LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 5 of total 5

Search options

  1. Article ; Online: The Kraken Wakes: induced EMT as a driver of tumour aggression and poor outcome.

    Redfern, Andrew D / Spalding, Lisa J / Thompson, Erik W

    Clinical & experimental metastasis

    2018  Volume 35, Issue 4, Page(s) 285–308

    Abstract: Epithelial mesenchymal transition (EMT) describes the shift of cells from an epithelial form to a contact independent, migratory, mesenchymal form. In cancer the change is linked to invasion and metastasis. Tumour conditions, including hypoxia, acidosis ... ...

    Abstract Epithelial mesenchymal transition (EMT) describes the shift of cells from an epithelial form to a contact independent, migratory, mesenchymal form. In cancer the change is linked to invasion and metastasis. Tumour conditions, including hypoxia, acidosis and a range of treatments can trigger EMT, which is implicated in the subsequent development of resistance to those same treatments. Consequently, the degree to which EMT occurs may underpin the entire course of tumour progression and treatment response in a patient. In this review we look past the protective effect of EMT against the initial treatment, to the role of the mesenchymal state, once triggered, in promoting disease growth, spread and future treatment insensitivity. In patients a correlation was found between the propensity of a treatment to induce EMT and failure of that treatment to provide a survival benefit, implicating EMT induction in accelerated tumour progression after treatment cessation. Looking to the mechanisms driving this detrimental effect; increased proliferation, suppressed apoptosis, stem cell induction, augmented angiogenesis, enhanced metastatic dissemination, and immune tolerance, can all result from treatment-induced EMT and could worsen outcome. Evidence also suggests EMT induction with earlier therapies attenuates benefits of later treatments. Looking beyond epithelial tumours, de-differentiation also has therapy-attenuating effects and reversal thereof may yield similar rewards. A range of potential therapies are in development that may address the diverse mechanisms and molecular control systems involved in EMT-induced accelerated progression. Considering the broad reaching effects of mesenchymal shift identified, successful deployment of such treatments could substantially improve patient outcomes.
    MeSH term(s) Animals ; Disease Progression ; Epithelial-Mesenchymal Transition ; Humans ; Neoplasm Metastasis ; Neoplasms/pathology ; Neoplasms/therapy ; Treatment Outcome
    Language English
    Publishing date 2018-06-08
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 604952-7
    ISSN 1573-7276 ; 0262-0898
    ISSN (online) 1573-7276
    ISSN 0262-0898
    DOI 10.1007/s10585-018-9906-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: The SUB-urothelial DUrvalumab InjEction-1 (SUBDUE-1) trial: first-in-human trial in patients with bladder cancer.

    Hayne, Dickon / Ong, Katherine / Swarbrick, Nicole / McCombie, Steve P / Moe, Andrew / Hawks, Cynthia / Viswambaram, Pravin / Conduit, Ciara / Liow, Elizabeth / Spalding, Lisa / Lim, Jayne / Ferguson, Thomas / Meehan, Katie / Davis, Ian D / Redfern, Andrew D

    BJU international

    2024  

    Abstract: Objectives: To assess the safety of sub-urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations.: Patients and methods: The patients were chemotherapy and immunotherapy naïve (bacille Calmette- ... ...

    Abstract Objectives: To assess the safety of sub-urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations.
    Patients and methods: The patients were chemotherapy and immunotherapy naïve (bacille Calmette-Guérin allowed) with non-metastatic muscle-invasive bladder cancer or non-muscle-invasive bladder cancer planned for radical cystectomy (RC). The study was a Phase Ib 3 + 3 dose-escalation design with sub-urothelial injection of durvalumab at three pre-determined doses (25, 75, 150 mg) diluted in 25 mL normal saline, injected at 25 locations (25 × 1 mL injections), at least 2 weeks before RC.
    Results: A total of 11 patients were recruited (10 male, one female). No significant changes were reported on American Urological Association Symptom Score or O'Leary Interstitial Cystitis Scale. In all, 14 adverse events (AEs) were reported (10 Grade 1, three Grade 2, one Grade 3), none considered immune-related. No Grade 4 or 5 AEs were recorded. All the patients underwent RC. Tissue immune populations changed following durvalumab injection (P = 0.012), with a statistically significant increase in M2-macrophage (CD163) when comparing the 25-150 mg dose (P = 0.021). Basal/mixed cancers showed a larger CD163 increase than luminal cancers (P = 0.033).
    Conclusion: Sub-urothelial injection of durvalumab is feasible and safe without immune-related AEs and shows local immunological effects.
    Language English
    Publishing date 2024-03-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 1462191-5
    ISSN 1464-410X ; 1464-4096 ; 1358-8672
    ISSN (online) 1464-410X
    ISSN 1464-4096 ; 1358-8672
    DOI 10.1111/bju.16325
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: PD-L1+ dendritic cells in the tumor microenvironment correlate with good prognosis and CD8+ T cell infiltration in colon cancer.

    Miller, Timothy J / Anyaegbu, Chidozie C / Lee-Pullen, Tracey F / Spalding, Lisa J / Platell, Cameron F / McCoy, Melanie J

    Cancer science

    2021  Volume 112, Issue 3, Page(s) 1173–1183

    Abstract: Background: The prognostic value of tumor-associated dendritic cells (DC) in colon cancer remains poorly understood. This may be in part due to the interchangeable expression of immunostimulatory and immunoinhibitory molecules on DC. Here we ... ...

    Abstract Background: The prognostic value of tumor-associated dendritic cells (DC) in colon cancer remains poorly understood. This may be in part due to the interchangeable expression of immunostimulatory and immunoinhibitory molecules on DC. Here we investigated the prognostic impact of CD11c
    Methods: Tissue microarrays containing representative cores of central tumor, leading edge, and adjacent normal tissue from 221 patients with stage III colon cancer were immunostained for CD8, CD11c, PD-L1, and cytokeratin using immunofluorescent probes. Cells were quantified using StrataQuest digital image analysis software, with intratumoral and stromal regions analyzed separately. Kaplan-Meier estimates and Cox regression were used to assess survival.
    Results: Intratumoral CD8
    Conclusion: Here we showed that PD-L1-expressing DC in the tumor microenvironment are associated with improved survival in stage III colon cancer and likely reflect an immunologically "hot" tumor microenvironment. Further investigation into the expression of immunomodulatory molecules by tumor-associated DC may help to further elucidate their prognostic value.
    MeSH term(s) Aged ; B7-H1 Antigen/metabolism ; CD11c Antigen/metabolism ; CD8-Positive T-Lymphocytes/immunology ; Chemotherapy, Adjuvant ; Colectomy ; Colon/pathology ; Colon/surgery ; Colonic Neoplasms/blood ; Colonic Neoplasms/immunology ; Colonic Neoplasms/mortality ; Colonic Neoplasms/therapy ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphocytes, Tumor-Infiltrating/immunology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Tumor Microenvironment/immunology
    Chemical Substances B7-H1 Antigen ; CD11c Antigen ; CD274 protein, human
    Language English
    Publishing date 2021-01-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2115647-5
    ISSN 1349-7006 ; 1347-9032
    ISSN (online) 1349-7006
    ISSN 1347-9032
    DOI 10.1111/cas.14781
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Estrogen receptor beta expression in triple negative breast cancers is not associated with recurrence or survival.

    Takano, Elena A / Younes, Melissa M / Meehan, Katie / Spalding, Lisa / Yan, Max / Allan, Prue / Fox, Stephen B / Redfern, Andy / Clouston, David / Giles, Graham G / Christie, Elizabeth L / Anderson, Robin L / Zethoven, Magnus / Phillips, Kelly-Anne / Gorringe, Kylie / Britt, Kara L

    BMC cancer

    2023  Volume 23, Issue 1, Page(s) 459

    Abstract: Background: Triple negative BCa (TNBC) is defined by a lack of expression of estrogen (ERα), progesterone (PgR) receptors and human epidermal growth factor receptor 2 (HER2) as assessed by protein expression and/or gene amplification. It makes up ~ 15% ... ...

    Abstract Background: Triple negative BCa (TNBC) is defined by a lack of expression of estrogen (ERα), progesterone (PgR) receptors and human epidermal growth factor receptor 2 (HER2) as assessed by protein expression and/or gene amplification. It makes up ~ 15% of all BCa and often has a poor prognosis. TNBC is not treated with endocrine therapies as ERα and PR negative tumors in general do not show benefit. However, a small fraction of the true TNBC tumors do show tamoxifen sensitivity, with those expressing the most common isoform of ERβ1 having the most benefit. Recently, the antibodies commonly used to assess ERβ1 in TNBC have been found to lack specificity, which calls into question available data regarding the proportion of TNBC that express ERβ1 and any relationship to clinical outcome.
    Methods: To confirm the true frequency of ERβ1 in TNBC we performed robust ERβ1 immunohistochemistry using the specific antibody CWK-F12 ERβ1 on 156 primary TNBC cancers from patients with a median of 78 months (range 0.2-155 months) follow up.
    Results: We found that high expression of ERβ1 was not associated with increased recurrence or survival when assessed as percentage of ERβ1 positive tumor cells or as Allred > 5. In contrast, the non-specific PPG5-10 antibody did show an association with recurrence and survival.
    Conclusions: Our data indicate that ERβ1 expression in TNBC tumours does not associate with prognosis.
    MeSH term(s) Humans ; Female ; Estrogen Receptor beta/genetics ; Estrogen Receptor alpha/genetics ; Triple Negative Breast Neoplasms/metabolism ; Breast Neoplasms/drug therapy ; Tamoxifen/therapeutic use ; Prognosis ; Receptors, Estrogen ; Receptor, ErbB-2/therapeutic use ; Receptors, Progesterone/metabolism
    Chemical Substances Estrogen Receptor beta ; Estrogen Receptor alpha ; Tamoxifen (094ZI81Y45) ; Receptors, Estrogen ; Receptor, ErbB-2 (EC 2.7.10.1) ; Receptors, Progesterone
    Language English
    Publishing date 2023-05-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041352-X
    ISSN 1471-2407 ; 1471-2407
    ISSN (online) 1471-2407
    ISSN 1471-2407
    DOI 10.1186/s12885-023-10795-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article: Nonredundant functions for tumor protein D52-like proteins support specific targeting of TPD52.

    Shehata, Mona / Bièche, Ivan / Boutros, Rose / Weidenhofer, Judith / Fanayan, Susan / Spalding, Lisa / Zeps, Nikolajs / Byth, Karen / Bright, Robert K / Lidereau, Rosette / Byrne, Jennifer A

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2008  Volume 14, Issue 16, Page(s) 5050–5060

    Abstract: Purpose: Tumor protein D52 (TPD52 or D52) is frequently overexpressed in breast and other cancers and present at increased gene copy number. It is, however, unclear whether D52 amplification and overexpression target specific functional properties of ... ...

    Abstract Purpose: Tumor protein D52 (TPD52 or D52) is frequently overexpressed in breast and other cancers and present at increased gene copy number. It is, however, unclear whether D52 amplification and overexpression target specific functional properties of the encoded protein.
    Experimental design: The expression of D52-like genes and MAL2 was compared in breast tissues using quantitative reverse transcription-PCR. The functions of human D52 and D53 genes were then compared by stable expression in BALB/c 3T3 fibroblasts and transient gene knockdown in breast carcinoma cell lines. In situ D52 and MAL2 protein expression was analyzed in breast tissue samples using tissue microarray sections.
    Results: The D52 (8q21.13), D54 (20q13.33), and MAL2 (8q24.12) genes were significantly overexpressed in breast cancer tissue (n = 95) relative to normal breast (n = 7; P </= 0.005) unlike the D53 gene (6q22.31; P = 0.884). Subsequently, D52-expressing but not D53-expressing 3T3 cell lines showed increased proliferation and anchorage-independent growth capacity, and reduced D52 but not D53 expression in SK-BR-3 cells significantly increased apoptosis. High D52 but not MAL2 expression was significantly associated with reduced overall survival in breast carcinoma patients (log-rank test, P < 0.001; n = 357) and was an independent predictor of survival (hazard ratio, 2.274; 95% confidence interval, 1.228-4.210; P = 0.009; n = 328).<br />Conclusion: D52 overexpression in cancer reflects specific targeting and may contribute to a more proliferative, aggressive tumor phenotype in breast cancer.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Animals ; Apoptosis/physiology ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Proliferation ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Mice ; Middle Aged ; Myelin and Lymphocyte-Associated Proteolipid Proteins ; Neoplasm Proteins/metabolism ; Proteolipids/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tissue Array Analysis ; Transfection ; Vesicular Transport Proteins/metabolism
    Chemical Substances MAL2 protein, human ; Myelin and Lymphocyte-Associated Proteolipid Proteins ; Neoplasm Proteins ; Proteolipids ; TPD52 protein, human ; TPD52L1 protein, human ; Vesicular Transport Proteins
    Language English
    Publishing date 2008-08-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-07-4994
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top