Abstract:
:Carcinoma-associated fibroblasts (CAFs) play a key onco-supportive role during prostate cancer (PCa) development and progression. We previously reported that the reactive oxygen species (ROS)-producing enzyme NADPH oxidase 4 (Nox4) is essential for TGFβ1-mediated activation of primary prostate human fibroblasts to a CAF-like phenotype. This study aimed to further investigate the functional relevance of prostatic Nox4 and determine whether pharmacological inhibition of stromal Nox4 abrogates paracrine-mediated PCa-relevant processes. RNA in situ hybridization revealed significantly elevated Nox4 mRNA levels predominantly in the peri-tumoral stroma of clinical PCa with intense stromal Nox4 staining adjacent to tumor foci expressing abundant TGFβ protein levels. At pharmacologically relevant concentrations, the Nox1/Nox4 inhibitor GKT137831 attenuated ROS production, CAF-associated marker expression and migration of TGFβ1-activated but not nonactivated primary human prostate fibroblasts. Similar effects were obtained upon shRNA-mediated silencing of Nox4 but not Nox1 indicating that GKT137831 primarily abrogates TGFβ1-driven fibroblast activation via Nox4 inhibition. Moreover, inhibiting stromal Nox4 abrogated the enhanced proliferation and migration of PCa cell lines induced by TGFβ1-activated prostate fibroblast conditioned media. These effects were not restricted to recombinant TGFβ1 as conditioned media from PCa cell lines endogenously secreting high TGFβ1 levels induced fibroblast activation in a stromal Nox4- and TGFβ receptor-dependent manner. Importantly, GKT137831 also attenuated PCa cell-driven fibroblast activation. Collectively, these findings suggest the TGFβ-Nox4 signaling axis is a key interface to dysregulated reciprocal stromal-epithelial interactions in PCa pathophysiology and provide a strong rationale for further investigating the applicability of Nox4 inhibition as a stromal-targeted approach to complement current PCa treatment modalities.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Sampson N,Brunner E,Weber A,Puhr M,Schäfer G,Szyndralewiez C,Klocker Hdoi
10.1002/ijc.31316subject
Has Abstractpub_date
2018-07-15 00:00:00pages
383-395issue
2eissn
0020-7136issn
1097-0215journal_volume
143pub_type
杂志文章abstract::We present a pilot study that aims to examine the possibility to easily and noninvasively detect and discriminate females with ovarian cancer (OC) from females that have no tumor(s) and from females that have benign genital tract neoplasia, using exhaled breath samples. The study is based on clinical samples and data ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29166
更新日期:2015-03-15 00:00:00
abstract::Limited and inefficient treatment options exist for metastatic relapsed cervical cancer (MRCC), and there are currently no reliable indicators to guide therapeutic selection. We performed deep sequencing analyses targeting 322 cancer-related genes in plasma cell-free DNA and matched white blood cells in 173 serial blo...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.33362
更新日期:2021-02-15 00:00:00
abstract::Marfe, G., Pucci, B., De Martino, L., Fiorito, F., Di Stefano, C., Indelicato, M., Aventaggiato, M., Russo, M. A. and Tafani, M. (2009), Heat-shock pretreatment inhibits sorbitol-induced apoptosis in K562, U937 and HeLa cells. Int. J. Cancer, 125: 2077-2085. doi: 10.1002/ijc.24572 The above article, published online o...
journal_title:International journal of cancer
pub_type: 撤回出版物
doi:10.1002/ijc.32281
更新日期:2019-08-15 00:00:00
abstract::A cyclin-dependent kinase inhibitor CDKN2A (p16/Ink4a) is a tumor suppressor and upregulated in cellular senescence. CDKN2A promoter methylation and gene silencing are associated with the CpG island methylator phenotype (CIMP) in colon cancer. However, prognostic significance of CDKN2A methylation or loss of CDKN2A (p...
journal_title:International journal of cancer
pub_type: 杂志文章,评审
doi:10.1002/ijc.25432
更新日期:2011-03-01 00:00:00
abstract::Sexual behavior has been consistently identified as a major risk factor for cervical cancer. Population-based studies have demonstrated that risk related to sexual activity is mediated by human papillomavirus (HPV) infection. We conducted a case-control study of 199 cases with low-grade squamous intraepithelial lesion...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960301)65:5<601::AID-IJC
更新日期:1996-03-01 00:00:00
abstract::In this registry-based cohort study, we estimated the risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer in renal transplant recipients (RTRs) compared to a nontransplanted comparison cohort. We identified all first-time RTRs in Denmark during 1990-2015 in a nationwide nephrology register...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.32565
更新日期:2020-05-01 00:00:00
abstract::The murine B16 melanoma (H-2b) was transfected with a retroviral vector containing the mouse IFN-alpha 1 gene. IFN-alpha 1-transfected cells produced IFN-alpha in vitro and exhibited an altered phenotype characterized by a decreased rate of multiplication, enhanced expression of H-2 antigens, an antiviral state to VSV...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910600216
更新日期:1995-01-17 00:00:00
abstract::Cord blood transplantation (CBT) is an effective option for treating hematological malignancies, but graft failure (GF) remains the primary cause of therapy failure. Thus, based on myeloablative conditioning (MAC) of busulfan with cyclophosphamide (Bu/Cy) or total body irradiation with Cy (TBI/Cy), fludarabine (Flu) w...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31339
更新日期:2018-08-01 00:00:00
abstract::Previously, the induction of pancreatic carcinogenesis in the rat using azaserine has involved a multiple-dose treatment protocol. The objective of the present study was to determine the effect of multiple azaserine treatments on pancreatic DNA synthesis and to develop a protocol for a single-dose initiation of pancre...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910280511
更新日期:1981-11-15 00:00:00
abstract::Suramin has been shown to have antiproliferative activity, either by blocking the binding of growth factors to their receptors or by inhibiting critical cellular enzymes. In 6 different cell lines from 5 tumour types (MCF-7, MCF-7/ADRR, PC3, HT-29, UM-SCC-11B and SW-1573/IR500), we studied the effect of scheduling of ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910510615
更新日期:1992-07-30 00:00:00
abstract::A displacement assay with tamoxifen, based on the relative binding affinity of tamoxifen and estradiol for the estrogen receptor (ER), was proposed in 1990 as prognostic indicator for breast-cancer patients. Validation of its predictive results in relation to the outcome of 73 patients with ER+ tumors is analyzed. ER,...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19971114)73:4<486::aid-ijc
更新日期:1997-11-14 00:00:00
abstract::The aim of our study was to analyze the alterations of some candidate tumor suppressor genes (TSGs) viz. LIMD1, LTF, CDC25A, SCOTIN, RASSF1A and CACNA2D2 located in the chromosomal region 3p21.31 associated with the development of early dysplastic lesions of head and neck. In analysis of 72 dysplastic lesions and 116 ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23834
更新日期:2008-12-01 00:00:00
abstract::Lysine-specific demethylase-1 (LSD1) removes the methyl groups from mono- and di-methylated lysine 4 of histone H3. Previous studies have linked LSD1 to malignancy in several human tumors, and LSD1 is considered to epigenetically regulate the energy metabolism genes in adipocytes and hepatocellular carcinoma. This stu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29714
更新日期:2016-01-15 00:00:00
abstract::We screened 29 human esophageal squamous cell carcinoma (ESC) cell lines for mutations of the p53 gene through all coding exons and exon-intron junctions. Mutations were found in 22 cell lines (76%), consisting of 20 single-base substitutions, 2 small deletions and 1 single-base insertion. Out of 20 single-base substi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960126)65:3<372::AID-IJC
更新日期:1996-01-26 00:00:00
abstract::The evolution of precancerous cervical lesions is poorly understood. A widely held model of cervical intraepithelial neoplasia grade 3 (CIN3) development is sequential progression from normal through CIN1 and CIN2 to CIN3. Another hypothesis, the "molecular switch" model, postulates that CIN3 can evolve directly from ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31549
更新日期:2018-10-01 00:00:00
abstract::MicroRNAs (mirs) are small noncoding RNA molecules (~22 nucleotides) that regulate posttranscriptional gene expression. Currently, there has not been a comprehensive study of their role in primary head and neck squamous cell carcinoma (HNSCC). To determine the role of mirs in HNSCC, we screened for altered microRNA ex...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23831
更新日期:2008-12-15 00:00:00
abstract::It was suggested that the brain microenvironment plays a role in glioma progression. Here we investigate the mechanism by which astrocytes which are abundant in glioma tumors, promote cancer cell invasion. In this study, we evaluated the effects of astrocytes on glioma biology both in vitro and in vivo and determined ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29380
更新日期:2015-09-01 00:00:00
abstract::Trifluorothymidine (TFT) is part of the oral drug formulation TAS-102. Both 5-fluorouracil (5-FU) and TFT can inhibit thymidylate synthase and be incorporated into DNA. TFT shows only moderate cross-resistance to 5-FU. Therefore, we examined whether mechanistic differences in cell death could underlie their different ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24943
更新日期:2010-05-15 00:00:00
abstract::Protocadherin 10 (PCDH10), a novel tumor suppressor gene in human cancers, is located in a common deleted region at chromosome 4q28 in colorectal cancer (CRC). This study aimed to ascertain the genetic loss of PCDH10 and its clinical relevance in CRC and to explore the tumor suppressor function of PCDH10. The genetic ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28899
更新日期:2014-12-01 00:00:00
abstract::In this report, we quantified HTLV-I provirus load using the AmpliSensor system, which utilizes fluorescence to measure PCR products. With this method, provirus loads could be measured within 6 hr, and the results obtained correlated well with those obtained by other methods. Samples from 256 blood donors, who were po...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19990611)81:6<859::aid-ijc
更新日期:1999-06-11 00:00:00
abstract::A series of 42 patients with malignant melanoma treated with BCG adjuvant immunotherapy were studied for sequential changes in cellular immune reactivity to non-specific mitogens. Lymphocyte preparations were made monthly and stored in a viable condition in liquid nitrogen. After 6 months of treatment, all lymphocyte ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910190104
更新日期:1977-01-01 00:00:00
abstract::Experimental evidence suggests that vitamin D might play a role in the development of breast cancer. Although the results of case-control studies indicate that circulating 25-hydroxyvitamin D [25(OH)D] is inversely associated with the risk of breast cancer, the results of prospective studies are inconsistent. A case-c...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.28172
更新日期:2013-10-01 00:00:00
abstract::Markers of exposure to polycyclic aromatic hydrocarbons (urinary 1-hydroxypyrene-glucuronide) and aromatic amines (4-aminobiphenyl-hemoglobin adducts), as well as urinary mutagenicity, were measured in 47 healthy smokers and 50 nonsmokers. DNA adducts were determined by P32-postlabeling in the exfoliated bladder cells...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960126)65:3<314::AID-IJC
更新日期:1996-01-26 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::In vitro infection of EBV-negative lymphoma cell lines with immortalizing strains of Epstein-Barr virus induces the cell-surface expression of B-cell markers, such as the EBV receptor/CR2 (CD21) and the CD23 antigen. The non-immortalizing EBV variant, P3HRI, which carries a deletion encompassing the EBV nuclear antige...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910460418
更新日期:1990-10-15 00:00:00
abstract::OCT-4 (also known as POU5F1) is a key regulator of self-renewal in embryonic stem cells. Regarding the new cancer stem cell concept, the expression of such genes is potentially correlated with tumorigenesis and can affect some aspects of tumor behavior, such as tumor recurrence or resistance to therapies. Although OCT...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.22508
更新日期:2007-04-01 00:00:00
abstract::CD4(+) T cells have been shown to be crucial for the induction and maintenance of cytotoxic T cell responses and to be also capable of mediating direct tumor rejection. Therefore, the anticancer therapeutic efficacy of peptide-based vaccines may be improved by addition of HLA class II epitopes to stimulate T helper c...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.26365
更新日期:2012-07-01 00:00:00
abstract::The paired-like homeodomain transcription factor 2 (PITX2), a downstream effector of wnt/β-catenin signaling, is well known to play critical role during normal embryonic development. However, the possible involvement of PITX2 in human tumorigenesis remains unclear. In this study, we extend its function in human esopha...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.27930
更新日期:2013-06-01 00:00:00
abstract::The therapeutic potential of the somatostatin analogue RC-160 radiolabeled with 188Re was evaluated in nude mice bearing xenografts of human prostate adenocarcinoma. 188Re-RC-160 was selectively retained in both DU-145 and PC-3 tumors following direct intra-tumor injection at all time points examined (2, 6 and 24 hr p...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960117)65:2<214::AID-IJC
更新日期:1996-01-17 00:00:00
abstract::Cytokines such as Interleukin (IL)-12p70 ("IL-12") and IL-23 can influence tumor progression. We tested the hypothesis that blood levels of IL-12p40, the common subunit of both cytokines, are associated with melanoma progression. Blood from 2,048 white melanoma patients were collected at a single institution between M...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29182
更新日期:2015-04-15 00:00:00