and oxidation-dependent DNA damage in human liver cells.

Perrini, Sebastio / Tortosa, Federica / Natalicchio, Annalisa / Pacelli, Consiglia / Cignarelli, Angelo / Palmieri, Vincenzo O / Caccioppoli, Cristina / De Stefano, Francesca / Porro, Stefania / Leonardini, Anna / Ficarella, Romina / De Fazio, Michele / Cocco, Tiziana / Puglisi, Francesco / Laviola, Luigi / Palasciano, Giuseppe / Giorgino, Francesco

American journal of physiology. Gastrointestinal and liver physiology

2015 Volume 309, Issue 10, Page(s) G826–40

Abstract: The p66Shc protein mediates oxidative stress-related injury in multiple tissues. Steatohepatitis is characterized by enhanced oxidative stress-mediated cell damage. The role of p66Shc in redox signaling was investigated in human liver cells and alcoholic ...

Abstract	The p66Shc protein mediates oxidative stress-related injury in multiple tissues. Steatohepatitis is characterized by enhanced oxidative stress-mediated cell damage. The role of p66Shc in redox signaling was investigated in human liver cells and alcoholic steatohepatitis. HepG2 cells with overexpression of wild-type or mutant p66Shc, with Ser36 replacement by Ala, were obtained through infection with recombinant adenoviruses. Reactive oxygen species and oxidation-dependent DNA damage were assessed by measuring dihydroethidium oxidation and 8-hydroxy-2'-deoxyguanosine accumulation into DNA, respectively. mRNA and protein levels of signaling intermediates were evaluated in HepG2 cells and liver biopsies from control and alcoholic steatohepatitis subjects. Exposure to H2O2 increased reactive oxygen species and phosphorylation of p66Shc on Ser36 in HepG2 cells. Overexpression of p66Shc promoted reactive oxygen species synthesis and oxidation-dependent DNA damage, which were further enhanced by H2O2. p66Shc activation also resulted in increased Erk-1/2, Akt, and FoxO3a phosphorylation. Blocking of Erk-1/2 activation inhibited p66Shc phosphorylation on Ser36. Increased p66Shc expression was associated with reduced mRNA levels of antioxidant molecules, such as NF-E2-related factor 2 and its target genes. In contrast, overexpression of the phosphorylation defective p66Shc Ala36 mutant inhibited p66Shc signaling, enhanced antioxidant genes, and suppressed reactive oxygen species and oxidation-dependent DNA damage. Increased p66Shc protein levels and Akt phosphorylation were observed in liver biopsies from alcoholic steatohepatitis compared with control subjects. In human alcoholic steatohepatitis, increased hepatocyte p66Shc protein levels may enhance susceptibility to DNA damage by oxidative stress by promoting reactive oxygen species synthesis and repressing antioxidant pathways.
MeSH term(s)	Cell Culture Techniques ; DNA Damage ; Fatty Liver, Alcoholic/metabolism ; Forkhead Box Protein O3 ; Forkhead Transcription Factors/metabolism ; Hepatocytes/metabolism ; Humans ; Oncogene Protein v-akt/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Phosphorylation ; Reactive Oxygen Species/metabolism ; Shc Signaling Adaptor Proteins/genetics ; Shc Signaling Adaptor Proteins/metabolism ; Signal Transduction ; Src Homology 2 Domain-Containing, Transforming Protein 1
Chemical Substances	FOXO3 protein, human ; Forkhead Box Protein O3 ; Forkhead Transcription Factors ; Reactive Oxygen Species ; SHC1 protein, human ; Shc Signaling Adaptor Proteins ; Src Homology 2 Domain-Containing, Transforming Protein 1 ; Oncogene Protein v-akt (EC 2.7.11.1)
Language	English
Publishing date	2015-11-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00041.2015
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Article ; Online: Exendin-4 prevents c-Jun N-terminal protein kinase activation by tumor necrosis factor-alpha (TNFalpha) and inhibits TNFalpha-induced apoptosis in insulin-secreting cells.

Natalicchio, Annalisa / De Stefano, Francesca / Orlando, Maura Roberta / Melchiorre, Mariangela / Leonardini, Anna / Cignarelli, Angelo / Labarbuta, Rossella / Marchetti, Piero / Perrini, Sebastio / Laviola, Luigi / Giorgino, Francesco

Endocrinology

2010 Volume 151, Issue 5, Page(s) 2019–2029

Abstract: Glucagon-like peptide-1 and its analogs may preserve pancreatic beta-cell mass by promoting resistance to cytokine-mediated apoptosis. The mechanisms of TNFalpha-induced apoptosis and of its inhibition by exendin-4 were investigated in insulin-secreting ... ...

Abstract	Glucagon-like peptide-1 and its analogs may preserve pancreatic beta-cell mass by promoting resistance to cytokine-mediated apoptosis. The mechanisms of TNFalpha-induced apoptosis and of its inhibition by exendin-4 were investigated in insulin-secreting cells. INS-1 and MIN6 insulinoma cells were exposed to 20 ng/ml TNFalpha, with or without pretreatment with 10 nm exendin-4. Treatment with TNFalpha increased c-Jun N-terminal protein kinase (JNK) phosphorylation 2-fold, reduced inhibitor-kappaBalpha (IkappaBalpha) protein content by 50%, induced opposite changes in caspase-3 and Bcl-2 protein content, and increased cellular apoptosis. Moreover, exposure to TNFalpha resulted in increased serine phosphorylation of both insulin receptor substrate (IRS)-1 and IRS-2 and reduced basal and insulin-induced Akt phosphorylation. However, in the presence of a JNK inhibitor, TNFalpha-induced apoptosis was diminished and serine phosphorylation of IRS proteins was prevented. When cells were pretreated with exendin-4, TNFalpha-induced JNK and IRS-1/2 serine phosphorylation was markedly reduced, Akt phosphorylation was increased, caspase-3 and Bcl-2 protein levels were restored to normal, and TNFalpha-induced apoptosis was inhibited by 50%. This was associated with a 2-fold increase in IRS-2 expression levels. A similar ability of exendin-4 to prevent TNFalpha-induced JNK phosphorylation was found in isolated pancreatic human islets. The inhibitory effect of exendin-4 on TNFalpha-induced JNK phosphorylation was abrogated in the presence of the protein kinase A inhibitor H89. In conclusion, JNK activation mediates TNFalpha-induced apoptosis and impairment of the IRS/Akt signaling pathway in insulin-secreting cells. By inhibiting JNK phosphorylation in a PKA-dependent manner, exendin-4 counteracts TNFalpha-mediated apoptosis and reverses the inhibitory events in the IRS/Akt pathway, resulting in promotion of cell survival.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Cell Line, Tumor ; Enzyme Activation/drug effects ; Humans ; Hypoglycemic Agents/pharmacology ; I-kappa B Proteins/metabolism ; Immunoblotting ; Insulin Receptor Substrate Proteins/metabolism ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Isoquinolines/pharmacology ; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases/metabolism ; NF-KappaB Inhibitor alpha ; Peptides/pharmacology ; Phosphorylation/drug effects ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-akt/metabolism ; Serine/metabolism ; Sulfonamides/pharmacology ; Time Factors ; Tumor Necrosis Factor-alpha/pharmacology ; Venoms/pharmacology
Chemical Substances	Hypoglycemic Agents ; I-kappa B Proteins ; Insulin Receptor Substrate Proteins ; Isoquinolines ; NFKBIA protein, human ; Peptides ; Protein Kinase Inhibitors ; Sulfonamides ; Tumor Necrosis Factor-alpha ; Venoms ; NF-KappaB Inhibitor alpha (139874-52-5) ; Serine (452VLY9402) ; exenatide (9P1872D4OL) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide (M876330O56)
Language	English
Publishing date	2010-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2009-1166
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Article: Involvement of the p66Shc protein in glucose transport regulation in skeletal muscle myoblasts.

Natalicchio, Annalisa / De Stefano, Francesca / Perrini, Sebastio / Laviola, Luigi / Cignarelli, Angelo / Caccioppoli, Cristina / Quagliara, Anna / Melchiorre, Mariangela / Leonardini, Anna / Conserva, Antonella / Giorgino, Francesco

American journal of physiology. Endocrinology and metabolism

2009 Volume 296, Issue 2, Page(s) E228–37

Abstract: The p66(Shc) protein isoform regulates MAP kinase activity and the actin cytoskeleton turnover, which are both required for normal glucose transport responses. To investigate the role of p66(Shc) in glucose transport regulation in skeletal muscle cells, ... ...

Abstract	The p66(Shc) protein isoform regulates MAP kinase activity and the actin cytoskeleton turnover, which are both required for normal glucose transport responses. To investigate the role of p66(Shc) in glucose transport regulation in skeletal muscle cells, L6 myoblasts with antisense-mediated reduction (L6/p66(Shc)as) or adenovirus-mediated overexpression (L6/p66(Shc)adv) of the p66(Shc) protein were examined. L6/(Shc)as myoblasts showed constitutive activation of ERK-1/2 and disruption of the actin network, associated with an 11-fold increase in basal glucose transport. GLUT1 and GLUT3 transporter proteins were sevenfold and fourfold more abundant, respectively, and were localized throughout the cytoplasm. Conversely, in L6 myoblasts overexpressing p66(Shc), basal glucose uptake rates were reduced by 30% in parallel with a approximately 50% reduction in total GLUT1 and GLUT3 transporter levels. Inhibition of the increased ERK-1/2 activity with PD98059 in L6/(Shc)as cells had a minimal effect on increased GLUT1 and GLUT3 protein levels, but restored the actin cytoskeleton, and reduced the abnormally high basal glucose uptake by 70%. In conclusion, p66(Shc) appears to regulate the glucose transport system in skeletal muscle myoblasts by controlling, via MAP kinase, the integrity of the actin cytoskeleton and by modulating cellular expression of GLUT1 and GLUT3 transporter proteins via ERK-independent pathways.
MeSH term(s)	Actin Cytoskeleton/metabolism ; Actin Cytoskeleton/physiology ; Animals ; Biological Transport/drug effects ; Biological Transport/genetics ; Cells, Cultured ; Gene Knockdown Techniques ; Glucose/metabolism ; Glucose Transporter Type 1/metabolism ; Glucose Transporter Type 1/physiology ; Glucose Transporter Type 3/metabolism ; Glucose Transporter Type 3/physiology ; MAP Kinase Signaling System/drug effects ; MAP Kinase Signaling System/physiology ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Myoblasts, Skeletal/drug effects ; Myoblasts, Skeletal/metabolism ; RNA, Small Interfering/pharmacology ; Rats ; Shc Signaling Adaptor Proteins/antagonists & inhibitors ; Shc Signaling Adaptor Proteins/genetics ; Shc Signaling Adaptor Proteins/physiology ; Src Homology 2 Domain-Containing, Transforming Protein 1
Chemical Substances	Glucose Transporter Type 1 ; Glucose Transporter Type 3 ; RNA, Small Interfering ; Shc Signaling Adaptor Proteins ; Shc1 protein, rat ; Slc2a1 protein, rat ; Slc2a3 protein, rat ; Src Homology 2 Domain-Containing, Transforming Protein 1 ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2009-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603841-4
ISSN	1522-1555 ; 0193-1849
ISSN (online)	1522-1555
ISSN	0193-1849
DOI	10.1152/ajpendo.90347.2008
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Article: Insulin signaling in human visceral and subcutaneous adipose tissue in vivo.

Laviola, Luigi / Perrini, Sebastio / Cignarelli, Angelo / Natalicchio, Annalisa / Leonardini, Anna / De Stefano, Francesca / Cuscito, Marilena / De Fazio, Michele / Memeo, Vincenzo / Neri, Vincenzo / Cignarelli, Mauro / Giorgino, Riccardo / Giorgino, Francesco

Diabetes

2006 Volume 55, Issue 4, Page(s) 952–961

Abstract: In this study, we evaluated the activation of various insulin signaling molecules in human fat in vivo and compared signaling reactions in visceral and subcutaneous fat depots. Paired abdominal omental and subcutaneous fat biopsies were obtained from ... ...

Abstract	In this study, we evaluated the activation of various insulin signaling molecules in human fat in vivo and compared signaling reactions in visceral and subcutaneous fat depots. Paired abdominal omental and subcutaneous fat biopsies were obtained from nonobese subjects with normal insulin sensitivity under basal conditions and 6 and 30 min following administration of intravenous insulin. Insulin receptor phosphorylation was more intense and rapid and insulin receptor protein content was greater in omental than in subcutaneous adipose tissue (P < 0.05). Insulin-induced phosphorylation of Akt also occurred to a greater extent and earlier in omental than in subcutaneous fat (P < 0.05) in the absence of significant changes in Akt protein content. Accordingly, phosphorylation of the Akt substrate glycogen synthase kinase-3 was more responsive to insulin stimulation in omental fat. Protein content of extracellular signal-regulated kinase (ERK)-1/2 was threefold higher in omental than in subcutaneous fat (P < 0.05), and ERK phosphorylation showed an early 6-min peak in omental fat, in contrast with a more gradual increase observed in subcutaneous fat. In conclusion, the adipocyte insulin signaling system of omental fat shows greater and earlier responses to insulin than that of subcutaneous fat. These findings may contribute to explain the biological diversity of the two fat depots.
MeSH term(s)	3T3 Cells ; Adipocytes/cytology ; Adipocytes/physiology ; Adipose Tissue/cytology ; Adipose Tissue/physiology ; Animals ; Biopsy ; Blood Glucose/metabolism ; Cells, Cultured ; Female ; Humans ; Insulin/physiology ; Male ; Mice ; Middle Aged ; Omentum ; Receptor, Insulin/metabolism ; Reference Values ; Signal Transduction ; Skin ; Viscera
Chemical Substances	Blood Glucose ; Insulin ; Receptor, Insulin (EC 2.7.10.1)
Language	English
Publishing date	2006-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/diabetes.55.04.06.db05-1414
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