Expression of Immunohistochemical Markers (PCNA, Ki-67,486p and p53) on Paraffin Sections and Their Relation to the Recurrence Rate of Superficial Bladder Tumors

Vorreuther, R.; Hake, Roland; Borchmann, Peter; Lukowsky, S.; Thiele, Jüergen; Engelmann, U.

doi:10.1159/000283032

Cited by 17 publications

(4 citation statements)

References 21 publications

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“…IHC and H&E staining were performed as described previously [ 23 ] and were interpreted by two pathologists in our hospital independently. Ki-67 scoring was in accordance with a previous report [ 24 ]. Scoring for EGFR, pERK, and pS6 used the following scale: 0 = no staining, 1+ = weak or focal staining, 2+ = moderate staining, and 3+ = strong staining.…”

Section: Methodssupporting

confidence: 58%

Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered Src family kinases involved in acquired resistance

et al. 2018

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BackgroundNo approved targeted agents are available for esophageal squamous cell carcinoma (ESCC). Informative genomic analysis and mouse patient-derived xenografts (PDX) also called mouse avatar can greatly expedite drug discovery.MethodsSix ESCC cell lines and 7 out of 25 PDX models derived from 188 biopsies with clear molecular features were employed to evaluate the sensitivity of several EGFR blockers in vitro and in vivo, as well as the underlying antitumor mechanisms of the most promising EGFR-TKI afatinib. Mechanisms involved in acquired resistance of afatinib were explored based on established resistant cell lines and PDX models followed by an attempt to reverse resistance.ResultsCompared with other EGFR blockers, the second-generation EGFR-TKI afatinib exerted superior antitumor effects in ESCC, and EGFR copy number gain (CNG) or overexpression was proposed to be predictive biomarkers. Afatinib played its antitumor effects by inhibiting EGFR downstream pathways, as well as inducing apoptosis and cell cycle arrest at G1. It was increased phosphorylation of Src family kinases (SFKs), rather than MET upregulation, that conferred to acquired resistance of afatinib. Dual blockade of EGFR and SFKs could overcome afatinib resistance and warrants validation in clinical practice.ConclusionBoth ESCC cell lines and PDXs with EGFR CNG or overexpression are potential candidates for afatinib, and concomitant EGFR/SFKs inhibition could reverse afatinib-acquired resistance caused by SFKs activation in ESCC.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0651-z) contains supplementary material, which is available to authorized users.

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Section: Methodssupporting

confidence: 58%

Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered Src family kinases involved in acquired resistance

et al. 2018

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“…Sections were interpreted by pathologists from the Department of Pathology of Peking University Cancer Hospital who were blinded to this study. The scoring standard of Ki-67 was consistent with a previous report [ 26 ].…”

Section: Methodssupporting

confidence: 85%

Gimatecan exerts potent antitumor activity against gastric cancer in vitro and in vivo via AKT and MAPK signaling pathways

et al. 2017

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BackgroundWe investigated antitumor activity and underlying mechanisms of DNA topoisomerase I (TopI) inhibitor gimatecan and irinotecan in gastric cancer (GC) in vitro cell lines and in vivo patient-derived xenograft (PDX) models.MethodsGC cell lines SNU-1, HGC27, MGC803 and NCI-N87 were used to evaluate cell viability and apoptosis after gimatecan or irinotecan treatment, using a cell proliferation assay and flow cytometry, respectively. DNA TopI expression and critical molecules of PI3K/AKT, MAPK and apoptosis signaling pathways were analyzed with western blot. For in vivo studies, five PDXs models were treated with gimatecan or irinotecan to assess its antitumor activity. Immunohistochemistry staining of Ki-67 was performed after mice were sacrificed.ResultsGimatecan inhibited the proliferation of GC cells in vitro in a dose- and time-dependent manner by inducing apoptosis, and gimatecan had greater inhibitory effects than irinotecan. In addition, both gimatecan and irinotecan demonstrated significant tumor growth inhibition in in vivo PDX models. Gimatecan treatment significantly inhibited the expression of DNA TopI, phosphorylated AKT (pAKT), phosphorylated MEK (pMEK) and phosphorylated ERK (pERK). Meanwhile, gimatecan could also activate the JNK2 and p38 MAPK pathway as indicated by upregulation of phosphorylated p38 MAPK (p-p38) and phosphorylated JNK2 (pJNK2).ConclusionsFor the first time, we have shown that the antitumor activity of gimatecan in GC via suppressing AKT and ERK pathway and activating JNK2 and p38 MAPK pathway, which indicated that gimatecan might be an alternative to irinotecan in the treatment of GC.Electronic supplementary materialThe online version of this article (10.1186/s12967-017-1360-z) contains supplementary material, which is available to authorized users.

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“…The p53 tumor suppressor gene is probably the first molecular alteration that has been extensively studied, but there have been conf licting results regarding association with prognosis [9][10][11][12][13][14]. Using p53 as a single marker has issues due to multiple cell cycle regulators that may have overlapping roles.…”

Section: Prognostic Markers For Disease Recurrencementioning

confidence: 99%

Bladder Cancer Tissue-Based Biomarkers

Soria¹,

Sänchez‐Carbayo

Benderska-Söder³

et al. 2021

Société Internationale D’Urologie Journal

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This review aims to provide a practical update regarding the current role of tissue-based biomarkers in bladder cancer. Their prognostic and predictive role both in non-muscle-invasive (NMIBC) and in muscle-invasive disease (MIBC) has been reviewed with particular focus to their use in clinical practice. In summary, the literature on the prediction of disease recurrence in NMIBC is inconclusive, and there is little information on prediction of response to intravesical bacillus Calmette-Guerin (BCG). Concerning disease progression, external prospective validation studies suggest that FGFR3 mutation status and gene signatures may improve models that are based only on clinicopathologic information. In MIBC, tissue-based biomarkers are increasingly important, since they may predict the response to systemic chemotherapy and immunotherapy. In particular, the advent of molecular characterization promises to revolutionize the paradigm of decision-making in the treatment of MIBC. Molecular subtyping has been shown to improve the prediction of pathological stage at RC and to predict the response to systemic chemotherapy and immunotherapy. However, external and prospective validations are warranted to confirm these preliminary findings. Several different tissue-based biomarkers such as PD-1/PD-L1 expression, tumor mutational burden, and the analysis of tumor microenvironment, may in future play a role in selecting patients for systemic immunotherapy. However, to date, no pretreatment recommendations can be definitively made on the basis of any molecular predictors. In conclusion, despite the potential of tissue-based biomarkers, their use in bladder cancer should be limited to experimental settings.

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Expression of Immunohistochemical Markers (PCNA, Ki-67,486p and p53) on Paraffin Sections and Their Relation to the Recurrence Rate of Superficial Bladder Tumors

Cited by 17 publications

References 21 publications

Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered Src family kinases involved in acquired resistance

Mouse avatar models of esophageal squamous cell carcinoma proved the potential for EGFR-TKI afatinib and uncovered Src family kinases involved in acquired resistance

Gimatecan exerts potent antitumor activity against gastric cancer in vitro and in vivo via AKT and MAPK signaling pathways

Bladder Cancer Tissue-Based Biomarkers

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