7 research outputs found

    Oncolytic Virotherapy as Emerging Immunotherapeutic Modality: Potential of Parvovirus H-1

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    Human tumors develop multiple strategies to evade recognition and efficient suppression by the immune system. Therefore, a variety of immunotherapeutic strategies have been developed to reactivate and reorganize the human immune system. The recent development of new antibodies against immune check points may help to overcome the immune silencing induced by human tumors. Some of these antibodies have already been approved for treatment of various solid tumor entities. Interestingly, targeting antibodies may be combined with standard chemotherapy or radiation protocols. Furthermore, recent evidence indicates that intratumoral (it) or intravenous (iv) injections of replicative oncolytic viruses such as herpes simplex-, pox-, parvo- or adenoviruses may also reactivate the human immune system. By generating tumor cell lysates in situ, oncolytic viruses overcome cellular tumor resistance mechanisms and induce immunogenic tumor cell death resulting in the recognition of newly released tumor antigens.This is in particular the case of the oncolytic parvovirus H-1 (H-1PV) which is able to kill human tumor cells and stimulate an antitumor immune response through increased presentation of tumor-associated antigens, maturation of dendritic cells and release of proinflammatory cytokines. Current research and clinical studies aim to assess the potential of oncolytic virotherapy and its combination with immunotherapeutic agents or conventional treatments to further induce effective antitumoral immune responses

    Haemodynamic effects of plasma-expansion with hyperoncotic albumin in cirrhotic patients with renal failure: a prospective interventional study

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    <p>Abstract</p> <p>Background</p> <p>Patients with advanced cirrhosis of the liver typically display circulatory disturbance. Haemodynamic management may be critical for avoiding and treating functional renal failure in such patients. This study investigated the effects of plasma expansion with hyperoncotic albumin solution and the role of static haemodynamic parameters in predicting volume responsiveness in patients with advanced cirrhosis.</p> <p>Methods</p> <p>Patients with advanced cirrhosis (Child B and C) of the liver receiving albumin substitution because of renal compromise were studied using trans-pulmonary thermodilution. Paired measurements before and after two infusions of 200 ml of 20% albumin per patient were recorded and standard haemodynamic parameters such as central venous pressure (CVP), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), cardiac index (CI) and derived variables were assessed, including global end-diastolic blood volume index (GEDVI), a parameter that reflects central blood volume</p> <p>Results</p> <p>100 measurements in 50 patients (33 m/17 w; age 56 years (¬Ī 8); Child-Pugh-score 12 (¬Ī 2), serum creatinine 256 őľmol (¬Ī 150) were analyzed. Baseline values suggested decreased central blood volumes GEDVI = 675 ml/m<sup>2 </sup>(¬Ī 138) despite CVP within the normal range (11 mmHg (¬Ī 5). After infusion, GEDVI, CI and CVP increased (682 ml/m<sup>2 </sup>(¬Ī 128) vs. 744 ml/m<sup>2 </sup>(¬Ī 171), p < 0.001; 4.3 L/min/m<sup>2 </sup>(¬Ī 1.1) vs. 4.7 L/min/m<sup>2 </sup>(¬Ī 1.1), p < 0.001; 12 mmHg (¬Ī 6) vs. 14 mmHg (¬Ī 6), p < 0.001 respectively) and systemic vascular resistance decreased (1760 dyn s/cm<sup>5</sup>/m<sup>2 </sup>(¬Ī 1144) vs. 1490 dyn s/cm<sup>5</sup>/m<sup>2 </sup>(¬Ī 837); p < 0.001). Changes in GEDVI, but not CVP, correlated with changes in CI (r<sup>2 </sup>= 0.51; p < 0.001). To assess the value of static haemodynamic parameters at baseline in predicting an increase in CI of 10%, receiver-operating-characteristic curves were constructed. The areas under the curve were 0.766 (p < 0.001) for SVRI, 0.723 (p < 0.001) for CI, 0.652 (p = 0.010) for CVP and 0.616 (p = 0.050) for GEDVI.</p> <p>Conclusion</p> <p>In a substantial proportion of patients with advanced cirrhosis, plasma expansion results in an increase in central blood volume. GEDVI but not CVP behaves as an indicator of cardiac preload, whereas high baseline SVRI is predictive of fluid responsiveness.</p

    Supp_1 ‚Äď Supplemental material for Cytokeratin-18 fragments predict treatment response and overall survival in gastric cancer in a randomized controlled trial

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    <p>Supplemental material, Supp_1 for Cytokeratin-18 fragments predict treatment response and overall survival in gastric cancer in a randomized controlled trial by Michael Nagel, Julia Schulz, Annett Maderer, Katrin Goepfert, Nadine Gehrke, Thomas Thomaidis, Peter C Thuss-Patience, Salah E Al-Batran, Susanna Hegewisch-Becker, Peter Grimminger, Peter Robert Galle, Markus Möhler and Jörn Markus Schattenberg in Tumor Biology</p

    Virotherapy in Germany‚ÄĒRecent Activities in Virus Engineering, Preclinical Development, and Clinical Studies

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    Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review‚ÄĒas part of the special edition on ‚ÄúState-of-the-Art Viral Vector Gene Therapy in Germany‚ÄĚ‚ÄĒthe German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their clinical translation in investigator-initiated and sponsored multi-center trials. Preclinical research explores multiple viral platforms, including new isolates, serotypes, or fitness mutants, and pursues unique approaches to engineer them towards increased safety, shielded or targeted delivery, selective or enhanced replication, improved immune activation, delivery of therapeutic proteins or RNA, and redirecting antiviral immunity for cancer cell killing. Moreover, several oncolytic virus-based combination therapies are under investigation. Clinical trials in Germany explore the safety and potency of virotherapeutics based on parvo-, vaccinia, herpes, measles, reo-, adeno-, vesicular stomatitis, and coxsackie viruses, including viruses encoding therapeutic proteins or combinations with immune checkpoint inhibitors. These research advances represent exciting vantage points for future endeavors of the German virotherapy community collectively aimed at the implementation of effective virotherapeutics in clinical oncology

    Immunotherapy in gastrointestinal cancer: Recent results, current studies and future perspectives

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    The new therapeutic approach of using immune checkpoint inhibitors as anticancer agents is a landmark innovation. Early studies suggest that immune checkpoint inhibition might also be effective in patients with gastrointestinal cancer. To improve the efficacy of immunotherapy, different strategies are currently under evaluation. This review summarises the discussion during the European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Translational Research Meeting in Mainz in November 2014 and provides an update on the most recent results of immune therapy in gastrointestinal cancers. Knowledge of potential relationships between tumour cells and their microenvironment including the immune system will be essential in gastrointestinal malignancies. In this context, the density of T cell infiltration within colorectal cancer metastases has been associated with response to chemotherapy, and a high expression of programmed cell death ligand 1 (PD-L1) in advanced gastric cancer has been related with poor prognosis. Effective targets might include neo-antigens encoded from genes carrying tumour-specific somatic mutations. Tailored immunotherapy based on such mutations could enable the effective targeting of an individual patient's tumour with vaccines produced on demand. Other strategies considering checkpoint inhibitors have shown efficacy by targeting cytotoxic T-lymphocyte-associated protein 4 and PD-1 or PD-L1. DNA mismatch repair-deficient tumours appear to be potentially the best candidates for these therapies. Finally, the combination of oncolytic viruses with immunotherapy might boost antitumour activity as well. Further evaluation of these promising immunological therapeutic approaches will require large prospective clinical studies