Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
1.
Braz. j. med. biol. res ; 53(4): e9114, 2020. tab, graf
Article in English | LILACS | ID: biblio-1089357

ABSTRACT

This study aimed to explore the prognostic role of dipeptidyl peptidase 4 (DPP4) expression in hepatocellular carcinoma (HCC). DPP4 expression was measured in formalin-fixed paraffin-embedded specimens that were gathered from 327 HCC patients. Immunohistochemistry analyses were utilized to examine DPP4 expression characteristics and prognostic values (overall survival (OS) and time to recurrence) of DDP4 in HCC tissues. In addition, a patient-derived xenograft (PDX) model was used to assess the correlation between DPP4 expression and tumor growth in vivo. DPP4 was expressed in low levels in HCC tissues in contrast to paired peritumoral tissues (38 cases were down-regulated in a total of 59 cases, 64.4%. P=0.0202). DPP4 expression was significantly correlated with TNM stage (P=0.038), tumor number (P=0.035), and vascular invasion (P=0.024), and significantly reduced in patients who were in TNM stages II and III-V, with multiple tumors, and with microvascular invasion compared to patients with TNM stage I, single tumor, and no microvascular invasion. Notably, HCC tissues with low expression of DPP4 had poor OS (P=0.016) compared with HCC tissues with high expression of DPP4, and results from PDX model showed that tumor growth was significantly faster in HCC patients that lowly expressed DPP4 compared to those with highly expressed DPP4. Our findings suggested that low levels of DPP4 could impact the aggressiveness of HCC and contribute to a poor prognosis.


Subject(s)
Humans , Animals , Male , Female , Middle Aged , Carcinoma, Hepatocellular/metabolism , Dipeptidyl Peptidase 4/metabolism , Liver Neoplasms/metabolism , Prognosis , Immunohistochemistry , Biomarkers, Tumor , Follow-Up Studies , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/mortality , Xenograft Model Antitumor Assays , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Neoplasm Recurrence, Local
2.
Article in English | WPRIM | ID: wpr-58415

ABSTRACT

A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray, and the patient was placed on a mechanical ventilator because of progressive respiratory failure. Urinary protein excretion steadily increased for a microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks after the onset of symptoms. Acute tubular necrosis was the main finding, and proteinaceous cast formation and acute tubulointerstitial nephritis were found. There were no electron dense deposits observed with electron microscopy. We could not verify the virus itself by in situ hybridization and confocal microscopy (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary virus excretion, and timely kidney biopsy results should be investigated with thorough precautions to reveal the direct effects of MERS-CoV with respect to renal complications.


Subject(s)
Aged , Humans , Male , Biopsy , Coronavirus Infections/diagnosis , Creatinine/blood , Dipeptidyl Peptidase 4/metabolism , In Situ Hybridization, Fluorescence , Kidney/metabolism , Microscopy, Confocal , Microscopy, Electron , Middle East Respiratory Syndrome Coronavirus/genetics , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , Serum Albumin/analysis
3.
Article in English | WPRIM | ID: wpr-186438

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) causes high fever, cough, acute respiratory tract infection and multiorgan dysfunction that may eventually lead to the death of the infected individuals. MERS-CoV is thought to be transmitted to humans through dromedary camels. The occurrence of the virus was first reported in the Middle East and it subsequently spread to several parts of the world. Since 2012, about 1368 infections, including ~487 deaths, have been reported worldwide. Notably, the recent human-to-human \'superspreading' of MERS-CoV in hospitals in South Korea has raised a major global health concern. The fatality rate in MERS-CoV infection is four times higher compared with that of the closely related severe acute respiratory syndrome coronavirus infection. Currently, no drug has been clinically approved to control MERS-CoV infection. In this study, we highlight the potential drug targets that can be used to develop anti-MERS-CoV therapeutics.


Subject(s)
Animals , Humans , Antiviral Agents/pharmacology , Cell Line , Coronavirus Infections/drug therapy , Dipeptidyl Peptidase 4/metabolism , Disease Outbreaks , Drug Discovery , Host-Pathogen Interactions/drug effects , Middle East Respiratory Syndrome Coronavirus/drug effects , Molecular Targeted Therapy , Spike Glycoprotein, Coronavirus/metabolism
4.
Article in English | WPRIM | ID: wpr-92367

ABSTRACT

Despite strict pre- and post-transplantation screening, the incidence of new-onset diabetes after transplantation (NODAT) remains as high as 60%. This complication affects the risk of cardiovascular events and patient and graft survival rates. Thus, reducing the impact of NODAT could improve overall transplant success. The pathogenesis of NODAT is multifactorial, and both modifiable and nonmodifiable risk factors have been implicated. Monitoring and controlling the blood glucose profile, implementing multidisciplinary care, performing lifestyle modifications, using a modified immunosuppressive regimen, administering anti-metabolite agents, and taking a conventional antidiabetic approach may diminish the incidence of NODAT. In addition to these preventive strategies, inhibition of dipeptidyl peptidase-4 (DPP4) by the gliptin family of drugs has recently gained considerable interest as therapy for type 2 diabetes mellitus and NODAT. This review focuses on the role of DPP4 inhibitors and discusses recent literature regarding management of NODAT.


Subject(s)
Animals , Humans , Blood Glucose/drug effects , Diabetes Mellitus/diagnosis , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Organ Transplantation/adverse effects , Risk Assessment , Risk Factors , Treatment Outcome
5.
Article in English | WPRIM | ID: wpr-93094

ABSTRACT

Dipeptidylpeptidase (DPP) 4, also known as CD26, is an enzyme present on the surface of a number of different cell types. It is also found within cells and as a soluble protein in body fluids. It can specifically truncate proteins at the penultimate N-terminus residue for some amino acids, such as alanine, proline, serine, and perhaps others. DPP4 has been implicated in regulating the in vitro and in vivo functional activities of a number of hematopoietically active molecules, and this information, along with that on inhibition of DPP4, has been studied in efforts to enhance hematopoietic cell transplantation (HCT), hematopoiesis after stress in mouse models, and in the clinical setting of single-unit cord blood (CB) HCT. This article reviews the current status of this compound's effects on regulatory proteins, the field of CB HCT, a potential role for modulating DPP4 activity in enhancing single-unit CB HCT in adults, and future aspects in context of other cellular therapies and the area of regenerative medicine.


Subject(s)
Animals , Humans , Cord Blood Stem Cell Transplantation , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Hematopoiesis/drug effects , Hematopoietic Stem Cells/drug effects , Regenerative Medicine/methods , Signal Transduction/drug effects
6.
Rev. argent. endocrinol. metab ; 47(3): 39-54, jul.-set. 2010. ilus, tab
Article in Spanish | LILACS | ID: lil-641977

ABSTRACT

En los últimos años se reconoce un nuevo mecanismo involucrado en la fisiopatología de la Diabetes Mellitus tipo 2: el déficit de producción y/o acción de las incretinas. Las incretinas son enterohormonas que estimulan la secreción de insulina en respuesta a la ingesta de nutrientes. Glucagon like peptide-1 (GLP1) y Polipéptido insulinotrópico glucosa dependiente (GIP) son las principales incretinas descubiertas hasta hoy. Ambas presentan también efecto trófico sobre las células beta de los islotes pancreáticos. GLP-1 presenta otras acciones como son la inhibición de la secreción de glucagón, enlentecimiento del vaciamiento gástrico e inhibición del apetito. Ambas incretinas son rápidamente clivadas por la enzima dipeptidil peptidasa 4 (DPP-4). Nuevas drogas como los incretinomiméticos, análogos y los inhibidores de DPP-4 se presentan como una terapéutica prometedora para los pacientes con diabetes tipo 2. Conflicto de intereses: Dr. León Litwak - Miembro del Board Latinoamericano de Eli Lilly y Sanofi Aventis - Miembro del Board Nacional de los laboratorios Novo Nordisk, Novartis, GlaxoSmithKline, Sanofi Aventis, Boheringer Ingelheim, Bristol Myers, Astra Zeneca - Investigador principal de protocolos pertenecientes a Eli Lilly, Novo Nordisk, Novartis, GlaxoSmithKline, Takeda, PPDF, Pfizer, Merck Sharp and Dôhme, Amger, Roche, Minimed, Quintiles - Conferencista de los laboratorios mencionados.


Two main pathophysiological mechanisms are currently involved in Type 2 Diabetes (T2DM), insulin resistance and impairment of beta cell function. However, in recent years a new mechanism was reported: a significant decrease in incretins production and/or action. Incretins are gastrointestinal hormones whose main action is stimulating insulin secretion in response to nutrients. The best known incretins are glucagon like peptide-1 (GLP-1) and Gastric insulinotropic peptide (GIP). GLP-1 and GIP not only increase insulin secretion, but also decrease glucagon secretion, slow gastric emptying and reduce apetite, generating weight loss. Both incretins are rapidly clived by the enzyme dipeptidil peptidase 4 (DPP4). In order to emulate incretins action, several drugs were developed: GLP-1 receptor agonists, GLP-1 mimetics, and DPP4 inhibitors. All of them seem to became a very promising tool for the treatment of T2DM. Financial Interests: Dr. León Litwak - Member of the Latin American Board of Eli Lilly and Sanofi Aventis - Member of the National Board of the following laboratories: Novo Nordisk, Novartis, GlaxoSmithKlein Sanofi, Aventis, Boheringer Ingelheim, Bristol Myers, Astra Zeneca - Principal Investigator of Protocols from: Eli Lilly, Novo Nordisk, Novartis, GlaxoSmithKlein, Takeda, PPDF, Pfizer, Merck Sharp and Dôhme, Amgen, Roche, Minimed, Quintiles - Lecturer for the former laboratories.


Subject(s)
Humans , Male , Female , Dipeptidyl Peptidase 4/metabolism , Diabetes Mellitus, Type 2/therapy , Incretins/therapeutic use , Glucagon-Like Peptide 1/agonists , Incretins/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL