SCHEDULE

We have scheduled our Programs dividing them into Day 1, Day 2, Day 3 in order to make it convenient for you to attend in absolute comfort.

25 Jan
Day 1

keynote 1

Bernd Kaina

Institute of Toxicology, University Medical Center, Mainz ,Germany

Title: DNA repair and damage response in personalized cancer chemotherapy

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Biography:

Dr. Kaina holds a doctoral degree from the University of Halle. He worked as a postdoctoral fellow at various institutions and, in 1993, was appointed head of the Division of Applied Toxicology at the University of Mainz. From 2004 to 2008 he was Chairman of the Institute of Toxicology at the Medical Center in Mainz. His working field includes the genotoxic effects of environmental carcinogens as well as cancer therapeutics, the mechanisms of cell death, senescence, mutagenesis and carcinogenesis with special emphasis on DNA repair and DNA damage signaling. He is author of more than 400 original and review papers and book chapters. 

This paper focuses on alkylating agents that are used 1st-line in glioblastoma therapy. One of the alkylating drugs is temozolomide, which methylates the DNA and induces, among other adducts, O6-methylguanine -a highly cytotoxic and mutagenic lesion. Toxicity rests on conversion of the lesion through mismatch repair into DNA double-strand breaks (DSB) that trigger downstream pathways including apoptosis, autophagy and senescence1. Consequently, corresponding repair pathways are expected to have a great impact on temozolomide resistance, and evidence was provided for the involvement of MGMT, mismatch repair, DSB repair by homologous recombination through BRCA2 and Rad512 as well as XRCC33. However, only MGMT found the way in the clinique, being used as predictor for therapy outcome4. We have established methods of determining the MGMT promoter methylation status, which corresponds to MGMT silencing and therapy, showing MS-HRM to be superior compared to MS-PCR5. - Downstream of O6-methylguanine derived DSBs are ATR/ATM triggered pathways that activate apoptosis and senescence. Data will be shown demonstrating that the SIAH1-HIPK2-p53ser46 pathway plays a key role in regulating temozolomide-induced apoptosis6. The question of whether there are threshold doses for activating survival and death pathways will also be addressed and senescence pathways will be discussed7. References: 1) Knizhnik et al., PLoS One, 8, e55665, 2013, 2) Quiros et al., PLoS One, 6, e27183, 2011, 3) Roos et al., Cancer Letters, 424, 119-126, 2018, 4) Wiewrodt et al., Int. J. Cancer, 122, 1391-99, 2008, 5) Switzeny et al., Clinical Epigenetics, 8, 49, 2016, 6) He et al., Mol. Cancer Res., 2019, in press, 7) He and Kaina, Int. J. Mol. Sci., Mar 28, 20 (7) 2019.

Abstract:

This paper focuses on alkylating agents that are used 1st-line in glioblastoma therapy. One of the alkylating drugs is temozolomide, which methylates the DNA and induces, among other adducts, O6-methylguanine -a highly cytotoxic and mutagenic lesion. Toxicity rests on conversion of the lesion through mismatch repair into DNA double-strand breaks (DSB) that trigger downstream pathways including apoptosis, autophagy and senescence1. Consequently, corresponding repair pathways are expected to have a great impact on temozolomide resistance, and evidence was provided for the involvement of MGMT, mismatch repair, DSB repair by homologous recombination through BRCA2 and Rad512 as well as XRCC33. However, only MGMT found the way in the clinique, being used as predictor for therapy outcome4. We have established methods of determining the MGMT promoter methylation status, which corresponds to MGMT silencing and therapy, showing MS-HRM to be superior compared to MS-PCR5. - Downstream of O6-methylguanine derived DSBs are ATR/ATM triggered pathways that activate apoptosis and senescence. Data will be shown demonstrating that the SIAH1-HIPK2-p53ser46 pathway plays a key role in regulating temozolomide-induced apoptosis6. The question of whether there are threshold doses for activating survival and death pathways will also be addressed and senescence pathways will be discussed7. References: 1) Knizhnik et al., PLoS One, 8, e55665, 2013, 2) Quiros et al., PLoS One, 6, e27183, 2011, 3) Roos et al., Cancer Letters, 424, 119-126, 2018, 4) Wiewrodt et al., Int. J. Cancer, 122, 1391-99, 2008, 5) Switzeny et al., Clinical Epigenetics, 8, 49, 2016, 6) He et al., Mol. Cancer Res., 2019, in press, 7) He and Kaina, Int. J. Mol. Sci., Mar 28, 20 (7) 2019.

keynote 2
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Biography:

Dr. Magda Carvajal-Moreno, research-professor in mycotoxins, Institute of Biology, National Autonomous University of Mexico (UNAM), she has two carreers, Biology and Philosophy, done simultaneouly, Mastership in Plant Pathology and PhD in Mycotoxins, winning “Gabino Barreda” PhD studies medal. She was President of the Mycology Society of Mexico, President of the LatinAmerican Society of Mycotoxicology, National Prize of Science and Food Technology (2012), with 191 publications, 384 works in congresses, 27 organized congresses, 42 graduated students. She directed the Government Control Program of Aflatoxins with 60,000 analysis, 44 laboratories, and 1.5 million tons of maize analyzed for AFs  for 5 years.

 

Abstract:

Aflatoxins (AFs) are secondary metabolites, bis-dihydro-furan-coumarins,  mainly from the fungi Aspergillus flavus, A. parasiticus and A. nomius; they stand temperatures above 200-300 °C without inactivation, and they are not very soluble in water. AFs are the most frequent and dangerous carcinogens in foods (cereals, dairy products, eggs, meats, spices and oilseeds) ingested by animals and humans. Animal liver biotransforms AFs into hydroxylated metabolites (AFM1, AFM2, AFP1 and aflatoxicol) in animal foods (milk, eggs, cheeses, and meats),  to make them soluble in water and eliminate them, lowering their toxicity.  Around 17% AFs link to DNA, RNA and proteins, and form AFB1-DNA adducts which are the active carcinogens, and recognized biomarkers of disease. AFs cause hepatitis, cirrhosis, immunodepression, miscarriages, malformations, hemorrhages, diarrhea and different cancers when they are stored in DNA for years. IARC (2002) considers AFB1 a carcinogen Grade I proven for humans. ELISA Indirect Inhibition test allows to recover one molecule of AFB1 in 10-15 nucleotides of human malignant tumors, and the AF-DNA adduct chemical synthesis is required. AFB1-DNA adducts in cervical, colorectal, liver, pancreas and lung malignant tumors will be shown.  We found, for the first time worldwide, a synergism of AF adducts with Human Papilloma viruses (VPH) 16 and 18 from Papanicolau samples positive to cervical cancer, which is caused by both HPV and AFs. Finally, the control of the fungi and the AFB1 mutagenesis by apoptosis-like cell death  induction, and gene regulation by thyme, clove and Rosemarinus officinalis  essential oils  and with probiotics will be shown.

 

keynote 3

Barbara Kofler

University Hospital of the Paracelsus Medical University, M├╝llner Hauptstra├če 48, 5020 Salzburg ,Austria

Title: Ketogenic diet in the treatment of cancer - where do we stand?

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Biography:

Barbara Kofler received her PhD in biochemistry from the University of Innsbruck, Austria. After a postdoctoral training at the Garvan Institute of Medical Research, Sydney Australia she established the special and research labs at the Department of Pediatrics in Salzburg Austria.. After characterization of cancer cell metabolism for more than ten years, she decided to target the altered cancer metabolism by dietary intervention. Her team is testing different types of ketogenic diets in combination with classical therapeutic approaches in a range of preclinical tumor models. Albeit being excited by the effects ketogenic diets have on tumor growth in preclinical studies she is likewise quite reluctant in suggesting the diet to cancer patients, as there are so far not enough clinical trials available in humans.

Abstract:

Cancer is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of standard anticancer therapies. The ketogenic diet, a high-fat, low-carbohydrate diet with adequate amounts of protein, appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells, making the diet a promising candidate as an adjuvant cancer therapy.In the lecture available preclinical and clinical evidence regarding the ketogenic diet in the context of cancer therapy will be provided. Furthermore, important mechanisms that could explain the potential antitumor effects of the ketogenic diet will be highlighted.The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy. The majority of preclinical and several clinical studies argue for the use of the ketogenic diet in combination with standard therapies based on its potential to enhance the antitumor effects of classic chemo- and radiotherapy, its overall good safety and tolerability and increase in quality of life. However, to further elucidate the mechanisms of the ketogenic diet as a therapy and evaluate its application in clinical practice, more molecular studies as well as uniformly controlled clinical trials are needed.

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