Imbalanced redox homeostasis, involving either oxidative stress or reductive stress, can profoundly impact cellular functions, contributing to various diseases. While the implications of oxidative stress in the adverse effects of nanoparticles have been extensively studied, our comprehension of reductive stress within the context of nano-redox system interactions remains limited. Here we illuminate a domino effect initiated by the dehydrogenase-like activity of transition metal borides. Specifically, seven transition metal borides were identified to emulate the enzymatic activity of natural dehydrogenases, resulting in heightened levels of reductive constituents within critical biological redox pairs in cells. Mass cytometry analysis provides compelling evidence that reductive stress initiates an immunosuppressive environment within lung tissues, promoting the metastasis of breast cancer cells to the lungs. In summary, our study unveils the chemical basis of nano-induced reductive stress and establishes a mechanistic axis that interlinks dehydrogenase-like activity, reductive stress, immunosuppression and tumour metastasis.

• MeSH
• katalýza MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory plic sekundární   imunologie   MeSH
• nádory prsu patologie   imunologie   MeSH
• oxidace-redukce MeSH
• oxidační stres * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Early surgical treatment of giant cell tumour of the bone has very good functional outcomes with a relatively low risk of local recurrence and metastatic spread.In case of a pathologic fracture, extraosseous extension, and tumor location in an anatomically difficult area, surgical treatment may represent a big challenge with an uncertain functional outcome.Our case report presents a 35-year-old patient with a delayed diagnosis of giant cell tumor of the proximal radius of the dominant limb, with pulmonary metastases. Following neoadjuvant Denosumab therapy, with a major treatment effect on both the primary tumor and pulmonary metastases, we performed a wide resection and combined biological reconstruction with fibular autograft, radial head endoprosthesis, and comprehensive elbow ligament reconstruction.At 24 months after surgery, the patient is self-sufficient, capable of more physically demanding work, with a satisfactory functional outcome of reconstruction (MSTS 66.6%, TESS 69%), with no signs of local recurrence and regression of pulmonary metastases at 18 months after the last administration of Denosumab.

• Klíčová slova
• Denosumab, biological reconstruction., giant cell tumor of the bone, proximal radius, wide resection,
• MeSH
• denosumab terapeutické užití   MeSH
• dospělí MeSH
• fibula transplantace   chirurgie   MeSH
• inhibitory kostní resorpce terapeutické užití   MeSH
• lidé MeSH
• nádory kostí * chirurgie   sekundární   MeSH
• nádory plic * chirurgie   sekundární   MeSH
• obrovskobuněčný nádor kosti * chirurgie   MeSH
• radius * chirurgie   MeSH
• transplantace kostí metody   MeSH
• zákroky plastické chirurgie * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• denosumab MeSH
• inhibitory kostní resorpce MeSH

Breast cancer metastases are the main reason for women´s highest cancer mortality. Even though tumor cell dissemination via circulating tumor cells (CTC) released from the primary site is a very ineffective process, distant metastases appear in 46% of triple-negative breast cancer (TNBC) patients corresponding to the disease aggressiveness. Laboratory models for functional testing which mimic the spread of metastatic cells are needed for efficient investigation of the underlying mechanisms and therapeutic intervention. Here, we describe novel isogenic variants LMC3 and CTC3 of human TNBC cell line MDA-MB-231 that were derived by repeated injection of tumor cells into the tail vein of immunodeficient mice and subsequent selection of metastatic cells from lung metastases. These variants have increased migration potential, altered expression profiles, and elevated tumorigenic potential. Moreover, cell line CTC3 readily produces metastases in the lungs and bone marrow and detectable viable circulating tumor cells in the blood. This model enables rapid and cost-efficient strategies for biomarker exploration and novel intervention approaches to limit the CTC presence in the blood and hence tumor dissemination.

• MeSH
• biologické markery MeSH
• lidé MeSH
• metastázy nádorů MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádorové cirkulující buňky * metabolismus   MeSH
• nádory plic * sekundární   MeSH
• triple-negativní karcinom prsu * genetika   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH

BACKGROUND/AIM: The lungs are the second most common site of cancer dissemination. The aim of this study was to analyze a cohort of patients operated for pulmonary metastases from colorectal carcinoma over a period of 18 years. PATIENTS AND METHODS: In a group of 104 patients, relations were sought between overall survival or disease-free survival and preoperative levels of selected biomarkers, number of metastases and the condition of the intrathoracic lymphatic nodes. Median observation period was 63 months. RESULTS: The 5-year survival rate was 54.3%. Risk of disease progression and risk of death increases in case of occurrence of 2 or more metastases, affection of intrathoracic lymph nodes and levels of CA 19-9, TPS or CEA above cut-off value. CONCLUSION: Prognostic factors that determine overall survival as well as disease-free survival are the number of metastases, the condition of intrathoracic lymphatic nodes and the preoperative levels of biomarkers.

• Klíčová slova
• Lung cancer, biomarker, colorectal carcinoma, prognosis, pulmonary metastases, surgery,
• MeSH
• dospělí MeSH
• kolorektální nádory komplikace   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory plic sekundární   chirurgie   MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Spitzoid melanocytic lesions represent a heterogeneous group of proliferations with ambiguous and overlapping terminology. The exact distinction of a Spitz nevus from a Spitzoid melanoma can be very difficult or, in some cases, impossible. Among the Spitzoid lesions, there is a lesion termed an atypical Spitz tumour (AST) that has intermediate histopathologic features between those of a Spitz nevus and a Spitzoid melanoma and thus uncertain malignant potential. There are several rare cases of patients with a Spitzoid melanoma initially misdiagnosed as a Spitz nevus or an AST with fatal consequences. It is, therefore, advised to perform a molecular characterization in cases where uncertain skin lesions are presented, as it may provide extended set of information with a possible impact on the treatment options. Furthermore, preventive measures, such as regular physical and skin examinations, as well as thorough scheduling of individual follow-up visits, are essential in patients with potentially malignant skin nevi. CASE REPORT: We report a case of a young adult female with a history of AST excision with a negative sentinel lymph node biopsy (SLNB) and insufficient follow-up. Four years after the primary dermatological diagnosis, she presented with a giant tumour in the right hemithorax. Radical en bloc resection of the tumour with right pneumonectomy and resection of the pericardium with reconstruction of the pericardium using mesh was performed. A definitive histopathological examination revealed a metastatic melanoma. The association of the previously diagnosed AST and subsequent appearance of melanoma metastases led to a retrospective re-evaluation of the initial lesion. The suspected diagnosis of Spitzoid melanoma, however, was not confirmed. Moreover, the molecular examination revealed a major discordance between the initial lesion and the lung tumour, which most likely excluded the possible association of the lung metastasis with the initial skin lesion. The initial skin lesion was a BRAF-mutant melanoma with Spitzoid features and termed as AST, while the giant lung metastasis was NRAS-mutant melanoma. The subsequent postoperative course was complicated by the appearance of brain metastases that were stereotactically irradiated. Nevertheless, despite complex specialised medical care, the patient's clinical condition rapidly deteriorated. By this time, no active oncological treatment was possible. The patient was delegated to local hospice for palliative care six months after the surgery and died three weeks later. CONCLUSIONS: Our patient was surgically treated at the age of 20 for AST and died four years later of metastatic NRAS-mutant melanoma most likely of different occult origin. Molecular characterization, as well as the close clinical follow-up should be always precisely performed in patients with uncertain skin lesions, such as AST.

• Klíčová slova
• Atypical spitz tumour, Case report, Conventional melanoma, Metastasis, Molecular analysis, Spitz nevus, Spitzoid melanoma,
• MeSH
• epiteloidní a vřetenobuněčný névus genetika   patologie   MeSH
• GTP-fosfohydrolasy genetika   MeSH
• lidé MeSH
• maligní melanom kůže MeSH
• melanom genetika   sekundární   MeSH
• membránové proteiny genetika   MeSH
• mladý dospělý MeSH
• mnohočetné primární nádory genetika   patologie   MeSH
• mutace MeSH
• nádory kůže genetika   patologie   sekundární   MeSH
• nádory plic sekundární   MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• GTP-fosfohydrolasy MeSH
• membránové proteiny MeSH
• NRAS protein, human MeSH Prohlížeč
• protoonkogenní proteiny B-Raf MeSH

The incidence of cutaneous malignant melanoma has been steadily increasing worldwide for several decades. This phenomenon seems to follow the trend observed in many types of malignancies caused by multiple significant factors, including ageing. Despite the progress in cutaneous malignant melanoma therapeutic options, the curability of advanced disease after metastasis represents a serious challenge for further research. In this review, we summarise data on the microenvironment of cutaneous malignant melanoma with emphasis on intercellular signalling during the disease progression. Malignant melanocytes with features of neural crest stem cells interact with non‑malignant populations within this microenvironment. We focus on representative bioactive factors regulating this intercellular crosstalk. We describe the possible key factors and signalling cascades responsible for the high complexity of the melanoma microenvironment and its premetastatic niches. Furthermore, we present the concept of melanoma early becoming a systemic disease. This systemic effect is presented as a background for the new horizons in the therapy of cutaneous melanoma.

• Klíčová slova
• melanoma, cancer microenvironment, cancer-associated fibroblast, cytokine, chemokine, growth factor,
• MeSH
• kůže cytologie   patologie   MeSH
• lidé MeSH
• melanocyty patologie   MeSH
• melanom sekundární   MeSH
• mezibuněčná komunikace * MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• nádorové mikroprostředí * MeSH
• nádory kůže patologie   MeSH
• nádory mozku sekundární   MeSH
• nádory plic sekundární   MeSH
• progrese nemoci MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

PURPOSE: The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS: From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS: Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION: In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

• MeSH
• adjuvantní radioterapie MeSH
• autologní transplantace MeSH
• časové faktory MeSH
• dítě MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• Ewingův sarkom mortalita   sekundární   terapie   MeSH
• hodnocení rizik MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory kostí mortalita   patologie   terapie   MeSH
• nádory plic mortalita   sekundární   terapie   MeSH
• neoadjuvantní terapie * škodlivé účinky   mortalita   MeSH
• pneumektomie MeSH
• předškolní dítě MeSH
• progrese nemoci MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   škodlivé účinky   MeSH
• rizikové faktory MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   mortalita   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

The association between kidney and liver polycystosis and arterial aneurysms is well documented. However, it remains unclear whether these patients are at increased risk of malignant transformation. In this article, we describe a case of a primary angiosarcoma of the femoral artery with metastatic spread into the lungs and hilar lymph node arising in a 74-year-old man with kidney and liver polycystosis and multiple arterial aneurysms.

• Klíčová slova
• Aneurysm, Angiosarcoma, Femoral artery, Polycystic kidney,
• MeSH
• aneurysma komplikace   diagnóza   MeSH
• arteria femoralis * chemie   patologie   MeSH
• biopsie MeSH
• cysty komplikace   diagnóza   MeSH
• hemangiosarkom chemie   komplikace   sekundární   MeSH
• imunohistochemie MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• nádorové biomarkery analýza   MeSH
• nádory plic chemie   komplikace   sekundární   MeSH
• nemoci jater komplikace   diagnóza   MeSH
• polycystická choroba ledvin komplikace   diagnóza   MeSH
• senioři MeSH
• vaskulární nádory chemie   komplikace   patologie   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• systematický přehled MeSH
• Názvy látek
• nádorové biomarkery MeSH

INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) is the most common kidney tumor. If feasible, metastasectomy is preferably indicated in metastatic disease. OBJECTIVE: The aim of this study was to determine the outcome of patients after pulmonary metastasectomy (PM). METHODS: PM for ccRCC was performed in 35 patients in the period of January 2001-2019. Clinical characteristics, type of surgery, histopathology results, and follow-up data were recorded. Progression-free survival (PFS) after PM and overall survival (OS) were defined as outcome endpoints. RESULTS: A total of 77 PMs were performed in 35 patients after nephrectomy for ccRCC. The mean size of pulmonary metastasis was 19.0 mm (4-90). With a median follow-up after PM of 79.2 months, the 3- and 5-year OS rates were 63.5 and 44.9%, respectively. The only statistically significant prognostic factor affecting both PFS (p = 0.019) and OS (p = 0.015) was the dimension of pulmonary metastases. CONCLUSIONS: The prognosis of metastatic ccRCC is generally poor, particularly in cases of larger size of metastasis. PM might improve the individual prognosis of patients with lung metastasis even in cases with higher number of metastases, bilaterality, synchronous metastasis, or a short progression-free interval after nephrectomy.

• Klíčová slova
• Clear cell renal cell carcinoma, Metastasectomy, Pulmonary metastasis,
• MeSH
• časové faktory MeSH
• karcinom z renálních buněk sekundární   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázektomie * MeSH
• nádory ledvin patologie   chirurgie   MeSH
• nádory plic sekundární   chirurgie   MeSH
• nefrektomie MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Growing teratoma syndrome (GTS) is an uncommon clinical finding in patients treated for testicular cancer. It is diagnosed during or after chemotherapy as an expanding tumour mass not responding to the treatment while the serum tumour markers are within the normal range. Pathological evaluation of resected tissue confirms the structures of benign mature teratoma. CASE: Authors report a case of metastatic germ cell testicular cancer treated with 2 lines of chemotherapy and everolimus, that had finally been subjected for the resection of voluminous metastatic masses. We give a brief overview of current records concerning clinical management of GTS, and support the major role of surgical treatment in GTS. RESULTS: Patient with metastatic mixed germ cell tumour of testis underwent a radical orchiectomy and completed the 1st line treatment with BEP (bleomycin, etoposide, cisplatin) regimen. Radiographic restaging showed considerable disease progression to the retroperitoneum and supraclavicular lymph nodes. Second-line treatment with VIP (etoposide, ifosfamide, cisplatin) did not reverse the progression and the patient was consulted at our institute. Following the enrolment to the clinical study with everolimus, the patient exhibited continual metastatic growth in contrast to serum markers decrease. GTS was confirmed after resection of enormous retroperitoneal tumour mass, as well as from the specimen obtained from the subsequent supraclavicular and hepatal metastasectomy. The patient attained complete remission and has been closely observed over the last 31 months since the last surgery. CONCLUSION: GTS is resistant to chemotherapy and radiation and complete surgical resection results in excellent disease control. Clinicians should be aware of this infrequent presentation of testicular tumours, to ensure the timely diagnosis and the appropriate surgical removal without any delay. Despite the great extent and vital vasculature encasement, surgery may be feasible and successful, as we report in our case, consistently with the published data.

• Klíčová slova
• prognosis, surgery, teratoma, testicular neoplasms,
• MeSH
• dospělí MeSH
• germinální a embryonální nádory patologie   chirurgie   MeSH
• lidé MeSH
• management nemoci MeSH
• mladý dospělý MeSH
• nádory jater sekundární   chirurgie   MeSH
• nádory plic sekundární   chirurgie   MeSH
• prognóza MeSH
• retroperitoneální nádory patologie   chirurgie   MeSH
• teratom patologie   chirurgie   MeSH
• testikulární nádory patologie   chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH