Search results for " Targeted therapy"
showing 10 items of 198 documents
Glucagon-like peptide-2 and mouse intestinal adaptation to a high-fat diet.
2013
Endogenous glucagon-like peptide-2 (GLP2) is a key mediator of refeeding-induced and resection-induced intestinal adaptive growth. This study investigated the potential role of GLP2 in mediating the mucosal responses to a chronic high-fat diet (HFD). In this view, the murine small intestine adaptive response to a HFD was analyzed and a possible involvement of endogenous GLP2 was verified using GLP2 (3–33) as GLP2 receptor (GLP2R) antagonist. In comparison with animals fed a standard diet, mice fed a HFD for 14 weeks exhibited an increase in crypt–villus mean height (duodenum, 27.5±3.0%; jejunum, 36.5±2.9%;P<0.01), in the cell number per villus (duodenum, 28.4±2.2%; jejunum, 32.0±2.9%;P&l…
The nonalcoholic steatohepatitis (NASH) drug development graveyard: established hurdles and planning for future success
2020
Contains fulltext : 229341.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Numerous pharmacological compounds that target the different molecular targets involved in the pathobiology of nonalcoholic steatohepatitis (NASH) are currently in clinical testing. So far, there are no regulatory approvals. AREAS COVERED: This paper sheds light on the molecular pathways involved in NASH and the drugs targeting these pathways. We have identified 10 compounds whose clinical development program has been halted. Moreover, we explore early phase clinical trials and dissect the reasons for termination of development. EXPERT OPINION: The main goal of NASH pharmacotherapy is to halt or reverse hepati…
HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma
2015
Abstract: The diagnosis and treatment of hepatocellular carcinoma (HCC) underwent a huge advancement in the last years. Recently, microRNAs (miRNAs) have been also studied to provide a new tool for early diagnosis of high risk patients, for prognostic classification to identify those patients who benefit cancer treatment and for predictive definition to select the right targeted drug. In this review we revised all the available data obtained to explore the role of miRNAs in HCC. This analysis led to identification of miRNAs which could gain a diagnostic, prognostic or predictive role. The results of studies on miRNAs involved in HCC are initial and far from providing scientific evidences to…
Mcl-1 targeting could be an intriguing perspective to cure cancer
2018
The Bcl-2 family, which plays important roles in controlling cancer development, is divided into antiapoptotic and proapoptotic members. The change in the balance between these members governs the life and death of the cells. Mcl-1 is an antiapoptotic member of this family and its distribution in normal and cancerous tissues strongly differs from that of Bcl-2. In human cancers, where upregulation of antiapoptotic proteins is common, Mcl-1 expression is regulated independent of Bcl-2 and its inhibition promotes senescence, a major barrier to tumorigenesis. Cancer chemotherapy determines various kinds of responses, such as senescence and autophagy; however, the ideal response to chemotherapy…
Tumor Microenvironment And Epithelial Mesenchymal Transition As Targets To Overcome Tumor Multidrug Resistance
2020
It is well established that multifactorial drug resistance hinders successful cancer treatment. Tumor cell interactions with the tumor microenvironment (TME) are crucial in epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR). TME-induced factors secreted by cancer cells and cancer-associated fibroblasts (CAFs) create an inflammatory microenvironment by recruiting immune cells. CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSCs) and inflammatory tumor associated macrophages (TAMs) are main immune cell types which further enhance chronic inflammation. Chronic inflammation nurtures tumor-initiating/cancer stem-like cells (CSCs), induces both EMT and MDR leading to tumor re…
miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance
2015
AbstractThe ErbB tyrosine kinase receptor family has been shown to have an important role in tumorigenesis, and the expression of its receptor members is frequently deregulated in many types of solid tumors. Various drugs targeting these receptors have been approved for cancer treatment. Particularly, in breast cancer, anti-Her2/EGFR molecules represent the standard therapy for Her2-positive malignancies. However, in a number of cases, the tumor relapses or progresses thus suggesting that not all cancer cells have been targeted. One possibility is that a subset of cells capable of regenerating the tumor, such as cancer stem cells (CSCs), may not respond to these therapeutic agents. Accumula…
Malignant PEComa With Metastatic Disease at Diagnosis and Resistance to Several Chemotherapy Regimens and Targeted Therapy (m-TOR Inhibitor).
2017
Perivascular epithelioid cell tumors (PEComas) are infrequent neoplasms with peculiar myomelanocytic differentiation. The aggressive abdominopelvic variant is rare, with only a small number of published cases. We present an additional case of this unusual variant, which showed an aggressive histologic and clinical behavior with multiple liver metastases and resistance to several therapies. We also discuss the histological and immunohistochemical profiles as well as the differential diagnosis.
GSK-3 in liver diseases: Friend or foe?
2020
Liver diseases, including hepatitis due to hepatitis B or C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma pose major challenges for overall health due to limited curative treatment options. Thus, there is an urgent need to develop new therapeutic strategies for the treatment of these diseases. A better understanding of the signaling pathways involved in the pathogenesis of liver diseases can help to improve the efficacy of emerging therapies, mainly based on pharmacological approaches, which influence one or more specific molecules involved in key signal transduction pathways. These emerging therapies are very promising for the prevention and treatment of …
2-Triazenoazaindoles: Α novel class of triazenes inducing transcriptional down-regulation of EGFR and HER-2 in human pancreatic cancer cells
2012
Pancreatic cancer is a complex malignancy arising from the accumulation of genetic and epigenetic defects in the affected cells. Standard chemotherapy for patients with advanced disease shows only modest effects and is associated with considerable toxicity. Overexpression or aberrant activation of members of the epidermal growth factor receptor tyrosine kinase family, which includes EGFR and HER-2, occurs frequently and is associated with multiple drug resistance and decreased patient survival. In this study, we have investigated the therapeutic potential of AS104, a novel compound of the triazene class, with potential inhibitory effects on EGFR. We found that treatment of cells with AS104 …
NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib resistance
2016
AbstractSorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). However, its benefits are modest, and as its mechanisms of action remain elusive, a better understanding of its anticancer effects is needed. Based on our previous study results, we investigated here the implication of the nuclear protein 1 (NUPR1) in HCC and its role in sorafenib treatment. NUPR1 is a stress-inducible protein that is overexpressed in various malignancies, but its role in HCC is not yet fully understood. We found that NUPR1 expression was significantly higher in primary human HCC samples than in the normal liver. Knockdown of NUPR1 signi…