A new therapeutic option for human hepatocyte cancer

September 24, 2008

p53-impaired tumors may be particularly suitable to parvovirus H-1-induced therapy. Although the p53 deficiency in tumors may induce resistance to chemotherapeutic agents, this will not affect the tumor cell susceptibility to H-1 PV-induced oncolytic infections. The parvovirus H-1 may also overcome other tumor resistance mechanisms developed in these tumor entities. So H-1 PV is a suitable agent to circumvent the resistance of p53-negative human hepatocellular carcinoma (HCC) cells to genotoxic agents, and enhances the apoptotic process which is dependent on functional PML. Thus, H-1 PV may be considered as therapeutic options for HCC, especially for p53-negative tumors.

The research team led by Prof. Markus Moehler from First Department of Internal Medicine of Johannes Gutenberg University of Mainz evaluated the synergistic targeting and killing of human HCC cells lacking p53 by the oncolytic autonomous PV H-1 with chemotherapeutic agents. This was published on 28 June 2008, in the World Journal of Gastroenterology.

Their result shows that parvovirus H-1 PV triggers an apoptotic type of death in human HCC cells, and that p53 is dispensable for this process. In contrast, PML, which is induced by H-1 PV infection, helps the parvovirus to kill the carcinoma cells, irrespective of their p53 status. Given the known dependence of apoptosis induction by radio-chemotherapeutic agents on the p53 status of target cells, parvoviruses appear to be suitable adjuvants to eliminate tumor cell populations with resistance against these agents by means of combined treatments. Parvovirus H-1 will be a new option for patients with human HCC and clinical phase I-II trials with these oncolytic gene therapy vectors should be done in the near future.

Many viruses are known to be pathogenic and increase carcinogenesis. In the contrary, the autonomous parvoviruses destroy tumors, activate the immune system and may thus even be good for the health of men.

World Journal of Gastroenterology

---

---

	Viruses and Bone Marrow (Hematology) by Neal Young (Editor) This reference offers detailed descriptions of the interaction of viruses with human and animal haematopoietic cells, examines the role of viruses in human disease and important animal models, and elucidates the relationship of the immune reponse both in restricting infections and mediating organ damage.;Supplying rigorous, focussed discussions which should be of benefit to both clinicians and basic scientists, Viruses and Bone Marrow: gives a general overview of viral infection in haematopoietic cells, including immune response and pathological mechanisms; describes human parvovirus and feline panleukopenia virus; presents the latest information on Epstein-Barr virus and cytomegalovirus; indicates the role of hepatitis viruses and flaviviruses in cytopenias; highlights HIV, Friend...
	Parvoviruses (Hodder Arnold Publication) by Jonathan R. Kerr M.D. (Editor), Susan F. Cotmore (Editor), Marshall E. Bloom M.D. (Editor), R. Michael Linden (Editor), Colin R. Parrish (Editor) This comprehensive reference work brings together for the first time information on every aspect of the parvoviruses in a single volume. It presents the new system of parvovirus classification, as agreed by the International Committee for the Taxonomy of Viruses (ICTV), and includes cutting edge information on the virology, molecular and cellular biology, immunology and clinical manifestations of infection with each known and proposed member of the family Parvoviridae. The book also describes the rapidly expanding basic and clinical science which underpins gene therapy applications using helper-dependent and helper-independent parvoviruses. The respected editorial group has drawn together renowned contributors from around the world to produce what will undoubtedly become the standard...
	Viral Therapy of Human Cancers (Basic and Clinical Oncology) by Joseph G. Sinkovics (Editor), Joseph Horvath (Editor) Surveys possible research pathways for the treatment of human cancers. Examines the regression of tumors in virally-infected patients, as well as controversies involved in viral oncolysis. Analyzes gene therapy and active specific immunotherapy of human tumors by viral vectors.
	PCR in Bioanalysis (Methods in Molecular Biology) by Stephen J Meltzer (Editor) PCR in Bioanalysis offers powerful PCR-based protocols and assays in actual use or potential use in clinical medicine and commercial biology. The main focus of the book is on the commercial applications of PCR, as opposed to basic research uses. Topics covered include the measurement of hormone levels using PCR, transcription factor isolation, detection of viruses using PCR, detection of tumor contamination of stem cells, evaluation of grafts for tumor cells, and more.
	Current Cancer Research 2002 by Deutsches Krebsforschungszentrum (Editor) Every two to three years the German Cancer Research Centre in Heidelberg publishes a report that describes the current status of cancer research in Germany. This monograph is written with oncologists, radiologists and biologists in mind.
	Mouse as a Model Organism: From Animals to Cells by Cord Brakebusch (Editor), Taina Pihlajaniemi (Editor) Cell culture based research is important for our understanding of biological processes at the cellular and molecular level. Using this approach, the previous decades have produced a wealth of mechanistic information in all areas of biomedical research. Such in vitro research, however, lacks the complexity of in vivo investigations, where many different cell types interact with each other in a normal, three-dimensional environment, with normal levels of cytokines and growth factors. Furthermore, complex human diseases, such as cancer, diabetes or chronic inflammation, can only be modeled in vivo. Due to its small size, its short reproduction time, and the possibility to introduce specific gene mutations, the mouse has become the favourite mammalian model organism to study in vivo function...
	Ultraviolet Germicidal Irradiation Handbook: UVGI for Air and Surface Disinfection by Wladyslaw Kowalski (Author) This book is a comprehensive source for technical information regarding ultraviolet germicidal irradiation (UVGI) and its application to air and surface disinfection for the control of pathogens and allergens. The primary focus is on airborne microbes and surface contamination applications for hospitals, commercial facilities, and residential homes. All aspects of UVGI systems, including design methods, sizing methods, modeling, safety, installation, testing, guidelines, and disinfection theory are addressed in detail. An extensive database of over six hundred UV rate constant studies is included as well as tabular performance data for UV lamps and products. Providing this information in one single source simplifies the design and installation of UVGI systems, helps guarantee effective...
	Emerging Cancer Therapy: Microbial Approaches and Biotechnological Tools (Wiley Series in Biotechnology and Bioengineering) by Arsenio Fialho (Editor), Ananda Chakrabarty (Editor) Explores current and emerging applications of microbes as cancer-fighting agentsToday, treatment options for cancer patients typically include surgery, radiation therapy, immunotherapy, and chemotherapy. While these therapies have saved lives and reduced pain and suffering, cancer still takes millions of lives every year around the world. In recent years, researchers have been working on a new strategy: developing microbes and microbial products that specifically attack cancer cells.This book breaks new ground in emerging cancer treatment modalities by presenting recent advances in the use of microorganisms and viruses as well as their products in cancer therapy. Seventeen chapters review the application of live microorganisms, high and low molecular weight products derived from...
	Heat Shock Proteins: Potent Mediators of Inflammation and Immunity by Alexzander A.A. Asea (Editor), Antonio De Maio (Editor) This book provides the most up-to-date review on new mechanisms and provides exciting insights into how heat shock proteins modulate the hosts’ immune response. Written by leaders in the field of heat shock protein immunobiology, the chapters systematically and in a step-wise fashion take the reader through the fascinating sequence of events by which heat shock proteins activate immune responses and provide answers as to its biological significance to the host.
	Tumor Suppressing Viruses, Genes, and Drugs: Innovative Cancer Therapy Approaches by Hiroshi Maruta (Editor) Tumor Suppressing Viruses, Genes, and Drugs profiles the new generation of cancer treatments now in development. The book examines the innovative new approaches of viral, gene, and signal therapies that promise to replace or enhance conventional methods such as surgery, radiation, and chemotherapy. The timely information presented by this book should be of interest to anyone concerned with advancing cancer treatment beyond current medical practices.