Abstract:
PURPOSE:PARP inhibitors (PARPi) are used in a wide range of human solid tumours but a limited evidence is reported in rhabdomyosarcoma (RMS), the most frequent childhood soft-tissue sarcoma. The cellular and molecular effects of Olaparib, a specific PARP1/2 inhibitor, and AZD2461, a newly synthesized PARP1/2/3 inhibitor, were assessed in alveolar and embryonal RMS cells both as single-agent and in combination with ionizing radiation (IR). METHODS:Cell viability was monitored by trypan blue exclusion dye assays. Cell cycle progression and apoptosis were measured by flow cytometry, and alterations of specific molecular markers were investigated by, Real Time PCR, Western blotting and immunofluorescence experiments. Irradiations were carried out at a dose rate of 2 Gy (190 UM/min) or 4 Gy (380 UM/min). Radiosensitivity was assessed by using clonogenic assays. RESULTS:Olaparib and AZD2461 dose-dependently reduced growth of both RH30 and RD cells by arresting growth at G2/M phase and by modulating the expression, activation and subcellular localization of specific cell cycle regulators. Downregulation of phospho-AKT levels and accumulation of γH2AX, a specific marker of DNA damage, were significantly and persistently induced by Olaparib and AZD2461 exposure, this leading to apoptosis-related cell death. Both PARPi significantly enhanced the effects of IR by accumulating DNA damage, increasing G2 arrest and drastically reducing the clonogenic capacity of RMS-cotreated cells. CONCLUSIONS:This study suggests that the combined exposure to PARPi and IR might display a role in the treatment of RMS tumours compared with single-agent exposure, since stronger cytotoxic effects are induced, and compensatory survival mechanisms are prevented.
journal_name
J Cancer Res Clin Oncoljournal_title
Journal of cancer research and clinical oncologyauthors
Camero S,Ceccarelli S,De Felice F,Marampon F,Mannarino O,Camicia L,Vescarelli E,Pontecorvi P,Pizer B,Shukla R,Schiavetti A,Mollace MG,Pizzuti A,Tombolini V,Marchese C,Megiorni F,Dominici Cdoi
10.1007/s00432-018-2774-6subject
Has Abstractpub_date
2019-01-01 00:00:00pages
137-152issue
1eissn
0171-5216issn
1432-1335pii
10.1007/s00432-018-2774-6journal_volume
145pub_type
杂志文章abstract:INTRODUCTION:Non-adherence to anti-hormonal therapy is a major problem in gynecologic oncology. Reasons reported are side effects and lack of support. The aim of our study was an analysis of influence of experiences of patients with endocrine therapy and communication and information on this topic and their influence o...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-014-1779-z
更新日期:2015-01-01 00:00:00
abstract::After a single pulse dose of DMBA, rats develop bone-marrow hypoplasia, which is almost compensated for by regeneration after 16 weeks. Subsequently, dysplastic signs of hemopoiesis appear in all experimental animals as massive extrusion of normoblasts into the peripheral blood, red-cell aniso- and poikilocytosis, nuc...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00406245
更新日期:1982-01-01 00:00:00
abstract::Some ellipticine derivative salts, including 9-chloro-2-methylellipticinium (CME), have been found to have a marked selectivity against all eight brain tumor cell lines of the U.S. National Cancer Institute's disease-oriented in vitro screen. We initiated in vivo antitumor studies to explore the feasibility for furthe...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320050128
更新日期:1998-01-01 00:00:00
abstract::In this study we investigated the presence of epidermal growth factor receptors (EGF-R) and the tissue levels of EGF-like factors (EGF-F) in ovarian, endometrial, cervical and breast carcinomas. EGF-R were found in 33/40 (83%) cervical, 15/26 (58%) endometrial, 64/141 (45%) ovarian, and 19/59 (33%) breast carcinomas. ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00397923
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:As previously described, SPC/myc transgenic mice developed bronchioloalveolar adenocarcinomas derived from alveolar type II (AT II) cells within 10-14 months, whereas SPC/IgEGF transgenic mice developed hyperplasias. Our purpose was to determine the potential interplay of environmental and genetic factors in lu...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-002-0400-z
更新日期:2003-02-01 00:00:00
abstract::A phase II trial of etoposide (100 mg/m2) on days 4, 5, 6, doxorubicin (Adriamycin, 20 mg/m2) on days 1, 7, and cisplatin (30 mg/m2) on days 2, 8 (EAP) was carried out in order to reduce toxicity associated with a full-dose EAP regimen for advanced and/or metastatic gastric adenocarcinoma. Out of 21 evaluable patients...
journal_title:Journal of cancer research and clinical oncology
pub_type: 临床试验,杂志文章
doi:10.1007/BF01221033
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:Only few immunohistochemical markers besides c-kit exist for gastrointestinal stromal tumors (GISTs). Thy-1, a cell-surface glycoprotein, is a marker for several types of stem cells and particularly for neuronal precursor cells. The aim of this study was to determine Thy-1 expression in GISTs. MATERIALS AND ME...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-007-0238-5
更新日期:2007-12-01 00:00:00
abstract::The occurrence of malignancies during pregnancy has increased over the last decades. They complicate approximately 1 per 1000 pregnancies. The most common malignancies associated with pregnancy include malignant melanoma, malignant lymphomas and leukemia, and cancer of the cervix, breast, ovary, colon and thyroid. Sin...
journal_title:Journal of cancer research and clinical oncology
pub_type: 社论
doi:10.1007/s00432-002-0406-6
更新日期:2003-03-01 00:00:00
abstract::The highly metabolized nitrosourea carmustine (BCNU) is an anticancer agent which alkylates DNA and is metabolized to both active and inactive species by cytochrome P-450 enzymes. Other highly metabolized anticancer drugs have altered toxicities when some histamine H2 antagonists are coadministered. To test this hypot...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00391598
更新日期:1989-01-01 00:00:00
abstract::Mononuclear cells from peripheral blood and draining lymph nodes of 40 patients with invasive mammary carcinoma were examined for various immunological cell surface markers including surface membrane immunoglobulins and rosetting properties (E, EA, EAC). No significant relationship could be established to anyone of th...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00411111
更新日期:1979-09-01 00:00:00
abstract:PURPOSE:We performed deep sequencing of target genes in head and neck squamous cell carcinoma (HNSCC) tumors to identify somatic mutations that are associated with induction chemotherapy (IC) response. METHODS:Patients who were diagnosed with HNSCC were retrospectively identified. Patients who were treated with IC wer...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-015-2083-2
更新日期:2016-04-01 00:00:00
abstract::Repeated doses of beta-radiation in the mouse skin model have been reported to produce carcinomas and sarcomas with equal frequency. Among sarcomas, fibrosarcomas and osteosarcomas have been the predominant reported histologies. In this report we describe the beta-radiation induction of rhabdomyosarcoma (RMS), a histo...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320050272
更新日期:1999-01-01 00:00:00
abstract:PURPOSE:Long interspersed nuclear element 1 (LINE-1 or L1) is a dominant non-long terminal repeat (non-LTR) retrotransposon in the human genome that has been implicated in the overexpression of MET. Both the canonical MET and L1-MET transcripts are considered to play a role in hepatocellular carcinoma (HCC) development...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-020-03395-4
更新日期:2021-01-01 00:00:00
abstract:PURPOSE:To study an association between IL-6 signaling and resistance to radiotherapy of prostate cancer (PCa) and explore the molecular mechanisms involved. METHODS:IL-6 expressing C4-2 and CWR22Rv1 (C4-2IL-6/CWRIL-6) and vector control (C4-2vec/CWRvec) cell lines were developed. Radiation-sensitivities of these cell...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-019-02917-z
更新日期:2019-06-01 00:00:00
abstract:PURPOSE:This study aimed to determine the dose effect of smoking on the mutational frequency and spectrum of epidermal growth factor receptor (EGFR) gene in Korean non-small cell lung cancer (NSCLC). METHODS:Detailed smoking histories were obtained from 324 consecutively enrolled Korean NSCLC patients. Mutational stat...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-010-0853-4
更新日期:2010-12-01 00:00:00
abstract::Osteosarcoma cells derived from patients have been isolated and subsequently cultured for the past 35 years. To date though, there have been no major breakthroughs in the development of a model for osteosarcoma that uses orthotopic implantation of human osteosarcoma cells and that closely emulates the clinical progres...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章,评审
doi:10.1007/s00432-006-0157-x
更新日期:2007-03-01 00:00:00
abstract:PURPOSE:The orphan, membrane-bound estrogen receptor (GPER) is expressed at high levels in a large fraction of breast cancer patients, and its expression is favorable for patients' survival. We investigated the role of GPER as a potential tumor suppressor in MCF-7 and SK-BR-3 breast cancer cells. METHODS:The effect of...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-014-1598-2
更新日期:2014-04-01 00:00:00
abstract:BACKGROUND:Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-003-0526-7
更新日期:2004-04-01 00:00:00
abstract:PURPOSE:Melanoma antigen gene A3 (MAGE-A3) is aberrantly expressed in a number of cancer types. Because of its high specificity, MAGE-A3 has shown to be a promising candidate for cancer immunotherapy. Dendritic cells (DCs) have emerged as the natural agents for antigen delivery. DCs transduced with antigen may increase...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-013-1552-8
更新日期:2014-02-01 00:00:00
abstract::A short-term organ culture of rat tracheal epithelium was used to detect the ability of 53 chemicals to induce UDS. In this system all direct-acting compounds (ultimate or proximate carcinogens) tested induced UDS. Of 24 compounds requiring metabolism (procarcinogens), nine induced UDS, viz., 4NQO, AF-2, BP, DMN, DEN,...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00410663
更新日期:1981-01-01 00:00:00
abstract::Carboplatin therapy has a more favorable toxicity profile than cisplatin and, given in appropriate doses, is equivalent in efficacy to cisplatin for suboptimal ovarian cancer. However myelosuppression frequently curtails therapy with carboplatin. Diethyldithiocarbamate (DDTC) is a thiol compound and heavy-metal-chelat...
journal_title:Journal of cancer research and clinical oncology
pub_type: 临床试验,杂志文章
doi:10.1007/BF01208846
更新日期:1993-01-01 00:00:00
abstract::Methods have been developed in an in vitro system (1) of assessing the number of disseminated tumor cells in peripheral blood and (2) of enriching tumor cells from peripheral blood samples for further characterization. Cells from three human carcinoma lines (E 14, ChaGo, and LEDWiDr) were mixed with leukocytes from no...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00391886
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:To calculate the accuracy of the Tokuhashi score (TS) in recent patients with vertebral metastasis (VM), candidates or not to surgical treatment, and thus to assess the external validity of TS. METHODS:Retrospective analysis of prospectively collected data from 90 patients (55 men, 35 women) with VM between 20...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-012-1222-2
更新日期:2012-09-01 00:00:00
abstract:PURPOSE:To determine the incidence of hepatocellular carcinoma in cirrhosis and to examine the influence of age and sex, and the contribution of etiological factors. METHODS:967 patients with liver cirrhosis and free of hepatocellular carcinoma were enrolled in this longitudinal, retrospective and observational study....
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320050215
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:Long-term human papillomavirus (HPV) infection is a prerequisite for cervical cancer. IL-1beta and IL-1Ra expression levels play an important role in cervical carcinogenesis. Several functional genetic variants in IL1B and IL-RN have been reported to be associated with IL-1beta expression and cancer susceptibil...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-009-0710-5
更新日期:2010-05-01 00:00:00
abstract::Soft-agar clonogenicity of L1210 mouse leukemia cells and of xenografts of a human melanoma and a carcinoma of the cervix was studied sectionally by the sizes of the colonies grown under hypoxic gradients and aerobic condition. Soft-agar plating efficiency was increased in cultured L1210 cells with decreasing oxygen c...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF00402464
更新日期:1984-01-01 00:00:00
abstract::The antitumor and anti-metastatic effects of a potent angiogenesis inhibitor, O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in a highly metastatic model of human hepatocellular carcinoma-LCI-D20. Small pieces of LCI-D20 tumor tissue were implanted subcutaneously into the right axillary region of 24 ...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/BF01240121
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:Tumor suppressor gene therapy and cytokine gene therapy have limited antitumor effects when used alone. Thus, in the present study, we investigated the antitumor potentials of the combined transfer of the p16 tumor suppressor gene and the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) gene. M...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s004320000187
更新日期:2001-02-01 00:00:00
abstract:PURPOSE:The aim of this study was to assess the effectiveness and safety of ultrasound guided percutaneous radiofrequency ablation (RFA) of cervical metastatic lymph nodes (LNs) from papillary thyroid carcinoma. METHODS:54 metastatic LNs confirmed by percutaneous biopsy in 33 patients with previous total thyroidectomy...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-017-2386-6
更新日期:2017-08-01 00:00:00
abstract:PURPOSE:The objective was to compare the prognostic factors and outcomes among primary ovarian cancer (OC), fallopian tube cancer (FC), and peritoneal cancer (PC) patients in a population-based setting. METHODS:We analysed 5399 OC, 327 FC, and 416 PC patients diagnosed between 1998 and 2014 in the catchment area of th...
journal_title:Journal of cancer research and clinical oncology
pub_type: 杂志文章
doi:10.1007/s00432-017-2422-6
更新日期:2017-09-01 00:00:00