Epigenetics will certainly present a revolution in understanding people's concept of their health.
In order to understand the formation of living beings, Aristoteles (384-322 A.C.) developed the model of Epigenesis (ἐπιγένησις). From amorphous substances the specific structures of a living being were formed. The environment has a central role here.
How this occurs and what it means to us becomes more evident day by day through the countless new scientific discoveries in biology and medicine.
Men will increasingly come to the conclusion that they are not victims of old age, defenseless from their rigid mechanisms of genetic donations. Instead, epigenetics teaches us that human genes are able to respond to the action of external factors, for example, adapting its regulation, which can also mean an adaptation of the organism. Therefore, external factors include food, climate, stress, UV rays, bacteria, toxins, viruses, chemicals, but also other substances found in nature, such as Medication.
Added external factors and the genetics of each, our organism forms an entity with the environment that determines its health, quality of life and life time.
EPIPROCARE proposes the task of bringing this important knowledge of epigenetics as soon as possible to the application for the benefit of human beings.
Fortunately, humans are, in principle, able to consciously determine the influence of these external factors on their organisms and genes. Nevertheless, we must pay attention to what the EPIGENETICS will teach us, because it explores the connections between environmental influences and gene regulation.
EPIPROCARE proposes to bring this important knowledge of epigenetics as quickly as possible for application to the benefit of the human being.
Just as EPIGENETICS works between external environmental influences and gene regulation, E P I P R O C A R E will act between the findings of scientific research and its clinical application, acting directly on the quality of human life.
In this way, humans should be able to test and improve your (there) health, and even prevent and combat diseases.
For this purpose, EPIPROCARE was founded by internationally renowned biologists and physicians from top universities, with over 20 years of experience in the areas of Epigenetics and Clinical Urology.
The first practical application of EPIPROCARE is the scientific determination of the biological age of a person to show ways to have a positive impact on their aging process and in their quality of life in elderly patients.
Other scientific discoveries and determinations are also foreseen in the diagnosis and prognosis of urological neoplasms, such as prostate and bladder cancer first and then to be extended to almost all cancer entities, e.g. breast, lung, hepatocellular and gastric carcinoma, chronic lymphocytic leukemia (CLL) and others.
Has developed and presents a new method of reliably measuring epigenetic changes, scientifically tested, proven, published and patented, that for the first time accurately detects epigenetic changes in clinical specimens, which are subjected to genetic alterations, e.g. as it is the case in elderly individuals and cancer samples.
The method is IDLN-MSP: Idiolocal normalization of real-time methylation-specific PCR (Polymerase Chain Reaction) (Santourlidis et al. 2016) and constitutes the central pillar of epiprocare´s platform technology to provide a superior level of epigenetic diagnosis and prognosis for many cancer entities, e.g. bladder, prostate, breast, lung, hepatocellular and gastric carcinoma, chronic lymphocytic leukemia (CLL) and others. This technology allows the successful transfer in the personalized medicine to support and help any individual patient since for the first time, based on EPIPROCARE´S unique technology, it is possible to comparatively measure tumor samples and samples of aged individuals with disturbed genetics.
Marcelo Bendhack, Master and Doctor in Urology by the Federal University of Paraná (UFPR/1999). Pos-Doc in Uro-Oncology by the University Düsseldorf, Germany (2001). Specialist by the Brazilian Society of Urology (SBU) and President of the Latin American Society of Uro-Oncology (UROLA). Member of the Board – World Federation of Uro-Oncology (WUOF), medical member of the Nossa Senhora das Graças Hospital (Curitiba/PR) and Santa Catarina Hospital (São Paulo/SP).
He has internationally recognized expertise in early diagnosis (screening), prostate biopsy guided by ultrasound (since 1994), ultrasound of the genitourinary system, and special skills in treatments in uro-oncology – cancer of the following organs: kidney, ureter, bladder, prostate, urethra and testicles.
Outstanding procedures: radical prostatectomy, HIFU for prostate cancer, transurethral resection of the prostate, ultrasound-guided prostate biopsy, transurethral resection of the bladder tumor, radical cystectomy with orthotopic neobladder, partial and radical nephrectomy (kidney tumors), minimally invasive treatments for kidney and prostate cancer.
In 2011, he was pioneer in Brazil in the treatment of localized and recurrent prostate cancer with HIFU technology (High Intensity Focused Ultrasonography). After his training in Europe and returning to Brazil, he performed multiple functions in Universities, postgraduate activities and others related to the Government of Paraná State.
He was postgraduation professor at the Catholic University of Paraná (PUC-PR) and Positivo University. Coordinator of the Medical Residency Program in Urology, at Nossa Senhora das Graças Hospital (2004-2007). Founder, head and coordinator of the Medical Residency Program in Urology, Hospital da Cruz Vermelha, Paraná, Universidade Positivo (since 2009). Medical Technical Director in Focal Therapy Centers for Prostate Cancer, in Curitiba and São Paulo (SP), since January 2011.
His first contact with the HIFU technique was in 1994, in Düsseldorf, Germany, still during his postgraduation at the German University, where prostates were treated with this technology. This first worldwide study on HIFU and prostate allowed the publication of 1995 by Prof. Ackermann (im memoriam) et al. In 1999, he assisted the first brazilian patient with prostate cancer treated with HIFU in Europe. This first patient showed good prognosis and no recurrence, with a follow-up of more than 20 years.
HIFU was subsequently used in some patients abroad. Based on new scientific studies, especially since 2013, the technique was considered as treatment for localized prostate cancer. Dr. Marcelo Bendhack then performed treatments with HIFU in Mexico (2007) and Argentina (2008). Both patients showed good prognosis (oncologic). After receiving the Sonablate®500 equipment, produced by Sonacaremedical Inc. (Indianapolis, USA), in December 2010, Bendhack performed the first HIFU treatment in Brazil, on January 19th, 2011, at the Nossa Senhora das Graças Hospital, in Curitiba.
M. Bendhack has training with ultrasound and HIFU since 1994. Currently (May 2020), more than 360 patients were treated by him, the vast majority with favorable evolution. His medical skills and experience related to this technology and ultrasound were developed over 26 years.
Between 1999 and 2001 M. Bendhack has written 3 scientific thesis (1 in Germany and 2 in Brazil) about serum and molecular tumor markers for testicular and prostate cancer. Hereby he evaluated patients with the following markers: AFP, B-HCG, PLAP, PSMA and PSA.
Among the milestones of his specialization, Dr. Marcelo Bendhack participated in events on HIFU and multiparametric magnetic resonance imaging, among them, in April 2014, at the Royal College of Surgeons, with Prof. Mark Emberton, London.
From 2004 to 2018, he was President of International Symposia of Uro-Oncology, leading the Latin American Association (UROLA), in the following locations: Curitiba (BR), Montevideo (UR), Monterrey (MX), Córdoba (AR) and Campinas (BR) . In the city of Campinas, the event (IX SIUO) received support from important Brazilian institutions, such as UNICAMP, UNESP and USP-RP. In recent years, he has participated as organizer and moderator of sessions on Prostate Cancer in North American Congresses and the World Federation of Uro-Oncology (WUOF).
Dr. rer. nat. degree (magna cum laude). Habilitation and Venia Legendi for Molecular Medicine at the Medical Faculty of the Heinrich-Heine University Düsseldorf. Promotion to "außerplanmäßiger Professor" (associate professor) for Molecular Medicine at the Medical Faculty of the Heinrich-Heine University Düsseldorf.
1. Basic Hallmarks of Urothelial Cancer Unleashed in Primary Uroepithelium by Interference with the Epigenetic Master Regulator ODC1.
Erichsen L, Seifert HH, Schulz WA, Hoffmann MJ, Niegisch G, Araúzo-Bravo MJ, Bendhack ML, Poyet C, Hermanns T, Beermann A, Hassan M, Theis L, Mahmood W, Santourlidis S.
Sci Rep. 2020 Mar 2;10(1):3808.
2. Epigenetics Meets CRISPR/Cas to Fight Cancer Simeon Santourlidis J Cancer Res Therap Oncol. 2020 March 03, 8: 1-5.
3. Evaluation of nanoselenium and nanogold activities against murine intestinal schistosomiasis. Dkhil MA, Khalil MF, Diab MSM, Bauomy AA, Santourlidis S., Al-Shaebi EM, Al-Quraishy S. Saudi J Biol Sci. 2019 Nov;26(7):1468-1472.
4. Tumor necrosis factor-α triggers opposing signals in head and neck squamous cell carcinoma and induces apoptosis via mitochondrial- and non-mitochondrial-dependent pathways. Selimovic D, Wahl RU, Ruiz E, Aslam R, Flanagan TW, Hassan SY, Santourlidis S., Haikel Y, Friedlander P, Megahed M, Kandil E, Hassan M. Int J Oncol. 2019 Dec;55(6):1324-1338.
5. Genome-wide hypomethylation of LINE-1 and Alu retroelements in cell-free DNA of blood is an epigenetic biomarker of human aging. Erichsen L, Beermann A, Arauzo-Bravo MJ, Hassan M, Dkhil MA, Al-Quraishy S, Hafiz TA, Fischer JC, Santourlidis S.. Saudi J Biol Sci. 2018 Sep;25(6):1220-1226.
6. Author Correction: Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis. Erichsen L, Ghanjati F, Beermann A, Poyet C, Hermanns T, Schulz WA, Seifert HH, Wild PJ, Buser L, Kröning A, Braunstein S, Anlauf M, Jankowiak S, Hassan M, Bendhack ML, Araúzo-Bravo MJ, Santourlidis S. Sci Rep. 2018 Apr 11;8(1):6051.
7. Aberrant methylated key genes of methyl group metabolism within the molecular etiology of urothelial carcinogenesis. Erichsen L, Ghanjati F, Beermann A, Poyet C, Hermanns T, Schulz WA, Seifert HH, Wild PJ, Buser L, Kröning A, Braunstein S, Anlauf M, Jankowiak S, Hassan M, Bendhack ML, Araúzo-Bravo MJ, Santourlidis S. Sci Rep. 2018 Feb 22;8(1):3477.
8. Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice. Al-Quraishy S, Dkhil MA, Abdel-Baki AS, Ghanjati F, Erichsen L, Santourlidis S., Wunderlich F, Araúzo-Bravo MJ. Parasitol Res. 2017 May;116(5):1463-1477.
9. Interferon gamma-induced apoptosis of head and neck squamous cell carcinoma is connected to indoleamine-2,3-dioxygenase via mitochondrial and ER stress-associated pathways. El Jamal SM, Taylor EB, Abd Elmageed ZY, Alamodi AA, Selimovic D, Alkhateeb A, Hannig M, Hassan SY, Santourlidis S., Friedlander PL, Haikel Y, Vijaykumar S, Kandil E, Hassan M. Cell Div. 2016 Aug 2;11:11.
10. IDLN-MSP: Idiolocal normalization of real-time methylation-specific PCR for genetic imbalanced DNA specimens. Santourlidis S., Ghanjati F, Beermann A, Hermanns T, Poyet C. Biotechniques. 2016 Feb 1;60(2):84-7.
11. Effect on Multipotency and Phenotypic Transition of Unrestricted Somatic Stem Cells from Human Umbilical Cord Blood after Treatment with Epigenetic Agents. Ghanjati F, Santourlidis S. Stem Cells Int. 2016;2016:7643218.
12. Age-Related Increase of EED Expression in Early Hematopoietic Progenitor Cells is Associated with Global Increase of the Histone Modification H3K27me3. Graffmann N, Brands J, Görgens A, Vitoriano da Conceição Castro S, Santourlidis S., Reckert A, Michele I, Ritz-Timme S, Fischer JC, Adjaye J, Kögler G, Giebel B, Uhrberg M. Stem Cells Dev. 2015 Sep 1;24(17):2018-31.
13. Corrigendum to "Bortezomib/proteasome inhibitor triggers both apoptosis and autophagydependent pathways in melanoma cells". [Cell Signal. 25(1)Jan 2013 308-18]. Selimovic D, Porzig BB, El-Khattouti A, Badura HE, Ahmad M, Ghanjati F, Santourlidis S., Haikel Y, Hassan M. Cell Signal. 2015 Feb 6.
14. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin. Dorn I, Klich K, Arauzo-Bravo MJ, Radstaak M, Santourlidis S., Ghanjati F, Radke TF, Psathaki OE, Hargus G, Kramer J, Einhaus M, Kim JB, Kögler G, Wernet P, Schöler HR, Schlenke P, Zaehres H. Haematologica. 2015 Jan;100(1):32-41.
15. Origin-dependent neural cell identities in differentiated human iPSCs in vitro and after transplantation into the mouse brain. Hargus G, Ehrlich M, Araúzo-Bravo MJ, Hemmer K, Hallmann AL, Reinhardt P, Kim KP, Adachi K, Santourlidis S., Ghanjati F, Fauser M, Ossig C, Storch A, Kim JB, Schwamborn JC, Sterneckert J, Schöler HR, Kuhlmann T, Zaehres H. Cell Rep. 2014 Sep 25;8(6):1697-1703.
16. Unreserved application of epigenetic methods to define differences of DNA methylation between urinary cellular and cell-free DNA. Ghanjati F, Beermann A, Hermanns T, Poyet C, Araúzo-Bravo MJ, Seifert HH, Schmidtpeter M, Goering W, Sorg R, Wernet P, Santourlidis S. Cancer Biomark. 2014;14(5):295-302.
17. Genome-wide screening identifies Plasmodium chabaudi-induced modifications of DNA methylation status of Tlr1 and Tlr6 gene promoters in liver, but not spleen, of female C57BL/6 mice. Al-Quraishy S, Dkhil MA, Abdel-Baki AA, Delic D, Santourlidis S., Wunderlich F. Parasitol Res. 2013 Nov;112(11):3757-70.
18. Vinblastine-induced apoptosis of melanoma cells is mediated by Ras homologous A protein (Rho A) via mitochondrial and non-mitochondrial-dependent mechanisms. Selimovic D, Badura HE, El-Khattouti A, Soell M, Porzig BB, Spernger A, Ghanjati F, Santourlidis S., Haikel Y, Hassan M. Apoptosis. 2013 Aug;18(8):980-97.
19. Bortezomib/proteasome inhibitor triggers both apoptosis and autophagy-dependent pathways in melanoma cells. Selimovic D, Porzig BB, El-Khattouti A, Badura HE, Ahmad M, Ghanjati F, Santourlidis S., Haikel Y, Hassan M. Cell Signal. 2013 Jan;25(1):308-18. Erratum in: Cell Signal. 2015 Mar;27(3):727. Cell Signal. 2015 May;27(5):1019-1020.
20. Methods for Separate Isolation of Cell-Free DNA and Cellular DNA from Urine-Application of Methylation-Specific PCR on both DNA Fractions Agnes Beermann, Foued Ghanjati, Thomas Hermanns, Cedric Poyet, Joana Pereira, Johannes Fischer, Peter Wernet and Simeon Santourlidis. The Open Biomarkers Journal, 2011, 4, 15-17.
21. Unrestricted somatic stem cells (USSC) from human umbilical cord blood display uncommitted epigenetic signatures of the major stem cell pluripotency genes. Santourlidis S., Wernet P, Ghanjati F, Graffmann N, Springer J, Kriegs C, Zhao X, Brands J, Araúzo-Bravo MJ, Neves R, Koegler G, Uhrberg M. Stem Cell Res. 2011 Jan;6(1):60-9.
22. Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells. Neves R, Scheel C, Weinhold S, Honisch E, Iwaniuk KM, Trompeter HI, Niederacher D, Wernet P, Santourlidis S., Uhrberg M. BMC Res Notes. 2010 Aug 3;3:219.
23. Induction of pluripotency in human cord blood unrestricted somatic stem cells. Zaehres H, Kögler G, Arauzo-Bravo MJ, Bleidissel M, Santourlidis S., Weinhold S, Greber B, Kim JB, Buchheiser A, Liedtke S, Eilken HM, Graffmann N, Zhao X, Meyer J, Reinhardt P, Burr B, Waclawczyk S, Ortmeier C, Uhrberg M, Schöler HR, Cantz T, Wernet P. Exp Hematol. 2010 Sep;38(9):809-18, 818.e1-2.
24. The HOX Code as a "biological fingerprint" to distinguish functionally distinct stem cell populations derived from cord blood. Liedtke S, Buchheiser A, Bosch J, Bosse F, Kruse F, Zhao X, Santourlidis S., Kögler G. Stem Cell Res. 2010 Jul;5(1):40-50.
25. Induction of indoleamine 2, 3-dioxygenase by death receptor activation contributes to apoptosis of melanoma cells via mitochondrial damage-dependent ROS accumulation. Cetindere T, Nambiar S, Santourlidis S, Essmann F, Hassan M. Cell Signal. 2010 Feb;22(2):197-211.
26. Lineage-specific transition of histone signatures in the killer cell Ig-like receptor locus from hematopoietic progenitor to NK cells. Santourlidis S., Graffmann N, Christ J, Uhrberg M. J Immunol. 2008 Jan 1;180(1):418-25.
27. Nucleolin regulates gene expression in CD34-positive hematopoietic cells. Grinstein E, Du Y, Santourlidis S, Christ J, Uhrberg M, Wernet P. J Biol Chem. 2007 Apr 27;282(17):12439-49.
28. Nucleolin activates expression of CD34 and Bcl-2in CD34-positive hematopoietic cells. Grinstein E, Santourlidis S., Fischer J, Uhrberg M, Wernet P. J Stem Cells Regen Med. 2007 May 16;2(1):18-9.
29. Direct and quantitative analysis of chromatin accessibility by MIRECAL--a Micrococcus nuclease/real-time PCR chromatin accessibility assay with locus specificity. Graffmann N, Santourlidis S., Christ J, Wernet P, Uhrberg M. Anal Biochem. 2006 Jul 15;354(2):308-10. Epub 2006 Apr 19.
30. Molecular characterization of KIR3DL3. Trundley AE, Hiby SE, Chang C, Sharkey AM, Santourlidis S., Uhrberg M, Trowsdale J, Moffett A. Immunogenetics. 2006 Jan;57(12):904-16. 31. Three structurally and functionally divergent kinds of promoters regulate expression of clonally distributed killer cell Ig-like receptors (KIR), of KIR2DL4, and of KIR3DL3. Trompeter HI, Gómez-Lozano N, Santourlidis S., Eisermann B, Wernet P, Vilches C, Uhrberg M. J Immunol. 2005 Apr 1;174(7):4135-43.
32. Suppression of clonogenicity by mammalian Dnmt1 mediated by the PCNA-binding domain. Santourlidis S., Kimura F, Fischer J, Schulz WA. Biochem Cell Biol. 2004 Oct;82(5):589-96.
33. Downregulation of CD44v6 in colorectal carcinomas is associated with hypermethylation of the CD44 promoter region. Stallmach A, Wittig BM, Kremp K, Goebel R, Santourlidis S., Zeitz M, Menges M, Raedle J, Zeuzem S, Schulz WA. Exp Mol Pathol. 2003 Jun;74(3):262-6.
34. Decrease of DNA methyltransferase 1 expression relative to cell proliferation in transitional cell carcinoma. Kimura F, Seifert HH, Florl AR, Santourlidis S., Steinhoff C, Swiatkowski S, Mahotka C, Gerharz CD, Schulz WA. Int J Cancer. 2003 May 1;104(5):568-78.
35. Crucial role of DNA methylation in determination of clonally distributed killer cell Ig-like receptor expression patterns in NK cells. Santourlidis S., Trompeter HI, Weinhold S, Eisermann B, Meyer KL, Wernet P, Uhrberg M. J Immunol. 2002 Oct 15;169(8):4253-61.
36. Genomewide DNA hypomethylation is associated with alterations on chromosome 8 in prostate carcinoma. Schulz WA, Elo JP, Florl AR, Pennanen S, Santourlidis S., Engers R, Buchardt M, Seifert HH, Visakorpi T. Genes Chromosomes Cancer. 2002 Sep;35(1):58-65.
37. Refined mapping of allele loss at chromosome 10q23-26 in prostate cancer. Leube B, Drechsler M, Mühlmann K, Schäfer R, Schulz WA, Santourlidis S., Anastasiadis A, Ackermann R, Visakorpi T, Müller W, Royer-Pokora B. Prostate. 2002 Feb 15;50(3):135-44.
38. Hypermethylation of the tumor necrosis factor receptor superfamily 6 (APT1, Fas, CD95/Apo-1) gene promoter at rel/nuclear factor kappaB sites in prostatic carcinoma. Santourlidis S., Warskulat U, Florl AR, Maas S, Pulte T, Fischer J, Müller W, Schulz WA. Mol Carcinog. 2001 Sep;32(1):36-43.
39. High frequency of alterations in DNA methylation in adenocarcinoma of the prostate. Santourlidis S., Florl A, Ackermann R, Wirtz HC, Schulz WA. Prostate 1999 May 15;39(3):166-74.
40. Identification of the physiological promoter for spinocerebellar ataxia 2 gene reveals a CpG island for promoter activity situated into the exon 1 of this gene and provides data about the origin of the nonmethylated state of these types of islands. Aguiar J, Santourlidis S., Nowok J, Alexander C, Rudnicki D, Gispert S, Schulz W, Auburger G. Biochem Biophys Res Commun. 1999 Jan 19;254(2):315-8.
Prof. Dr. Rolf Ackermann died on February 11th, 2015. His clinical and scientific training included education in Germany and the United States. He was “instrumental in making German urology visible beyond the borders of the German-speaking world in the post–World War II era.”
Born in Ulm, Germany, he trained in Vienna, Austria, and Würzburg, Germany. He continued his training in Joe Kaufman’s Department of Urology at the University of California, Los Angeles. Having completed such an excellent education in clinical and scientific urology, Dr. Ackermann was well placed to take on a position as Professor and Chairman of the Department of Urology at the University of Düsseldorf (1983–2007). Apart from his clinical and surgical work, he focused his clinical and scientific research on uro-oncology and immunology. In 1989, he was elected as an international member of the prestigious American Association of Genitourinary Surgeons. He was a well-respected and well-liked urologist in Canada and internationally. He will be remembered as a dear friend of the Canadian Urological Association. He received honorable distinctions from the German Society of Urology (DGU), American Society of Urology (AUA) and European Association of Urology (EAU). Leader and Mentor, he was President of the German Society of Urology (DGU, 1996) and Director of the Heinrich-Heine University Düsseldorf (HHU). Certainly his career and life were strongly influenced and supported by his beloved wife Fr. Dra. Christl Ackermann-Schopf.
Informations and documents kindly provided by Frau Dra. Christl Ackermann-Schopf