Abstract：
BACKGROUND:Immune checkpoint blockade (ICB) therapy improved the prognosis of cancer patients, but general administration of ICBs occasionally induces side effects that include immune-related adverse events and tumour hyper-progression. Here, we established a protein-based system, by which endogenous expression of IC molecule in natural killer (NK) cells was transiently repressed on enhancement of their antitumour activity. METHODS:A protein-based genome modulator (GM) system is composed of a transcription activator-like effector (TALE), DNA methyltransferase and a newly identified potent cell-penetrating peptide with nuclear-trafficking property named NTP. TALE was designed to target the promoter region of the programmed cell death-1 (PD-1) gene. After culturing human NK cells in the presence of NTP-GM protein, we examined endogenous PD-1 expression and antitumour activity of the treated cells. RESULTS:NTP-GM protein efficiently downregulated PD-1 expression in NK cells with increased CpG DNA methylation in the promoter region. The antitumour activity of the treated NK cells was enhanced, and repeated intraperitoneal administrations of the treated NK cells attenuated tumour growth of programmed death-ligand 1-positive tumour cells in vivo. CONCLUSIONS:Because the incorporated NTP-GM protein was quickly degraded and negligible in the administered NK cells, the NTP-GM system could be an alternative option of an ICB without side effects.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Teratake Y,Takashina T,Iijima K,Sakuma T,Yamamoto T,Ishizaka Ydoi
10.1038/s41416-019-0708-ysubject
Has Abstractpub_date
2020-03-01 00:00:00pages
823-834issue
6eissn
0007-0920issn
1532-1827pii
10.1038/s41416-019-0708-yjournal_volume
122pub_type
杂志文章abstract：BACKGROUND:Colorectal cancer (CRC) is usually categorised as proximal or distal CRC. Recently, many researchers have tried to determine the molecular heterogeneity of CRCs along bowel subsites. However, the differential effects of the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) on the cl...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.430
更新日期：2013-08-20 00:00:00
abstract：:Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604152
更新日期：2008-03-25 00:00:00
abstract：:The aim of this study was to determine the concentration of PDGF in vivo in neoplastic and non-neoplastic brain lesions. Fluid from cystic lesions and cerebrospinal fluid was tested in a radioreceptor assay that detects all described PDGF isoforms. High concentration of PDGF were found in cyst fluids from several astr...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.184
更新日期：1994-05-01 00:00:00
abstract：:Wistar rats were sensitized to rat embryonic tissue by immunization with irradiated (5000 rad) rat embryo cells (2 X 10(6) s.c. + 1 X 10(6) i.p.) derived from embryos aged 14-15 days, or by implantation of irradiated (5000 rad) tissue grafts from these embryos. Three to five immunizations were given at weekly interval...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1976.94
更新日期：1976-06-01 00:00:00
abstract：:Cancer of the colon and rectum is one of the most frequent malignancies both in the US and Europe. Standard palliative therapy is based on 5-fluorouracil/folinic acid combinations, with or without oxaliplatin or irinotecan, given intravenously. Oral medication has the advantage of greater patient convenience and accep...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/sj.bjc.6600781
更新日期：2003-03-10 00:00:00
abstract：:A case-control study of lung cancer involving interviews with 965 female patients and 959 controls in Shenyang and Harbin, two industrial cities which have among the highest rates of lung cancer in China, revealed that cigarette smoking is the main causal factor and accounted for about 35% of the tumours among women. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.421
更新日期：1990-12-01 00:00:00
abstract：:gamma-Irradiated rat hepatoma cells are immunogenic in syngeneic WAB/Not rats, so that immunized animals are protected against tumour-cell challenge and circulating tumour-specific antibody is produced. Treatment of the immunizing cells with glutaraldehyde at concentrations of 0.001% or greater for 30 min rendered the...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.113
更新日期：1979-06-01 00:00:00
abstract：:The goal of the study was to identify any normal genes that may become inactivated in malignant cells, with associated modifications or loss of gene products. Consequently, attempts were made to identify such products by generating monoclonal antibodies using an immune tolerisation-immunisation procedure. Using such a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.80
更新日期：1994-03-01 00:00:00
abstract：BACKGROUND:The clinical course of World Health Organisation grade II gliomas remains variable and their time point of transformation into a more malignant phenotype is unpredictable. Identification of biological markers that can predict prognosis in individual patients is of great clinical value. PROX1 is a transcripti...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.162
更新日期：2011-05-24 00:00:00
abstract：BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) has poor survival and treatment options. PDAC cells shift their metabolism towards glycolysis, which fuels the plasma membrane calcium pump (PMCA), thereby preventing Ca2+-dependent cell death. The ATP-generating pyruvate kinase-M2 (PKM2) is oncogenic and overexpressed...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0675-3
更新日期：2020-01-01 00:00:00
abstract：:To: (1) estimate the prevalence of clinically significant emotional distress in patients attending a cancer outpatient department and (2) determine the associations between distress and demographic and clinical variables, we conducted a survey of outpatients attending selected clinics of a regional cancer centre in Ed...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603626
更新日期：2007-03-26 00:00:00
abstract：:The metabolism of serotonin was studied in cancer patients of their first day of their first course of chemotherapeutic drugs either with strongly or moderately emetogenic regimens. It was observed that strongly emetogenic treatments induce greater increases in serotonin release than moderately emetogenic regimens. Hi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.242
更新日期：1992-07-01 00:00:00
abstract：:HER-2/neu is a tumour antigen that is overexpressed in human breast tumours. Among the vaccine strategies developed to overcome immune tolerance to self-proteins, vaccination with anti-idiotypic (anti-Id) antibodies has been described as a promising approach for treatment of several malignant diseases. To develop an a...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601825
更新日期：2004-05-17 00:00:00
abstract：:To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpressi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.171
更新日期：1995-04-01 00:00:00
abstract：BACKGROUND:8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most abundant marker of DNA damage and it reflects oxidative stress. Human 8-oxoguanine glycosylase (hOGG1) is a DNA-repair enzyme that participates in 8-oxodG removal. METHODS:hOGG1 protein expression was immunohistochemically studied in 96 patients with...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.518
更新日期：2012-01-17 00:00:00
abstract：:In the present study the putative chemopreventive effect of dietary fish oil (MaxEPA) on azaserine-induced pancreatic carcinogenesis in rats was investigated. Groups of rats were maintained on a semipurified low-fat (LF; 5 wt%) diet or on semipurified high-fat (HF; 25 wt%) diets containing 5 wt% linoleic acid (LA) and...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.7
更新日期：1996-01-01 00:00:00
abstract：:Genomic alterations in the p53 tumour-suppressor gene and overexpression of p53 protein, resulting from gene mutations, are frequently found in pancreatic cancer. In this study we analysed the sera of 160 patients with malignant and benign pancreatic diseases for the presence of circulating antibodies to the p53 prote...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.443
更新日期：1994-11-01 00:00:00
abstract：:Even though the majority of patients with bladder malignancies initially present with low stage disease, the clinical epidemiology of these so-called superficial bladder tumours is not well known. In this paper, disease characteristics at initial presentation and during follow-up are described in 1,745 primary cases d...
journal_title：British journal of cancer
pub_type： 杂志文章,多中心研究
doi：10.1038/bjc.1993.147
更新日期：1993-04-01 00:00:00
abstract：:The incidence of colorectal carcinoma is rising at an alarming pace in Asian urban societies such as Hong Kong. Detailed examination of the epidemiological pattern and genetic mutation of colorectal cancer in the Hong Kong Chinese population is overdue. We compared the reported age incidence of colorectal carcinoma in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.605
更新日期：1997-01-01 00:00:00
abstract：BACKGROUND:The lipogenic transcription factor carbohydrate response element-binding protein (ChREBP) may play a key role in malignant progression of breast cancer by allowing metabolic adaptations to take place in response to changes in oxygenation. METHODS:Immunohistochemical analysis of ChREBP was carried out in hum...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2013.765
更新日期：2014-02-04 00:00:00
abstract：:The use of oncolytic viruses has received considerable attention in recent years and many viruses have proved to be effective against a variety of cancer models and a few are currently being used in clinical trials. However, the possible emergence and outcome of virus-resistant tumour cells has not been addressed. We ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603363
更新日期：2006-10-23 00:00:00
abstract：:The presence of specific and high affinity epidermal growth factor receptors (EGF-R) has been demonstrated in human prostate cancer (CaP). Scatchard analysis of the binding data revealed a linear plot consistent with a single class of binding sites with a mean dissociation constant (Kd) +/- s.d. = 1.6 +/- 0.4 nmol 1-1...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1989.216
更新日期：1989-07-01 00:00:00
abstract：BACKGROUND:Therapies targeting ERBB2 have shown success in the clinic. However, response is not determined solely by expression of ERBB2. Levels of ERBB3, its preferred heterodimerisation partner and ERBB ligands may also have a role. METHODS:We measured NRG1 expression by real-time quantitative RT-PCR and ERBB recept...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.39
更新日期：2011-03-29 00:00:00
abstract：BACKGROUND:We aimed to analyse clinical and gene expression profiles to predict pathologic complete response and disease-free survival using two consecutive, prospective, preoperative chemotherapy trial cohorts. METHODS:Clinicopathological and gene expression data were evaluated in a cohort from two consecutive phase ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.184
更新日期：2016-08-09 00:00:00
abstract：:Sera from patients with nasopharyngeal carcinoma (NPC), a disease associated with Epstein-Barr virus (EBV), were found to be cytotoxic at 15% degrees C in the presence of complement for a panel of human lymphocytes, with a higher frequency than those of matched controls. The cold lymphocytotoxic antibodies (LTA) respo...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1977.64
更新日期：1977-04-01 00:00:00
abstract：BACKGROUND:The recently described navigator proteins have a multifaceted role in cytoskeletal dynamics. We report here on the relevance of one of them, navigator 3 (NAV3), in colorectal cancer (CRC). METHODS:We analysed changes in chromosome 12 and NAV3 copy number in CRC/adenoma samples of 59 patients and in 6 CRC ce...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.553
更新日期：2012-01-31 00:00:00
abstract：:We have evaluated the relation between cancer of the lower urinary tract ("bladder cancer") and the use of artificial sweeteners, by means of case-control studies in Manchester, U.K., and Nagoya, Japan, areas where extensive use occurred 30-40 years ago. In each area, a broadly based series of cases (555 in Manchester...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1982.59
更新日期：1982-03-01 00:00:00
abstract：:L-Glutamine is a requirement for many cells in tissue culture, an intermediate in many metabolic pathways, and an alternative substrate to glucose for energy metabolism. These properties suggest that glutamine concentration might be a determinant of cell viability in tumours, especially in regions that are deficient i...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.234
更新日期：1986-11-01 00:00:00
abstract：:Using a panel of ten polymorphic markers, we examined the frequency of loss of heterozygosity (LOH) on chromosome 17 in 55 sporadic ovarian tumours. LOH on 17p and 17q was observed to be 50% and 62% respectively. LOH at D17S5 was detected in 24/36 (67%) of malignant cases and in 19/43 (44%) at TP53; the marker D17S855...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.594
更新日期：1996-11-01 00:00:00
abstract：BACKGROUND:Antihypertensives may inhibit pancreatic carcinogenesis. We examined the association between use of these drugs and pancreatic cancer in patients with chronic pancreatitis. METHODS:We conducted a nationwide population-based cohort study of all chronic pancreatitis patients diagnosed in Denmark during 1996-2...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0562-y
更新日期：2019-10-01 00:00:00
