Impact of CDK Inhibitors on Expression in Chordoma Cell Lines Including the First Stable Cell Line of a High-Grade Chordoma.

Chordomas are very rare malignant neoplasms of the bone occurring almost exclusively along the spine. As the tumours are thought to arise from notochordal remnants, the vast majority of chordomas express the gene, resulting in detectable nuclear amounts of its gene product brachyury. This T-Box transcription factor is commonly recognised as being essential in chordoma cells, and limiting expression is thought to be the key factor in controlling this tumour.

[Giant cell tumor of bone-an update].

In the past few years, numerous new insights have been gained in the field of giant cell tumor of bone (GCTB). On the one hand, the detection of the highly characteristic histone mutation in the H3F3A gene in GCTB is becoming increasingly important in diagnostics in differentiating GCTB from other giant cell-rich lesions of bone as well as for defining rare variants of GCTB without osteoclastic giant cells. On the other hand, the effects of the H3F3A mutation were shown to have an impact on the epigenetic profile of tumor-driving stromal cells, providing new insights into tumorigenesis of GCTB.

Histomorphometric Analysis of 38 Giant Cell Tumors of Bone after Recurrence as Compared to Changes Following Denosumab Treatment.

Giant cell tumor of bone (GCTB) is an osteolytic tumor driven by an -mutated mononuclear cell with the accumulation of osteoclastic giant cells. We analyzed tissue from 13 patients with recurrence and 25 patients with denosumab therapy, including two cases of malignant transformation. We found a decrease in the total number of cells ( = 0.

Giant Cells of Various Lesions Are Characterised by Different Expression Patterns of HLA-Molecules and Molecules Involved in the Cell Cycle, Bone Metabolism, and Lineage Affiliation: An Immunohistochemical Study with a Review of the Literature.

Giant cells (GCs) are thought to originate from the fusion of monocytic lineage cells and arise amid multiple backgrounds. To compare GCs of different origins, we immunohistochemically characterised the GCs of reactive and neoplastic lesions ( = 47). We studied the expression of 15 molecules including HLA class II molecules those relevant to the cell cycle, bone metabolism and lineage affiliation.

Prognostic Relevance and In Vitro Targeting of Concomitant PTEN and p16 Deficiency in Chordomas.

Chordomas are rare bone tumors arising along the spine. Due to high resistance towards chemotherapy, surgical resection-often followed by radiation therapy-is currently the gold standard of treatment. So far, targeted systemic therapies have not been approved.

Emergence of SARS-CoV-2 spike protein at the vaccination site.

Background: The anti-coronavirus disease 2019 (COVID-19) vaccines are of paramount importance in the fight against the COVID-19 pandemic. Both viral vector- and nucleic acid-based vaccines are known to effectively induce protection against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus by generating high antibody titers and effective T-cell responses to the spike protein they encode. Although these vaccines are being applied worldwide and have been extensively investigated, the immunomorphological events at the vaccination site with respect to SARS-CoV-2 spike protein expression have not yet been described.

Nutrient regime modulates drought response patterns of three temperate tree species.

Against the backdrop of global change, the intensity, duration, and frequency of droughts are projected to increase and threaten forest ecosystems worldwide. Tree responses to drought are complex and likely to vary among species, drought characteristics, and site conditions. Here, we examined the drought response patterns of three major temperate tree species, s.

[Chordoma-An update].

Chordomas are rare malignant tumors of the axial skeleton with notochordal differentiation. From a morphological point of view, chordomas display a broad spectrum ranging from the classical, conventional form not otherwise specified (NOS) to forms with hepatoid or renal carcinoma-like differentiation or even poorly or dedifferentiated variants. The detection of brachyury is highly characteristic, though not exclusive.

Epigenetic lockdown of CDKN1A (p21) and CDKN2A (p16) characterises the neoplastic spindle cell component of giant cell tumours of bone.

Giant cell tumour of bone (GCTB) comprises the eponymous osteoclastic multinucleated giant cells eliciting bone lysis, an H3F3A-mutated neoplastic mononucleated fibroblast-like cell population, and H3F3A wild-type mononucleated stromal cells. In this study, we characterised four new cell lines from GCTB. Furthermore, we compared the genome-wide DNA methylation profile of 13 such tumours and three further cell lines with giant cell-rich lesions comprising three H3F3B-mutated chondroblastomas, three USP6-rearranged aneurysmal bone cysts, three non-ossifying fibromas, two hyperparathyroidism-associated brown tumours as well as mesenchymal stem cells, osteoblasts, and osteoclasts.

A Survey of Multigenic Protein-Altering Variant Frequency in Familial Exudative Vitreo-Retinopathy (FEVR) Patients by Targeted Sequencing of Seven FEVR-Linked Genes.

While Inherited Retinal Diseases (IRDs) are typically considered rare diseases, Familial Exudative Vitreo-Retinopathy (FEVR) and Norrie Disease (ND) are more rare than retinitis pigmentosa. We wanted to determine if multigenic protein-altering variants are common in FEVR subjects within a set of FEVR-related genes. The potential occurrence of protein-altering variants in two different genes has been documented in a very small percentage of patients, but potential multigenic contributions to FEVR remain unclear.

CARD9 Forms an Alternative CBM Complex in Richter Syndrome.

Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, mostly diffuse large B-cell lymphoma (DLBCL). Despite intensive therapy, patients with RS have an unfavorable clinical outcome. The detailed pathobiology of Richter transformation still needs to be elucidated.

Molecular features and vulnerabilities of recurrent chordomas.

Background: Tumor recurrence is one of the major challenges in clinical management of chordoma. Despite R0-resection, approximately 50% of chordomas recur within ten years after initial surgery. The underlying molecular processes are poorly understood resulting in the lack of associated therapeutic options.

Ciprofloxacin enhances phototoxicity of 5-aminolevulinic acid mediated photodynamic treatment for chordoma cell lines.

Background: Chordoma are uncommon aggressive tumors of the skeleton. Surgical resection is often subtotal and adjuvant treatment possibilities are limited as chordomas are highly chemo- and radioresistant. In the present study we examined the impact of 5-ALA PDT on different human chordoma cell lines.

H3F3A-mutated giant cell tumour of bone without giant cells-clinical presentation, radiology and histology of three cases.

Aims: Giant cell tumour of bone (GCTB) is histologically defined as a lesion containing reactive giant cells and a neoplastic mononuclear cell population; in up to 92% of cases, GCTB is characterised by a specific mutation of the histone gene H3F3A. The cellular composition ranges from giant-cell-rich to giant-cell-poor. The diagnosis of GCTB can be challenging, and several other lesions need to be excluded, e.

Profiling of three H3F3A-mutated and denosumab-treated giant cell tumors of bone points to diverging pathways during progression and malignant transformation.

Giant cell tumor of bone (GCTB) is a locally aggressive lesion of intermediate malignancy. Malignant transformation of GCTB is a rare event. In 2013, the humanized monoclonal antibody against receptor activator of nuclear factor-κb-Ligand (RANKL) denosumab was approved for treatment of advanced GCTB.

U-RT1 - A new model for Richter transformation.

The advent of highly effective treatments targeting the disease biology of chronic lymphocytic leukemia (CLL) has transformed the therapeutic field tremendously. However, transformation into an aggressive B-cell lymphoma, called Richter syndrome (RS), remains highly challenging since the treatment options for this condition are still insufficient. Exploratory drug testing and experimental studies are restricted by the lack of satisfactory models.

U-DCS: characterization of the first permanent human dendritic sarcoma cell line.

A dendritic cell sarcoma cell line, U-DCS, was established from a dendritic cell sarcoma in a 53-year-old Caucasian male patient. Since its establishment, U-DCS has maintained stable phenotypic characteristics in vitro and has a doubling time of approximately 2 days under standard culture conditions. U-DCS is growing with typical dendritic cell morphology in tissue and expresses the dendritic cell sarcoma immunophenotypic markers S100 protein, MHCI, MHCII, and vimentin.

Clostridial C3 Toxins Enter and Intoxicate Human Dendritic Cells.

C3 protein toxins produced by and are mono-ADP-ribosyltransferases, which specifically modify the GTPases Rho A/B/C in the cytosol of monocytic cells, thereby inhibiting Rho-mediated signal transduction in monocytes, macrophages, and osteoclasts. C3 toxins are selectively taken up into the cytosol of monocytic cells by endocytosis and translocate from acidic endosomes into the cytosol. The C3-catalyzed ADP-ribosylation of Rho proteins inhibits essential functions of these immune cells, such as migration and phagocytosis.

The impact of SOCS1 mutations in diffuse large B-cell lymphoma.

Mutations in SOCS1 are frequent in primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma. In the latter, SOCS1 mutations affect the length of the encoded protein (major mutations) and are associated with shorter patient survival. Two independent studies examined the prognostic impact of SOCS1 mutations in diffuse large B-cell lymphoma (DLBCL) and showed differing results.

Characterization of Three Novel H3F3A-mutated Giant Cell Tumor Cell Lines and Targeting of Their Wee1 Pathway.

The giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor that is composed of mononuclear stroma cells, scattered macrophages, and multinucleated osteoclast-like giant cells which cause pathologic osteolysis. The stroma cells represent the neoplastic population of the tumor and are characterized by the H3F3A mutation G34W. This point mutation is regarded as the driver mutation of GCTB.

Analysis of the CDK4/6 Cell Cycle Pathway in Leiomyosarcomas as a Potential Target for Inhibition by Palbociclib.

Leiomyosarcoma (LMS) is characterized by high genomic complexity, and to date, no specific targeted therapy is available. In a genome-wide approach, we profiled genomic aberrations in a small cohort of eight primary tumours, two relapses, and eight metastases across nine different patients. We identified CDK4 amplification as a recurrent alteration in 5 out of 18 samples (27.

[H3F3A mutated multicentric giant cell tumor of bone : A very rare primary bone disease].

This article presents the case of a metachronic multicentric giant cell tumor of bone (GCTB). The patient obtained his first diagnosis of GCTB in the left humerus at the age of 47 years. Furthermore, he suffered from a GCTB in the head of his 4th left metacarpal bone and from a recurrence of the latter.

Restoring functional neurofibromin by protein transduction.

In Neurofibromatosis 1 (NF1) germ line loss of function mutations result in reduction of cellular neurofibromin content (NF1+/-, NF1 haploinsufficiency). The Ras-GAP neurofibromin is a very large cytoplasmic protein (2818 AA, 319 kDa) involved in the RAS-MAPK pathway. Aside from regulation of proliferation, it is involved in mechanosensoric of cells.