Modifying scaffolds with agents that at the same time positively influence osteogenic cells and have a negative impact on cancerous growth, is a promising solution for patients with bone tissue defects following tumor excision. Such materials may not only boost tissue regeneration but also limit the risk of cancer reoccurrence. In our study, we developed novel bifunctional scaffolds containing magnetic nanoparticles grafted with PCL (MNP@PCL) and tannic acid (TA), which may be directed to support normal bone cells and suppress osteosarcoma cells. First, MNPs were postsynthetically surface-modified, by grafting poly(ε-caprolactone) (PCL) from the surface via ring opening polymerization of ε-caprolactone, to provide their uniform distribution within the polymer matrix. Then, fiber mats containing a fixed amount of MNPs (2 wt %) and increasing content of TA (0, 1, 5, and 10 wt %) were prepared by electrospinning method. Both MNP@PCL and TA decreased polymer crystallinity. The interaction between the MNPs and TA significantly influenced the mat morphology, thermal properties, and initial hydrolytic performance. The most intensive TA release was observed mainly within first 6 h of incubation, and it was 3.5-fold higher (ca. 0.02 mg of TA/per mg of mat) for mfPCL@TA-10 compared to mfPCL@TA-5. Moreover, TA-containing magnetic mats suppressed the metabolic activity of osteosarcoma cells. They also demonstrated enhanced antimicrobial properties against the bacteria typically accompanying orthopedic complications, reducing the population of Gram-positive bacteria by more than 90% compared to the neat PCL mat. This proves the high potential of these materials for combining cancer treatment with bone tissue engineering.

• Klíčová slova
• antibacterial, bone regeneration, fiber scaffolds, magnetic nanoparticles, nanocomposites, tannic acid,
• MeSH
• antibakteriální látky * farmakologie   chemie   MeSH
• kosti a kostní tkáň účinky léků   MeSH
• lidé MeSH
• magnetické nanočástice * chemie   MeSH
• nádorové buněčné linie MeSH
• nádory kostí * farmakoterapie   patologie   MeSH
• osteosarkom * farmakoterapie   patologie   MeSH
• polyestery * chemie   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• taniny * chemie   farmakologie   MeSH
• tkáňové inženýrství * metody   MeSH
• tkáňové podpůrné struktury chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• magnetické nanočástice * MeSH
• polycaprolactone MeSH Prohlížeč
• polyestery * MeSH
• polyfenoly MeSH
• protinádorové látky * MeSH
• taniny * MeSH
• tannic acid MeSH Prohlížeč

Reconstruction of the anatomic defect following extra-articular shoulder resection is a challenging problem, particularly in cases when function of the deltoid muscle and rotator cuff are compromised. Standard reconstruction techniques often result in either instability or rigidity. Constrained implants have been used to overcome these problems; however, they have been associated with a high rate of aseptic loosening. Recently, a novel double-constrained implant has been introduced, yielding promising functional results. Nonetheless, this implant exhibited a cosmetic defect related to protrusion of the humeral component that becomes apparent with time as result of surrounding muscle atrophy. An updated improved design of the implant has been developed to counteract this.We report the case of a 15-year-old patient who underwent an extra-articular (Malawer type V) shoulder resection due to osteosarcoma and received an innovated custom-made double-constrained implant. Moreover, we describe a new modification of the Malawer utilitarian approach to the shoulder girdle that enhances tumor visibility and allows safer dissection. The patient recovered well with satisfactory outcomes at 18 months follow-up, highlighting the potential benefits of this implant design and surgical approach.

• Klíčová slova
• Double-constrained implant, Extra-articular resection, Malawer type V resection, Osteosarcoma, Shoulder reconstruction,
• MeSH
• artroplastika ramenního kloubu * metody   MeSH
• lidé MeSH
• mladiství MeSH
• nádory kostí * chirurgie   patologie   MeSH
• náhrada ramenního kloubu * MeSH
• osteosarkom * chirurgie   patologie   MeSH
• ověření koncepční studie MeSH
• prognóza MeSH
• protézy - design * MeSH
• ramenní kloub * chirurgie   patologie   MeSH
• výsledek terapie MeSH
• zákroky plastické chirurgie * metody   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The diagnosis of Ewing sarcoma can be challenging, particularly when the tumor is present in an atypical location and resembles histologic mimics. The hallmark feature of Ewing sarcoma is chromosomal translocation, t(11;22)(q24;q12), involving EWSR1 and ETS gene family members. For decades, fluorescence in situ hybridization with a break-apart EWSR1 probe has been the diagnostic gold standard. However, EWSR1 rearrangements have been identified in other malignancies; thus, the detection of chimeric EWSR1 transcripts has become a preferable approach. Occasionally, insufficient tissue, severe RNA degradation, or economic constraints hamper molecular testing. This study evaluated Protein Kinase C Beta II (PKC β II) expression in >1000 tumors and assessed the utility of PKC β II immunohistochemistry in the differential diagnosis of Ewing sarcoma. Tumors harboring EWSR1 :: FLI1 (n=26), EWSR1 :: ERG , EWSR1 :: ETV4 (n=1), and FUS :: ERG (n=6) fusions were evaluated, revealing strong diffuse immunoreactivity, although a patchy pattern was seen in 3 cases. Undifferentiated round cell sarcomas (n=46), including BCOR -, CIC -, NFATC2 -, NUTM1 -, and PATZ1 rearranged/fusion-sarcomas were negative. Two of the 130 synovial sarcomas, including 1 with a poorly differentiated morphology, showed diffuse, moderate-to-strong positivity. One of the 26 poorly differentiated carcinomas from the head and neck region, probably small cell lung carcinoma metastasis, showed strong PKC β II expression. Neuroblastomas (>50%) expressed PKC β II, although none showed a strong diffuse pattern. Diffuse moderate-to-strong immunoreactivity was observed in 2 sarcomatoid mesotheliomas and 2 metastatic melanomas. Diffuse but weak staining was observed in 73% (11/15) of the T-cell lymphoblastic lymphomas, including 10 CD99-positive cases. Similarly, weak predominantly patchy staining was seen in half (40/80) of other non-Hodgkin lymphomas and sporadically in embryonal rhabdomyosarcoma, Merkel cell carcinoma, small cell lung carcinoma, and Wilms tumor. Thus, diffuse and strong PKC β II immunoreactivity appears to be a reliable diagnostic marker for distinguishing classic Ewing sarcoma from histologic mimics.

• Klíčová slova
• Ewing sarcoma, Ewing-like sarcoma, immunohistochemistry, oncogenic fusions, undifferentiated round cell sarcoma,
• MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• dospělí MeSH
• Ewingův sarkom * diagnóza   genetika   enzymologie   patologie   MeSH
• imunohistochemie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové biomarkery * analýza   genetika   MeSH
• nádory kostí * diagnóza   enzymologie   genetika   patologie   MeSH
• prediktivní hodnota testů MeSH
• protein EWS vázající RNA MeSH
• proteinkinasa C beta * analýza   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• EWSR1 protein, human MeSH Prohlížeč
• nádorové biomarkery * MeSH
• PRKCB protein, human MeSH Prohlížeč
• protein EWS vázající RNA MeSH
• proteinkinasa C beta * MeSH

BACKGROUND: Periprosthetic infections pose a devastating complication in skeletally immature patients treated for an orthopaedic oncological condition. Reconstructive approaches to revision procedures are often limited, and many cases still require amputation. CASE PRESENTATION: In this report, we present our unique experience with the bio-expandable MUTARS® BioXpand prosthesis, utilized during the second stage of a revision surgery in an adolescent female patient. Initially, the patient underwent reconstruction using a conventional endoprosthesis following the resection of a high-grade distal femur osteosarcoma; however, she developed a deep infection six months later. During a two-stage revision procedure, the infection was successfully eradicated at the cost of loss of growth potential at also the site of proximal tibia. The initial 5 cm limb-length discrepancy was restored through the application of bioexpandable endoprosthesis, which allowed for an 8 cm gain in bone stock. At the last follow-up appointment, the patient was fully weight-bearing and demonstrated excellent clinical outcomes, with no evidence of infection or tumor recurrence. CONCLUSION: This successful limb-salvage procedure indicates that bioexpandable endoprosthesis may serve as a viable and effective reconstructive option in revision surgery for skeletally immature individuals.

• Klíčová slova
• Bioexpandable prosthesis, Knee revision, Lengthening nail, Limb-salvage surgery, MUTARS® BioXpand, Periprosthetic infection, Precise nail,
• MeSH
• femur * chirurgie   patologie   MeSH
• infekce spojené s protézou * chirurgie   etiologie   MeSH
• lidé MeSH
• mladiství MeSH
• nádory femuru * chirurgie   patologie   MeSH
• nádory kostí * chirurgie   patologie   MeSH
• osteosarkom * chirurgie   patologie   MeSH
• prognóza MeSH
• reoperace MeSH
• záchrana končetiny * metody   MeSH
• zákroky plastické chirurgie * metody   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Specific patterns of mitochondrial dynamics have been repeatedly reported to promote drug resistance in cancer. However, whether targeting mitochondrial fission- and fusion-related proteins could be leveraged to combat multidrug-resistant pediatric sarcomas is poorly understood. Here, we demonstrated that the expression and activation of the mitochondrial fission mediator DRP1 are affected by chemotherapy exposure in common pediatric sarcomas, namely, rhabdomyosarcoma and osteosarcoma. Unexpectedly, decreasing DRP1 activity through stable DRP1 knockdown neither attenuated sarcoma drug resistance nor affected growth rate or mitochondrial network morphology. The minimal impact on sarcoma cell physiology, along with the up-regulation of fission adaptor proteins (MFF and FIS1) detected in rhabdomyosarcoma cells, suggests an alternative DRP1-independent mitochondrial fission mechanism that may efficiently compensate for the lack of DRP1 activity. By exploring the upstream mitophagy and mitochondrial fission regulator, AMPKα1, we found that markedly reduced AMPKα1 levels are sufficient to maintain AMPK signaling capacity without affecting chemosensitivity. Collectively, our findings challenge the direct involvement of DRP1 in pediatric sarcoma drug resistance and highlight the complexity of yet-to-be-characterized noncanonical regulators of mitochondrial dynamics.

• MeSH
• chemorezistence * genetika   MeSH
• dynaminy * metabolismus   genetika   MeSH
• GTP-fosfohydrolasy metabolismus   genetika   MeSH
• lidé MeSH
• membránové proteiny metabolismus   genetika   MeSH
• mitochondriální dynamika * účinky léků   MeSH
• mitochondriální proteiny * metabolismus   genetika   MeSH
• mitochondrie * metabolismus   účinky léků   MeSH
• mitofagie účinky léků   genetika   MeSH
• nádorové buněčné linie MeSH
• osteosarkom metabolismus   patologie   farmakoterapie   genetika   MeSH
• proteiny asociované s mikrotubuly metabolismus   genetika   MeSH
• protinádorové látky farmakologie   MeSH
• rhabdomyosarkom metabolismus   genetika   patologie   MeSH
• sarkom * metabolismus   genetika   farmakoterapie   patologie   MeSH
• signální transdukce účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNM1L protein, human MeSH Prohlížeč
• dynaminy * MeSH
• FIS1 protein, human MeSH Prohlížeč
• GTP-fosfohydrolasy MeSH
• membránové proteiny MeSH
• Mff protein, human MeSH Prohlížeč
• mitochondriální proteiny * MeSH
• proteiny asociované s mikrotubuly MeSH
• protinádorové látky MeSH

PURPOSE: Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep-learning strategies on histology samples to predict outcome for osteosarcoma in the neoadjuvant setting. EXPERIMENTAL DESIGN: Our study relies on a training cohort from New York University (NYU; New York, NY) and an external cohort from Charles University (Prague, Czechia). We trained and validated the performance of a supervised approach that integrates neural network predictions of necrosis/tumor content and compared predicted overall survival (OS) using Kaplan-Meier curves. Furthermore, we explored morphology-based supervised and self-supervised approaches to determine whether intrinsic histomorphologic features could serve as a potential marker for OS in the neoadjuvant setting. RESULTS: Excellent correlation between the trained network and pathologists was obtained for the quantification of necrosis content (R2 = 0.899; r = 0.949; P < 0.0001). OS prediction cutoffs were consistent between pathologists and the neural network (22% and 30% of necrosis, respectively). The morphology-based supervised approach predicted OS; P = 0.0028, HR = 2.43 (1.10-5.38). The self-supervised approach corroborated the findings with clusters enriched in necrosis, fibroblastic stroma, and osteoblastic morphology associating with better OS [log-2 hazard ratio (lg2 HR); -2.366; -1.164; -1.175; 95% confidence interval, (-2.996 to -0.514)]. Viable/partially viable tumor and fat necrosis were associated with worse OS [lg2 HR; 1.287; 0.822; 0.828; 95% confidence interval, (0.38-1.974)]. CONCLUSIONS: Neural networks can be used to automatically estimate the necrosis to tumor ratio, a quantitative metric predictive of survival. Furthermore, we identified alternate histomorphologic biomarkers specific to the necrotic and tumor regions, which could serve as predictors.

• MeSH
• deep learning * MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• konvoluční neuronové sítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory kostí * mortalita   patologie   terapie   MeSH
• nekróza patologie   MeSH
• neoadjuvantní terapie MeSH
• neuronové sítě * MeSH
• osteosarkom * mortalita   patologie   terapie   MeSH
• prognóza MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Sarcomas are rare cancers with many subtypes in soft tissues, bone and cartilage. International survival trends in these cancers are not well known. We present 50-year survival trends for soft tissue sarcoma (STS) and bone sarcoma (BS) in Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE). METHODS: Relative 1-, 5/1 conditional- and 5-year survival data were obtained from the NORDCAN database for years 1971-20. We additionally estimated annual changes in survival rates and determined significant break points. RESULTS: In the last period, 2016-20, 5-year survival in STS was best for NO men (74.6%) and FI women (71.1%). For the rarer BS, survival rates for SE men (72.0%) and DK women (71.1%) were best. Survival in BS was lower than that in STS in 1971-75 and the difference remained in 2016-20 for men, but for women the rates were almost equal. Sex- and country-specific differences in survival in STS were small. The 50-year improvement in 5-year survival in STS was highest in NO men, 34.0 % units and FI women, 30.0 % units. The highest improvements in BS were in SE men 26.2 % units and in FI women 29.2 % units. CONCLUSIONS: The steady development in survival over the half century suggests contribution by stepwise improvements in diagnostics, treatment and care. The 10-15% mortality in the first year probably indicates diagnostic delays which could be improved by organizing patient pathways for aggressive rare diseases. Early diagnosis would also reduce metastatic disease and breakthroughs in treatment are a current challenge.

• Klíčová slova
• Conditional survival, Diagnostics, Incidence, Relative survival, Treatment,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory kostí * mortalita   epidemiologie   patologie   MeSH
• nádory měkkých tkání mortalita   epidemiologie   patologie   MeSH
• osteosarkom mortalita   epidemiologie   patologie   terapie   MeSH
• registrace MeSH
• sarkom * mortalita   epidemiologie   patologie   terapie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Finsko epidemiologie   MeSH
• Skandinávie a severské státy epidemiologie   MeSH

Recent studies have highlighted the significant role of 5-hydroxymethylcytosine (5hmC) in carcinogenesis. However, the specific role of 5hmC in osteosarcoma (OS) remains largely unexplored. The-re-fore, this study aimed to investigate the function of 5hmC and TET3 in OS. In this study, we found a decreased total level of 5hmC in OS tissues. The expression of the TET3 protein was also decreased in OS. Importantly, the decreased levels of TET3 were associated with a decreased disease-free survival (DFS) rate in patients. To investigate the role of TET3 and 5hmC in OS, we manipulated the levels of TET3 in MG-63 cells. Silencing TET3 in these cells resulted in a twofold increase in proliferation. Additio-nally, the level of 5hmC decreased in these cells. Con-versely, over-expression of TET3 in MG-63 cells led to the expected inhibition of proliferation and invasion, accompanied by an increase in 5hmC levels. In conclusion, both 5hmC and TET3 protein levels were decreased in OS. Additionally, the over-expression of TET3 inhibited the proliferation of MG-63 cells, while the suppression of TET3 had the opposite effect. These findings suggest that decreased levels of 5hmC and TET3 may serve as potential markers for OS.

• Klíčová slova
• 5hmC, Osteosarcoma, TET3,
• MeSH
• 5-methylcytosin * analogy a deriváty   metabolismus   MeSH
• demetylace DNA * MeSH
• dioxygenasy * metabolismus   MeSH
• epigeneze genetická * MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory kostí genetika   metabolismus   patologie   MeSH
• osteosarkom genetika   metabolismus   patologie   MeSH
• proliferace buněk * MeSH
• protoonkogenní proteiny metabolismus   genetika   MeSH
• regulace genové exprese u nádorů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 5-hydroxymethylcytosine MeSH Prohlížeč
• 5-methylcytosin * MeSH
• dioxygenasy * MeSH
• protoonkogenní proteiny MeSH
• TET3 protein, human MeSH Prohlížeč

The aim of this study was to develop multifunctional magnetic poly(ε-caprolactone) (PCL) mats with antibacterial properties for bone tissue engineering and osteosarcoma prevention. To provide good dispersion of magnetic iron oxide nanoparticles (IONs), they were first grafted with PCL using a novel three-step approach. Then, a series of PCL-based mats containing a fixed amount of ION@PCL particles and an increasing content of ascorbic acid (AA) was prepared by electrospinning. AA is known for increasing osteoblast activity and suppressing osteosarcoma cells. Composites were characterized in terms of morphology, mechanical properties, hydrolytic stability, antibacterial performance, and biocompatibility. AA affected both the fiber diameter and the mechanical properties of the nanocomposites. All produced mats were nontoxic to rat bone marrow-derived mesenchymal cells; however, a composite with 5 wt.% of AA suppressed the initial proliferation of SAOS-2 osteoblast-like cells. Moreover, AA improved antibacterial properties against Staphylococcus aureus and Escherichia coli compared to PCL. Overall, these magnetic composites, reported for the very first time, can be used as scaffolds for both tissue regeneration and osteosarcoma prevention.

• Klíčová slova
• L‐ascorbic acid, iron oxide nanoparticles, nanocomposites, poly(ε‐caprolactone),
• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• Escherichia coli účinky léků   MeSH
• kosti a kostní tkáň MeSH
• krysa rodu Rattus MeSH
• kyselina askorbová * chemie   farmakologie   MeSH
• lidé MeSH
• magnetické nanočástice chemie   MeSH
• nádorové buněčné linie MeSH
• nanokompozity chemie   MeSH
• osteoblasty metabolismus   cytologie   MeSH
• osteosarkom patologie   MeSH
• polyestery * chemie   MeSH
• Staphylococcus aureus * účinky léků   růst a vývoj   MeSH
• testování materiálů MeSH
• tkáňové inženýrství * MeSH
• tkáňové podpůrné struktury chemie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• kyselina askorbová * MeSH
• magnetické nanočástice MeSH
• polycaprolactone MeSH Prohlížeč
• polyestery * MeSH

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and biobanking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientific progress, promote collaboration, and improve outcomes.

• MeSH
• banky biologického materiálu MeSH
• Ewingův sarkom * terapie   patologie   diagnóza   MeSH
• lidé MeSH
• nádorové biomarkery MeSH
• nádory kostí * terapie   patologie   MeSH
• odběr biologického vzorku * metody   normy   MeSH
• osteosarkom * terapie   patologie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• nádorové biomarkery MeSH