Abstract:
:It has been established that disturbances in intracellular signaling pathways play a considerable part in the oncologic process. Phosphatidylinositol-3-kinase (PI3K) has become of key interest in cancer therapy because of its high mutation frequency and/or gain in function of its catalytic subunits in cancer cells. We investigated the therapeutic value of BYL719, a new specific PI3Kα inhibitor that blocks the ATP site, on osteosarcoma and bone cells. The in vitro effects of BYL719 on proliferation, apoptosis, and cell cycle were assessed in human and murine osteosarcoma cell. Its impact on bone cells was determined using human mesenchymal stem cells (hMSC) and human CD14+ osteoclast precursors. Two different murine preclinical models of osteosarcoma were used to analyze the in vivo biological activities of BYL719. BYL719 decreased cell proliferation by blocking cell cycle in G0/G1 phase with no outstanding effects on apoptosis cell death in HOS and MOS-J tumor cells. BYL719 inhibited cell migration and can thus be considered as a cytostatic drug for osteosarcoma. In murine preclinical models of osteosarcoma, BYL719 significantly decreased tumor progression and tumor ectopic bone formation as shown by a decrease of Ki67+ cells and tumor vascularization. To explore the maximum therapeutic potential of BYL719, the drug was studied in combination with conventional chemotherapeutic drugs, revealing promising efficacy with ifosfamide. BYL719 also exhibited dual activities on osteoblast and osteoclast differentiation. Overall, the present work shows that BYL719 is a promising drug in either a single or multidrug approach to curing bone sarcoma.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Gobin B,Huin MB,Lamoureux F,Ory B,Charrier C,Lanel R,Battaglia S,Redini F,Lezot F,Blanchard F,Heymann Ddoi
10.1002/ijc.29040subject
Has Abstractpub_date
2015-02-15 00:00:00pages
784-96issue
4eissn
0020-7136issn
1097-0215journal_volume
136pub_type
杂志文章abstract::Therapeutic effectiveness against metastatic or even locally advanced pancreatic ductal adenocarcinoma (PDAC) is dismal, with 5-year survival less than 5%. Even in patients who undergo potentially curative resection, most patients' tumors recur in the liver. Improving therapies targeting or preventing liver metastases...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30110
更新日期:2016-08-01 00:00:00
abstract::Human papillomavirus-induced cervical carcinomas often show impaired expression of MHC class I molecules resulting in the inability of tumor cells to directly present viral peptides to cytotoxic T lymphocytes. Loss of MHC class I expression combined with the expression of activating NK cell receptor ligands renders tu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23733
更新日期:2008-11-15 00:00:00
abstract::We report a population based case-control study of exposure to pesticides as risk factor for non-Hodgkin lymphoma (NHL). Male and female subjects aged 18-74 years living in Sweden were included during December 1, 1999, to April 30, 2002. Controls were selected from the national population registry. Exposure to differe...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23589
更新日期:2008-10-01 00:00:00
abstract::Retinoids play essential roles in the regulation of cell differentiation and in the proliferation of various epithelial tissues, and atRA is one such active metabolite of retinoids. However, despite the known functions of atRA, its clinical applications are limited due to the induced metabolism by the specific cytochr...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11354
更新日期:2003-10-20 00:00:00
abstract::Breast carcinomas were examined by the immunoperoxidase technique using antisera specific for lymphocyte subsets, monocytes, NK cells and major histocompatibility antigens (HLA-A, -B, -C; Ia-like). Sixty-four per cent of the patients had a moderate or strong mononuclear cell infiltration, 77% of the patients without m...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910350610
更新日期:1985-06-15 00:00:00
abstract::The variants within the human melanocortin 1 receptor (MC1R) gene are associated with an increased risk of different skin cancers. In this study, we genotyped by direct sequencing, 529 cases of basal cell carcinoma of the skin (BCC) and 533 healthy controls for polymorphisms in the entire MC1R gene. In addition to 10 ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23257
更新日期:2008-04-15 00:00:00
abstract::We, and others, have recently shown that recombinant feline leukaemia viruses (FeLV) containing the myc gene (FeLV-myc) occur in up to 30% of naturally occurring cases of T-cell lymphosarcoma. Investigation of the disease spectrum of two FeLV-myc isolates showed that they induced clonal or oligoclonal T-cell tumours a...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910400108
更新日期:1987-07-15 00:00:00
abstract::Cervical mucosal expression of cytokines involved in mediating cellular immunity is believed to influence the persistence of human papillomavirus (HPV) infection, a necessary prerequisite for the development of cervical intraepithelial neoplasia (CIN). Additionally, regulatory T (Treg) cells are increasingly understoo...
journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/ijc.24117
更新日期:2009-03-15 00:00:00
abstract::The association between subtypes of hepatitis C virus (HCV) and risk of hepatocellular carcinoma (HCC) remained inconclusive and evaluated in both case-control and cohort studies. In the case-control study, 397 HCC cases from medical centers were compared with 410 community-based non-HCC controls. All of them were ant...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28753
更新日期:2014-09-01 00:00:00
abstract::The assessment of tumor molecular features in combination with the detection of occult malignant cells may provide important clinical information, beyond the standard staging of breast cancer. Using a nested RT-PCR technique, we assessed prospectively the presence of cytokeratin-19 (CK19) mRNA positive cells in the bl...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.11593
更新日期:2004-02-10 00:00:00
abstract::Childhood cancers (age at diagnosis: 0-14 years) comprise a variety of malignancies, with incidence varying worldwide by age, sex, ethnicity and geography, that provide insights into cancer etiology. A total of 1,334 childhood cancers registered in population-based cancer registry, Chennai, India, during 1990-2001 and...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23428
更新日期:2008-06-01 00:00:00
abstract::Long noncoding RNAs (lncRNAs) are involved in the pathology of colorectal cancer (CRC). Current efforts to eradicate CRC predominantly focused on targeting the proliferation of rapidly growing cancer epithelial cells. This is largely ineffective with resistance arising in most tumors after exposure to chemotherapy. De...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32608
更新日期:2020-03-15 00:00:00
abstract::Polyunsaturated fatty acids (PUFAs) have been suggested, on the basis of animal-model studies, to be related not only to cancer development but also to chemotherapeutic effects. Controversy persists, however, as to which types of PUFAs are beneficial in terms of chemosensitivity. In this study, we used the NIH3T3 cell...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970127)70:3<357::aid-ijc
更新日期:1997-01-27 00:00:00
abstract::The autophagy lysosome pathway is essential to maintain cell viability and homeostasis in response to many stressful environments, which is reported to play a vital role in cancer development and therapy. However, the association of genetic alterations of this pathway with risk of cancer remains unclear. Based on geno...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31288
更新日期:2018-07-01 00:00:00
abstract::Paracrine motogenic cytokines secreted by normal cells can stimulate metastatic cell invasion. For example, human fibroblasts secrete hepatocyte growth factor/scatter factor (HGF/SF), which stimulates paracrine migration of epithelial and certain carcinoma cells, and migration-stimulating factor (MSF), which stimulate...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910620516
更新日期:1995-09-04 00:00:00
abstract::Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (n ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.33123
更新日期:2020-10-15 00:00:00
abstract::Oncostatin M is a leukocyte product that has been reported to have anti-proliferative effects directly on melanoma and other cancer cell lines in vitro. However, its function(s) in cancers in vivo appears complex and its roles in cancer growth in lungs are unknown. Here, we show that OSM promotes marked growth of tumo...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29055
更新日期:2015-02-15 00:00:00
abstract::Exfoliated nasopharyngeal (NP) cells from 62 normal Cantonese Chinese having IgA/VCA antibodies for more than a year and from 39 similar persons without IgA/VCA antibodies, were tested for the presence of EBV/DNA sequences by spot followed by blot hybridization tests, using the cloned internal repeat of B95-8 viral DN...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910320504
更新日期:1983-11-15 00:00:00
abstract::Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here, we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture. The results ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25255
更新日期:2010-11-15 00:00:00
abstract::ET-743, an experimental antitumor drug with promising activity in sarcoma, breast and ovarian carcinoma, is currently under phase 2 clinical evaluation. It is hepatotoxic in animals and patients. We tested the hypothesis that indole-3-carbinol (I3C), the hydrolysis product of glucosinolates occurring in cruciferous ve...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.20356
更新日期:2004-10-10 00:00:00
abstract::A human cancer vaccine composed of autologous tumor cells modified with the hapten dinitrofluorobenzene (DNP) induces cell-mediated immunity to the tumor cells and the development of inflammatory responses within metastatic sites. In this study we determined whether DNP vaccine could induce regression of established m...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1506.abs
更新日期:2001-11-01 00:00:00
abstract::Patients with head-and-neck cancer commonly have immune defects. It was reported that these patients have raised serum IgA levels. We investigated whether IgA-anti-Fab autoantibodies, which occur in association with immune dysfunction, are present in patients with head-and-neck cancer. Sera of 101 patients with squamo...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910570109
更新日期:1994-04-01 00:00:00
abstract::Protein phosphatase 2A (PP2A) consists of 3 subunits: the catalytic subunit, C, and the regulatory subunits, A and B. The A and C subunits both exist as 2 isoforms (alpha and beta) and the B subunit as multiple forms subdivided into 3 families, B, B' and B". It has been reported that the genes encoding the Aalpha and ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1423
更新日期:2001-09-01 00:00:00
abstract::Resistance to cisplatin-based chemotherapy is a major cause of treatment failure in human ovarian cancer. Wild-type TP53 status is often, but not always, associated with cisplatin sensitivity, suggesting that additional factors may be involved. Overexpression/activation of the phosphatidylinositol-3-kinase/Akt pathway...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23086
更新日期:2008-02-01 00:00:00
abstract::TAAs of the MAGE family are mostly studied as targets of specific immune responses. Their potential relevance as tumor markers has also been underlined. We used a MAb, 57B, recognizing MAGE-A4 protein in paraffin-embedded sections, to evaluate its expression in bladder cancers by employing TMA including 2,317 samples ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10540
更新日期:2002-08-20 00:00:00
abstract::The variable domain of functional heavy chain antibodies (VHH) devoid of light chains, found in camels, constitute the smallest intact antigen-binding domain fragment. Two camel single-domain fragments, cAb-Lys2 and cAb-Lys3, recognizing an overlapping epitope of lysozyme with a dissociation constant of 2 nM and 65 nM...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.10212
更新日期:2002-03-20 00:00:00
abstract::We have used immunoprecipitation to test tumor biopsies and normal adult and fetal human tissues for p97, a tumor-associated protein. Five of nine melanoma biopsies contained p97 in low to very high levels. Three of seven non-melanoma tumors contained p97, but in smaller amounts. No p97 was detected in any of the norm...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910270204
更新日期:1981-02-15 00:00:00
abstract::Experimental studies have consistently shown a protective effect of nonsteroidal antiinflammatory drugs (NSAIDs) against nonmelanoma skin cancers (NMSC). However, little human epidemiological research has been done in this regard. We used data from the Skin Cancer Chemoprevention Study to explore the association of NS...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.21878
更新日期:2006-08-01 00:00:00
abstract::Squamous cell carcinoma of the esophagus has an uneven geographic distribution, with a high incidence in the Transkei region of Eastern Cape Province, South Africa. The precise molecular events associated with tumorigenesis of esophageal cancer in this region have not been characterized. DNA from human esophageal squa...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19981123)78:5<544::aid-ijc
更新日期:1998-11-23 00:00:00
abstract::The aim of this study was to compare the seasonal variation in performance of a faecal immunochemical test for haemoglobin (FIT) and a guaiac test (gFOBT) for colorectal cancer screening. From June 2009 to May 2011, 18,290 screening participants (50-74 years old) performed OC-SENSOR quantitative FIT (1 sample) and Hem...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29187
更新日期:2015-04-15 00:00:00