Abstract:
:MEK1/2 inhibitors like U0126 can potentiate or antagonize the antitumor activity of cytotoxic agents such as cisplatin, paclitaxel or vinblastine, depending on the drug or the target cells. We now investigated whether U0126, differentially regulates melanoma signaling in response to UV radiation or betulinic acid, a drug lethal against melanoma. This report shows that U0126 inhibits early response (ERK) kinase activation and cyclin A expression in wt p53 C8161 melanoma exposed to either UV radiation or betulinic acid. However, U0126 does not protect from UV damage, but counteracts betulinic acid-mediated apoptosis in the same cells. Protection from the latter drug by joint treatment with U0126 was also evident in wt p53 MelJuso melanoma and mutant p53 WM164 melanoma. The latter cells were the most responsive to betulinic acid, showing a selective decline in the cdk4 protein, without a comparable change in other key cell cycle proteins like cdc2, cdk2, cdk7 or cyclin A, prior to apoptosis-associated PARP fragmentation. Laser scanning cytometry also showed that betulinic acid induced a significant increase in chromatin condensation in WM164 melanoma irrespective of whether they were in adherent form or as multicellular spheroids. All these betulinic acid-induced changes were counteracted by U0126. Our data show for the first time that (a) cdk4 protein is an early target of betulinic acid-induced apoptosis and (b) unrestricted ERK signaling favours betulinic acid-induced apoptosis, but this is counteracted by U0126, partly through counteracting chromatin condensation and restoring Akt activation decreased by betulinic acid treatment.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Rieber M,Rieber MSdoi
10.1002/ijc.21478keywords:
subject
Has Abstractpub_date
2006-03-01 00:00:00pages
1135-43issue
5eissn
0020-7136issn
1097-0215journal_volume
118pub_type
杂志文章abstract::The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in various developmental processes. Although GRHL2 recently has attracted considerable interest in that it could be identified as a novel suppressor of the epithelial-to-mesenchymal transition, evidence is emerging that GRHL2 also exhibits tumour-...
journal_title:International journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1002/ijc.29841
更新日期:2016-02-15 00:00:00
abstract::Laser scanning confocal microscopy has been used to follow the uptake and efflux of the 2-fluoroglycoside of doxorubicin, ME2303, in live cultures of the human ovarian cancer cell line A2780 and its doxorubicin-resistant variant A2780AD. Our methods combine confocal laser scanning microscopy and image analysis to exam...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910590118
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abstract::Treatment of human colorectal tumor cells (LS174T, HT-29, and WiDr) with analogues of cyclic AMP (cAMP) (dibutyryl-cAMP and 8-Cl-cAMP) selectively enhances the expression of carcinoembryonic antigen (CEA). Dose and temporal kinetics results revealed that 8-Cl-cAMP was approximately 100-fold more potent than dibutyryl-...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910480319
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abstract::We analyzed the role of reproductive factors on the risk of endometrial cancer using data from a case-control study conducted in Italy. Cases were 752 women with histologically confirmed endometrial cancer < 75 years of age. Controls were 2,606 patients < 75 years of age admitted for acute, non-gynecological non-hormo...
journal_title:International journal of cancer
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abstract::Our study explored the drug interaction of all-trans retinoic acid (ATRA) and RAD001 (everolimus), the inhibitor of mammalian target of rapamycin complex 1 (mTORC1), in acute myelogenous leukemia (AML) NB4 and HL60 cells. RAD001 (10 nM) significantly enhanced the ATRA-induced growth arrest and differentiation of these...
journal_title:International journal of cancer
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abstract::This report describes the appearance of ectopic chromosome around centrosome (ECAC) in metaphase cell nuclei of high-risk HPV-associated cervical neoplasms. ECAC are clearly visible on HE-stained sections as a tiny (approx. 0.7 micro), round, dark structure or an aggregate of filamentous chromosome, often symmetrical ...
journal_title:International journal of cancer
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abstract::Individuals differ in their ability to repair DNA damage induced by carcinogens. Studies have shown that polymorphisms in DNA repair genes contribute to individual variation in DNA repair capacity and cancer risk. In a hospital-based case-control study, we tested the hypothesis that a C to T variant (Thr241Met) of DNA...
journal_title:International journal of cancer
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abstract::Epithelial-mesenchymal transition (EMT) is a cell plasticity process required for metastasis and chemoresistance of carcinoma cells. We report a crucial role of the signal adaptor proteins CRK and CRKL in promoting EMT and tumor aggressiveness, as well as resistance against chemotherapy in colorectal and pancreatic ca...
journal_title:International journal of cancer
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abstract::We assessed prospectively whether residual cervical intraepithelial neoplasia (CIN) after treatment for high-grade CIN can be predicted by genotype-specific high-risk HPV (HR-HPV) detection in follow-up cervical scrapes. A broad spectrum, highly sensitive SPF(10)-LiPA-PCR HPV detection technique was used on cervical s...
journal_title:International journal of cancer
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更新日期:2002-11-10 00:00:00
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journal_title:International journal of cancer
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doi:10.1002/ijc.2910630205
更新日期:1995-10-09 00:00:00
abstract::Using a direct binding liquid competition radioimmunoassay, the amount of the ras oncogene protein product, p21, was quantitated in a variety of human tumors and adjacent apparently normal tissues. In 48 of 50 matched tumor and normal tissue biopsy specimens from 50 patients, more ras p21 was detected in the tumor tha...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910430315
更新日期:1989-03-15 00:00:00
abstract::CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation. Telomerase plays an important role in the development of cellular immortality and oncogenesis. To gain insight into the role of epigenetic aberration of telomerase-related genes in hepatocarcinogenesis, we det...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23650
更新日期:2008-09-01 00:00:00
abstract::Distribution of miscarriages, stillbirths and infant deaths in the families of a population-based series of children with soft-tissue sarcoma was examined in relation to index case histology (rhabdomyosarcoma or other soft-tissue sarcoma) and to the possible presence of genetic predisposition to cancer in the families...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910560507
更新日期:1994-03-01 00:00:00
abstract::Interest has increased in the potential role of circulating tumour cells in cancer management. Most cell-based studies have been designed to determine the number of circulating tumour cells in a given volume of blood. Ability to understand the biology of the cancer cells would increase the clinical potential. The purp...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29680
更新日期:2016-01-01 00:00:00
abstract::Resveratrol, which may occur in wine, was suggested to act as a chemopreventive agent against the carcinogenic effects of ethanol. The assumption was based on data from experimental animals, which have shown that resveratrol above certain thresholds may reduce the incidence of tumours in several of the alcohol-related...
journal_title:International journal of cancer
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doi:10.1002/ijc.28336
更新日期:2014-01-01 00:00:00
abstract::Human T-cell leukemia virus type I (HTLV-I) is etiologically associated with adult T-cell leukemia/lymphoma (ATL). We cloned and sequenced host DNA adjacent to the long terminal repeats of HTLV-I from uncultured leukemic cells of 4 ATL patients. The region flanking the provirus was generally A/T-rich (60-64% A/T), and...
journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:1996-01-03 00:00:00
abstract::Although preliminary evidence suggests that germline variation in genes involved in steroid hormone metabolism may alter breast cancer prognosis, this has not been systematically evaluated. We examined associations between germline polymorphisms in 6 genes involved in the steroid hormone metabolism and signaling pathw...
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pub_type: 杂志文章,随机对照试验
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更新日期:2009-12-01 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
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journal_title:International journal of cancer
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abstract::Trends in the incidence of stomach cancer among 52,604 patients notified to the National Swedish Cancer Registry in 1960 through 1984 were analysed. Age-standardized incidence rates declined throughout the period, from 47.1 to 24.6 per 10(5) in males and from 23.8 to 12.7 per 10(5) in females. Among males the decline ...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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abstract::Immunosuppressed patients who develop non-Hodgkin's lymphoma (NHL) have abnormal antibody responses against the Epstein-Barr virus (EBV) prior to the diagnosis of malignancy. To see if this is also true of "spontaneous" cases in the general population, we undertook a collaborative serologic case-control study. From 4 ...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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abstract::There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investi...
journal_title:International journal of cancer
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abstract::In sub-Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross-sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtaine...
journal_title:International journal of cancer
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abstract::Smoking is a major contributor to all-cause mortality in Europe and accounts for one-fifth of the cancer-related deaths. Monitoring the tobacco epidemic via an analysis of lung cancer trends is essential in helping countries arrest the effects of tobacco epidemic in the region. The study aims to provide a comprehensiv...
journal_title:International journal of cancer
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abstract::The incidence of non-Hodgkin's lymphoma (NHL) has markedly increased in the US and other westernized countries in recent years and presents a considerable clinical challenge. NHL is divided into subtypes that follow an aggressive or indolent course. Follicular lymphoma (FL), the most common indolent subtype, and mantl...
journal_title:International journal of cancer
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abstract::Mutations of the p53 tumor-suppressor gene universally occur on exons 5-8 in human cancer. We analyzed these mutations in esophageal cancer tissue from 207 patients in China using 2 methods, single-strand conformation polymorphism (SSCP), one of the most frequently used methods, and the recently developed denaturing h...
journal_title:International journal of cancer
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abstract::Metastasis is a multistep process that involves the dissemination of cells from the primary tumor and colonization of distant secondary organs. Epithelial cells at the invasive front of a carcinoma acquire an enhanced migratory phenotype in a process called epithelial-to-mesenchymal transition (EMT). This cellular pla...
journal_title:International journal of cancer
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更新日期:2016-07-15 00:00:00