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  1. Article ; Online: Programmed death-ligand 1 (PD-L1) expression in primary gastric adenocarcinoma and matched metastases.

    Liu, Drolaiz H W / Grabsch, Heike I / Gloor, Beat / Langer, Rupert / Dislich, Bastian

    Journal of cancer research and clinical oncology

    2023  Volume 149, Issue 14, Page(s) 13345–13352

    Abstract: Background: Combination of immunotherapy and chemotherapy is recommended for first line treatment of gastric adenocarcinoma (GC) patients with locally advanced unresectable disease or metastatic disease. However, data regarding the concordance rate ... ...

    Abstract Background: Combination of immunotherapy and chemotherapy is recommended for first line treatment of gastric adenocarcinoma (GC) patients with locally advanced unresectable disease or metastatic disease. However, data regarding the concordance rate between PD-L1 combined positive score (CPS) in primary GC and matched regional lymph node metastasis (LNmet) or matched distant metastasis (Dmet) is limited.
    Methods: Tissue microarray sections from primary resected GC, LNmet and Dmet were immunohistochemically stained with anti-PD-L1 (clone SP263). PD-L1 expression was scored separately in tumour cells and immune cells and compared between matched primary GC, LNmet and/or Dmet. CPS was calculated and results for CPS cut-offs 1 and 5 were compared between matched samples.
    Results: 275 PD-L1 stained GC were analysed. 189 primary GC had matched LNmet. CPS cut-off 1 concordance rate between primary GC and LNmet was 77%. 23 primary GC had matched Dmet but no matched LNmet, CPS cut-off 1 concordance rate was 70%. 63 primary GC had both matched LNmet and matched Dmet, CPS cut-off 1 concordance rate of 67%. CPS cut-off 5 results were similar. The proportion of PD-L1 positive tumour cells increased from primary GC (26%) to LNmet (42%) and was highest in Dmet (75%).
    Conclusion: Our study showed up to 33% discordance of PD-L1 CPS between primary GC and LNmet and/or Dmet suggesting that multiple biopsies of primary GC and metastatic sites might need to be tested before considering treatment options. Moreover, this is the first study that seems to suggest that tumour cells acquire PD-L1 expression during disease progression.
    Language English
    Publishing date 2023-07-25
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 134792-5
    ISSN 1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
    ISSN (online) 1432-1335
    ISSN 0171-5216 ; 0084-5353 ; 0943-9382
    DOI 10.1007/s00432-023-05142-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Clinical Features of Gastric Signet Ring Cell Cancer: Results from a Systematic Review and Meta-Analysis.

    Dal Cero, Mariagiulia / Bencivenga, Maria / Liu, Drolaiz H W / Sacco, Michele / Alloggio, Mariella / Kerckhoffs, Kelly G P / Filippini, Federica / Saragoni, Luca / Iglesias, Mar / Tomezzoli, Anna / Carneiro, Fátima / Grabsch, Heike I / Verlato, Giuseppe / Torroni, Lorena / Piessen, Guillaume / Pera, Manuel / de Manzoni, Giovanni

    Cancers

    2023  Volume 15, Issue 21

    Abstract: Background: Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer ... ...

    Abstract Background: Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies.
    Methods: A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed.
    Results: A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma.
    Conclusions: Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications.
    Language English
    Publishing date 2023-10-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15215191
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tumour infiltrating lymphocytes and survival after adjuvant chemotherapy in patients with gastric cancer: post-hoc analysis of the CLASSIC trial.

    Liu, Drolaiz H W / Kim, Young-Woo / Sefcovicova, Nina / Laye, Jon P / Hewitt, Lindsay C / Irvine, Andrew F / Vromen, Vincent / Janssen, Yannick / Davarzani, Naser / Fazzi, Gregorio E / Jolani, Shahab / Melotte, Veerle / Magee, Derek R / Kook, Myeong-Cherl / Kim, Hyunki / Langer, Rupert / Cheong, Jae-Ho / Grabsch, Heike I

    British journal of cancer

    2023  Volume 128, Issue 12, Page(s) 2318–2325

    Abstract: Background: Only a subset of gastric cancer (GC) patients with stage II-III benefits from chemotherapy after surgery. Tumour infiltrating lymphocytes per area (TIL density) has been suggested as a potential predictive biomarker of chemotherapy benefit.!# ...

    Abstract Background: Only a subset of gastric cancer (GC) patients with stage II-III benefits from chemotherapy after surgery. Tumour infiltrating lymphocytes per area (TIL density) has been suggested as a potential predictive biomarker of chemotherapy benefit.
    Methods: We quantified TIL density in digital images of haematoxylin-eosin (HE) stained tissue using deep learning in 307 GC patients of the Yonsei Cancer Center (YCC) (193 surgery+adjuvant chemotherapy [S + C], 114 surgery alone [S]) and 629 CLASSIC trial GC patients (325 S + C and 304 S). The relationship between TIL density, disease-free survival (DFS) and clinicopathological variables was analysed.
    Results: YCC S patients and CLASSIC S patients with high TIL density had longer DFS than S patients with low TIL density (P = 0.007 and P = 0.013, respectively). Furthermore, CLASSIC patients with low TIL density had longer DFS if treated with S + C compared to S (P = 0.003). No significant relationship of TIL density with other clinicopathological variables was found.
    Conclusion: This is the first study to suggest TIL density automatically quantified in routine HE stained tissue sections as a novel, clinically useful biomarker to identify stage II-III GC patients deriving benefit from adjuvant chemotherapy. Validation of our results in a prospective study is warranted.
    MeSH term(s) Humans ; Biomarkers ; Chemotherapy, Adjuvant ; Lymphocytes, Tumor-Infiltrating/pathology ; Prognosis ; Stomach Neoplasms/drug therapy ; Stomach Neoplasms/surgery
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-04-07
    Publishing country England
    Document type Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-023-02257-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  4. Article ; Online: Spatial Metabolomics Identifies Distinct Tumor-Specific Subtypes in Gastric Cancer Patients.

    Wang, Jun / Kunzke, Thomas / Prade, Verena M / Shen, Jian / Buck, Achim / Feuchtinger, Annette / Haffner, Ivonne / Luber, Birgit / Liu, Drolaiz H W / Langer, Rupert / Lordick, Florian / Sun, Na / Walch, Axel

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

    2022  Volume 28, Issue 13, Page(s) 2865–2877

    Abstract: Purpose: Current systems of gastric cancer molecular classification include genomic, molecular, and morphological features. Gastric cancer classification based on tissue metabolomics remains lacking. This study aimed to define metabolically distinct ... ...

    Abstract Purpose: Current systems of gastric cancer molecular classification include genomic, molecular, and morphological features. Gastric cancer classification based on tissue metabolomics remains lacking. This study aimed to define metabolically distinct gastric cancer subtypes and identify their clinicopathological and molecular characteristics.
    Experimental design: Spatial metabolomics by high mass resolution imaging mass spectrometry was performed in 362 patients with gastric cancer. K-means clustering was used to define tumor and stroma-related subtypes based on tissue metabolites. The identified subtypes were linked with clinicopathological characteristics, molecular features, and metabolic signatures. Responses to trastuzumab treatment were investigated across the subtypes by introducing an independent patient cohort with HER2-positive gastric cancer from a multicenter observational study.
    Results: Three tumor- and three stroma-specific subtypes with distinct tissue metabolite patterns were identified. Tumor-specific subtype T1(HER2+MIB+CD3+) positively correlated with HER2, MIB1, DEFA-1, CD3, CD8, FOXP3, but negatively correlated with MMR. Tumor-specific subtype T2(HER2-MIB-CD3-) negatively correlated with HER2, MIB1, CD3, FOXP3, but positively correlated with MMR. Tumor-specific subtype T3(pEGFR+) positively correlated with pEGFR. Patients with tumor subtype T1(HER2+MIB+CD3+) had elevated nucleotide levels, enhanced DNA metabolism, and a better prognosis than T2(HER2-MIB-CD3-) and T3(pEGFR+). An independent validation cohort confirmed that the T1 subtype benefited from trastuzumab therapy. Stroma-specific subtypes had no association with clinicopathological characteristics, however, linked to distinct metabolic pathways and molecular features.
    Conclusions: Patient subtypes derived by tissue-based spatial metabolomics are a valuable addition to existing gastric cancer molecular classification systems. Metabolic differences between the subtypes and their associations with molecular features could provide a valuable tool to aid in selecting specific treatment approaches.
    MeSH term(s) Biomarkers, Tumor/genetics ; Forkhead Transcription Factors ; Humans ; Metabolomics ; Prognosis ; Receptor, ErbB-2/metabolism ; Stomach Neoplasms/classification ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/drug therapy ; Trastuzumab/therapeutic use
    Chemical Substances Biomarkers, Tumor ; Forkhead Transcription Factors ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK)
    Language English
    Publishing date 2022-04-08
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Observational Study ; 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-21-4383
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4223: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Neoadjuvant chemotherapy improves survival in patients with oesophageal mucinous adenocarcinoma: Post-hoc analysis of the UK MRC OE02 and OE05 trials.

    Liu, Drolaiz H W / Šefčovičová, Nina / Emmerson, Jake / Spaans, Louisa N / Saito, Yuichi / Hutchins, Gordon / Nankivell, Matthew G / Langley, Ruth E / Allum, William / Cunningham, David / Langer, Rupert / Grabsch, Heike I

    European journal of cancer (Oxford, England : 1990)

    2022  Volume 170, Page(s) 140–148

    Abstract: Background: Adenocarcinoma with more than 50% extracellular mucin is a relatively rare histological subtype of gastrointestinal adenocarcinomas. The clinical impact of extracellular mucin in oesophageal adenocarcinoma (OeAC) has not been investigated in ...

    Abstract Background: Adenocarcinoma with more than 50% extracellular mucin is a relatively rare histological subtype of gastrointestinal adenocarcinomas. The clinical impact of extracellular mucin in oesophageal adenocarcinoma (OeAC) has not been investigated in detail. We hypothesised that patients with mucinous OeAC (OeAC
    Methods: OeAC patients either treated by surgery alone in the OE02 trial (S-patients) or by neoadjuvant chemotherapy followed by surgery (CS-patients) in OE02 or OE05 trials were included. Cancers from 1055 resection specimens (OE02 [test cohort]: 187 CS, 185 S; OE05 [validation cohort]: 683 CS) were classified as either mucinous (more than 50% of the tumour area consists of extracellular mucin, OeAC
    Results: Overall, 7.3% and 9.6% OeAC were classified as OeAC
    Conclusions: This is the first study to suggest in a post-hoc analysis of material from two independent phase III clinical trials that the poor survival of patients with mucinous OeAC can be improved by neoadjuvant chemotherapy. Future studies are warranted to identify potential underlying biological, biochemical or pharmacokinetic interactions between extracellular mucin and chemotherapy.
    MeSH term(s) Adenocarcinoma/pathology ; Adenocarcinoma, Mucinous/pathology ; Esophageal Neoplasms/pathology ; Humans ; Mucins/therapeutic use ; Neoadjuvant Therapy ; Prognosis ; United Kingdom
    Chemical Substances Mucins
    Language English
    Publishing date 2022-05-27
    Publishing country England
    Document type Clinical Trial, Phase III ; Journal Article
    ZDB-ID 82061-1
    ISSN 1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
    ISSN (online) 1879-0852
    ISSN 0277-5379 ; 0959-8049 ; 0964-1947
    DOI 10.1016/j.ejca.2022.04.026
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    Zs.A 456: Show issues Location:
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    Zs.MO 583: Show issues

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  6. Article: Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer.

    Heij, Lara R / Tan, Xiuxiang / Kather, Jakob N / Niehues, Jan M / Sivakumar, Shivan / Heussen, Nicole / van der Kroft, Gregory / Damink, Steven W M Olde / Lang, Sven / Aberle, Merel R / Luedde, Tom / Gaisa, Nadine T / Bednarsch, Jan / Liu, Drolaiz H W / Cleutjens, Jack P M / Modest, Dominik P / Neumann, Ulf P / Wiltberger, Georg J

    Journal of clinical medicine

    2021  Volume 10, Issue 3

    Abstract: B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better ...

    Abstract B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome. The desmoplastic stroma is a complex system in which crosstalk takes place between cancer-associated fibroblasts, immune cells and cancer cells. Indirect and direct cellular interactions within the tumor microenvironment (TME) drive key processes such as tumor progression, metastasis formation and treatment resistance. In order to understand the aggressiveness of PDAC and its resistance to therapeutics, the TME needs to be further unraveled. There are some limited data about the influence of nerve fibers on cancer progression. Here we show that small nerve fibers are located at lymphoid aggregates in PDAC. This unravels future pathways and has potential to improve clinical outcome by a rational development of new therapeutic strategies.
    Language English
    Publishing date 2021-01-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm10030490
    Database MEDical Literature Analysis and Retrieval System OnLINE

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