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  • Online Resource  (40)
  • Wiley  (40)
  • 1
    In: Cancer Cytopathology, Wiley, Vol. 123, No. 11 ( 2015-11), p. 669-677
    Abstract: Fine‐needle aspiration is feasible for collecting tumor samples that are sufficient for whole‐exome sequencing analysis. The higher purity obtained using this method may make it more reliable for genomic studies.
    Type of Medium: Online Resource
    ISSN: 1934-662X , 1934-6638
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2599218-1
    detail.hit.zdb_id: 2594979-2
    detail.hit.zdb_id: 1429-1
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  • 2
    In: International Journal of Cancer, Wiley, Vol. 152, No. 2 ( 2023-01-15), p. 320-330
    Abstract: Muscle‐invasive urothelial carcinoma (MIUC) of the bladder shows highly aggressive tumor behavior, which has prompted the quest for robust biomarkers predicting invasion. To discover such biomarkers, we first employed high‐throughput proteomic method and analyzed tissue biopsy cohorts from patients with bladder urothelial carcinoma (BUC), stratifying them according to their pT stage. Candidate biomarkers were selected through bioinformatic analysis, followed by validation. The latter comprised 2D and 3D invasion and migration assays, also a selection of external public datasets to evaluate mRNA expression and an in‐house patient‐derived tissue microarray (TMA) cohort to evaluate protein expression with immunohistochemistry (IHC). Our multilayered platform‐based analysis identified tubulin beta 6 class V (TUBB6) as a promising prognostic biomarker predicting MIUC of the bladder. The in vitro 2D and 3D migration and invasion assays consistently showed that inhibition of TUBB6 mRNA significantly reduced cell migration and invasion ability in two BUC cell lines with aggressive phenotype ( TUBB6 migration, P  = .0509 and P   〈  .0001; invasion, P  = .0002 and P  = .0044; TGFBI migration, P  = .0214 and P  = .0026; invasion, P   〈  .0001 and P  = .0001; T24 and J82, respectively). Validation through multiple public datasets, including The Cancer Genome Atlas (TCGA) and selected GSE (Genomic Spatial Event) databases, confirmed TUBB6 as a potential biomarker predicting MIUC. Further protein‐based validation with our TMA cohort revealed concordant results, highlighting the clinical implication of TUBB6 expression in BUC patients (overall survival: P   〈  .001). We propose TUBB6 as a novel IHC biomarker to predict invasion and poor prognosis, also select the optimal treatment in BUC patients.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 218257-9
    detail.hit.zdb_id: 1474822-8
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  • 3
    In: PROTEOMICS – Clinical Applications, Wiley, Vol. 12, No. 5 ( 2018-09)
    Abstract: Secretory carcinoma (SC) of the breast is defined as an indolent tumor but is still categorized into a basal‐like triple‐negative breast cancer (BL‐TNBC) subgroup that generally shows aggressive behavior according to the current classification. Despite the unique clinical behavior of SC, molecular characteristics that reflect biological behaviors of SC remain largely unknown. Experimental design A combinatorial approach of whole‐exome sequencing and mass spectrometry–based in‐depth quantitative proteomics to determine the entire molecular landscape of SC using three SC formalin‐fixed paraffin‐embedded (FFPE) tissues is employed. Results Exome sequencing and proteomic analysis of SC identified 419 unique somatic mutations and 721 differentially expressed proteins as compared with triple‐negative breast cancer (TNBC), respectively. Several pathways related to cancer metabolism were significantly upregulated in the SC group. Comparative analyses with multiple datasets revealed that SC shares genomic mutations and biological pathways more closely related to hormone receptor–positive breast cancer than BL‐TNBC. Conclusion and clinical relevance These multi‐omic analyses provide evidence that SC harbors substantially different molecular genomic and proteomic landscapes compared with BL‐TNBC. These results provide an entire spectrum of in‐depth molecular landscapes to support the hypothesis that SC is distinct from BL‐TNBC.
    Type of Medium: Online Resource
    ISSN: 1862-8346 , 1862-8354
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2317130-3
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  • 4
    In: Molecular Oncology, Wiley, Vol. 16, No. 9 ( 2022-05), p. 1795-1815
    Abstract: Metabolic dysregulation is an important hallmark of cancer. Nicotinamide (NAM), a water‐soluble amide form of niacin (vitamin B3), is currently available as a supplement for maintaining general physiologic functions. NAM is a crucial regulator of mitochondrial metabolism and redox reactions. In this study, we aimed to identify the mechanistic link between NAM‐induced metabolic regulation and the therapeutic efficacy of NAM in triple‐negative breast cancer (TNBC). The combined analysis using multiomics systems biology showed that NAM decreased mitochondrial membrane potential and ATP production, but increased the activities of reverse electron transport (RET), fatty acid β‐oxidation and glycerophospholipid/sphingolipid metabolic pathways in TNBC, collectively leading to an increase in the levels of reactive oxygen species (ROS). The increased ROS levels triggered apoptosis and suppressed tumour growth and metastasis of TNBC in both human organoids and xenograft mouse models. Our results showed that NAM treatment leads to cancer cell death in TNBC via mitochondrial dysfunction and activation of ROS by bifurcating metabolic pathways (RET and lipid metabolism); this provides insights into the repositioning of NAM supplement as a next‐generation anti‐metabolic agent for TNBC treatment.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2322586-5
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  • 5
    Online Resource
    Online Resource
    Wiley ; 2011
    In:  Journal of Hepato-Biliary-Pancreatic Sciences Vol. 18, No. 4 ( 2011-07), p. 544-550
    In: Journal of Hepato-Biliary-Pancreatic Sciences, Wiley, Vol. 18, No. 4 ( 2011-07), p. 544-550
    Abstract: Heat shock protein 70 (HSP70) and glutamine synthetase (GS) have been proposed to be promising markers for the differentiation of malignant and benign hepatocellular lesions. The aim of this study was to investigate the clinicopathological significance of the expression of HSP70 and GS in surgically resected hepatocellular carcinoma (HCC). Methods The authors collected 412 HCC samples and 120 non‐neoplastic hepatic tissue samples and performed an immunohistochemical study. Results HSP70 staining was observed in 282 of 392 HCC samples (71.9%), and GS immunoreactivity was observed in 212 of 395 HCC cases (53.7%). Of the several clinicopathological parameters examined, microscopic vascular invasion, a large tumor size, and a high Edmonson–Steiner grade were found to be correlated with positive staining for HSP70 ( p = 0.032, 0.002, and 0.012, respectively). Survival analysis showed a correlation between HSP70 expression and disease‐free survival. GS was not found to be related to clinicopathological parameters. Conclusions The findings of the present study suggest that HSP70 be viewed as a predictor of prognosis as well as a useful diagnostic marker for HCC.
    Type of Medium: Online Resource
    ISSN: 1868-6974 , 1868-6982
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2536390-6
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  • 6
    In: Cancer Medicine, Wiley, Vol. 12, No. 9 ( 2023-05), p. 10363-10370
    Abstract: Urine cytology is the most widely used noninvasive screening tool for urothelial carcinoma diagnosis and surveillance. Although highly specific, urine cytology exhibits suboptimal sensitivity. This study aimed to determine whether hTERT immunocytochemistry (ICC) could be applicable as an ancillary test in routine cytology practice. Methods A total of 561 urinary tract samples were initially screened in this study. All of them were prepared using SurePath liquid‐based cytology (LBC), while additional LBC slides were made and subsequently used for hTERT (SCD‐A7) ICC. Results From the 561 samples screened, 337 were finally analyzed, all having an adequate cellularity and available follow‐up histology. The hTERT ICC‐positive rate was 95.9% ( n  = 208/217), 96% ( n  = 24/25), and 100% ( n  = 4/4) in cytology samples with high‐grade urothelial carcinoma, carcinoma in situ, and low‐grade urothelial carcinoma subsequent histology. Among the 64 atypical cytology cases histologically confirmed as urothelial carcinomas, 92.2% ( n  = 59/64) were immunoreactive to hTERT, whereas the two histologically benign cases were ICC‐negative. 87/90 (96.7%) of the cytology cases confirmed to be benign in follow‐up were hTERT‐negative. The overall sensitivity and specificity of hTERT ICC were 96.3% and 98.8%, respectively (AUROC = 0.963; 95% CI = 0.960–0.967). Conclusions The hTERT ICC test exhibited consistent and intense staining in malignant urothelial cells, suggesting its value as an ancillary test in liquid‐based urine cytology.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2659751-2
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  • 7
    In: Molecular Oncology, Wiley, Vol. 16, No. 2 ( 2022-01), p. 466-484
    Abstract: The spatial tumor shape is determined by the complex interactions between tumor cells and their microenvironment. Here, we investigated the role of a newly identified breast cancer‐related gene, calsequestrin 2 ( CASQ2 ), in tumor–microenvironment interactions during tumor growth and metastasis. We analyzed gene expression and three‐dimensional tumor shape data from the breast cancer dataset of The Cancer Genome Atlas (TCGA) and identified CASQ2 as a potential regulator of tumor–microenvironment interaction. In TCGA breast cancer cases containing information of three‐dimensional tumor shapes, CASQ2 mRNA showed the highest correlation with the spatial tumor shapes. Furthermore, we investigated the expression pattern of CASQ2 in human breast cancer tissues. CASQ2 was not detected in breast cancer cell lines in vitro but was induced in the xenograft tumors and human breast cancer tissues. To evaluate the role of CASQ2, we established CASQ2 ‐overexpressing breast cancer cell lines for in vitro and in vivo experiments. CASQ2 overexpression in breast cancer cells resulted in a more aggressive phenotype and altered epithelial–mesenchymal transition (EMT) markers in vitro . CASQ2 overexpression induced cancer‐associated fibroblast characteristics along with increased hypoxia‐inducible factor 1α (HIF1α) expression in stromal fibroblasts. CASQ2 overexpression accelerated tumorigenesis, induced collagen structure remodeling, and increased distant metastasis in vivo . CASQ2 conferred more metaplastic features to triple‐negative breast cancer cells. Our data suggest that CASQ2 is a key regulator of breast cancer tumorigenesis and metastasis by modulating diverse aspects of tumor–microenvironment interactions.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2322586-5
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  • 8
    In: Diagnostic Cytopathology, Wiley, Vol. 52, No. 2 ( 2024-02), p. 69-75
    Abstract: To compare the immunochemical expression of EGFR, PD‐L1, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6 between matched malignant effusions obtained before and following the administration of chemotherapy in patients with high‐grade serous tubo‐ovarian carcinoma (HGSC). Methods In the enrolled HGSCs, matched formalin‐fixed and paraffin‐embedded cell blocks (CBs) from effusions sampled before (treatment‐naïve patients) and during recurrence (following chemotherapy administration), in addition to their matched HGSC tissues obtained from the ovaries at initial diagnosis (treatment‐naïve patients), were subjected to EGFR, PD‐L1, and MMR immunochemical analysis. Results EGFR was more often overexpressed in effusions obtained after chemotherapy administration compared to both effusions (100% vs. 57.1%) and their matched tubo‐ovarian tumors (100% vs. 7.1%) from treatment‐naïve patients, respectively. EGFR immunochemistry was concordant in just 9.1% of the effusions sampled during recurrence and their paired ovarian samples before recurrence. Whereas all HGSC treatment‐naïve samples (ovarian lesions and effusions) were PD‐L1 negative, 3/11 (27.3%) malignant effusions obtained during recurrence showed PD‐L1 overexpression. Lastly, none of the tested HGSC samples exhibited MMR deficiency. Conclusion Measuring biomarkers using CBs from malignant effusions may provide clinicians with significant information related to HGSC prognosis and therapy selection, especially in patients with resistance to chemotherapy.
    Type of Medium: Online Resource
    ISSN: 8755-1039 , 1097-0339
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 2001251-2
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  • 9
    In: Cancer Medicine, Wiley, Vol. 11, No. 11 ( 2022-06), p. 2193-2203
    Abstract: High‐grade serous ovarian carcinoma (HGSOC), the most common histologic subtype of ovarian epithelial cancer, is associated with treatment resistance, enhanced recurrence rates, and poor prognosis. HGSOCs often metastasize to the peritoneal cavity, while fluid cytology examination could identify such metastases. This retrospective study aimed to identify potential biomarker discrepancies between paired HGSOC primary tissues and metastatic peritoneal fluid cytology samples, processed as cell blocks (CBs). Methods Twenty‐four pairs of formalin‐fixed, paraffin‐embedded primary tissues and metastatic CBs from an equal number of treatment‐naïve patients were used, and immunohistochemistry (IHC) for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor, programmed cell death‐1 ligand 1 (PD‐L1), and CD147 was applied. Results 13/24 pairs showed discordant EGFR IHC results; in all these 13 patients, EGFR was positive (≥1+ membranous staining intensity found in at least 10% of the cancer cells) in the peritoneal, yet negative in the primary tissue samples. Notably, EGFR IHC was positive in 15/24 of the metastatic, whereas in just 2/24 of the primary HGSOC samples (p  〈  0.001). Although most PD‐L1 results were concordant, 5/24 and 6/24 pairs exhibited discordant results when stained with the E1L3N and 22C3 clones, respectively. Lastly, CD147 overexpression was found more often in the metastatic rather than the matched primary HGSOCs stained with CD147, though the difference was not significant. Conclusions Cytology from effusions could be considered for biomarker testing when present, even when tissue from the primary cancer is also available and adequately cellular, as it could provide additional information of potential clinical significance.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2659751-2
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  • 10
    In: Diagnostic Cytopathology, Wiley, Vol. 46, No. 10 ( 2018-10), p. 833-839
    Abstract: Although the Papanicolaou (Pap) test is the first‐line screening method for cervical cancer, it has low sensitivity for detection of human papillomavirus (HPV)‐infected cervical lesion compared to the HPV test. The aims of this study are to determine novel cytomorphologic parameters for HPV infection in patients previously diagnosed as negative for intraepithelial lesion or malignancy (NILM) and to comparatively analyze the detection performance of 3 HPV tests: nested PCR, the DNA Chip test, and the Liquid Beads Microarray (LBMA) assay. Methods In total, 232 patients diagnosed with NILM were enrolled and assessed using 8 cytomorphologic parameters. Results Six non‐classical cytomorphologic features were identified as novel characteristics suggesting HPV infection in patients initially diagnosed with NILM. A combination of these 6 variables showed the best predictive performance for HPV infection (area under the curve, 0.722). In terms of diagnostic ability, the LBMA assay showed better performance in detection of HPV infection (39.7%) in NILM cases compared to the other tests. Conclusions Our results suggest that the novel cytomorphologic features used in this study can be used as supportive morphologic parameters to increase the sensitivity of cytological screening tests. The LBMA assay could be used as an advanced method for HPV detection.
    Type of Medium: Online Resource
    ISSN: 8755-1039 , 1097-0339
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2001251-2
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