Starting in 1983 Vladimir F.Niculescu was Partner at SeroScreen GmbH in Hannover and Augsburg and Consultant for Infectious Diseases , Lab Diagnostics and Epidemiology Phone: Fax +4982384364 Address: 86420 Diedorf, Germany (Augsburg, Germany)
 Evolutionary Cancer Cell Biology (ECCB) reveals that the majority of cancer hallmarks trace thei... more  Evolutionary Cancer Cell Biology (ECCB) reveals that the majority of cancer hallmarks trace their origins back to the premetazoic era, approximately 2300 to 1750 million years ago. These cancer stem cell hallmarks share deep homology with the oxygen-sensitive non-gametogenic NG (Urgermline), which evolved from the common ancestor of Amoebozoan, Metazoan, and Fungi (AMF). The genes, gene modules, and gene regulatory networks of the premetazoic cell system are preserved in the ancestral genome compartment of metazoans and humans. The Urgermline serves as a blueprint for all germ and stem cell lineages, including parasitic amoebae. As observed in amoebae, DNA double-strand breaks (DSBs) manifest in the homologous recombination (HR) genes of NG germlines and stem cell lineages when exposed to specific hyperoxic conditions, referred to as AMF hyperoxia, characterized by an oxygen content exceeding 6.0%. The cells lose their stemness and differentiation potential but persist in proliferation as low-grade polyploids (4n) through defective symmetric cell division (DSCD phenotype). Genomic integrity can be restored through homotypic cell and nuclear fusion, resulting in the formation of high-grade polyploids known as multinuclear genome repair syncytia (MGRSs), or by inductive hyperpolyploidization of more than 64n, as observed in single-celled polyploid giant cancer cells (PGCCs). Interestingly, low-, middle-, and high-grade polyploidization are not exclusive to cancer. Therefore, we investigate (i) functional polyploidies that occur in healthy cells, including humans, mammals, and protists, (ii) dysfunctional polyploidies that occur in cells with impaired homologous recombination (HR) and irreparable DNA DSB defects, and (iii) the restoration of genome integrity through cyst-like and high-grade polyploidization events. Additionally, we explore dysfunction in aging stem cells, hepatocytes, and cardiomyocytes.Â
Background: One of the most astounding discoveries of recent times is the recognition that cancer... more Background: One of the most astounding discoveries of recent times is the recognition that cancer embodies a transition from a higher level of metazoan cell organization to a more foundational premetazoic state. This shift is steered by genes housed within the ancestral genome compartment, pervasive across all metazoan genomes, encompassing humans, and governed by a premetazoic ancestral gene regulatory network. This work aims to highlight the emerging field of evolutionary cancer cell biology (ECCB), which points to the deep homology between cancer and protist life cycles tracing back to the common ancestor of amoebozoans, metazoans, and fungi (AMF). The ECCB analysis reveals the essence of the non-gametogenic germline of the AMF ancestor, which serves as a blueprint for all metazoan germlines and stem cell lineages and controls the life cycle of cancer. Every germ and stem cell lineage of humans and metazoans traces its lineage back to this Urgermline, transmitting crucial processes such as asymmetric cell cycling, differentiation, stemness, and phenomena like germ-to-soma GST and soma-to-germ transition (aka epithelial-mesenchymal transition EMT and MET) to their subsequent evolutionary descendants. Oxygen-sensitive germline and stem cells suffer DNA double-strand breaks due to stress and oxygen ranges reminiscent of ancestral hyperoxia, leading to cell senescence. Cells that can overcome senescence can proliferate as defective symmetric cell division, paving the way for malignancy and polyploid giant cancer cell cancers. Conclusions: Understanding cancer from its evolutionary origins may help break some of the logjams in cancer prevention and open up new therapeutic pathways.
The life cycle of cancer follows the life cycle of the common ancestor of amoebozoans, metazoans,... more The life cycle of cancer follows the life cycle of the common ancestor of amoebozoans, metazoans, and fungi (AMF) and its systemic germline, which serves as a blueprint for all germlines capable of asymmetric cell division (ACD) and stem cell differentiation. Consequently, the oxygen sensitivity of the ancient non-gametogenic germline (Urgermline) was inherited by all germ and stem cell lines including the cancer germline. They all respond to Ugermline’s hyperoxia with loss of stemness and ACD ability and a dysregulated phenotype with irreparable DNA defects and defective symmetric cell divisions (DSCD). In protists, defective DSCD cells undergo an ancient MGRS repair program involving cell and nuclear fusion and hyperploid giant nuclei that restores the damaged genome to its former pre-DSCD state, with ACD potential and stemness. Human and metazoan DSCD use the same MGRS repair program inherited from the AMF ancestor. Ectopic DSCDs and DSCD-like phenotypes can survive in humans for...
The concept of cancer stem cells (CSCs) is the hot topic of the day and everyone is talking about... more The concept of cancer stem cells (CSCs) is the hot topic of the day and everyone is talking about them. Patients with metastases now know that their condition is due to recurrent CSCs with increased resistance to chemotherapeutics (rCSCs). However, there is confusion and controversy about the origin and development of CSCs in the scientific community. Where do CSCs come from and how do they develop during cancer progression?. Even now, the origin of CSCs remains unclear.1 Some confusion lies in the fact that most theories have in mind tumorigenic stem cells and suspect therefore that CSCs arise in specific cancer cell niches by oncogenic reprogramming of progenitor cells, adult stem cells or dedifferentiated cells;2,3 accordingly, it would be the cancer cell niche (CSN) that control CSC development, self-renewal, proliferation and phenotypic diversification.1,4 Regarding the cellular origin of cancer, many researchers share the idea that CSCs originate from a human stem cell (hSC) that evades the normal regulation of the adult stem cell niche (CSN) and forms cancer progenitor cells (CPCs).5‒7 In their opinion CSCs and CPCs are equivalent to normal stem cells and CSCs take over the stemness features of the normal hSCs. Other researchers mean CSCs come from damaged human stem cells undergoing excessive cell repair.8 Many terms such as cell-of-origin and non-stem-cells forming CSCs, transformed cells and mutated genes are ambiguous and less suitable. It was Nguyen9 that demands clarification and a more adequate terminology.
In the past, contradictory statements have been made about the age of cancer genes. While phylost... more In the past, contradictory statements have been made about the age of cancer genes. While phylostratigraphic studies suggest that cancer genes emerged during the transitional period from unicellularians (UC) to early metazoans (EM), life cycle studies suggest that they arose earlier. This controversy could not be resolved. Phylostratigraphic methods use data from somatic tumor gene collections containing or lacking polyploidy genes (PGCC genes) and compare them to genes from evolutionary node taxa. I analyze whether the selected taxa are suitable to resolve the above contradiction or not. Both cancer and amoebae life cycles have a reproductive asexual germline that produces germline stem cells (GSCs) and somatic cell lines that cannot. When the germline loses its reproductive function, the soma-to-germ transition forms a new reproductive germline. The reproductive polyploidy of cancer is homologous to the reproductive polyploidy of unicellular cysts. PGCCs repair DNA defects, reorganize the involved genome architecture and produce new GSCs. The present study refutes the dogma of the early metazoan origin of cancer. Cancer has a unicellular life cycle that was adopted by early metazoans to rescue themselves from evolutionary dead ends. Early metazoans controlled the unicellular life cycle through suppressor and anti-suppressor genes that could suspend or reactivate it. They are the archetypes of tumor suppressor genes and oncogenes. Cells of mammalians and humans that reach a similar impasse as early metazoans can reactivate the conserved life cycle of unicellularians.
Extracellular signaling and mechanisms of cell differentiation in Entamoeba are misunderstood. Th... more Extracellular signaling and mechanisms of cell differentiation in Entamoeba are misunderstood. The main reason is the popular use of axenic media, which do not correspond to the natural habitats of Entamoeba. The axenic environment lacks the exogenous activators and repressors provided by natural habitats. Absent bacterial commensals understanding of the development of the amoebic cell system remains deficient. The present Aa(Sm) culture method using mixed sediments of antibiotically repressed Aerobacter aerogens and amoebae was developed to model in vitro extracellular signaling that induce multicellularity in cultures of E. invadens. Repressed oxygen consuming sediment bacteria supply E. invadens the hypoxic environment needed for differentiation and development. The amoebae themselves alter the environment by consuming the bacteria by phagocytosis thus reversing hypoxia. Exogenous activators are in this manner down regulated and suppressed. This feedback effect controls amoebic development and differentiation. Co-existing cell types and cell fractions with different life spans and cell cycle length could be identified. Aa(Sm) long term cultures contain continuous and non-continuous self renewing cell lines producing quiescent and terminally differentiated daughter cells (precysts) by asymmetric division. This culturing method helps to understand the intimate relationship between hypoxic environments and the multicellular behaviour of E. invadens and the interrelations existing between the distinct cell types.
 Evolutionary Cancer Cell Biology (ECCB) reveals that the majority of cancer hallmarks trace thei... more  Evolutionary Cancer Cell Biology (ECCB) reveals that the majority of cancer hallmarks trace their origins back to the premetazoic era, approximately 2300 to 1750 million years ago. These cancer stem cell hallmarks share deep homology with the oxygen-sensitive non-gametogenic NG (Urgermline), which evolved from the common ancestor of Amoebozoan, Metazoan, and Fungi (AMF). The genes, gene modules, and gene regulatory networks of the premetazoic cell system are preserved in the ancestral genome compartment of metazoans and humans. The Urgermline serves as a blueprint for all germ and stem cell lineages, including parasitic amoebae. As observed in amoebae, DNA double-strand breaks (DSBs) manifest in the homologous recombination (HR) genes of NG germlines and stem cell lineages when exposed to specific hyperoxic conditions, referred to as AMF hyperoxia, characterized by an oxygen content exceeding 6.0%. The cells lose their stemness and differentiation potential but persist in proliferation as low-grade polyploids (4n) through defective symmetric cell division (DSCD phenotype). Genomic integrity can be restored through homotypic cell and nuclear fusion, resulting in the formation of high-grade polyploids known as multinuclear genome repair syncytia (MGRSs), or by inductive hyperpolyploidization of more than 64n, as observed in single-celled polyploid giant cancer cells (PGCCs). Interestingly, low-, middle-, and high-grade polyploidization are not exclusive to cancer. Therefore, we investigate (i) functional polyploidies that occur in healthy cells, including humans, mammals, and protists, (ii) dysfunctional polyploidies that occur in cells with impaired homologous recombination (HR) and irreparable DNA DSB defects, and (iii) the restoration of genome integrity through cyst-like and high-grade polyploidization events. Additionally, we explore dysfunction in aging stem cells, hepatocytes, and cardiomyocytes.Â
Background: One of the most astounding discoveries of recent times is the recognition that cancer... more Background: One of the most astounding discoveries of recent times is the recognition that cancer embodies a transition from a higher level of metazoan cell organization to a more foundational premetazoic state. This shift is steered by genes housed within the ancestral genome compartment, pervasive across all metazoan genomes, encompassing humans, and governed by a premetazoic ancestral gene regulatory network. This work aims to highlight the emerging field of evolutionary cancer cell biology (ECCB), which points to the deep homology between cancer and protist life cycles tracing back to the common ancestor of amoebozoans, metazoans, and fungi (AMF). The ECCB analysis reveals the essence of the non-gametogenic germline of the AMF ancestor, which serves as a blueprint for all metazoan germlines and stem cell lineages and controls the life cycle of cancer. Every germ and stem cell lineage of humans and metazoans traces its lineage back to this Urgermline, transmitting crucial processes such as asymmetric cell cycling, differentiation, stemness, and phenomena like germ-to-soma GST and soma-to-germ transition (aka epithelial-mesenchymal transition EMT and MET) to their subsequent evolutionary descendants. Oxygen-sensitive germline and stem cells suffer DNA double-strand breaks due to stress and oxygen ranges reminiscent of ancestral hyperoxia, leading to cell senescence. Cells that can overcome senescence can proliferate as defective symmetric cell division, paving the way for malignancy and polyploid giant cancer cell cancers. Conclusions: Understanding cancer from its evolutionary origins may help break some of the logjams in cancer prevention and open up new therapeutic pathways.
The life cycle of cancer follows the life cycle of the common ancestor of amoebozoans, metazoans,... more The life cycle of cancer follows the life cycle of the common ancestor of amoebozoans, metazoans, and fungi (AMF) and its systemic germline, which serves as a blueprint for all germlines capable of asymmetric cell division (ACD) and stem cell differentiation. Consequently, the oxygen sensitivity of the ancient non-gametogenic germline (Urgermline) was inherited by all germ and stem cell lines including the cancer germline. They all respond to Ugermline’s hyperoxia with loss of stemness and ACD ability and a dysregulated phenotype with irreparable DNA defects and defective symmetric cell divisions (DSCD). In protists, defective DSCD cells undergo an ancient MGRS repair program involving cell and nuclear fusion and hyperploid giant nuclei that restores the damaged genome to its former pre-DSCD state, with ACD potential and stemness. Human and metazoan DSCD use the same MGRS repair program inherited from the AMF ancestor. Ectopic DSCDs and DSCD-like phenotypes can survive in humans for...
The concept of cancer stem cells (CSCs) is the hot topic of the day and everyone is talking about... more The concept of cancer stem cells (CSCs) is the hot topic of the day and everyone is talking about them. Patients with metastases now know that their condition is due to recurrent CSCs with increased resistance to chemotherapeutics (rCSCs). However, there is confusion and controversy about the origin and development of CSCs in the scientific community. Where do CSCs come from and how do they develop during cancer progression?. Even now, the origin of CSCs remains unclear.1 Some confusion lies in the fact that most theories have in mind tumorigenic stem cells and suspect therefore that CSCs arise in specific cancer cell niches by oncogenic reprogramming of progenitor cells, adult stem cells or dedifferentiated cells;2,3 accordingly, it would be the cancer cell niche (CSN) that control CSC development, self-renewal, proliferation and phenotypic diversification.1,4 Regarding the cellular origin of cancer, many researchers share the idea that CSCs originate from a human stem cell (hSC) that evades the normal regulation of the adult stem cell niche (CSN) and forms cancer progenitor cells (CPCs).5‒7 In their opinion CSCs and CPCs are equivalent to normal stem cells and CSCs take over the stemness features of the normal hSCs. Other researchers mean CSCs come from damaged human stem cells undergoing excessive cell repair.8 Many terms such as cell-of-origin and non-stem-cells forming CSCs, transformed cells and mutated genes are ambiguous and less suitable. It was Nguyen9 that demands clarification and a more adequate terminology.
In the past, contradictory statements have been made about the age of cancer genes. While phylost... more In the past, contradictory statements have been made about the age of cancer genes. While phylostratigraphic studies suggest that cancer genes emerged during the transitional period from unicellularians (UC) to early metazoans (EM), life cycle studies suggest that they arose earlier. This controversy could not be resolved. Phylostratigraphic methods use data from somatic tumor gene collections containing or lacking polyploidy genes (PGCC genes) and compare them to genes from evolutionary node taxa. I analyze whether the selected taxa are suitable to resolve the above contradiction or not. Both cancer and amoebae life cycles have a reproductive asexual germline that produces germline stem cells (GSCs) and somatic cell lines that cannot. When the germline loses its reproductive function, the soma-to-germ transition forms a new reproductive germline. The reproductive polyploidy of cancer is homologous to the reproductive polyploidy of unicellular cysts. PGCCs repair DNA defects, reorganize the involved genome architecture and produce new GSCs. The present study refutes the dogma of the early metazoan origin of cancer. Cancer has a unicellular life cycle that was adopted by early metazoans to rescue themselves from evolutionary dead ends. Early metazoans controlled the unicellular life cycle through suppressor and anti-suppressor genes that could suspend or reactivate it. They are the archetypes of tumor suppressor genes and oncogenes. Cells of mammalians and humans that reach a similar impasse as early metazoans can reactivate the conserved life cycle of unicellularians.
Extracellular signaling and mechanisms of cell differentiation in Entamoeba are misunderstood. Th... more Extracellular signaling and mechanisms of cell differentiation in Entamoeba are misunderstood. The main reason is the popular use of axenic media, which do not correspond to the natural habitats of Entamoeba. The axenic environment lacks the exogenous activators and repressors provided by natural habitats. Absent bacterial commensals understanding of the development of the amoebic cell system remains deficient. The present Aa(Sm) culture method using mixed sediments of antibiotically repressed Aerobacter aerogens and amoebae was developed to model in vitro extracellular signaling that induce multicellularity in cultures of E. invadens. Repressed oxygen consuming sediment bacteria supply E. invadens the hypoxic environment needed for differentiation and development. The amoebae themselves alter the environment by consuming the bacteria by phagocytosis thus reversing hypoxia. Exogenous activators are in this manner down regulated and suppressed. This feedback effect controls amoebic development and differentiation. Co-existing cell types and cell fractions with different life spans and cell cycle length could be identified. Aa(Sm) long term cultures contain continuous and non-continuous self renewing cell lines producing quiescent and terminally differentiated daughter cells (precysts) by asymmetric division. This culturing method helps to understand the intimate relationship between hypoxic environments and the multicellular behaviour of E. invadens and the interrelations existing between the distinct cell types.
Uploads
Papers by Vladimir F. Niculescu