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1. xOpat: eXplainable Open Pathology Analysis Tool.

Author

Horák, J., Furmanová, K., Kozlíková, B., Brázdil, T., Holub, P., Kačenga, M., Gallo, M., Nenutil, R., Byška, J., and Rusňák, V.

Subjects
IMAGE segmentation, EVIDENCE gaps, ARTIFICIAL intelligence, PATHOLOGY, PATHOLOGISTS, MEDICAL research
Abstract

Histopathology research quickly evolves thanks to advances in whole slide imaging (WSI) and artificial intelligence (AI). However, existing WSI viewers are tailored either for clinical or research environments, but none suits both. This hinders the adoption of new methods and communication between the researchers and clinicians. The paper presents xOpat, an open‐source, browser‐based WSI viewer that addresses these problems. xOpat supports various data sources, such as tissue images, pathologists' annotations, or additional data produced by AI models. Furthermore, it provides efficient rendering of multiple data layers, their visual representations, and tools for annotating and presenting findings. Thanks to its modular, protocol‐agnostic, and extensible architecture, xOpat can be easily integrated into different environments and thus helps to bridge the gap between research and clinical practice. To demonstrate the utility of xOpat, we present three case studies, one conducted with a developer of AI algorithms for image segmentation and two with a research pathologist. [ABSTRACT FROM AUTHOR]

Published
2023
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10. Abstracts from the 4th ImmunoTherapy of Cancer Conference

Author

Ženka, J., primary, Caisová, V., additional, Uher, O., additional, Nedbalová, P., additional, Kvardová, K., additional, Masáková, K., additional, Krejčová, G., additional, Paďouková, L., additional, Jochmanová, I., additional, Wolf, K. I., additional, Chmelař, J., additional, Kopecký, J., additional, Loumagne, L., additional, Mestadier, J., additional, D’agostino, S., additional, Rohaut, A., additional, Ruffin, Y., additional, Croize, V., additional, Lemaître, O., additional, Sidhu, S. S., additional, Althammer, S., additional, Steele, K., additional, Rebelatto, M., additional, Tan, T., additional, Wiestler, T., additional, Spitzmueller, A., additional, Korn, R., additional, Schmidt, G., additional, Higgs, B., additional, Li, X., additional, Shi, L., additional, Jin, X., additional, Ranade, K., additional, Koeck, S., additional, Amann, A., additional, Gamerith, G., additional, Zwierzina, M., additional, Lorenz, E., additional, Zwierzina, H., additional, Kern, J., additional, Riva, M., additional, Baert, T., additional, Coosemans, A., additional, Giovannoni, R., additional, Radaelli, E., additional, Gsell, W., additional, Himmelreich, U., additional, Van Ranst, M., additional, Xing, F., additional, Qian, W., additional, Dong, C., additional, Xu, X., additional, Guo, S., additional, Shi, Q., additional, Quandt, D., additional, Seliger, B., additional, Plett, C., additional, Amberger, D. C., additional, Rabe, A., additional, Deen, D., additional, Stankova, Z., additional, Hirn, A., additional, Vokac, Y., additional, Werner, J., additional, Krämer, D., additional, Rank, A., additional, Schmid, C., additional, Schmetzer, H., additional, Guerin, M., additional, Weiss, J. M., additional, Regnier, F., additional, Renault, G., additional, Vimeux, L., additional, Peranzoni, E., additional, Feuillet, V., additional, Thoreau, M., additional, Guilbert, T., additional, Trautmann, A., additional, Bercovici, N., additional, Doraneh-Gard, F., additional, Boeck, C. L., additional, Gunsilius, C., additional, Kugler, C., additional, Schmohl, J., additional, Kraemer, D., additional, Ismann, B., additional, Schmetzer, H. M., additional, Markota, A., additional, Ochs, C., additional, May, P., additional, Gottschlich, A., additional, Gosálvez, J. Suárez, additional, Karches, C., additional, Wenk, D., additional, Endres, S., additional, Kobold, S., additional, Hilmenyuk, T., additional, Klar, R., additional, Jaschinski, F., additional, Augustin, F., additional, Manzl, C., additional, Hoflehner, E., additional, Moser, P., additional, Zelger, B., additional, Köck, S., additional, Schäfer, G., additional, Öfner, D., additional, Maier, H., additional, Sopper, S., additional, Prado-Garcia, H., additional, Romero-Garcia, S., additional, Sandoval-Martínez, R., additional, Puerto-Aquino, A., additional, Lopez-Gonzalez, J., additional, Rumbo-Nava, U., additional, Van Hoylandt, A., additional, Busschaert, P., additional, Vergote, I., additional, Laengle, J., additional, Pilatova, K., additional, Budinska, E., additional, Bencsikova, B., additional, Sefr, R., additional, Nenutil, R., additional, Brychtova, V., additional, Fedorova, L., additional, Hanakova, B., additional, Zdrazilova-Dubska, L., additional, Allen, Chris, additional, Ku, Yuan-Chieh, additional, Tom, Warren, additional, Sun, Yongming, additional, Pankov, Alex, additional, Looney, Tim, additional, Hyland, Fiona, additional, Au-Young, Janice, additional, Mongan, Ann, additional, Becker, A., additional, Tan, J. B. L., additional, Chen, A., additional, Lawson, K., additional, Lindsey, E., additional, Powers, J. P., additional, Walters, M., additional, Schindler, U., additional, Young, S., additional, Jaen, J. C., additional, Yin, S., additional, Chen, Y., additional, Gullo, I., additional, Gonçalves, G., additional, Pinto, M. L., additional, Athelogou, M., additional, Almeida, G., additional, Huss, R., additional, Oliveira, C., additional, Carneiro, F., additional, Merz, C., additional, Sykora, J., additional, Hermann, K., additional, Hussong, R., additional, Richards, D. M., additional, Fricke, H., additional, Hill, O., additional, Gieffers, C., additional, Pinho, M. P., additional, Barbuto, J. A. M., additional, McArdle, S. E., additional, Foulds, G., additional, Vadakekolathu, J. N., additional, Abdel-Fatah, T. M. A., additional, Johnson, C., additional, Hood, S., additional, Moseley, P., additional, Rees, R. C., additional, Chan, S. Y. T., additional, Pockley, A. G., additional, Rutella, S., additional, Geppert, C., additional, Hartmann, A., additional, Kumar, K. Senthil, additional, Gokilavani, M., additional, Wang, S., additional, Redondo-Müller, M., additional, Heinonen, K., additional, Marschall, V., additional, Thiemann, M., additional, Zhang, L., additional, Mao, B., additional, Jin, Y., additional, Zhai, G., additional, Li, Z., additional, Wang, Z., additional, An, X., additional, Qiao, M., additional, Zhang, J., additional, Weber, J., additional, Kluger, H., additional, Halaban, R., additional, Sznol, M., additional, Roder, H., additional, Roder, J., additional, Grigorieva, J., additional, Asmellash, S., additional, Meyer, K., additional, Steingrimsson, A., additional, Blackmon, S., additional, Sullivan, R., additional, Sutanto, W., additional, Guenther, T., additional, Schuster, F., additional, Salih, H., additional, Babor, F., additional, Borkhardt, A., additional, Kim, Y., additional, Oh, I., additional, Park, C., additional, Ahn, S., additional, Na, K., additional, Song, S., additional, Choi, Y., additional, Poprach, A., additional, Lakomy, R., additional, Selingerova, I., additional, Demlova, R., additional, Kozakova, S., additional, Valik, D., additional, Petrakova, K., additional, Vyzula, R., additional, Aguilar-Cazares, D., additional, Galicia-Velasco, M., additional, Camacho-Mendoza, C., additional, Islas-Vazquez, L., additional, Chavez-Dominguez, R., additional, Gonzalez-Gonzalez, C., additional, Lopez-Gonzalez, J. S., additional, Yang, S., additional, Moynihan, K. D., additional, Noh, M., additional, Bekdemir, A., additional, Stellacci, F., additional, Irvine, D. J., additional, Volz, B., additional, Kapp, K., additional, Oswald, D., additional, Wittig, B., additional, Schmidt, M., additional, Kleef, R., additional, Bohdjalian, A., additional, McKee, D., additional, Moss, R. W., additional, Saeed, Mesha, additional, Zalba, Sara, additional, Debets, Reno, additional, ten Hagen, Timo L. M., additional, Javed, S., additional, Becher, J., additional, Koch-Nolte, F., additional, Haag, F., additional, Gordon, E. M., additional, Sankhala, K. K., additional, Stumpf, N., additional, Tseng, W., additional, Chawla, S. P., additional, Suárez, N. González, additional, Báez, G. Bergado, additional, Rodríguez, M. Cruz, additional, Pérez, A. Gutierrez, additional, García, L. Chao, additional, Fernández, D. Hernández, additional, Pous, J. Raymond, additional, Ramírez, B. Sánchez, additional, Jacoberger-Foissac, C., additional, Saliba, H., additional, Seguin, C., additional, Brion, A., additional, Frisch, B., additional, Fournel, S., additional, Heurtault, B., additional, Otterhaug, T., additional, Håkerud, M., additional, Nedberg, A., additional, Edwards, V., additional, Selbo, P., additional, Høgset, A., additional, Jaitly, T., additional, Dörrie, J., additional, Schaft, N., additional, Gross, S., additional, Schuler-Thurner, B., additional, Gupta, S., additional, Taher, L., additional, Schuler, G., additional, Vera, J., additional, Rataj, F., additional, Kraus, F., additional, Grassmann, S., additional, Chaloupka, M., additional, Lesch, S., additional, Heise, C., additional, Cadilha, B. M. Loureiro, additional, and Dorman, K., additional

Published
2017
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12. Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma

Author

Staufer, K, Gao, CF, Valik, D, Greplova, K, Muller, P, Nenutil, R, Mikulits, W, Man, K, Trauner, M, Starlinger, P, Fang, M, Reichl, P, Yu, J, Gruenberger, T, Dooley, S, Shen, J, and Brostjan, C

Subjects
Liver Cirrhosis, Male, Carcinoma, Hepatocellular, Liver Neoplasms, Receptor Protein-Tyrosine Kinases, Enzyme-Linked Immunosorbent Assay, Hep G2 Cells, Kaplan-Meier Estimate, Middle Aged, Axl Receptor Tyrosine Kinase, digestive system diseases, Article, Diagnosis, Differential, Early Diagnosis, ROC Curve, Solubility, Cell Line, Tumor, Proto-Oncogene Proteins, Biomarkers, Tumor, Humans, Female, alpha-Fetoproteins, neoplasms, Neoplasm Staging
Abstract

If diagnosed at early stages, patients with hepatocellular carcinoma (HCC) can receive curative therapies, whereas therapeutic options at later stages are very limited. Here, we addressed the potential of soluble Axl (sAxl) as a biomarker of early HCC by analyzing levels of sAxl in 311 HCC and 237 control serum samples from centers in Europe and China. Serum concentrations of sAxl were significantly increased in HCC (18.575 ng/mL) as compared to healthy (13.388 ng/mL) or cirrhotic (12.169 ng/mL) controls. Receiver operating characteristic curve analysis of sAxl in very early stage HCC patients (BCLC 0) showed an area under the curve (AUC) of 0.848, with a sensitivity of 76.9% and a specificity of 69.2%. α-Fetoprotein (AFP)-negative HCC patients displayed an AUC of 0.803, with sensitivity and specificity of 73% and 70.8%. Combination of sAxl and AFP improved diagnostic accuracy to 0.936 in very early HCC patients and to 0.937 in all HCC. Differential diagnosis of very early HCC versus liver cirrhosis showed a combined performance for sAxl and AFP of 0.901 with a sensitivity of 88.5% and a specificity of 76.7%. Furthermore, sAxl levels failed to be elevated in primary ovarian, colorectal and breast carcinomas as well as in secondary hepatic malignancies derived from colon. In summary, sAxl outperforms AFP in detecting very early HCC as compared to healthy or cirrhotic controls and shows high diagnostic accuracy for AFP-negative patients. sAxl is specific for HCC and suggested as a biomarker for routine clinical use.

Published
2015

13. [KRAS mutation testing in therapeutic algorithm for treatment of metastatic colorectal carcinoma]

Author

Dubská L, Vyskocilová M, Nenutil R, Valík D, Knoflícková D, Fabian P, Kocáková I, Demlová R, Beránek M, Drastíková M, Vosmiková H, Bóday A, Horká K, Símová J, Jiri Drabek, Ehrmann J, Hajdúch M, Matejcková M, Síma R, Tvrdík D, Povýsil C, and Ryska A

Subjects
Genes, ras, Panitumumab, Mutation, Antibodies, Monoclonal, Cetuximab, Humans, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Colorectal Neoplasms
Abstract

Targeted therapy has become an integral part of treatment procedures of malignant tumors. Colorectal carcinomas are frequently targeted with monoclonal anti-EGFR antibodies (cetuximab and panitumumab). Activating somatic mutations in codons 12 and 13 of the exon 2 of KRAS gene are considered negative predictive factors of response to anti-EGFR therapy in patients with metastatic colorectal cancer. In the Czech Republic, evaluation of mutational status of KRAS gene is performed in several referral laboratories. In 2009, these laboratories performed 2580 tests of the KRAS mutational status--out of these, 60.2% cases reported non-mutated, wild-type KRAS. In one of the referral laboratories, we demonstrate the logistics of KRAS testing procedure. Stratification of patients with metastatic colorectal tumors based on their KRAS mutational status has evolved to a standard procedure. Laboratories performing these methods shall therefore adhere to the recommendations of the professional and accredited societies.

Published
2011

14. 185 Combined proteomics and transcriptomics identifies carboxypeptidase B1 and NF-κB associated proteins as putative biomarkers of metastasis in low grade breast cancer

Author

Bouchal, P., primary, Dvořáková, M., additional, Roumeliotis, T., additional, Bortlíček, Z., additional, Ihnatová, I., additional, Procházková, I., additional, Ho, J.T.C., additional, Maryáš, J., additional, Imrichová, H., additional, Budinská, E., additional, Vyzula, R., additional, Garbis, S.D., additional, Vojtěšek, B., additional, and Nenutil, R., additional

Published
2015
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15. P0346 : Multicenter analysis of soluble Axl reveals diagnostic value for very early stage hepatocellular carcinoma

Author

Reichl, P., primary, Fang, M., additional, Starlinger, P., additional, Staufer, K., additional, Nenutil, R., additional, Muller, P., additional, Greplova, K., additional, Valik, D., additional, Dooley, S., additional, Brostjan, C., additional, Gruenberger, T., additional, Shen, J., additional, Man, K., additional, Trauner, M., additional, Yu, J., additional, Gao, C.F., additional, and Mikulits, W., additional

Published
2015
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16. Expression of p53, cyclin D1 and EGFR correlates with histological grade of adult soft tissue sarcomas: a study on tissue microarrays

Author

Michal Jurajda, Nenutil R, Vesela M, and Vesely K

Subjects
Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Adolescent, Biology, Cyclin D1, medicine, Humans, Grading (tumors), Aged, Aged, 80 and over, Tissue microarray, Soft tissue sarcoma, Clinical course, Soft tissue, Sarcoma, Middle Aged, NM23 Nucleoside Diphosphate Kinases, medicine.disease, Immunohistochemistry, ErbB Receptors, Oncology, Tissue Array Analysis, Ki-67, biology.protein, Female, Tumor Suppressor Protein p53
Abstract

Soft tissue sarcomas (STSs) are rare heterogeneous tumors with variable clinical course and outcome. The management of STSs depends upon the accurate histopathological diagnosis and assessing their histological grade. Currently, core needle biopsies are becoming increasingly popular for diagnosing STSs but value of histological grading is limited from this type of specimens. To evaluate the immunohistochemical expression of p53, mdm-2, cyclin D1, p16, nm23, EGFR and Ki-67 labelling index in adult STSs patients and their association with histological grade of STSs, we analysed 101 primary untreated STSs of the limbs and trunk using the tissue microarray technique on formalin-fixed, paraffin-embedded tissue samples. The cases consisted of 15 G1, 28 G2 and 58 G2 sarcomas. Ki-67 labelling index (LI) was calculated from whole block sections for the possibility to select the most proliferative regions. The LI ranged from 1.26 to 75.5% (median 26.7%) and strongly correlated with the mitotic count (p rs for adult patients with STSs and may assist in establishment of the histological grade in STSs.

Published
2009

21. Function and importance of p63 in normal oral mucosa and squamous cell carcinoma of the head and neck

Author

Thurfjell, N., Coates, P.J., Boldrup, L., Lindgren, B., Bäcklund, B., Uusitalo, T., Mahani, D., Dabelsteen, E., Dahlqvist, Å., Sjöström, B., Roos, G., Vojtesek, B., Nenutil, R., Nylander, K., Thurfjell, N., Coates, P.J., Boldrup, L., Lindgren, B., Bäcklund, B., Uusitalo, T., Mahani, D., Dabelsteen, E., Dahlqvist, Å., Sjöström, B., Roos, G., Vojtesek, B., Nenutil, R., and Nylander, K.

Published
2005

30. Histological grading and DNA content as predictors of distant metastases in squamous cell carcinoma of the uterine cervix

Author

Zaloudík J, Nenutil R, and Anton M

Subjects
Pathology, medicine.medical_specialty, Adjuvant chemotherapy, medicine.medical_treatment, Uterine Cervical Neoplasms, chemistry.chemical_compound, medicine, Parametrium, Humans, Basal cell, Neoplasm Metastasis, Grading (tumors), Neoplasm Staging, Cervical cancer, Chemotherapy, business.industry, Obstetrics and Gynecology, General Medicine, DNA, Neoplasm, medicine.disease, Aneuploidy, Flow Cytometry, Prognosis, Combined Modality Therapy, Diploidy, Uterine cervix, medicine.anatomical_structure, chemistry, Chemotherapy, Adjuvant, Carcinoma, Squamous Cell, Female, business, DNA
Abstract

Squamous cell carcinoma of the uterine cervix with distant metastases can be treated by adjuvant chemotherapy. The at-risk patients are those with histologically proven metastases, the presence of tumour in paracervical tissue and parametrium, evidence of vascular invasion, a great depth of invasion, or poor tumour differentiation. Our studies lead us to believe that differentiation and DNA content are also important criteria.

Published
1991

35. MONITOR.

Author

Ehrmann, J., Daum, O., Nenutil, R., Campr, V., Dušková, J., Honsová, E., Jirásek, T., Laco, J., Matĕj, R., Rychlý, B., Šteiner, I., Škapa, P., Veselý, K., Dundr, P., Hes, O., and Švajdler ml., M.

Published
2014

41. MONITOR.

Author

Hes, O., Nenutil, R., Dušková, J., Švajdler, M., Campr, V., Honsová, E., Veselý, K., Daum, O., Ehrmann, J., Škapa, P., Szépe, P., Dundr, P., Rychlý, B., Ryška, A., Laco, J., Jirásek, T., and Matĕj, R.

Published
2012

48. [Relevance of p53 protein and its mutations for novel strategies in cancer therapy]

Author

Petr Muller, Nenutil, R., and Vojtesek, B.

Subjects
Neoplasms, Cell Cycle, Mutation, Humans, Apoptosis, Gene Silencing, Tumor Suppressor Protein p53, Genes, p53
Abstract

Mutational inactivation of the p53 gene products is one of the most common genetic events that occur in human cancer confirming the central role of p53 as a tumour suppressor. The wild type p53 protein acts as a powerful transcription factor binding as many as 300 different promoter sequences in the genome. As a transcription factor, p53 can broadly alter patterns of specific gene expression leading to cell-cycle arrest and/or apoptosis. The transcriptional activity of the p53 protein is precisely regulated and its basal activity is enhanced in cells exposed to a wide variety of stress signals. This stress regulated transactivation function of p53 is driven by its sequence-specific DNA-binding domain and is co-ordinated by specific protein-protein interactions that can be modulated by covalent and non-covalent modifications. The mutant forms of p53 protein are defective in sequence specific DNA-binding because the missense mutation affects one or all of the assembly pathways. Analysis of p53 mutant has shown that different conformational classes of mutants exist and the reactivation of each class requires a different strategy depending on the mechanism of p53 protein misfolding. Potential reactivation of both wild type and mutant p53 protein in vivo raises our hopes of developing anti-cancer drugs useful in combination with sophisticated diagnostics for the treatment of cancer.

50. New monoclonal antibodies recognizing p53 protein phosphorylated by casein kinase II at serine 392

Author

Pospísilová S, Katerina Kankova, Svitáková M, Nenutil R, and Vojtesek B

Subjects
Ovarian Neoplasms, Mice, Inbred BALB C, Protein Denaturation, Hybridomas, Recombinant Fusion Proteins, Blotting, Western, Immunoblotting, Molecular Sequence Data, Antibodies, Monoclonal, Enzyme-Linked Immunosorbent Assay, Cross Reactions, Protein Serine-Threonine Kinases, Neoplasm Proteins, Mice, Phosphoserine, Antibody Specificity, Animals, Humans, Female, Amino Acid Sequence, Phosphorylation, Tumor Suppressor Protein p53, Casein Kinase II, Protein Processing, Post-Translational

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