Abstract：
:The signaling pathways that mediate the development of pancreatic ductal adenocarcinoma (PDAC) downstream of mutant Kras remain incompletely understood. Here, we focus on ribosomal protein S6 (rpS6), an mTOR effector not implicated previously in cancer. Phosphorylation of rpS6 was increased in pancreatic acinar cells upon implantation of the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) or transgenic expression of mutant Kras. To examine the functional significance of rpS6 phosphorylation, we used knockin mice lacking all five phosphorylatable sites in rpS6 (termed rpS6(P-/-) mice). Strikingly, the development of pancreatic cancer precursor lesions induced by either DMBA or mutant Kras was greatly reduced in rpS6(P-/-) mice. The rpS6 mutants expressing oncogenic Kras showed increased p53 along with increased staining of γ-H2AX and 53bp1 (Trp53bp1) in areas of acinar ductal metaplasia, suggesting that rpS6 phosphorylation attenuates Kras-induced DNA damage and p53-mediated tumor suppression. These results reveal that rpS6 phosphorylation is important for the initiation of pancreatic cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Khalaileh A,Dreazen A,Khatib A,Apel R,Swisa A,Kidess-Bassir N,Maitra A,Meyuhas O,Dor Y,Zamir Gdoi
10.1158/0008-5472.CAN-12-2014subject
Has Abstractpub_date
2013-03-15 00:00:00pages
1811-20issue
6eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-2014journal_volume
73pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Incubation of taxol with human hepatic microsomal fractions or freshly isolated human liver slices yields three metabolite high performance liquid chromatography peaks, metabolite A, metabolite B, and 6 alpha-hydroxytaxol. These metabolites are formed in patients given taxol, with 6 alpha-hydroxytaxol formation repres...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-08-01 00:00:00
abstract：:Expression of cyclooxygenase (COX)-2 protein in 4-nitroquinoline-1-oxide (4-NQO)-induced rat tongue lesions and the postinitiation chemopreventive potential of a selective COX-2 inhibitor, nimesulide (NIM), were examined in Fischer 344 male rats. NIM was administered in the diet at doses of 150, 300, and 600 ppm for 1...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-02-15 00:00:00
abstract：:The specific delivery of radioisotopes to a tumor at minimal radiation of normal tissue is the ultimate aim of radioimmunotherapy. In this respect a two-step pretargeting regimen generally leads to an improved tumor to normal tissue uptake ratio compared to direct administration of radioimmunoconjugates. In this paper...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-07-01 00:00:00
abstract：:Maximum rates of nitrofuran reduction by intact mammalian cells and homogenates of mouse liver are obtained under anaerobic conditions, although significant reduction does occur with gas mixtures containing 5% oxygen and less. Single-strand breaks in DNA, measured as a decrease in the sedimentation constant on alkalin...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-03-01 00:00:00
abstract：:Antigens in human adult feces related to carcinoembryonic antigen (CEA) were analyzed with respect to their molecular masses, CEA domain compositions, and N-terminal amino acid sequences. By avoiding perchloric acid treatment, new fecal antigens related to CEA were identified. The fecal antigens revealed by Western bl...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-08-01 00:00:00
abstract：:Effective treatment of malignant carcinomas requires identification of proteins regulating epithelial cell proliferation. To this end, we compared gene expression profiles in murine colonocytes and their c-Myc-transformed counterparts, which possess enhanced proliferative potential. A surprisingly short list of deregu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-1953
更新日期：2004-05-01 00:00:00
abstract：:We have investigated the antiproliferative and cytotoxic effects of selected enediynes against three Kaposi's sarcoma (KS) cell lines. The enediynes tested were found to be very potent in inhibiting the growth of KS cells. Treatment with concentrations of 10(-10) M or less were capable of producing 50% inhibition of g...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-08-15 00:00:00
abstract：:Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-1303
更新日期：2017-01-15 00:00:00
abstract：:Liblomycin (LBM), a novel bleomycin analogue, and bleomycin A2 (BLM A2) were compared with respect to their relative potential to inhibit growth in a human head and neck squamous carcinoma cell line and to produce DNA damage within cellular DNA and nuclei DNA and against isolated naked DNA. Against the BLM-sensitive c...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-03-15 00:00:00
abstract：:Ribonucleotide reductase (RR) is responsible for the de novo conversion of the ribonucleoside diphosphates to deoxyribonucleoside diphosphates, which are essential for DNA synthesis and repair. RR consists of two subunits, hRRM1 and hRRM2. p53R2 is a new RR family member. Because the majority of human tumors possess m...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-10-15 00:00:00
abstract：:The Th2 cytokines interleukin (IL)-4 and -13 are acknowledged regulators of lymphocyte proliferation and activation. They have also been well studied in the regulation of various myeloid-derived populations in tumor biology. It has become clear, however, that both cytokines can have direct effects on epithelial tumor ...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-12-3544
更新日期：2012-12-15 00:00:00
abstract：:Incidence of the loss of heterozygosity on chromosome 3p was evaluated using 7 polymorphic probes in 35 Japanese patients with sporadic renal cell carcinoma (RCC). Overall frequency of the loss of heterozygosity on 3p was 53%, representing 16 of 30 informative cases. Examination of the relationship between histopathol...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
abstract：:A hormone-dependent subline of the transplantable rat mammary tumor MTW9 contains binding sites for both prolactin and estrogen. Prolactin binding is saturable (K-d similar to 2 times 10-9 M), hormone specific, and destroyed by proteases. By contrast, an autonomous subline derived from the same parent tumor has lost m...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-04-01 00:00:00
abstract：:Cell multiplication in the absence of integrin-derived adhesive signals (anchorage-independent growth) is the phenotypic hallmark of neoplastic transformation. Therefore, the frequently observed up-regulation of some integrins in tumors has been interpreted as an epiphenomenon and not as a causative factor of oncogeni...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-2827
更新日期：2005-12-01 00:00:00
abstract：:The murine monoclonal antibodies TURP-27 and HNK-1 have been shown to detect antigens which are heavily expressed by benign prostatic hyperplasia and carcinoma of the prostate. Western blot analysis of prostate extracts showed that monoclonal antibodies TURP-27 and HNK-1 bound glycoproteins with molecular weights of 1...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Interleukin-6 (IL-6) and the subsequent Janus-activated kinase (JAK)-dependent signaling pathways play a critical role in the pathogenesis of multiple myeloma. Here, we compared the sensitivity and specificity of a novel pan-JAK inhibitor, tetracyclic pyridone 6 (P6), with that of AG490 in a panel of myeloma-derived c...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-4280
更新日期：2006-10-01 00:00:00
abstract：:Medulloblastoma is the most common malignant pediatric brain tumor and is one of the leading causes of cancer-related mortality in children. Treatment failure mainly occurs in children harboring metastatic tumors, which typically carry an isochromosome 17 or gain of 17q, a common hallmark of intermediate and high-risk...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-0592
更新日期：2010-10-15 00:00:00
abstract：:We have used a structure-activity approach to investigate whether the Vinca alkaloids inhibit cell proliferation primarily by means of their effects on mitotic spindle microtubules or by another mechanism or by a combination of mechanisms. Five Vinca alkaloids were used to investigate the relationship in HeLa cells be...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-04-15 00:00:00
abstract：:Four bifunctional and one trifunctional alpha-chloro ethers were tested for carcinogenicity. These compounds were bis-1,2-(chloromethoxy)ethane (Compound I), bis-1,4-(chloromethoxy)butane (Compound II), bis-1,6-(chloromethoxy) hexane (Compound III), bis-1,4-(chloromethoxy)-p-xylene (Compound IV), and tris-1,2,3-(chlor...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-09-01 00:00:00
abstract：:The anthracycline antineoplastic agents Adriamycin and N-trifluoroacetyl-Adriamycin-14-valerate were assayed in vivo and in vitro for ability to produce DNA lesions recognized by the UVRABC endonuclease, a DNA repair enzyme of Escherichia coli which recognizes large, bulky lesions in DNA. We found that, while both dru...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:Alteration in epidermal growth factor receptor (EGFR) expression is frequently associated with malignant transformation of epithelial tissues, including oral mucosa. This study examines the mutations in the coding region of the human EGFR gene in normal and malignant human oral keratinocytes. To examine the intragenic...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-08-15 00:00:00
abstract：:Transcription factor PAX3 has seven isoforms of which PAX3c has been studied extensively whereas the functions of the other isoforms are less well known. Here, we found that PAX3 isoforms in a stable transfection system have different biological functions in mouse melanocytes in vitro. PAX3a and PAX3b had negative eff...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-0947
更新日期：2006-09-01 00:00:00
abstract：:Phosphorylation of heat shock protein 27 (HSP27) has been suggested to play an important role in the regulation of F-actin dynamics in response to growth factors and stress. Because the microfilament network is one of the earliest targets of oxidative stress and because phosphorylation of HSP27 is strongly induced by ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-01-15 00:00:00
abstract：:Linomide is a p.o. active antiangiogenic agent that has been demonstrated to be effective in suppressing the in vivo growth of rat and human prostatic cancer xenografts. The present studies were conducted to determine whether the angiogenic molecules, vascular endothelial growth factor/vascular permeability factor (VE...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-03-15 00:00:00
abstract：:Alpha-particle immunotherapy by targeted alpha-emitters or alpha-emitting isotope generators is a novel form of extraordinarily potent cancer therapy. A major impediment to the clinical use of targeted actinium-225 (225Ac) in vivo generators may be the radiotoxicity of the systemically released daughter radionuclides....
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-3096
更新日期：2005-06-01 00:00:00
abstract：:Treatment of exponentially growing 9L monolayer cells with graded concentrations of methotrexate or 5-fluorouracil (5-FUra) resulted in approximately 95% cell kill, corresponding to the percentage of cells in this system labeled by autoradiography (98%). Additional cell kill could be obtained if 5-FUra was administere...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-10-01 00:00:00
abstract：:Two aminoanthraquinone analogs 1,4-bis(2-[(2-hydroxyethyl)amino]ethylamino)-9,10-anthracenedione (HAQ) and 1,4-dihydroxy-5,8-bis(2-[(2-hydroxyethyl)amino]ethylamino]-9,10-anthracenedione (DHAQ) have been shown to possess similar therapeutic activities against experimental tumors but different toxicities to the animal...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-02-01 00:00:00
abstract：:The formation of 7-(2-hydroxyethyl)guanine (7-HEG) in DNA of target and nontarget tissues was investigated in male B6C3F1 mice (20/group) and F344 rats (10/group) exposed to 0, 3, 10, 33, 100, or 300 (rats only) ppm ethylene oxide (ETO) by inhalation for 6 h/day for 4 weeks (5 days/week) and mice exposed to 100 ppm ET...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-08-15 00:00:00
abstract：:Immune checkpoint inhibitors show great promise as therapy for advanced melanoma, heightening the need to determine the most effective use of these agents. Here, we report that programmed death-1(high) (PD-1(high)) tumor antigen (TA)-specific CD8(+) T cells present at periphery and at tumor sites in patients with adva...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-3016
更新日期：2015-04-15 00:00:00
abstract：:2,6,10,14-Tetramethylpentadecane (pristane), s.c. injected simultaneously with plasmacytoma inocula, enhances the transplantability of tumor cells. The effect is dose and time dependent. The enhancement is shown only by plasmacytoma (MOPC-315 and MPC-11) and not by the murine lymphosarcoma and chondrosarcoma tested. V...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
