当前位置： SCI文献检索 > BRITISH JOURNAL OF CANCER期刊下所有文献 > Targeting the HGF/c-MET pathway in advanced pancreatic cancer: a key element of treatment that limits primary tumour growth and eliminates metastasis.

Targeting the HGF/c-MET pathway in advanced pancreatic cancer: a key element of treatment that limits primary tumour growth and eliminates metastasis.

Abstract：

BACKGROUND:Stromal-tumour interactions facilitate pancreatic cancer (PC) progression. The hepatocyte growth factor (HGF)/c-MET pathway is upregulated in PC and mediates the interaction between cancer cells and stromal pancreatic stellate cells (PSCs). This study assessed the effect of HGF/c-MET inhibition plus gemcitabine (G) on the progression of advanced PC. METHODS:Orthotopic PC was produced by implantation of luciferase-tagged human cancer cells + human PSCs into mouse pancreas. Tumours were allowed to develop without treatment for 4 weeks. Mice were then treated for 6 weeks with one of the following: IgG, G, HGF inhibitor (Hi), c-MET inhibitor (Ci), Hi + Ci, Hi + G, Ci + G, or Hi + Ci + G. RESULTS:Bioluminescence imaging showed similar tumour sizes in all mice at the initiation of treatments. Triple therapy (Hi + Ci + G): (1) completely eliminated metastasis; (2) significantly reduced tumour size as assessed by bioluminescence and at necropsy; (3) significantly reduced proliferating cancer cell density and stem cell marker DCLK1 expression in tumours. In vitro 3D culture studies supported our in vivo findings. CONCLUSION:Even at an advanced disease stage, a two-pronged approach, targeting (a) HGF/c-MET with relevant inhibitors and (b) cancer cells with chemotherapy, completely eliminated metastasis and significantly decreased tumour growth, suggesting that this is a promising treatment approach for PC.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Xu Z,Pang TCY,Liu AC,Pothula SP,Mekapogu AR,Perera CJ,Murakami T,Goldstein D,Pirola RC,Wilson JS,Apte MV

doi

10.1038/s41416-020-0782-1

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

1486-1495

issue

10

eissn

0007-0920

issn

1532-1827

pii

10.1038/s41416-020-0782-1

journal_volume

122

pub_type

杂志文章

相关文献

BRITISH JOURNAL OF CANCER文献大全
  • The role of microRNAs in liver cancer progression.

    abstract：:Primary liver cancer, predominantly consisting of hepatocellular carcinoma (HCC), is one of the most common and aggressive human malignancies worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression post-transcriptionally. Emerging evidence indicates that miRNAs are often deregu...

    journal_title：British journal of cancer

    pub_type： 杂志文章,评审

    doi：10.1038/sj.bjc.6606010

    authors： Huang S,He X

    更新日期：2011-01-18 00:00:00

  • Regulator of cullins-1 expression knockdown suppresses the malignant progression of muscle-invasive transitional cell carcinoma by regulating mTOR/DEPTOR pathway.

    abstract：BACKGROUND:Regulator of cullins-1 (ROC1) is a key subunit in the cullin-RING ligase (CRL) protein complex. Our previous study indicated that ROC1 was essential for bladder cancer cell survival and that ROC1 knockdown inhibited CRL activity, triggering G2 phase arrest and senescence. However, the role of ROC1 in the mal...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2015.444

    authors： Wang W,Chen H,Liu Z,Qu P,Lan J,Chen H,Zou L,Qiu J

    更新日期：2016-02-02 00:00:00

  • Altered expression of topoisomerase IIalpha contributes to cross-resistant to etoposide K562/MX2 cell line by aberrant methylation.

    abstract：:KRN 8602 (MX2) is a novel morpholino anthracycline derivative having the chemical structure 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. To investigate the mechanisms of resistance to MX2, we established an MX2-resistant phenotype (K562/MX2) of the human myelogeneous leukaemia cell line (K56...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6602498

    authors： Asano T,Nakamura K,Fujii H,Horichi N,Ohmori T,Hasegawa K,Isoe T,Adachi M,Otake N,Fukunaga Y

    更新日期：2005-04-25 00:00:00

  • Two novel human anti-ErbB2 immunoagents are active on trastuzumab-resistant tumours.

    abstract：BACKGROUND:Overexpression of ErbB2 receptor in breast cancer is associated with disease progression and poor prognosis. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer, has proven to be effective; however, a relevant problem for clinical practice is that a high fraction of breast can...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6605499

    authors： Gelardi T,Damiano V,Rosa R,Bianco R,Cozzolino R,Tortora G,Laccetti P,D'Alessio G,De Lorenzo C

    更新日期：2010-02-02 00:00:00

  • Reduction by anti-inflammatory corticosteroids of clonogenic growth of allogeneic tumour cells in normal and irradiated tissues of the rat.

    abstract：:Anti-inflammatory corticosteroids administered to rats in high dosages before intravenous injection of allogeneic tumour cells caused 5-10 fold reductions in "take" and clonogenic growth of the cells in lung and kidney and decreased growth and spread of the cells transplanted to leg muscle. Steroid therapy also reduce...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1974.84

    authors： Van Den Brenk HA,Kelly H,Orton C

    更新日期：1974-05-01 00:00:00

  • Increasingly strong reduction in breast cancer mortality due to screening.

    abstract：BACKGROUND:Favourable outcomes of breast cancer screening trials in the 1970s and 1980s resulted in the launch of population-based service screening programmes in many Western countries. We investigated whether improvements in mammography and treatment modalities have had an influence on the effectiveness of breast can...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2011.44

    authors： van Schoor G,Moss SM,Otten JD,Donders R,Paap E,den Heeten GJ,Holland R,Broeders MJ,Verbeek AL

    更新日期：2011-03-15 00:00:00

  • Declining mortality from breast cancer in Yorkshire, 1983-1998: extent and causes.

    abstract：:Incidence and mortality data, stage of disease and treatment information for female breast cancer were obtained for the years 1975-1999 for the former Yorkshire Regional Health Authority area, from the Northern and Yorkshire Cancer Registry and Information Service. Deaths by age group and 3-year calendar period were s...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6601614

    authors： Pisani P,Forman D

    更新日期：2004-02-09 00:00:00

  • The myth of pulmonary metastasectomy.

    abstract：:Pulmonary metastasectomy is widely and increasingly practiced in the belief that this intervention can cure patients with colorectal cancer, and that without it few survive 5 years. No good evidence exists supporting such convictions, indeed recent trial results challenge them. What evidence underpins this acceptance ...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/s41416-020-0927-2

    authors： Macbeth F,Fallowfield L

    更新日期：2020-08-01 00:00:00

  • Analysis of gene alterations of mitochondrial DNA D-loop regions to determine breast cancer clonality.

    abstract：BACKGROUND:It has been a challenge to determine breast cancer clonality accurately. The aim of the present study was to assess methods using formalin-fixed paraffin-embedded (FFPE) tissue to differentiate new primary tumours from true recurrences that are associated with poorer prognoses and often require more aggressi...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2012.505

    authors： Masuda S,Kadowaki T,Kumaki N,Tang X,Tokuda Y,Yoshimura S,Takekoshi S,Osamura RY

    更新日期：2012-12-04 00:00:00

  • Do cell lines in vitro reflect the properties of the tumours of origin? A study of lines derived from human melanoma xenografts.

    abstract：:The characteristics of 7 human melanoma cell lines were compared with those of the xenografts from which they were established. The ultrastructure, melanin content, isozyme pattern and chromosome numbers of the cell lines were closely similar to those of the corresponding xenografts. The different cell lines gave rise...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1981.276

    authors： Tveit KM,Pihl A

    更新日期：1981-12-01 00:00:00

  • A case-control study of cryptorchidism and maternal hormone concentrations in early pregnancy.

    abstract：:Serum samples taken between 6 and 20 weeks of gestation were obtained from 28 mothers who gave birth to cryptorchid sons (cases) and from 108 control mothers. In comparison with controls the cases had 10% higher geometric mean oestradiol (95% CI -13% to +39%: P=0.42) and 10% lower geometric mean testosterone (95% CI -...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1996.121

    authors： Key TJ,Bull D,Ansell P,Brett AR,Clark GM,Moore JW,Chilvers CE,Pike MC

    更新日期：1996-03-01 00:00:00

  • Transcriptional down-regulation of c-myc in human prostate carcinoma cells by the synthetic androgen mibolerone.

    abstract：:The mechanism of down-regulation of c-myc RNA associated with androgen-induced suppression of the transformed phenotype in the human prostate carcinoma cell line LNCaP was investigated. The synthetic androgen mibolerone (7 alpha-17 alpha-Dimethyl-19-nortestosterone) reversibly inhibits the proliferation of LNCaP cells...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1992.76

    authors： Wolf DA,Kohlhuber F,Schulz P,Fittler F,Eick D

    更新日期：1992-03-01 00:00:00

  • High dose melphalan, BCNU and etoposide with autologous bone marrow transplantation for Hodgkin's disease.

    abstract：:Thirty-eight patients with previously treated Hodgkin's disease were given high dose combination chemotherapy using melphalan and BCNU and autologous bone marrow transplantation. In 25 patients etoposide was added in conventional dosage. During the course of the study the dose of melphalan was increased from 80 to 140...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1989.128

    authors： Zulian GB,Selby P,Milan S,Nandi A,Gore M,Forgeson G,Perren TJ,McElwain TJ

    更新日期：1989-04-01 00:00:00

  • Effect of hormone depletion on cell survival in the EMR-86 rat mammary carcinoma.

    abstract：:Growth of the transplantable EMR-86 rat mammary carcinoma depends on elevated prolactin levels which are induced by oestrogenic stimulation of the pituitary. We investigated histological and cell kinetic changes during tumour regression after removal of implanted oestrogen pellets (EP), and we especially focused on th...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1996.232

    authors： Wijsman JH,Cornelisse CJ,Keijzer R,van de Velde CJ,Elvers B,van Dierendonck JH

    更新日期：1996-05-01 00:00:00

  • STAT3 is required but not sufficient for EGF receptor-mediated migration and invasion of human prostate carcinoma cell lines.

    abstract：:Growth factor-induced migration is a rate-limiting step in tumour invasiveness. The molecules that regulate this cellular behaviour would represent novel targets for limiting tumour cell progression. Epidermal growth factor (EGF) receptor (EGFR)-mediated motility, present in both autocrine and paracrine modes in prost...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6603234

    authors： Zhou W,Grandis JR,Wells A

    更新日期：2006-07-17 00:00:00

  • Determination of cell-free interleukin 2 receptor level in the serum of normal animals and of animals bearing IL-2 receptor positive tumours with high or low metastatic capacity.

    abstract：:Serum levels of cell-free interleukin-2 receptors were elevated above normal in mice bearing the IL-2R positive T-cell lymphoma Eb or its highly metastatic variant ESb. Although ESb cells expressed less IL-2R molecules than Eb cells on their cell surface, serum receptor levels were raised more quickly in ESb than in E...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1987.119

    authors： Schirrmacher V,Josimovic-Alasevic O,Osawa H,Diamantstein T

    更新日期：1987-06-01 00:00:00

  • The impact of vitamin D pathway genetic variation and circulating 25-hydroxyvitamin D on cancer outcome: systematic review and meta-analysis.

    abstract：BACKGROUND:Vitamin D has been linked with improved cancer outcome. This systematic review and meta-analysis investigates the relationship between cancer outcomes and both vitamin D-related genetic variation and circulating 25-hydroxyvitamin D (25OHD) concentration. METHODS:A systematic review and meta-analysis of pape...

    journal_title：British journal of cancer

    pub_type： 杂志文章,meta分析,评审

    doi：10.1038/bjc.2017.44

    authors： Vaughan-Shaw PG,O'Sullivan F,Farrington SM,Theodoratou E,Campbell H,Dunlop MG,Zgaga L

    更新日期：2017-04-11 00:00:00

  • Karyotype analysis of carcinogen-treated Chinese hamster cells in vitro evolving from a normal to a malignant phenotype.

    abstract：:The relationship of cytogenetic changes with the acquisition of an indefinite life span in vitro, the ability of cells to grow in soft agar and their tumourigenicity in syngeneic animals has been studied in control, trans-7,8-dihydrodiolbenzo(a)pyrene and 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrah...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1984.159

    authors： Connell JR

    更新日期：1984-08-01 00:00:00

  • Correction: Urine protein:creatinine ratio vs 24-hour urine protein for proteinuria management: analysis from the phase 3 REFLECT study of lenvatinib vs sorafenib in hepatocellular carcinoma.

    abstract：:This article was originally published under a standard license to Publish, but has now been made available under a CC BY license. The PDF and HTML versions of the paper have been modified accordingly.An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：British journal of cancer

    pub_type： 已发布勘误

    doi：10.1038/s41416-019-0534-2

    authors： Evans TRJ,Kudo M,Finn RS,Han KH,Cheng AL,Ikeda M,Kraljevic S,Ren M,Dutcus CE,Piscaglia F,Sung MW

    更新日期：2019-10-01 00:00:00

  • Recombinant ricin toxin A chain cytotoxicity against carcinoembryonic antigen expressing tumour cells mediated by a bispecific monoclonal antibody and its potentiation by ricin toxin B chain.

    abstract：:A bispecific monoclonal antibody recognising both carcinoembryonic antigen (CEA) and ricin toxin A chain (RTA) was tested for its ability to target recombinant RTA (r-RTA) to CEA-expressing tumour cells, alone and in combination with ricin B chain (RTB). The antibody, 636 (Robins et al., 1990), induced significant RTA...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1991.153

    authors： Embleton MJ,Charleston A,Robins RA,Pimm MV,Baldwin RW

    更新日期：1991-05-01 00:00:00

  • Association of perceived physician communication style with patient satisfaction, distress, cancer-related self-efficacy, and perceived control over the disease.

    abstract：:The aim of the study was to investigate the association of physician communication behaviours as perceived by the patient with patient reported satisfaction, distress, cancer-related self-efficacy, and perceived control over the disease in cancer patients. Questionnaires measuring distress, self-efficacy, and perceive...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6600798

    authors： Zachariae R,Pedersen CG,Jensen AB,Ehrnrooth E,Rossen PB,von der Maase H

    更新日期：2003-03-10 00:00:00

  • Influence of reduced concentration of L-glutamine on growth and viability of cells in monolayer, in spheroids, and in experimental tumours.

    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

    authors： Tannock IF,Steele D,Roberts J

    更新日期：1986-11-01 00:00:00

  • Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer.

    abstract：BACKGROUND:Locally advanced oesophageal cancer (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this phase I trial was to assess the maximum tolerated dose (MTD) of a novel weekly docetaxel and cisplatin regimen concurrent with radical radiotherapy. METHODS:Patients with unr...

    journal_title：British journal of cancer

    pub_type： 杂志文章,多中心研究

    doi：10.1038/sj.bjc.6606051

    authors： Day FL,Leong T,Ngan S,Thomas R,Jefford M,Zalcberg JR,Rischin D,McKendick J,Milner AD,Di Iulio J,Matera A,Michael M

    更新日期：2011-01-18 00:00:00

  • Long-term results and recurrence patterns from SCALOP: a phase II randomised trial of gemcitabine- or capecitabine-based chemoradiation for locally advanced pancreatic cancer.

    abstract：BACKGROUND:SCALOP, a randomised, phase II trial, tested the activity and safety of gemcitabine (GEM)-based and capecitabine (CAP)-based chemoradiation (CRT) for locally advanced pancreatic cancer (LAPC). Here we present the long-term outcomes. METHODS:Eligibility: histologically proven LAPC ⩽7 cm. Following 12 weeks o...

    journal_title：British journal of cancer

    pub_type： 杂志文章,随机对照试验

    doi：10.1038/bjc.2017.95

    authors： Hurt CN,Falk S,Crosby T,McDonald A,Ray R,Joseph G,Staffurth J,Abrams RA,Griffiths G,Maughan T,Mukherjee S

    更新日期：2017-05-09 00:00:00

  • Chromosome 11 allele imbalance and clinicopathological correlates in ovarian tumours.

    abstract：:Allele imbalance on chromosome 11 loci in ovarian cancer is a frequent event, suggesting the presence of tumour-suppressor genes for ovarian carcinogenesis on this chromosome. Ten highly polymorphic (CA) repeat microsatellites were used to determine allele imbalance in 60 primary ovarian tumours, including 47 epitheli...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1995.340

    authors： Gabra H,Taylor L,Cohen BB,Lessels A,Eccles DM,Leonard RC,Smyth JF,Steel CM

    更新日期：1995-08-01 00:00:00

  • Treatment and survival of lymphoid malignancy in the north-west of England: a population-based study.

    abstract：:Classification of lymphoid malignancy has changed markedly in recent years and advances have been made in therapy. This study investigated the variations in treatment and survival of 1622 patients in a population-based registry. A total of 1009 cases of malignant lymphoma (ML) were classified according to the Kiel cla...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1995.406

    authors： Youngson JH,Jones JM,Chang JG,Harris M,Banergee SS

    更新日期：1995-09-01 00:00:00

  • Combined modality management of local and disseminated adult soft tissue sarcomas: a review of 257 cases seen over 10 years at the Christie Hospital & Holt Radium Institute, Manchester.

    abstract：:Over a 10 year period, between 1974-1984, 257 adult cases of tissue sarcoma have been evaluated in the Department of Medical Oncology, Christie Hospital, Manchester. At registration locally advanced or metastatic diseases was present in 162 (63%). The male/female ratio was 1.5:1 and median age 54 years (range 14-85). ...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1985.43

    authors： Bramwell VH,Crowther D,Deakin DP,Swindell R,Harris M

    更新日期：1985-03-01 00:00:00

  • Fraction of radiobiologically hypoxic cells in human melanoma xenografts measured by using single-cell survival, tumour growth delay and local tumour control as end points.

    abstract：:Four human melanoma xenograft lines (A-07, D-12, R-18, U-25) grown orthotopically in Balb/c nu/nu mice were characterized with respect to the fraction of radiobiologically hypoxic cells. The purpose of the study was to establish a firm radiobiological basis for future use of the lines in the development and evaluation...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1998.598

    authors： Rofstad EK,Måseide K

    更新日期：1998-10-01 00:00:00

  • Expression of DNA damage response proteins and complete remission after radiotherapy of stage IB-IIA of cervical cancer.

    abstract：:The primary aim of this study was to investigate if the expression of the DNA damage identifying protein DNA-PKcs known to be involved in DNA repair after treatment with ionising radiation can be used as a predictive marker for radiotherapy (RT) response in cervical cancer. Formalin-fixed primary tumour biopsies from ...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6603153

    authors： Beskow C,Kanter L,Holgersson A,Nilsson B,Frankendal B,Avall-Lundqvist E,Lewensohn R

    更新日期：2006-06-05 00:00:00

  • Preferential potentiation of topoisomerase I poison cytotoxicity by PARP inhibition in S phase.

    abstract：BACKGROUND:Topoisomerase I (Topo I) poisons (e.g., camptothecin (CPT)), used to treat cancer, cause DNA breaks that are most cytotoxic during S phase. PARP-1 promotes DNA repair and PARP inhibitors (PARPi) sensitise cells to Topo I poisons. We aimed to determine whether chemosensitisation is also S phase specific using...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2014.378

    authors： Znojek P,Willmore E,Curtin NJ

    更新日期：2014-09-23 00:00:00