Abstract：
:Deletion of endoplasmic reticulum resident chaperone Grp78 results in activation of the unfolded protein response and causes rapid depletion of the entire intestinal epithelium. Whether modest reduction of Grp78 may affect stem cell fate without compromising intestinal integrity remains unknown. Here, we employ a model of epithelial-specific, heterozygous Grp78 deletion by use of VillinCreERT2-Rosa26ZsGreen/LacZ-Grp78+/fl mice and organoids. We examine models of irradiation and tumorigenesis, both in vitro and in vivo Although we observed no phenotypic changes in Grp78 heterozygous mice, Grp78 heterozygous organoid growth was markedly reduced. Irradiation of Grp78 heterozygous mice resulted in less frequent regeneration of crypts compared with nonrecombined (wild-type) mice, exposing reduced capacity for self-renewal upon genotoxic insult. We crossed mice to Apc-mutant animals for adenoma studies and found that adenomagenesis in Apc heterozygous-Grp78 heterozygous mice was reduced compared with Apc heterozygous controls (1.43 vs. 3.33; P < 0.01). In conclusion, epithelium-specific Grp78 heterozygosity compromises epithelial fitness under conditions requiring expansive growth such as adenomagenesis or regeneration after γ-irradiation. These results suggest that Grp78 may be a therapeutic target in prevention of intestinal neoplasms without affecting normal tissue.Significance: Heterozygous disruption of chaperone protein Grp78 reduces tissue regeneration and expansive growth and protects from tumor formation without affecting intestinal homeostasis. Cancer Res; 78(21); 6098-106. ©2018 AACR.
journal_name
Cancer Resjournal_title
Cancer researchauthors
van Lidth de Jeude JF,Spaan CN,Meijer BJ,Smit WL,Soeratram TTD,Wielenga MCB,Westendorp BF,Lee AS,Meisner S,Vermeulen JLM,Wildenberg ME,van den Brink GR,Muncan V,Heijmans Jdoi
10.1158/0008-5472.CAN-17-3600subject
Has Abstractpub_date
2018-11-01 00:00:00pages
6098-6106issue
21eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-17-3600journal_volume
78pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:The sonic hedgehog (SHH) receptor Patched 1 (Ptch1) is critical for embryonic development, and its loss is linked to tumorigenesis. Germ line inactivation of one copy of Ptch1 predisposes to basal cell carcinoma and medulloblastoma in mouse and man. In many cases, medulloblastoma arising from perturbations of Ptch1 fu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-0505
更新日期：2006-07-15 00:00:00
abstract：:HeLa cells were synchronized at the G1-S boundary by double thymidine block and treated for 1 hr with varying concentrations of the antibiotic anticancer protein neocarzinostatin (NCS). Cells were then released from the block and allowed to resume their cycle. Aliquots were removed at various times in order to monitor...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
abstract：:Cytidine dialdehyde inhibited the growth of leukemia L1210 cells in culture at a 50% inhibitory concentration of 3.5 X 10(-5) M and, when administered i.p. at 200 mg/kg daily for 5 days, increased the mean survival of L1210 tumor-bearing mice by up to 171%. Given by the s.c. or i.v. routes, the compound was ineffectiv...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-03-01 00:00:00
abstract：:Cellular immune competence was found to be impaired in previous studies of patients with malignant brain tumors. In patients with nonneural tumors, we recently found that serum levels of acute-phase proteins were related to immune status as well as to tumor extent. To determine whether the serum proteins in patients w...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:The presence of metastases in the regional lymph nodes is the major prognostic factor in breast cancer in the absence of overt distant metastases and is also an important indicator of the need for adjuvant therapy in "early" breast cancer. Currently, the accurate assessment of axillary lymph node status requires axill...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-03-15 00:00:00
abstract：:The possible contribution of endocrine disrupters to human disease, particularly those compounds that modulate the estrogen receptor (ER), has recently drawn considerable attention. The tissue specificity of effects mediated by the ER is well recognized, although the mechanism of this specificity is not understood suf...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-07-01 00:00:00
abstract：:BALB/c mice were hyperimmunized against a membrane preparation derived from a pool of transurethral resection specimens which included three benign prostatic hyperplasia and one prostate adenocarcinoma tissue samples. The activated lymphocytes were fused with the NS-1 mouse myeloma cell line, and supernatants from imm...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：:Southern blot-hybridization analysis of DNAs from human tumors demonstrated amplification of the epidermal growth factor (EGF) receptor gene in 10 of 12 squamous cell carcinoma cell lines tested and in none of 18 tumor cell lines of nonsquamous cell carcinomas. The degree of amplification in the squamous cells varied ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-01-01 00:00:00
abstract：:8-Azainosine (8-aza-HR) is of interest because of its activity against experimental tumors. Metabolic studies in cell cultures were performed with 8-aza-HR and with the structurally related nucleoside, 8-azaadenosine (9-beta-D-ribofuranosyl-8-azaadenine) (8-aza-AR), which has a lower degree of antitumor activity than ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-11-01 00:00:00
abstract：:Convection enhanced delivery (CED) is potentially a powerful method to improvethe targeting of macromolecules to the central nervous system by applying a pressure gradient to establish bulk flow through the brain interstitium during infusion. The purpose of the present study was to evaluate CED as a means to improve t...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-11-15 00:00:00
abstract：:In order to test the contention that metastasis is a selective process and that therefore metastases might show a more restricted pattern of phenotypic and genotypic characteristics than primary tumors, we compared the expression of carcinoembryonic antigen, Ca 19-9, secretory component, serotonin, and mucin productio...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-08-15 00:00:00
abstract：:Given that there are millions of single-nucleotide polymorphisms (SNPs) in the entire human genome, a major difficulty faced by scientists in planning costly population-based genotyping is to choose target SNPs that are most likely to affect phenotypic functions and ultimately contribute to disease development. Althou...
journal_title：Cancer research
pub_type： 杂志文章,meta分析
doi：10.1158/0008-5472.can-03-2800
更新日期：2004-03-15 00:00:00
abstract：:To enable antibodies to function as cytotoxic anticancer agents, they are modified either via attachment to protein toxins or highly potent, low-molecular-weight drugs. Such molecules, termed immunotoxins and antibody-drug conjugates, respectively, represent a second revolution in antibody-mediated cancer therapy. Thu...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-11-1374
更新日期：2011-10-15 00:00:00
abstract：:The phosphatidylinositol 3-kinase (PI3K)/Akt pathway can increase vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1alpha (HIF-1alpha) expression. We examined the effect of nelfinavir, an HIV protease inhibitor that inhibits Akt signaling, on VEGF and HIF-1alpha expression and on angiogenesis, tu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-1239
更新日期：2006-09-15 00:00:00
abstract：:The SMAD4 (DPC4) gene was initially isolated as a candidate tumor suppressor from the convergent site of homozygous deletions on 18q in a panel of pancreatic carcinoma cell lines. It encodes a common cytoplasmic signaling molecule shared by the transforming growth factor-beta, activin, and bone morphogenic pathways. W...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-12-15 00:00:00
abstract：:The small leucine-rich proteoglycan lumican was identified from a human placenta cDNA library by the expression cloning method as a gene product that interacts with membrane-type matrix metalloproteinase-1 (MT1-MMP). Coexpression of MT1-MMP with lumican in HEK293T cells reduced the concentration of lumican secreted in...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-1038
更新日期：2004-10-01 00:00:00
abstract：:8-Chloro-cAMP (8-Cl-cAMP) is a novel agent that is able to inhibit the growth of a wide variety of cancer cell types in vitro and in vivo and, at doses devoid of toxicity, to achieve plasma concentrations in cancer patients in a range effective for cancer cell growth inhibition. In this study, we have demonstrated tha...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-11-15 00:00:00
abstract：:In vivo tumor inhibitory activity of polymorphonuclear leukocytes (PMN) treated in vitro with lymphokine(s) (LK) was investigated with Winn's assay. Culture supernatants of BALB/c mouse spleen cells incubated with a streptococcal preparation, OK-432, were used as an LK source. With the use of a [3H]uridine release ass...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-11-15 00:00:00
abstract：:The effects of combined administration of cimetidine and tetragastrin on gastric acid secretion, the labeling index of the gastric mucosa, and the incidence of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin in de...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-03-15 00:00:00
abstract：:The chemotherapeutic agent 6-mercaptopurine was previously shown to inhibit the binding of 7r,8t-dihydroxy-9,10t-oxy-7,8,9,10-tetrahydro-benzo(a) pyrene (BPDE-I) to DNA in Chinese hamster ovary cells. Two compounds related to 6-mercaptopurine, 2,6-dithiopurine (DTP) and thiopurinol (TP), have been tested for inhibitio...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-09-15 00:00:00
abstract：:Recent three genome-wide association studies have mapped a lung cancer susceptibility locus to chromosome 15q25 in Caucasians. However, the reported risk single nucleotide polymorphisms (SNPs) are extremely rare in Asians, arguing against any of these being causative variants. This study sought to identify other varia...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-0081
更新日期：2009-06-15 00:00:00
abstract：:After the Chernobyl accident, the incidence of urinary bladder cancers in the Ukraine population increased gradually from 26.2 to 36.1 per 100,000 between 1986 and 1996. Urinary bladder epithelium biopsied from 45 male patients with benign prostatic hyperplasia living in radiocontaminated areas of Ukraine demonstrated...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-08-01 00:00:00
abstract：:Alterations in cellular biochemistry which are associated with the development of resistance to cytotoxic peptides, such as tumor necrosis factor (TNF), may also be responsible for changes in the response of cells to cytotoxic agents. Culturing ME-180 cervical carcinoma cells in the presence of escalating concentratio...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-09-01 00:00:00
abstract：:The ability to accurately distinguish remaining or recurrent high-grade astrocytoma from necrosis or edema following treatment is essential to optimal patient management. Thallium 201 planar gamma-camera imaging has been shown to be helpful in detecting recurrent high-grade astrocytoma; however, due to tissue heteroge...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-07-15 00:00:00
abstract：:Allelic loss of chromosome 9p21 is common in small cell lung cancer (SCLC), but inactivation of the tumor suppressor gene CDKN2a is rare, implying the existence of another target gene at 9p21. A recent deletion mapping study of chromosome 9p has also identified a site of deletion in non-small cell lung cancer (NSCLC) ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:Mitomycin C (MMC) is an anticancer drug that requires reductive activation to exert its toxicity. MMC is known to cross-link DNA that contributes significantly to the cytotoxicity and consequent cell death. Cytosolic NADPH:quinone oxidoreductase 1 (NQO1) and microsomal enzymes have been shown to mediate MMC-induced DN...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-09-15 00:00:00
abstract：:ARID1A, encoding a subunit of the SWI/SNF complex, is the most frequently mutated epigenetic regulator in human cancers and is mutated in more than 50% of ovarian clear cell carcinomas (OCCC), a disease that currently has no effective therapy. Inhibition of histone deacetylase 6 (HDAC6) suppresses the growth of ARID1A...
journal_title：Cancer research
pub_type： 评论,杂志文章
doi：10.1158/0008-5472.CAN-19-1302
更新日期：2019-11-01 00:00:00
abstract：:Bone marrow biopsy specimens from patients with myeloma were cultured in either 1 of 2 thin-film culture systems, a controlled environment steady state system or a rocker tube configuration of the system, for periods up to 42 days. Both functional and morphological characteristics of the myeloma cells were well-mainta...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-04-01 00:00:00
abstract：:In the diagnosis of non-Hodgkin's lymphomas, the ready characterization of the neoplastic cell lineage by analysis of cell surface markers is of great importance. We present evidence for the existence of a human B-leukemia-associated antigen recognized by a complement-fixing monoclonal antibody (anti-Y 29/55). A hybri...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：:XRCC1 is a key component of DNA base excision repair, single strand break repair, and backup nonhomologous end-joining pathway. XRCC1 (X-ray repair cross-complementing gene 1) deficiency promotes genomic instability, increases cancer risk, and may have clinical application in breast cancer. We investigated XRCC1 expre...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-12-2929
更新日期：2013-03-01 00:00:00
