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In November 2019, the paper „Incidental Use of Beta-Blockers Is Associated with Outcome of Metastatic Colorectal Cancer Patients Treated with Bevacizumab-Based Therapy: A Single-Institution Retrospective Analysis of 514 Patients“ was published in Cancers (Q1, IF2019: 6.162). This is an extensive retrospective study involving a total of 514 patients with metastatic colorectal cancer who were treated between 2005 and 2019 at the Department of Oncology and Radiotherapy, Faculty of Medicine and University Hospital in Pilsen, Charles University. The work, led by Assoc. Prof. Ondřej Fiala, M.D., Ph.D., is based on the systematic cooperation of the Department of Oncology and Radiotherapy, the Department of Surgery and the Faculty of Medicine in Pilsen, Charles University. This collaboration is carried out under the auspices of the Laboratory of Tumor Treatment and Tissue Regeneration of the Medical Faculty’s Biomedical Center, which has long been involved in various clinical and experimental aspects of colorectal cancer and primary liver tumours.

Beta-adrenergic signalling plays an essential role in several processes that are important for the development and progression of various cancers. These processes include angiogenesis. The effect of the use of beta-blockers on the prognosis of cancer patients treated with anti-angiogenic agents is unclear and has been scarcely studied clinically. The aim of this study was to evaluate the association between the use of beta-blockers and the effect of treatment with a combination of chemotherapy and bevacizumab (a monoclonal antibody against vascular endothelial growth factor), which blocks angiogenesis. The association between progression-free survival (PFS) and overall survival (OS) with the use of beta-blockers and other common antihypertensive agents was evaluated. Of the commonly used antihypertensive agents, only beta-blockers had a significant impact on survival. The medians of PFS and OS in patients using beta-blockers prolonged to 11.4 and 26.8 months compared to the baseline values of 8.3 and 21.0 months in patients not using beta-blockers (p = 0.006 and p = 0.009, respectively). In the Cox multivariate model, the use of beta-blockers was a significant factor predicting both PFS (HR = 0.763, p = 0.021) and OS (HR = 0.730, p = 0.020). The results of this study show a significant association between the use of beta-blockers and the effect of treatment based on a combination of chemotherapy and bevacizumab. This is the first study of this kind conducted in a clinically relevant group of patients suggesting that beta-blockers might be the preferred type of antihypertensive in patients with metastatic colorectal cancer treated with this type of targeted therapy.

“From a clinical point of view, comedication is an extremely interesting topic in cancer patients. Although the results of this study are interesting, they need to be interpreted with caution, mainly because of its non-randomized retrospective design. We will stay focused on this topic with respect to other malignancies where anti-angiogenic targeted treatment is used,” adds doc. Fiala.

www.ncbi.nlm.nih.gov/pubmed/31769417

Vaclav Liska

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The Laboratory of Cancer treatment and Tissue Regeneration successfully published an article ‚Experimental fortification of intestinal anastomoses with nanofibrous materials in a large animal model‘ in the Scientific Reports journal (Q1, IF = 4.116). The paper sums results of the first use of nanofibrous materials from polycaprolactone for intestinal anastomotic healing support in an experiment on pigs.

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In European Union-funded project on translational cancer research, headed by Professor Kari Hemminki, several postdoctoral positions with different areas of expertize are currently sought to work in Biomedical Center, Faculty of Medicine, Charles University in Pilsen, Czech Republic.

The focus will be initially on colorectal cancer. The aims are to assess genetic and cellular changes taking place in the progression of colorectal cancer from precursor tumors (adenomas) to single or multiple colorectal cancers and lastly to metastases. The results will help to understand the role of genetic and cellular events at different phases of tumor development with possible clues about therapeutic targets. While the evidence shows that majority of colorectal carcinomas evolve from adenomatous polyps it is also believed that most neoplastic adenomas may not evolve to cancer. Immune system plays a key role in trying to suppress malignant transformation. Under the pressure of immune surveillance, surviving tumor cells tend to selectively accumulate traits that help them evade immune destruction. A strongly immunogenic tumor in an immunocompetent host may result in optimal stimulation of the immune system and elimination of the tumor. Alternatively, mutated tumor cells selectively develop variants that have acquired insensitivity to immunologic surveillance (e.g., through increased tumor-induced immunosuppression) and that can expand in an unrestrained fashion. A general deterioration of an individual’s immune defense may contribute to tumor escape.

METHODS: Studies are carried out in close collaboration with clinical departments allowing access to human samples, Genomic, transcriptomic and epigenomic analyses will focus on use of pathological slides and frozen tissue samples from polyps of early adenomas, colorectal tumors and adjacent gut epithelial samples and tumor metastases. The analysis will include DNA and mRNA targeted and next generation sequencing, copy number analyses and epigenomic profiling. Detailed analysis of cellular evolution of tumors requires detection of the key immune cell types and cellular signaling modulators in pathological slides and frozen tissue samples. The results of cell composition are correlated with clinical and prognostic data.

QUALIFICATIONS

  • PhD or equivalent in biology, genetics, immunology or medicine
  • Scientific skills shown in publications
  • Technical skills in laboratory work
  • Motivation and ability to conduct collaborative work
  • Communication skills in oral and written English

TO APPLY BY March 2, 2020

  • Cover letter with short explanation of prior research and experience
  • Curriculum vitae with publication list
  • Copies of diplomas and PhD thesis (if completed; applicants close to completion would be eligible to apply)

SEND APPLICATIONS/INQUERIES BY E-MAIL to This email address is being protected from spambots. You need JavaScript enabled to view it.

Charles University is committed to employment equality (esp. European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers) and welcomes applications from all qualified candidates fulfilling requirements specified in this announcement.

This project has received funding from the European Union´s Horizon 2020 research and innovation programme under Grant Agreement No. 856620

Mgr. Petra Vakešová
HR department, Charles University, Faculty of Medicine in Pilsen
Husova 3, 306 05 Pilsen, Czech Republic

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The result of a successful cooperation of scientific and clinical teams of the Biomedical Center of the Faculty of Medicine in Pilsen, Charles University, is the publication of the article Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma in the journal Scientific Reports (Q1, IF2018: 4.116).

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Kamila Koucká MSc, doctoral student in Experimental surgery, working in Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University received Prize for best poster at PragueONCO Conference held in Prague 29. - 31. January 2020. Her study “Efficiency and transport of novel taxane derivatives in resistant in vitro and in vivo models of ovarian cancer cells“, was supported also by the project of the Grant Agency of Charles University no. UNCE/MED/006 - Center of clinical and experimental liver surgery.

doc. RNDr. Pavel Souček, CSc.

 

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We would like to introduce two major works of co-authors of Pavel Vodička, Ludmila Vodičková and Veronika Vymetálková from the team of the Laboratory of Cancer Treatment and Tissue Regeneration. These two publications published in Q1 journal Gastroenterology (IF 19.809) are based on the research they were working on.

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Charles University
Faculty of Medicine in Pilsen
Biomedical Center

alej Svobody 1655/76
323 00 Plzeň – Severní Předměstí

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