Histiocytic Sarcoma with an Unusual Clinical Manifestation Imitating Malignant Vascular Tumor: A Case Report.

BACKGROUND Histiocytic sarcoma is a rare malignant hematopoietic neoplasm with morphologic and immunohistochemical features of histiocytic differentiation, usually with unfavorable prognosis. Despite aggressive biological behavior, in subgroup of patients with localized disease, the prognosis can be very good. Few publications are available on localized cases of histiocytic sarcoma.

Development and extensive analytical validation of deep amplicon sequencing for detecting KRAS and NRAS mutations in metastatic colorectal cancer samples.

The presence of wild-type RAS alleles, as determined by genotyping codons 12, 13, 59, 61, 117, and 146, is a prerequisite for personalized anti-EGFR treatment of metastatic colorectal cancer (mCRC) patients. Here we describe analytical validation of in-house developed massively parallel sequencing technology (MPS) in comparison to the in vitro diagnostics (IVD) certified qPCR method. DNA extracted from FFPE samples from CRC patients (n=703) and reference standards (n=33) were tested for KRAS and NRAS mutations in 6 codons of exons 2, 3, and 4 using deep amplicon sequencing (DAS) on a MiSeq benchtop sequencer (Illumina).

[Use of PCR for diagnosing cat-scratch disease].

Objective: The diagnosis of Bartonella henselae by polymerase chain reaction (PCR) in lymph nodes removed in 10 patients with serologically confirmed evidence cat-scratch disease.

Material And Methods: The 2015-2018 group consisted of 10 patients with serologically confirmed cat-scratch disease, all of them having positive IgG antibodies and 6 patients also positive IgM antibodies against B. henselae.

IDH Mutation Analysis in Glioma Patients by CADMA Compared with SNaPshot Assay and two Immunohistochemical Methods.

Mutations in IDH1/2 genes are a marker of good prognosis for glioma patients, associated with low grade gliomas and secondary glioblastomas. Immunohistochemistry and Sanger sequencing are current standards for IDH1/2 genotyping while many other methods exist. The aim of this study was to validate Competitive amplification of differentially melting amplicons (CADMA) PCR for IDH genotyping by comparison with SNaPshot assay and two immunohistochemical methods.

[Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing].

Background: Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status.

Tumor growth accelerated by chemotherapy-induced senescent cells is suppressed by treatment with IL-12 producing cellular vaccines.

Standard-of-care chemo- or radio-therapy can induce, besides tumor cell death, also tumor cell senescence. While senescence is considered to be a principal barrier against tumorigenesis, senescent cells can survive in the organism for protracted periods of time and they can promote tumor development. Based on this emerging concept, we hypothesized that elimination of such potentially cancer-promoting senescent cells could offer a therapeutic benefit.

Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure induce strong immune responses and display therapeutic effects both in murine TC-1 and TRAMP-C2 tumors when combined with docetaxel chemotherapy.

High hydrostatic pressure (HHP) has been shown to induce immunogenic cell death of cancer cells, facilitating their uptake by dendritic cells (DC) and subsequent presentation of tumor antigens. In the present study, we demonstrated immunogenicity of the HHP-treated tumor cells in mice. HHP was able to induce immunogenic cell death of both TC-1 and TRAMP-C2 tumor cells, representing murine models for human papilloma virus-associated tumors and prostate cancer, respectively.

NOD2/CARD15 mutations and the risk of reoperation in patients with Crohns disease.

Introduction: Three NOD2/CARD15 gene variants (3020insC, R702W, G908R) have been identified as genetic risk factors for Crohns disease patients. However the diagnostic and therapeutic relevance for clinical practice remains limited. The aim of this study was to evaluate the association between these variants, the risk of reoperation and disease phenotype.

Comparison of the prevalence of KRAS-LCS6 polymorphism (rs61764370) within different tumour types (colorectal, breast, non-small cell lung cancer and brain tumours). A study of the Czech population.

Aims: A germline SNP (rs61764370) is located in a let-7 complementary site (LCS6) in the 3'UTR of KRAS oncogene, and it was found to alter the binding capability of the mature let-7 microRNA to the KRAS mRNA. The aim of the study was to evaluate the frequency of the KRAS-LCS6 variant allele in different cancer types that included patients with colorectal cancer (CRC), breast cancer (BC), non-small cell lung cancer (NSCLC) and brain tumour patient subgroups from the Czech Republic. The occurrence of this genetic variant was correlated with the presence of selected somatic mutations representing predictive biomarkers in the respective tumours.

[Crohn's disease - etiopathogenetic factors].

Crohn's disease is often purely inflammatory, but most patients develop complicated disease with strictures or fistulae. Specific etiopathogenesis of this severe disease is not definitely clear despite research efforts and learning of many pathogenetic mechanisms. Many studies have suggested that NOD2 mutations are associated with increased risk of complicated disease.

Epigenetic regulations in the IFNγ signalling pathway: IFNγ-mediated MHC class I upregulation on tumour cells is associated with DNA demethylation of antigen-presenting machinery genes.

Downregulation of MHC class I expression on tumour cells, a common mechanism by which tumour cells can escape from specific immune responses, can be associated with coordinated silencing of antigen-presenting machinery genes. The expression of these genes can be restored by IFNγ. In this study we documented association of DNA demethylation of selected antigen-presenting machinery genes located in the MHC genomic locus (TAP-1, TAP-2, LMP-2, LMP-7) upon IFNγ treatment with MHC class I upregulation on tumour cells in several MHC class I-deficient murine tumour cell lines (TC-1/A9, TRAMP-C2, MK16 and MC15).

Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells.

Fractionated ionizing radiation combined with surgery or hormone therapy represents the first-choice treatment for medium to high-risk localized prostate carcinoma. One of the main reasons for the failure of radiotherapy in prostate cancer is radioresistance and further dissemination of surviving cells. In this study, exposure of four metastasis-derived human prostate cancer cell lines (DU145, PC-3, LNCaP and 22RV1) to clinically relevant daily fractions of ionizing radiation (35 doses of 2 Gy) resulted in generation of two radiation-surviving populations: adherent senescent-like cells expressing common senescence-associated markers and non-adherent anoikis-resistant stem cell-like cells with active Notch signaling and expression of stem cell markers CD133, Oct-4, Sox2 and Nanog.

DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment.

MDSCs represent one of the key players mediating immunosuppression. These cells accumulate in the TME, lymphoid organs, and blood during tumor growth. Their mobilization was also reported after CY therapy.

Serum levels of matrix metalloproteinases 2 and 9 in patients with acute myocardial infarction.

The myocardial extracellular matrix plays an important role in maintaining the structural and functional integrity of the heart and is centrally involved in post-myocardial infarction repair processes. We analysed some genetic and proteomic aspects that could play an important role in the development of myocardial infarction. Matrix metalloproteinases are enzymes that contribute strongly to the degradation of extracellular matrix components.

Serum levels of matrix metalloproteinases 2 and 9 and TGFBR2 gene screening in patients with ascending aortic dilatation.

Development of ascending aortic dilatation (AAD) in about 10 % of patients operated for aortic valve disease (AVD) is probably based on intrinsic pathology of the aortic wall. This may involve an abnormality in the process of extracellular matrix remodelling. The present study evaluated the serum levels of specific metalloproteinases (MMP-2 and MMP-9) and investigated the gene for transforming growth factor receptor 2 (TGFBR2) in 28 patients with AVD associated with AAD (mean age 60.

Administration of anti-CD25 mAb leads to impaired α-galactosylceramide-mediated induction of IFN-γ production in a murine model.

CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) and CD1d-restricted invariant natural killer T (iNKT) cells are two cell types that are known to regulate immune reactions. Depletion or inactivation of Tregs using specific anti-CD25 antibodies in combination with immunostimulation is an attractive modality especially in anti-tumour immunotherapy. However, CD25 is not expressed exclusively on Tregs but also on subpopulations of activated lymphocytes.

Cyclophosphamide-induced myeloid-derived suppressor cell population is immunosuppressive but not identical to myeloid-derived suppressor cells induced by growing TC-1 tumors.

Myeloid-derived suppressor cells (MDSC) play an important role in tumor escape from antitumor immunity. MDSC accumulate in the lymphoid organs and blood during tumor growth and their mobilization was also reported after cyclophosphamide (CY) administration. In this communication, spleen MDSC accumulating after CY therapy (CY-MDSC) were compared with those expanded in mice bearing human papilloma viruses 16-associated TC-1 carcinoma (TU-MDSC).

Immunotherapy augments the effect of 5-azacytidine on HPV16-associated tumours with different MHC class I-expression status.

Background: Epigenetic mechanisms have important roles in the tumour escape from immune responses, such as in MHC class I downregulation or altered expression of other components involved in antigen presentation. Chemotherapy with DNA methyltransferase inhibitors (DNMTi) can thus influence the tumour cell interactions with the immune system and their sensitivity to immunotherapy.

Methods: We evaluated the therapeutic effects of the DNMTi 5-azacytidine (5AC) against experimental MHC class I-deficient and -positive tumours.

Genetically modified tumour vaccines producing IL-12 augment chemotherapy of HPV16-associated tumours with gemcitabine.

Genetically modified tumour cells producing cytokines such as interleukin 12 (IL-12) are potent activators of the antitumour immune responses and represent a promising therapeutic modality when combined with chemotherapy. The objective of this study was to examine whether IL-12-producing cellular vaccines can augment chemotherapy of human papilloma virus (HPV) 16-associated murine tumours with the cytostatic agent gemcitabine (GEM). We found that peritumoral administration of IL-12-producing tumour vaccines enhanced the effect of cytoreductive therapy with GEM both in non-metastasizing murine carcinoma TC-1 and in metastasizing murine carcinoma MK16.

NK1.1+ cells are important for the development of protective immunity against MHC I-deficient, HPV16-associated tumours.

Loss or downregulation of MHC class I molecules on tumour cells is a common mechanism by which tumours can escape T-cell mediated immune responses. In this study, we examined the role of different immune cell lineages in the development of immunity against tumours of the same aetiology but with different MHC class I expression. In vivo depletion of CD8+ cells, but not of CD4+ or NK1.

Induction of protective immunity against MHC class I-deficient, HPV16-associated tumours with peptide and dendritic cell-based vaccines.

Downregulation of MHC class I expression on the cell surface is a common mechanism by which tumour cells, including cervical carcinoma, can escape the T cell-mediated anti-tumour immunity. This downregulation represents an obstacle for the efficacy of anti-tumour vaccines. In this study, we investigated the efficacy of prophylactic peptide and peptide-pulsed dendritic cell-based vaccines in a murine model of experimental MHC class I-deficient tumours (TC-1/A9), expressing E6/E7 oncogenes derived from HPV16, and compared the efficacy of particular vaccination settings to anti-tumour protection against parental MHC class I-positive TC-1 tumours.

Genetically modified cellular vaccines against human papillomavirus type 16 (HPV16)-associated tumors: adjuvant treatment of minimal residual disease after surgery/chemotherapy.

Local recurrences at the site of tumor resection or after chemotherapy, as well as distant micrometastases represent major problems in oncology. Therapeutic strategies based on insertion of immunostimulatory genes into the genome of tumor cells followed by vaccination with the resulting genetically modified and irradiated cellular vaccines represent a new potential prospect for the treatment of cancer patients. These strategies are based on the presumption that many, if not all tumors, possess cell surface antigens capable of being recognized by defence effectors of the immune system, as well as on the presumption that local treatment of primary tumors can, due to its immunizing potential, result also in the inhibition of distant metastases.

Therapy for minimal residual tumor disease: beta-galactosylceramide inhibits the growth of recurrent HPV16-associated neoplasms after surgery and chemotherapy.

Natural killer T (NKT) cells are potent modulators of antitumor immunity. Their protective effects can be achieved upon their activation by glycolipid ligands presented in the context of the CD1d molecule. These CD1d-binding glycolipid antigens have been described as potent therapeutic agents against tumors, infections, as well as autoimmune diseases.