Abstract:
BACKGROUND:Osteosarcoma is the most frequent primary malignant bone tumor. Although survival has distinctly increased due to neoadjuvant chemotherapy in the past, patients with metastatic disease and poor response to chemotherapy still have an adverse prognosis. Hence, development of new therapeutic strategies is still of utmost importance. METHODS:Anticancer activity of KP46 against osteosarcoma cell models was evaluated as single agent and in combination approaches with chemotherapeutics and Bcl-2 inhibitors using MTT assay. Underlying mechanisms were tested by cell cycle, apoptosis and autophagy assays. RESULTS:KP46 exerted exceptional anticancer activity at the nanomolar to low micromolar range, depending on the assay format, against all osteosarcoma cell models with minor but significant differences in IC50 values. KP46 treatment of osteosarcoma cells caused rapid loss of cell adhesion, weak cell cycle accumulation in S-phase and later signs of apoptotic cell death. Furthermore, already at sub-cytotoxic concentrations KP46 reduced the migratory potential of osteosarcoma cells and exerted synergistic effects with cisplatin, a standard osteosarcoma chemotherapeutic. Moreover, the gallium compound induced signs of autophagy in osteosarcoma cells. Accordingly, blockade of autophagy by chloroquine but also by the Bcl-2 inhibitor obatoclax increased the cytotoxic activity of KP46 treatment significantly, suggesting autophagy induction as a protective mechanism against KP46. CONCLUSION:Together, our results identify KP46 as a new promising agent to supplement standard chemotherapy and possible future targeted therapy in osteosarcoma.
journal_name
J Exp Clin Cancer Resjournal_title
Journal of experimental & clinical cancer research : CRauthors
Kubista B,Schoefl T,Mayr L,van Schoonhoven S,Heffeter P,Windhager R,Keppler BK,Berger Wdoi
10.1186/s13046-017-0527-zsubject
Has Abstractpub_date
2017-04-12 00:00:00pages
52issue
1eissn
0392-9078issn
1756-9966pii
10.1186/s13046-017-0527-zjournal_volume
36pub_type
杂志文章abstract:BACKGROUND:Kindlin-2 is a member of the focal adhesion protein family that regulates invasion and metastasis in multiple malignancies; however, little is known about the role of Kindlin-2 in hepatocellular carcinoma (HCC) progression. METHODS:Immunohistochemistry was used to investigate Kindlin-2 expression in 177 pai...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0603-4
更新日期:2017-09-29 00:00:00
abstract:BACKGROUND:Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family (CMTM) is a gene family involved in multiple malignancies. CMTM4 is a member of this family and is located at chromosome 16q22.1, a locus that harbours a number of tumour suppressor genes. It has been defined as a regulator of ce...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0236-4
更新日期:2015-10-16 00:00:00
abstract:BACKGROUND:Antibody Directed Enzyme Prodrug Therapy (ADEPT) can be used to generate cytotoxic agents at the tumor site. To date non-human enzymes have mainly been utilized in ADEPT. However, these non-human enzymes are immunogenic limiting the number of times that ADEPT can be administered. To overcome the problem of i...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/1756-9966-28-147
更新日期:2009-12-03 00:00:00
abstract::The renal oncocytoma is a solid epithelial neoplasm with a generally benign course. The improved image diagnostics with the computerized tomography (CT) and magnetic resonance imaging (MRI) should today permit the identification of these lesions preoperatively so that conservative rather than radical surgery can be em...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract:BACKGROUND:Colon cancer is the second leading cancer worldwide. Recurrent disease and chemotherapeutic drug resistance are very common in the advanced stage of colon cancer. ATP-citrate lyase (ACLY), the first-step rate-controlling enzyme in lipid synthesis, is elevated in colon cancer. However, it remains unclear abou...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1391-9
更新日期:2019-09-12 00:00:00
abstract:BACKGROUND:Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The fu...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01704-w
更新日期:2020-10-28 00:00:00
abstract::We previously reported that the expression and the activity of SHP-1, a non-transmembrane protein tyrosine phosphatase (PTPase) increased during myeloid differentiation of an acute promyelocytic leukemia cell line (HT93) induced by all-trans retinoic acid (ATRA). To examine whether inhibition of SHP-1 activity attenua...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract:BACKGROUND:Prohibitin (PHB), a pleiotropic protein overexpressed in several tumor types, has been implicated in the regulation of cell proliferation, invasive migration and survival. However, PHB expression and its biological function in gallbladder cancer (GBC) remain largely unknown. METHODS:PHB and p-ERK protein ex...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0346-7
更新日期:2016-04-16 00:00:00
abstract:BACKGROUND:To evaluate activity and tolerability of two anthracycline-containing regimens as first-line treatment for anthracycline-naïve relapsed breast cancer patients. METHODS:Patients with relapsed breast cancer not previously treated with adjuvant anthracyclines were randomly assigned to epirubicin/vinorelbine (a...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1186/1756-9966-30-39
更新日期:2011-04-12 00:00:00
abstract::Seventeen adult urologic sarcomas treated at the Oncology Hospital of Ankara in the last ten-year period are described. There were six cases of paratesticular rhabdomyosarcoma (RMS), four cases of liposarcoma (LS), three cases of leiomyosarcoma (LMS); two cases of Kaposi sarcoma limited to glans penis, and only one pr...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,评审
doi:
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND:Metastasis is the primary cause of death in renal cell carcinoma (RCC). Loss of cell-to-cell adhesion, including tight junctions (TJs) is the initial step in the process of metastasis. Claudin-7 (CLDN7) is a major component of TJs. However, the clinical significance and its regulation of kidney tumorigenesis...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0924-y
更新日期:2018-11-14 00:00:00
abstract::Few cases of malignant glucagonomas have been described in the literature. In this paper we present a case of a 77-year-old woman with necrolytic migratory erythema and high plasma glucagon and chromogranin A levels caused by a neuroendocrine tumour. An abdominal CT scan suggested a pancreatic lesion and two liver met...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2006-03-01 00:00:00
abstract:BACKGROUND:Anti-angiogenic therapies demonstrate anti-tumor effects by decreasing blood supply to tumors and inhibiting tumor growth. However, anti-angiogenic therapy may leads to changes in tumor microenvironment and increased invasiveness of tumor cells, which in turn promotes distant metastasis and increased drug re...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1291-z
更新日期:2019-07-02 00:00:00
abstract:BACKGROUND:Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. MicroRNAs (miRNAs) have been indicated as crucial actors in cancer biology. Accumulating evidence suggests that miRNAs can be used as diagnostic and prognostic markers for NSCLC. METHODS:The purpose of this study was to characterize a...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-018-0882-4
更新日期:2018-09-18 00:00:00
abstract::Primary cancer of the gallbladder is not unusual. Most cases of gallbladder cancer are found at an advanced stage, accompanied by the invasion to the liver, metastases to the lymph nodes and distant organs, and peritoneal dissemination. In this study, we first examined the effect of mitogen-activated protein kinase ki...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract:BACKGROUND:Increased expression of epidermal growth factor receptor (EGFR) and its ligands is associated with poor prognosis and chemoresistance in many carcinoma types, but its role in head and neck squamous cell carcinoma (HNSCC) is unclear. Our aim was to clarify whether mRNA expression of EGFR-ligands was linked to...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0422-z
更新日期:2016-09-26 00:00:00
abstract::This study was conducted to establish a feasible intraperitoneal xenograft model in nude mice which mimicked the dynamic progression of human ovarian cancer and to explore its potential for preclinical trials. A human ovarian tumor line SKOV3 was originally injected s.c. to develop tumors; then the tumors were harvest...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:Cancer stem cells (CSCs) are important in the tumorigenesis and progression of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play crucial roles regulating CD133+ and EpCAM+ CSCs in HCC, although it is unclear whether miRNAs regulate CD90+ CSCs in HCC. METHODS:The miRNA profiles of CD90+ and CD90- HCC c...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0452-6
更新日期:2016-11-11 00:00:00
abstract:BACKGROUND:Hepatocellular carcinoma (HCC) is the major histological type of liver cancer with high morbidity and mortality worldwide. Long noncoding RNAs (lncRNA) has been proved to be associated with various cancer types, while its regulation in HCC is largely unknown. METHODS:To figure out the specific role of lncRN...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1128-9
更新日期:2019-04-10 00:00:00
abstract:UNLABELLED:PCR analysis has been demonstrated as a valuable tool for detection of minimal residual disease (MRD) in lymphoid malignancies. However, the finding that patients with evidence of MRD sometimes remain in long-lasting remission directs further investigations toward biology of residual disease and/or quantific...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:This study was designed to mainly evaluate the activity and safety of olanzapine compared with 5-hydroxytryptamine 3(5-HT3) receptor antagonists for prevention of chemotherapy-induced nausea and vomiting(CINV) in patients receiving highly or moderately emetogenic chemotherapy (HEC or MEC). The second goal wa...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章,随机对照试验
doi:10.1186/1756-9966-28-131
更新日期:2009-09-23 00:00:00
abstract:BACKGROUND:The recently identified phenomenon of double-stranded RNA (dsRNA)-mediated gene activation (RNAa) has been studied extensively, as it is present in humans, mice, and Caenorhabditis elegans, suggesting that dsRNA-mediated RNAa is an evolutionarily conserved mechanism. Previous studies have shown that dsP21-32...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-016-0423-y
更新日期:2016-09-17 00:00:00
abstract::Intraoperative radiotherapy with a single dose of electrons (ELIOT) in the conservative treatment of breast cancer is a possibility under evaluation in clinical trials. The costs of the mobile linear accelerator with a robotic arm, used in intraoperative radiotherapy, are prohibitive for poor countries. The aim of thi...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2007-09-01 00:00:00
abstract::In the present study we report twenty-nine patients with iatrogenic injuries and management during various operations for malignant conditions. The patients were reviewed in order to identify and study the incidence, type of treatment administered and outcome. The study group was composed of 29 patients with 31 iatrog...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:When a patient concomitantly uses two or more drugs, a drug-drug interaction (DDI) can possibly occur, potentially leading to an increased or decreased clinical effect of a given treatment. Cancer patients are at high risk of such interactions because they commonly receive multiple medications. Moreover, mos...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-015-0201-2
更新日期:2015-08-25 00:00:00
abstract:BACKGROUND:Glioblastoma is the most common and aggressive brain tumour in adults with a median overall survival of only 14 months after standard therapy with radiation therapy (IR) and temozolomide (TMZ). In a novel multimodal treatment approach we combined the checkpoint kinase 1 (Chk1) inhibitor SAR-020106 (SAR), dis...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-019-1434-2
更新日期:2019-10-21 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. T...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 社论
doi:10.1186/s13046-020-1534-z
更新日期:2020-01-31 00:00:00
abstract:BACKGROUND:Classical Kaposi's Sarcoma (cKS) is a rare vascular tumor, which develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host predisposing factors, viral genetic variants might possibly be related to disease development. The aim of this study was to identify HHV-8 variants in patients with...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-014-0119-0
更新日期:2015-01-16 00:00:00
abstract:BACKGROUND:The identification of novel targets for recovering sorafenib resistance is pivotal for Hepatocellular carcinoma (HCC) patients. Mitophagy is the programmed degradation of mitochondria, and is likely involved in drug resistance of cancer cells. Here, we identified hyperactivated mitophagy is essential for sor...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-020-01768-8
更新日期:2020-12-07 00:00:00
abstract:BACKGROUND:Novel therapies tailored to the molecular composition of esophageal squamous cell carcinoma (ESCC) are needed to improve patient survival. We investigated the regulatory network of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) and sex-determining region Y-box 9 (SOX9), and the...
journal_title:Journal of experimental & clinical cancer research : CR
pub_type: 杂志文章
doi:10.1186/s13046-017-0658-2
更新日期:2017-12-13 00:00:00