Background: Research on circulating tumor cells (CTCs) offers the opportunity to better understand the initial steps of blood-borne metastasis as main cause of cancer-related deaths. Here, we have used the colon cancer CTC-MCC-41 and breast cancer CTC-ITB-01 lines, which were both established from human CTCs as permanent cell lines as models to further study CTC biology with special emphasis on anchorage-independent survival and growth.
Methods And Results: Both cell lines showed a marked intrinsic plasticity to switch between suspension and adherent in vitro growth, in 2D adherent culture conditions, and established an equilibrium of both growth patterns with predominant adherent cells in the CTC-MCC-41 line (77%) and suspension cells in the CTC-ITB-01 line (85%).
Acute myeloid leukemia (AML) is a hematologic neoplasm, characterized by a blockage of differentiation and an unconstrained proliferation of immature myeloid cells. Recently, the survival of leukemia patients has increased thanks to the use of differentiating agents, though these may cause serious side effects. Hence, the search for safer differentiating compounds is necessary.
View Article and Find Full Text PDFBackground: In breast cancer, over one third of all patients harbor a somatic mutation in the PIK3CA gene, encoding the p110α catalytic subunit of the phosphatidylinositol 3-kinase (PI3K) in their tumor cells. Circulating tumor cells (CTCs) are cells shed from the primary tumor into the blood stream. Recently, the long-term stable breast cancer CTC-ITB-01 cell line with tumorigenic and metastatic capacity was established from liquid biopsy derived cells.
View Article and Find Full Text PDFThe clinical outcome of most cancer patients depends on the stage of the primary tumor, the lymph node status, and if distant metastases are present. According to the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), the Tumor Node Metastasis (TNM) classification of malignant tumors requires the examination of a minimum number of regional lymph nodes for each type of cancer to fulfill the criteria of high-quality surgical oncology. Due to the daily challenge of collecting an appropriate number of lymph nodes and time constraints when processing and assessing tissue samples, pathologists may be tempted to identify every histological lymphoid structure mimicking a lymph node as a "true" lymph node.
View Article and Find Full Text PDFImportance: Studies with nivolumab, an approved therapy for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy, demonstrate improved outcomes with added high-dose ipilimumab.
Objective: To assess efficacy and safety of a tailored approach using nivolumab + ipilimumab as an immunotherapeutic boost for mUC.
Design, Setting, And Participants: In this phase 2 nonrandomized trial, patients with mUC composed 2 cohorts.
Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages, limiting the prognoses of patients. Metastasis requires high tumor cell plasticity, implying phenotypic switching in response to changing environments. Here, epithelial-mesenchymal transition (EMT), being associated with an increase in cancer stem cell (CSC) properties, and its reversion are important.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) results in high mortality due to ineffective systemic therapy. Human immortalized cell lines are commonly used to study anti-tumor effects in the context of new anti-tumor therapies and tumor biology. As immortalized cell lines have limited biological relevance and heterogeneity compared to primary cells, patient-derived tumor tissues, and corresponding immune cells are the gold standards for studying the complexity of individual tumor entities.
View Article and Find Full Text PDFMost cancer patients ultimately die from the consequences of distant metastases. As metastasis formation consumes energy mitochondria play an important role during this process as they are the most important cellular organelle to synthesise the energy rich substrate ATP, which provides the necessary energy to enable distant metastasis formation. However, mitochondria are also important for the execution of apoptosis, a process which limits metastasis formation.
View Article and Find Full Text PDFAnnu Int Conf IEEE Eng Med Biol Soc
July 2023
In biomedical engineering, deep neural networks are commonly used for the diagnosis and assessment of diseases through the interpretation of medical images. The effectiveness of these networks relies heavily on the availability of annotated datasets for training. However, obtaining noise-free and consistent annotations from experts, such as pathologists, radiologists, and biologists, remains a significant challenge.
View Article and Find Full Text PDFBackground: Overall adherence in the treatment of chronic dermatoses is poor. Textbooks state an adherence dependence on galenics.
Trial Design: Prospective, randomized, parallel-grouped, single-blinded (investigator), monocentric clinical trial (phase IV) on the adherence to treatment of chronic mild to moderate hand eczema with topical methylprednisolone aceponate (MPA, Advantan®) in different vehicles.
Hematogenous metastasis limits the survival of colorectal cancer (CRC) patients. Here, we illuminated the roles of CD44 isoforms in this process. Isoforms 3 and 4 were predominantly expressed in CRC patients.
View Article and Find Full Text PDFBackground: Nivolumab plus ipilimumab is approved as first-line regimen for intermediate-risk or poor-risk metastatic renal cell carcinoma, and nivolumab monotherapy as second-line therapy for all risk groups. We aimed to examine the efficacy and safety of nivolumab monotherapy and nivolumab plus ipilimumab combination as an immunotherapeutic boost after no response to nivolumab monotherapy in patients with intermediate-risk and poor-risk clear-cell metastatic renal cell carcinoma.
Methods: TITAN-RCC is a multicentre, single-arm, phase 2 trial, done at 28 hospitals and cancer centres across Europe (Austria, Belgium, Czech Republic, France, Germany, Italy, Spain, and the UK).
Objective: Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC.
View Article and Find Full Text PDFOne critical step of metastasis formation is the extravasation of circulating tumor cells from the bloodstream. This process requires the dynamic interaction of cell adhesion molecules like E-selectin on endothelial cells with carbohydrate ligands on tumor cells. To characterize these glycans in a comprehensible approach, the rolling, tethering, and firm adhesion of nine human tumor cell lines on human umbilical vein endothelial cells was analyzed using laminar flow adhesion assays.
View Article and Find Full Text PDFBackground & Aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated.
Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764).
Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe.
View Article and Find Full Text PDFBackground: We explored the interrelation between prostate-specific membrane antigen (PSMA) expression on circulating tumor cells (CTCs) and that of solid metastatic lesions as determined by whole-body PSMA-targeted positron emission tomography (PET) to refine the prediction of response to subsequent PSMA-targeted radioligand therapy (RLT).
Methods: A prospective study was performed in 20 patients with advanced mCRPC. Of these, 16 underwent subsequent RLT with [ Lu]Lu-PSMA-617 at a dose of 7.
Early life is characterized by extraordinary challenges, including rapid tissue growth and immune adaptation to foreign antigens after birth. During this developmental stage, infants have an increased risk of immune-mediated diseases. Here, we demonstrate that tissue-resident, interleukin (IL)-13- and IL-4-producing group 2 innate lymphoid cells (ILC2s) are enriched in human infant intestines compared to adult intestines.
View Article and Find Full Text PDFTextbooks and atlases of human macroscopic and microscopic anatomy of the larynx generally provide, if at all, only sparse information on the laryngeal Musculus ventricularis. However, several studies indicate that this muscle takes over the function of vestibular (ventricular) fold phonation after denervation of the Musculus vocalis. In the present study, 29 laryngeal specimens were coronally dissected at different levels, i.
View Article and Find Full Text PDFIrregular bellies and insertions into neck muscles have been described in the literature. To the best of our knowledge, a right accessory muscle originating from the hyoid bone and inserting into the sternocleidomastoid muscle has not been reported to date. Here, we report the case of a 72-year-old male patient with an irregular muscle originating from the lesser horn of the hyoid bone and inserting into sternocleidomastoid muscle fibers.
View Article and Find Full Text PDFBone metastases develop in >90 % of patients with castration-resistant prostate cancer (PCa) through complex interactions between the bone microenvironment and tumor cells. Previous androgen-deprivation therapy (ADT), which is known to cause bone loss, as well as anti-resorptive agents such as zoledronic acid (ZA), used to prevent skeletal complications, may influence these interactions and thereby the growth of disseminated tumor cells (DTC) in the bone marrow (BM). Here, a spontaneously metastatic xenograft tumor model of human PCa was further optimized to mimic the common clinical situation of ADT (castration) combined with primary tumor resection in vivo.
View Article and Find Full Text PDFBackground: The immunological composition of the tumor microenvironment has a decisive influence on the biological course of cancer and is therefore of profound clinical relevance. In this study, we analyzed the cooperative effects of integrin β4 (ITGB4) on tumor cells and E-/P-selectin on endothelial cells within the tumor stroma for regulating tumor growth by shaping the local and systemic immune environment.
Methods: We used several preclinical mouse models for different solid human cancer types (xenograft and syngeneic) to explore the role of ITGB4 (shRNA-mediated knockdown in tumor cells) and E-/P-selectins (knockout in mice) for tumor growth; effects on apoptosis, proliferation and intratumoral signaling pathways were determined by histological and biochemical methods and 3D in vitro experiments; changes in the intratumoral and systemic immune cell composition were determined by flow cytometry and immunohistochemistry; chemokine levels and their attracting potential were measured by ELISA and 3D invasion assays.
Background: The disruption of epithelial features represents a critical step during breast cancer spread. In this context, the dysregulation of desmosomal proteins has been associated with malignant progression and metastasis formation. Curiously, both tumour suppressive and pro-metastatic roles have been attributed to desmosomal structures in different cancer entities.
View Article and Find Full Text PDFBackground: Nivolumab is used after platinum-based chemotherapy in patients with metastatic urothelial carcinoma. Studies suggest improved outcomes for dual checkpoint inhibition with high ipilimumab doses. We aimed to examine the safety and activity of nivolumab induction and high-dose ipilimumab as an immunotherapeutic boost as a second-line treatment for patients with metastatic urothelial carcinoma.
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