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Article ; Online: Management of pheochromocytomas and paragangliomas: Review of current diagnosis and treatment options.

Eid, Michal / Foukal, Jakub / Sochorová, Dana / Tuček, Štěpán / Starý, Karel / Kala, Zdeněk / Mayer, Jiří / Němeček, Radim / Trna, Jan / Kunovský, Lumír

Cancer medicine

2023 Volume 12, Issue 13, Page(s) 13942–13957

Abstract: Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they are called paragangliomas (PGLs) and arise from sympathetic and parasympathetic ... ...

Abstract	Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they are called paragangliomas (PGLs) and arise from sympathetic and parasympathetic ganglia, particularly of the para-aortic location. Up to 25% of PCCs/PGLs are associated with inherited genetic disorders. The majority of PCCs/PGLs exhibit indolent behavior. However, according to their affiliation to molecular clusters based on underlying genetic aberrations, their tumorigenesis, location, clinical symptomatology, and potential to metastasize are heterogenous. Thus, PCCs/PGLs are often associated with diagnostic difficulties. In recent years, extensive research revealed a broad genetic background and multiple signaling pathways leading to tumor development. Along with this, the diagnostic and therapeutic options were also expanded. In this review, we focus on the current knowledge and recent advancements in the diagnosis and treatment of PCCs/PGLs with respect to the underlying gene alterations while also discussing future perspectives in this field.
MeSH term(s)	Humans ; Pheochromocytoma/diagnosis ; Pheochromocytoma/genetics ; Pheochromocytoma/therapy ; Paraganglioma/diagnosis ; Paraganglioma/genetics ; Paraganglioma/therapy ; Carcinogenesis ; Cell Transformation, Neoplastic ; Adrenal Gland Neoplasms/diagnosis ; Adrenal Gland Neoplasms/genetics ; Adrenal Gland Neoplasms/therapy
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6010
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Volumetric Analysis of Hepatocellular Carcinoma After Transarterial Chemoembolization and its Impact on Overall Survival.

Hajkova, Monika / Andrasina, Tomas / Ovesna, Petra / Rohan, Tomas / Dostal, Marek / Valek, Vlastimil / Ostrizkova, Lenka / Tucek, Stepan / Sedo, Jiri / Kiss, Igor

In vivo (Athens, Greece)

2022 Volume 36, Issue 5, Page(s) 2332–2341

Abstract: Background/aim: To evaluate the prognostic value of Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST and volumetric analysis in patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE).: ... ...

Abstract	Background/aim: To evaluate the prognostic value of Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST and volumetric analysis in patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). Patients and methods: This single-center prospective cohort study included a total of 61 patients with HCC treated by transarterial chemoembolization (TACE). The response of TACE was evaluated on preprocedural and postprocedural CT by two radiologists using RECIST/mRECIST and volumetric response to treatment. Each response assessment method was used to classify the response as progressive disease, stable disease, partial response and complete response. Kaplan-Meier analysis with log-rank test was performed for each method to evaluate its ability to help predict overall survival and progression free survival. Interobserver variability and reproducibility was determined by the Pearson and Spearman correlation coefficients. Results: The median overall survival was 17.1 months and the median progression-free survival was 11.1 months. Volumetric assessment was proved to be a prognostic factor for overall survival (p<0.01) and progression-free survival (p<0.001), contrasting with RECIST and mRECIST. All three methods featured very small interobserver variability (p<0.001 for Pearson and Spearman correlation coefficients). The patients classified as having stable disease had a 3.8-fold higher risk of death than the patients classified as having a complete/partial response (HR=3.82; 95% Confidence Interval (CI)=1.32-11.02; p=0.013) and a 4.5-fold higher risk of progression (HR=4.46; 95% CI=1.72-11.61; p=0.002). Conclusion: The prognostic value of volumetric analysis in patients with HCC treated by TACE appears to be superior to RECIST and mRECIST, with a real impact in everyday practice.
MeSH term(s)	Carcinoma, Hepatocellular/diagnostic imaging ; Carcinoma, Hepatocellular/therapy ; Chemoembolization, Therapeutic/methods ; Humans ; Liver Neoplasms/therapy ; Prospective Studies ; Reproducibility of Results
Language	English
Publishing date	2022-09-13
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.12964
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Zs.A 2288: Show issues

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Article ; Online: Penis as a primary site of an extraskeletal Ewing sarcoma: A case report.

Krakorova, Dagmar Adamkova / Halamkova, Jana / Tucek, Stepan / Bilek, Ondrej / Kristek, Jan / Kazda, Tomas / Zambo, Iva Staniczkova / Demlova, Regina / Kiss, Igor

Medicine

2021 Volume 100, Issue 11, Page(s) e25074

Abstract: Rationale: The Ewing sarcoma family of malignant tumors is a group of tumors characterized by morphologically similar round-cell neoplasms and by the presence of a common chromosomal translocation; Ewing sarcoma family of tumors typically occur in ... ...

Abstract	Rationale: The Ewing sarcoma family of malignant tumors is a group of tumors characterized by morphologically similar round-cell neoplasms and by the presence of a common chromosomal translocation; Ewing sarcoma family of tumors typically occur in children and young adults between 4 to 15 years of age. The primary tumor usually originates in the bone, extraskeletal localization is rare. Patient concern: We present a case report concerning a 32-year-old male patient with a primary involvement of the penis. Diagnosis: The histopathology from the first penile biopsy showed a small-cell neuroendocrine carcinoma; however, that result was based on a sample obtained at a different facility than the Sarcoma Center, where the investigating pathologist did not have the adequate expertise. The patient then underwent a radical penectomy and a second reading of the histology was demanded after a radical penile amputation when Ewing sarcoma with R1 resection was confirmed. Interventions: The patient was referred to the national Sarcoma Center, where - using a multidisciplinary approach - the treatment was started with curative intent. However, it was preceded by a non-standard initiation of the therapy due to the poor primary diagnosis. Outcomes: The non-standard therapy at the onset of the disease caused a poor prognosis of an otherwise curable diagnosis. Despite all that, the patient survived for a relatively long time. Lessons: The treatment of sarcomas with atypical localizations should be conducted by an experienced multidisciplinary team in a center with experience in sarcoma treatment.
MeSH term(s)	Adult ; Humans ; Male ; Penile Neoplasms/pathology ; Penis/pathology ; Sarcoma, Ewing/pathology
Language	English
Publishing date	2021-03-24
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	80184-7
ISSN	1536-5964 ; 0025-7974
ISSN (online)	1536-5964
ISSN	0025-7974
DOI	10.1097/MD.0000000000025074
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Article ; Online: Type II hypersensitivity reactions after oxaliplatin rechallenge can be life threatening.

Vyskocil, Jiri / Tucek, Stepan / Kiss, Igor / Fedorova, Lenka / Nevrlka, Jiri / Zdrazilova-Dubska, Lenka

International immunopharmacology

2019 Volume 74, Page(s) 105728

Abstract: Background: Rechallenge with oxaliplatin is common in the treatment of colorectal cancer and increases the risk of a detrimental oxaliplatin-induced immune reaction. Allergic reactions to oxaliplatin may be partially avoided by desensitization protocols ...

Abstract	Background: Rechallenge with oxaliplatin is common in the treatment of colorectal cancer and increases the risk of a detrimental oxaliplatin-induced immune reaction. Allergic reactions to oxaliplatin may be partially avoided by desensitization protocols involving immune suppressive drugs, slow administration and gradually increasing chemotherapeutic doses. However, non-IgE-mediated immunopathologic reactions to oxaliplatin remain challenging and may be potentially life-threatening. Case presentation: Here we report two potentially fatal cases of type II hypersensitivity to oxaliplatin in metastatic colorectal cancer patients. Both patients manifested with severe thrombocytopenia, intravascular haemolysis, and acute kidney injury 4-6 h after oxaliplatin administration in a rechallenge setting. Serology revealed that the reactive entity for immune haemolysis was an IgG oxaliplatin-induced antibody. The course of anti-cancer treatment and severe adverse event after oxaliplatin rechallenge including diagnostic dilemma and the results of detailed routine clinical chemistry and hematology testing are described. Extended immunohaematology/serology testing revealed that the oxaliplatin-induced IgG antibody was present in the circulation prior to the onset of hypersensitivity, persisted for months and elicited cross-reactivity with other platinum agents. Conclusion: Development of type II hypersensitivity reaction manifesting as a sudden onset of severe thrombocytopenia and immune haemolysis must be considered in patients treated with oxaliplatin, especially those on long-term therapy or when rechallenged. Step-wise diagnosis involves clinical presentation, detection of haemolysis in patient's blood and/or urine, evaluation of platelet count, and direct anti-globulin Coombs test.
MeSH term(s)	Acute Kidney Injury ; Adenocarcinoma/complications ; Adenocarcinoma/diagnosis ; Adenocarcinoma/drug therapy ; Adrenal Cortex Hormones/therapeutic use ; Aged ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Desensitization, Immunologic ; Drug Hypersensitivity/diagnosis ; Drug Hypersensitivity/drug therapy ; Drug Hypersensitivity/etiology ; Drug-Related Side Effects and Adverse Reactions/diagnosis ; Drug-Related Side Effects and Adverse Reactions/drug therapy ; Drug-Related Side Effects and Adverse Reactions/etiology ; Female ; Hemolysis ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Oxaliplatin/adverse effects ; Oxaliplatin/therapeutic use ; Rectal Neoplasms/complications ; Rectal Neoplasms/diagnosis ; Rectal Neoplasms/drug therapy ; Thrombocytopenia
Chemical Substances	Adrenal Cortex Hormones ; Antineoplastic Agents ; Oxaliplatin (04ZR38536J)
Language	English
Publishing date	2019-07-06
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2019.105728
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Zs.A 5408: Show issues

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Article ; Online: Acetylsalicylic Acid and its Potential for Chemoprevention of Colorectal Carcinoma.

Podhorec, Ján / Hrstka, Roman / Bílek, Ondřej / Tuček, Štěpán / Navrátil, Jiří / Michalová, Eva / Vojtěšek, Bořivoj

Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti

2019 Volume 31, Issue Suppl 2, Page(s) 77–81

Abstract: Background: Non-steroidal anti-inflammatory drugs (NSAID) represent a group of medicaments inhibiting cyclooxygenase (COX) enzyme, and, in parallel, these drugs show also analgesic, antipyretic and anti-inflammatory effects. Due to their efficiency, ... ...

Title translation	Acetylsalicylová kyselina a její potenciál v chemoprevenci kolorektálního karcinomu.
Abstract	Background: Non-steroidal anti-inflammatory drugs (NSAID) represent a group of medicaments inhibiting cyclooxygenase (COX) enzyme, and, in parallel, these drugs show also analgesic, antipyretic and anti-inflammatory effects. Due to their efficiency, good tolerance and easy availability, they belong to the worlds most used drugs. For decades, evidence of their anti-tumor activity has been growing, with the largest amount of published work being related to colorectal cancer (CRC). Based on both in vitro and in vivo experiments and data obtained from epidemiological and clinical studies, potential application of NSAID as chemo-preventive treatment for CRC patients is recently discussed in order to prevent development or recurrence of precanceroses and tumors. Promising treatment for such indication would be acetylsalicylic acid (ASA), which is the oldest, more than 100 years used member of the NSAID family. Nonselective irreversible COX inhibition is an important but probably not solely mechanism of its anticancer activity. Notably, wider use of ASA in chemoprevention is also prevented due to particular concerns about gastrointestinal and renal toxicity caused especially by its long-term use. Aims: This review introduces the role of COX in tumor biology of CRC and highlights the results of the most interesting experiments illustrating the anti-tumor effect of ASA. Moreover, our work evaluates the most important published clinical analyzes of the ASA chemopreventive effect on CRC and discusses the current state. Key words: non-steroidal anti-inflammatory agents - acetylsalicylic acid - colorectal carcinoma - cyclooxygenase - chemoprevention This work was supported by the projects MEYS - NPS I - LO1413, MH CZ - DRO (MMCI, 00209805) and by Czech Science Foundation project no. 16-14829S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 10. 9. 2017.
MeSH term(s)	Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Anticarcinogenic Agents/therapeutic use ; Aspirin/therapeutic use ; Chemoprevention ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/prevention & control ; Humans ; Prostaglandin-Endoperoxide Synthases/metabolism
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Anticarcinogenic Agents ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1) ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2019-04-15
Publishing country	Czech Republic
Document type	Journal Article ; Review
ZDB-ID	1217739-8
ISSN	1802-5307 ; 0862-495X
ISSN (online)	1802-5307
ISSN	0862-495X
DOI	10.14735/amko20182S77
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Article: Prognostic Value of Scores Based on Malnutrition or Systemic Inflammatory Response in Patients With Metastatic or Recurrent Gastric Cancer

Sachlova, Milana / Majek, Ondrej / Tucek, Stepan

Nutrition and cancer. 2014 Nov. 17, v. 66, no. 8

2014

Abstract: Cancer patients are frequently affected by malnutrition and weight loss, which affects their prognosis, length of hospital stay, health care costs, quality of life and survival. Our aim was to assess the prognostic value of different scores based on ... ...

Abstract	Cancer patients are frequently affected by malnutrition and weight loss, which affects their prognosis, length of hospital stay, health care costs, quality of life and survival. Our aim was to assess the prognostic value of different scores based on malnutrition or systemic inflammatory response in 91 metastatic or recurrent gastric cancer patients considered for palliative chemotherapy at the Masaryk Memorial Cancer Institute. We investigated their overall survival according to the following measures: Onodera's Prognostic Nutritional Index (OPNI), Glasgow Prognostic Score (GPS), nutritional risk indicator (NRI), Cancer Cachexia Study Group (CCSG), as previously defined, and a simple preadmission weight loss. The OPNI, GPS, and CCSG provided very significant prognostic values for survival (log-rank test P value < 0.001). For example, the median survival for patients with GPS 0 was 12.3 mo [95% confidence interval (CI): 7.7–16.7], whereas the median survival for patients with GPS 2 was only 2.9 mo (95% CI: 1.9–4.8). A significantly worse survival of malnourished patients was also suggested by a multivariate model. The values of GPS, OPNI, and CCSG represent useful tools for the evaluation of patients’ prognosis and should be part of a routine evaluation of patients to provide a timely nutrition support.
Keywords	cachexia ; chemotherapy ; confidence interval ; health care costs ; inflammation ; malnutrition ; metastasis ; multivariate analysis ; nutrition ; patients ; prognosis ; quality of life ; risk ; stomach neoplasms ; weight loss
Language	English
Dates of publication	2014-1117
Size	p. 1362-1370.
Publishing place	Routledge
Document type	Article
ZDB-ID	2025822-7
ISSN	1532-7914 ; 0163-5581
ISSN (online)	1532-7914
ISSN	0163-5581
DOI	10.1080/01635581.2014.956261
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Prognostic value of scores based on malnutrition or systemic inflammatory response in patients with metastatic or recurrent gastric cancer.

Sachlova, Milana / Majek, Ondrej / Tucek, Stepan

Nutrition and cancer

2014 Volume 66, Issue 8, Page(s) 1362–1370

Abstract	Cancer patients are frequently affected by malnutrition and weight loss, which affects their prognosis, length of hospital stay, health care costs, quality of life and survival. Our aim was to assess the prognostic value of different scores based on malnutrition or systemic inflammatory response in 91 metastatic or recurrent gastric cancer patients considered for palliative chemotherapy at the Masaryk Memorial Cancer Institute. We investigated their overall survival according to the following measures: Onodera's Prognostic Nutritional Index (OPNI), Glasgow Prognostic Score (GPS), nutritional risk indicator (NRI), Cancer Cachexia Study Group (CCSG), as previously defined, and a simple preadmission weight loss. The OPNI, GPS, and CCSG provided very significant prognostic values for survival (log-rank test P value < 0.001). For example, the median survival for patients with GPS 0 was 12.3 mo [95% confidence interval (CI): 7.7-16.7], whereas the median survival for patients with GPS 2 was only 2.9 mo (95% CI: 1.9-4.8). A significantly worse survival of malnourished patients was also suggested by a multivariate model. The values of GPS, OPNI, and CCSG represent useful tools for the evaluation of patients' prognosis and should be part of a routine evaluation of patients to provide a timely nutrition support.
MeSH term(s)	Aged ; Cachexia ; Female ; Humans ; Inflammation/complications ; Male ; Malnutrition/complications ; Multivariate Analysis ; Neoplasm Metastasis/therapy ; Neoplasm Recurrence, Local ; Nutrition Assessment ; Nutritional Status ; Prognosis ; Quality of Life ; Stomach Neoplasms/complications ; Stomach Neoplasms/diagnosis ; Stomach Neoplasms/drug therapy ; Weight Loss
Language	English
Publishing date	2014
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424433-3
ISSN	1532-7914 ; 0163-5581
ISSN (online)	1532-7914
ISSN	0163-5581
DOI	10.1080/01635581.2014.956261
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Zs.A 1496: Show issues

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Article: The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma.

Eid, Michal / Karousi, Paraskevi / Kunovský, Lumír / Tuček, Štěpán / Brančíková, Dagmar / Kala, Zdeněk / Slabý, Ondřej / Mayer, Jiří / Kontos, Christos K / Trna, Jan

Biomedicines

2021 Volume 9, Issue 10

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is still associated with a high rate of mortality. Only a minority of patients are diagnosed in the early stage. Radical surgery is the only potential curative procedure. However, ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is still associated with a high rate of mortality. Only a minority of patients are diagnosed in the early stage. Radical surgery is the only potential curative procedure. However, radicality is reached in 20% of patients operated on. Despite the multidisciplinary approach in resectable tumors, early tumor recurrences are common. Options on how to select optimal candidates for resection remain limited. Nevertheless, accumulating evidence shows an important role of circulating non-coding plasma and serum microRNAs (miRNAs), which physiologically regulate the function of a target protein. miRNAs also play a crucial role in carcinogenesis. In PDAC patients, the expression levels of certain miRNAs vary and may modulate the function of oncogenes or tumor suppressor genes. As they can be detected in a patient's blood, they have the potential to become promising non-invasive diagnostic and prognostic biomarkers. Moreover, they may also serve as markers of chemoresistance. Thus, miRNAs could be useful for early and accurate diagnosis, prognostic stratification, and individual treatment planning. In this review, we summarize the latest findings on miRNAs in PDAC patients, focusing on their potential use in the early stage of the disease.
Language	English
Publishing date	2021-10-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines9101468
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Article ; Online: Indications for venous access in oncology - recommendations of national professional societies and current state in the Czech Republic.

Maňásek, Viktor / Charvát, Jiří / Chovanec, Vendelín / Sirotek, Lukáš / Linke, Zdeněk / Tuček, Štěpán / Šenkyřík, Michal / Michálek, Pavel / Polák, Martin / Fricová, Jitka / Daniš, Lukáš / Šeflová, Lenka / Lisová, Kateřina / Douglas, Martina

Klinicka onkologie : casopis Ceske a Slovenske onkologicke spolecnosti

2021 Volume 34, Issue 3, Page(s) 192–201

Abstract: Background: The aim of the paper is to present the current recommendations and indications of venous access in oncology which reflect and recognize the opinions of national and international professional societies. It focuses exclusively on the ... ...

Title translation	Indikace žilních vstupů v onkologii - doporučení národních odborných společností a současný stav v ČR.
Abstract	Background: The aim of the paper is to present the current recommendations and indications of venous access in oncology which reflect and recognize the opinions of national and international professional societies. It focuses exclusively on the indications of intravenous catheter placement for anticancer treatment, such as medium-term and long-term venous accesses. Materials and methods: The survey results obtained from a national questionnaire of 24 oncology centers identified the current situation in the Czech Republic. There were evaluated relevant data on the number of and the criteria for the introduction of venous accesses provided by physicians. Comparisons were made between current oncological practice and recommendations provided by evidence-based medicine. Results: At each center surveyed in the Czech Republic, an average of 130 ports and 80 permanent implanted central catheters are introduced annually. The ports are increasingly indicated, with over a half of the centers surveyed introducing ports to more than 100 patients a year, with four centers introducing a total of 1,600 ports annually. In all centers, the decision for venous access is made by an oncologist. However, most procedures are performed by a doctor of another specialization, most often by a surgeon, a radiologist or an anesthesiologist. More than a half of the indications for venous access placement result from poor peripheral venous system or complications of parenteral therapy, not from comprehensive assessment prior to the initiation of the therapy. Conclusion: Based on our findings, we developed general indications and recommendations for venous access to cancer patients which represent the consensus of an interdisciplinary team of specialists, predominantly from the committee of professional societies - the Society for Ports and Permanent Catheters, the Working Group of Nutritional Care in Oncology of the Czech Oncological Society and the Society of Clinical Nutrition and Intensive Metabolic Care. The number of introduced venous access catheters remains insufficient to meet the needs in the Czech Republic, which necessitates increased awareness and possibilities for safe drug administration.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Catheterization, Central Venous/standards ; Catheters, Indwelling/standards ; Humans ; Neoplasms/drug therapy ; Practice Guidelines as Topic/standards ; Societies, Medical ; Surveys and Questionnaires
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2021-07-15
Publishing country	Czech Republic
Document type	Journal Article ; Review
ZDB-ID	1217739-8
ISSN	1802-5307 ; 0862-495X
ISSN (online)	1802-5307
ISSN	0862-495X
DOI	10.48095/ccko2021192
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Article ; Online: Transcription factor c-Myb: novel prognostic factor in osteosarcoma.

Clinical & experimental metastasis

2022 Volume 39, Issue 2, Page(s) 375–390

Abstract: The transcription factor c-Myb is an oncoprotein promoting cell proliferation and survival when aberrantly activated/expressed, thus contributing to malignant transformation. Overexpression of c-Myb has been found in leukemias, breast, colon and adenoid ... ...

Abstract	The transcription factor c-Myb is an oncoprotein promoting cell proliferation and survival when aberrantly activated/expressed, thus contributing to malignant transformation. Overexpression of c-Myb has been found in leukemias, breast, colon and adenoid cystic carcinoma. Recent studies revealed its expression also in osteosarcoma cell lines and suggested its functional importance during bone development. However, the relevance of c-Myb in control of osteosarcoma progression remains unknown. A retrospective clinical study was carried out to assess a relationship between c-Myb expression in archival osteosarcoma tissues and prognosis in a cohort of high-grade osteosarcoma patients. In addition, MYB was depleted in metastatic osteosarcoma cell lines SAOS-2 LM5 and 143B and their growth, chemosensitivity, migration and metastatic activity were determined. Immunohistochemical analysis revealed that high c-Myb expression was significantly associated with poor overall survival in the cohort and metastatic progression in young patients. Increased level of c-Myb was detected in metastatic osteosarcoma cell lines and its depletion suppressed their growth, colony-forming capacity, migration and chemoresistance in vitro in a cell line-dependent manner. MYB knock-out resulted in reduced metastatic activity of both SAOS-2 LM5 and 143B cell lines in immunodeficient mice. Transcriptomic analysis revealed the c-Myb-driven functional programs enriched for genes involved in the regulation of cell growth, stress response, cell adhesion and cell differentiation/morphogenesis. Wnt signaling pathway was identified as c-Myb target in osteosarcoma cells. Taken together, we identified c-Myb as a negative prognostic factor in osteosarcoma and showed its involvement in the regulation of osteosarcoma cell growth, chemosensitivity, migration and metastatic activity.
MeSH term(s)	Animals ; Bone Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Osteosarcoma/pathology ; Prognosis ; Retrospective Studies ; Wnt Signaling Pathway
Language	English
Publishing date	2022-01-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604952-7
ISSN	1573-7276 ; 0262-0898
ISSN (online)	1573-7276
ISSN	0262-0898
DOI	10.1007/s10585-021-10145-4
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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

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