Abstract：
BACKGROUND:The poor prognosis of patients with colorectal-cancer liver metastases (CRLM) and the insufficiency of available treatments have raised the need for alternative curative strategies. We aimed to assess the therapeutic potential of TL-118, a new anti-angiogenic drug combination, for CRLM treatment, in a mouse model. METHODS:The therapeutic potential of TL-118 was evaluated and compared with B20-4.1.1 (B20; anti-VEGF antibody) and rapamycin in CRLM-bearing mice. Tumour progression and the vascular changes were monitored by MRI. Additionally, mice survival, cell proliferation, apoptosis and vessel density were evaluated. RESULTS:This study demonstrated an unequivocal advantage to TL-118 therapy by significantly prolonging survival (threefold) and reducing metastasis perfusion and vessel density (ninefold). The underlying mechanism for TL-118-treatment success was associated with hepatic perfusion attenuation resulting from reduced nitric-oxide (NO) serum levels as elucidated by using hemodynamic response imaging (HRI, a functional MRI combined with hypercapnia and hyperoxia). Further, systemic hepatic perfusion reduction during the initial treatment phase by adding NO inhibitor has proven to be essential for reaching maximal therapeutic effects for both TL-118 and B20. CONCLUSION:TL-118 harbours a potential clinical benefit to CLRM patients. Moreover, the reduction of hepatic perfusion at early stages of anti-angiogenic therapies by adding NO inhibitor is crucial for achieving maximal anti-tumour effects.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Edrei Y,Gross E,Corchia N,Abramovitch Rdoi
10.1038/bjc.2012.322subject
Has Abstractpub_date
2012-08-07 00:00:00pages
658-66issue
4eissn
0007-0920issn
1532-1827pii
bjc2012322journal_volume
107pub_type
杂志文章abstract：:Epithelial cadherin (E-CD) is a member of the cadherin family of cell adhesion molecules and has been implicated as an invasion suppressor molecule in vitro and in vivo. We analysed 174 breast tumours from the Nottingham/Tenovus Breast Cancer Series immunohistochemically for E-CD expression using the mouse monoclonal ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.2178
更新日期：2001-12-14 00:00:00
abstract：:It remains unclear whether any aspect of quality of life has a role in predicting survival in an unselected cohort of patients with gastro-oesophageal cancer. Therefore the aim of the present study was to examine the relationship between quality of life (EORTC QLQ-C30), clinico-pathological characteristics and surviva...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604248
更新日期：2008-03-11 00:00:00
abstract：:The aim of this study was to determine the correlation between changes in collagen metabolites (ICTP, mature cross-linked carboxy-terminal telopeptide of type I collagen; PINP, the amino-terminal propeptide of type I procollagen) and bone mineral density (BMD) in 206 pre- and post-menopausal breast cancer patients wit...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/bjc.1998.471
更新日期：1998-07-01 00:00:00
abstract：:Pancreatic cancers occurring in carriers of a pathogenic germline alteration in BRCA1/2 (gBRCA1/2) are assumed to demonstrate homologous recombination repair deficiency (HRD), associated with sensitivity to platinum-based chemotherapy and synthetic lethality with PARP inhibitors (PARPi). However, primary and secondary...
journal_title：British journal of cancer
pub_type： 评论,社论
doi：10.1038/s41416-019-0645-9
更新日期：2020-02-01 00:00:00
abstract：:Over a wide range of pH, the semiquinone free radicals formed by reduction of adriamycin exist as a form which is strongly stabilised by internal hydrogen bonding and resonance. They protonate with pKa = 2.9. Below this pH they exhibit absorption maxima at 430 nm (Emax = 13,200 dm3 mol-1 cm-1) and approximately 720 nm...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.74
更新日期：1985-04-01 00:00:00
abstract：:Exploring the fundamental mechanisms behind the low tumour uptake of labelled monoclonal antibodies (MoAbs) during in vivo immunotargeting, experiments were performed to estimate the in vivo value of the association constant (Ka) in an experimental targeting reaction. An artificial tumour model was utilised, based on ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1992.219
更新日期：1992-07-01 00:00:00
abstract：:A Phase I study of oral daily misonidazole (MISO) with conventional pelvic irradiation, has been conducted in patients with carcinoma of the cervix Stages IB, IIB, IIIB and IVA. MISO was administered in daily dosages to sequential groups of patients at doses of 0.15 g/m2, 0.30 g/m2 or 0.45 g/m2 for 22 days over 5 week...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1038/bjc.1982.138
更新日期：1982-06-01 00:00:00
abstract：:There is increasing evidence of a systemic inflammatory response associated with malignancy, which may have an impact on both drug disposition and resistance to cytotoxic therapy. The impact of inflammation on drug disposition was studied in mice bearing a number of common tumour xenografts. C57BL/6 mice were inoculat...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604101
更新日期：2008-01-15 00:00:00
abstract：BACKGROUND:We previously showed that activation of the nuclear factor of activated T cells (NFAT)1/Fas ligand (FasL) pathway induces glioma cell death. Lithium (Li) is an inhibitor of glycogen synthase kinase (GSK)-3 that activates NFAT1/FasL signalling. Temozolomide (TMZ) inhibits GSK-3 and activates Fas in tumour pro...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2017.89
更新日期：2017-05-09 00:00:00
abstract：:In 1977 a number of patients with soft-tissue sarcomas and previous exposure to phenoxyacetic acids were described. Following from these observations a matched case-control study was made. Exposure to chlorophenols was also included in this study. The results showed that exposure to phenoxyacetic acids or chlorophenol...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1979.125
更新日期：1979-06-01 00:00:00
abstract：:Preclinical models that can accurately predict outcomes in the clinic are much sought after in the field of cancer drug discovery and development. Existing models such as organoids and patient-derived xenografts have many advantages, but they suffer from the drawback of not contextually preserving human tumour archite...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/s41416-019-0672-6
更新日期：2020-03-01 00:00:00
abstract：:The level of expression of the multidrug resistance-associated protein (MRP1) in a panel of human ovarian carcinoma cell lines and their variants with acquired cisplatin resistance was determined using Western blotting. No overexpression of MRP1 was detected in any of the cell lines. In addition, we have transfected t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.461
更新日期：1998-07-01 00:00:00
abstract：:Hypoxic EMT-6 tumour cells displayed a high level of inducible nitric oxide synthase (iNOS) and an increased radiosensitivity after a 16 h exposure to lipopolysaccharide, a known activator of nuclear factor-kappaB (NF-kappaB). Both iNOS activation and radioresponse were impaired by the NF-kappaB inhibitors phenylarsin...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600678
更新日期：2003-01-13 00:00:00
abstract：:We investigated whether dietary intakes of total fat, monounsaturated fat (MUFA), polyunsaturated fat (PUFA) and saturated fat (SFA) were associated with breast cancer risk in a prospective cohort of 49 261 Swedish women (30-49 years at enrolment), which yielded 974 breast cancer cases by December 2005. Further, we ev...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604033
更新日期：2007-12-03 00:00:00
abstract：:Activation of Met by its ligand HGF has been shown to elicit both mitogenic and motogenic responses in thyrocytes in vitro. In the present study we have investigated the expression of Met in human anaplastic thyroid carcinoma cells in culture. There was a variation in expression level and size of Met in the different ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690406
更新日期：1999-05-01 00:00:00
abstract：:The aim of this study was to evaluate the expression of CC chemokine receptor 7 (CCR7) in squamous cell cancer of the tonsil with respect to patterns of spread, relapse-free, overall and disease-specific survival. Eighty-four patients with squamous cell cancer of the tonsil were identified. There was a male predominan...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603907
更新日期：2007-09-03 00:00:00
abstract：:Two hundred and thirteen lung tumours of primary site and 42 metastases were heterotransplanted into nude mice with an overall success rate of 44%. There were differences in success between the histological types. Squamous cell and adenocarcinoma had the highest success rate (51% and 43%, respectively) whereas large c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1985.29
更新日期：1985-02-01 00:00:00
abstract：:A cell-free plasmid reactivation assay was used to determine the fidelity of DNA double-strand break (DSB) repair in a panel of eight DSB repair-proficient human tumour cell lines. Nuclear protein extracts derived from radiosensitive tumour cells were less capable of correctly rejoining EcoRI-induced DSBs than were si...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.576
更新日期：1997-01-01 00:00:00
abstract：BACKGROUND:After radical prostatectomy (RP) for prostate cancer (PC), p53 alterations predict biochemical relapse (BCR), however, recent evidence suggests that metastatic relapse (MR) not BCR is a surrogate for PC specific mortality (PCSM). This updated analysis of a previously published study investigated the associat...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0549-8
更新日期：2019-10-01 00:00:00
abstract：:The pathophysiology of Raynaud's phenomenon after Cisplatin-Bleomycin-Vinblastine combination chemotherapy, its relationship to polyneuropathy, and response to transcutaneous nerve stimulation (TNS), was studied in eight patients previously treated for testicular cancer. Peripheral circulation in the index finger was ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.129
更新日期：1991-04-01 00:00:00
abstract：BACKGROUND:Lynch syndrome (LS) is associated with a significant lifetime risk of endometrial cancer (EC). There are limited data on factors modifying the EC risk in LS patients. METHODS:The study cohort included 136 LS mutation-positive women. Exposure data were collected by postal questionnaires. Cox regression model...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2016.193
更新日期：2016-07-26 00:00:00
abstract：:Effects of c-Myc overexpression on the DNA damage-induced G2/M checkpoint were studied in finite lifespan, normal human mammary epithelial cells (HMECs). Previously, we showed that c-Myc attenuates G1/S arrest and leads to an inappropriate entry of cells with damaged DNA into the S phase, following treatment with ioni...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6601307
更新日期：2003-10-20 00:00:00
abstract：:In a prospective cohort study, a close to two-fold elevated risk of bladder cancer was found among men reporting a history of gonorrhoea (relative risk=1.92, 95% CI=1.10-3.33). Our finding warrants further examination of the role of gonorrhoea in bladder carcinogenesis. ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603510
更新日期：2007-01-15 00:00:00
abstract：:A recent study showed an association between a single base substitution, T-->C, in the promotor region of the CYP17 gene, the risk of breast cancer and age at menarche in Asian, African-American and Latino women from California and Hawaii. The C allele was associated with increased risk of breast cancer, significantly...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.340
更新日期：1998-06-01 00:00:00
abstract：:Flavone acetic acid (FAA) was administered at a dose of 4.8 g m-2 over 1 h to patients with advanced malignant disease in combination with Interleukin II. A new high performance liquid chromatography method is described to determine both the parent compound and eight drug-related products, and the conditions required ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1993.250
更新日期：1993-06-01 00:00:00
abstract：:Novel synthetic antagonists of retinoic acid receptors (RARs) have been developed. To avoid interference by serum retinoids when testing these compounds, we established serum-free grown sub-lines (>3 years) of the prostate carcinoma lines LNCaP, PC3 and DU145. A high affinity pan-RAR antagonist (AGN194310, K(d) for bi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.2001.1939
更新日期：2001-08-03 00:00:00
abstract：:There is increasing evidence that essential fatty acids (EFA) may have a role to play in the aetiology of some types of cancer although their precise mode of action is unknown. Differences in the metabolism of EFA between patients with benign or malignant prostatic disease may help to elucidate their role in the latte...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1991.481
更新日期：1991-12-01 00:00:00
abstract：:Clonal subpopulations of different ploidy values and metastatic capacities, isolated from the RIF-1 mouse sarcoma, have been tested for in vitro X-radiation sensitivity, for in vitro sensitivity to adriamycin and for in vitro and in vivo sensitivity to melphalan and CCNU. Following X-radiation, no consistent differenc...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1983.139
更新日期：1983-06-01 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：BACKGROUND:Gastroesophageal adenocarcinoma (GOA) has poor clinical outcomes and lacks reliable blood markers. Here we present circulating tumour DNA (ctDNA) as an emerging biomarker. METHODS:Forty patients (17 palliative and 23 curative) were followed by serial plasma monitoring. Primary tumour DNA was analysed by tar...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-020-1002-8
更新日期：2020-10-01 00:00:00
