Molecular Concepts Research MCR

Bad Münster am Stein-Ebernburg, Germany

Molecular Concepts Research MCR

Bad Münster am Stein-Ebernburg, Germany
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Radulescu R.T.,Molecular Concepts Research MCR
Romanian Journal of Morphology and Embryology | Year: 2014

Tumor suppressors constitute the body's primary defense line against malignant transformation. Since Theodor Boveri's initial insight one century ago, a huge amount of knowledge on these molecules has been generated. However, the final step of application of this profound understanding in the clinical setting, i.e., the treatment of cancer patients with tumor suppressors and their derivatives, is still ahead. Nevertheless, the important success achieved with similar biomimetic approaches in the therapy of other diseases suggests that tumor suppressor-based antineoplastic interventions should be accomplished soon as they may be equally rewarding.


Radulescu R.T.,Molecular Concepts Research MCR
Romanian Journal of Morphology and Embryology | Year: 2014

In this brief survey, I look back upon a quarter of a century of my personal experience with synthetic peptides. Thereby, I focus on major steps in the design and experimental exploration of peptides that I have derived from the retinoblastoma tumor suppressor protein (RB). Along this way, both Merrifield's solid phase peptide synthesis method and collaborations with established investigators in the peptide and cancer research fields have played an important role.


Radulescu R.T.,Molecular Concepts Research MCR | Duckworth W.C.,Phoenix VA Health Care System | Levy J.L.,Research Service | Fawcett J.,Research Service
Biochemical and Biophysical Research Communications | Year: 2010

Previous investigations on proteasomal preparations containing insulin-degrading enzyme (IDE; EC 3.4.24.56) have invariably yielded a co-purifying protein with a molecular weight of about 110 kDa. We have now found both in MCF-7 breast cancer and HepG2 hepatoma cells that this associated molecule is the retinoblastoma tumor suppressor protein (RB). Interestingly, the amount of RB in this protein complex seemed to be lower in HepG2 vs. MCF-7 cells, indicating a higher (cytoplasmic) protein turnover in the former vs. the latter cells. Moreover, immunofluorescence showed increased nuclear localization of RB in HepG2 vs. MCF-7 cells. Beyond these subtle differences between these distinct tumor cell types, our present study more generally suggests an interplay between RB and IDE within the proteasome that may have important growth-regulatory consequences.


Hypertension ranks among the most important disease challenges on a global scale. Here, a novel hypothesis is presented which implicates angiotensinogen, i.e. the precursor protein for the hypertensive peptide angiotensin II, as a key culprit in the pathogenesis of hypertension. This hypothesis more precisely entails that intracellular angiotensinogen binds and thereby inactivates the retinoblastoma tumor suppressor protein (RB), consequently leading to an inflammatory and hyperproliferative state that significantly contributes to pathologically increasing blood pressure. Accordingly, a conceivable antihypertensive strategy could comprise RBderived compounds that neutralize angiotensinogen.


Radulescu R.T.,Molecular Concepts Research MCR
Romanian Journal of Morphology and Embryology | Year: 2015

More than 20 years ago, it was initially predicted that hormones and growth factors might promote cell growth by binding and thereby inactivating tumor suppressors, as exemplified by the proposed complex formation between insulin and retinoblastoma protein (RB). This mainly intracellular/nuclear growth-regulatory circuit was termed “the nucleocrine pathway” and the physical interaction between insulin and RB was subsequently proven through several methods, primarily by immunofluorescence and co-immunoprecipitation. Meanwhile, additional nucleocrine pairs have emerged through further experimental studies, specifically the FGF1-p53 and angiogenin-p53 heterodimers. Moreover, first experimental clues have been obtained as to the intranuclear presence of the previously surmised heterodimer between the EGF precursor and the p130 tumor suppressor. In addition, RB-binding motifs have recently been discovered in interleukin-6 (IL-6) and cellular apoptosis susceptibility (CAS) protein. These findings point to a more general significance of the nucleocrine pathway in cell growth regulation and as a particularly useful target in cancer therapy. © 2015, Editura Academiei Romane. All rights reserved.


Radulescu R.T.,Molecular Concepts Research MCR
Diabetology and Metabolic Syndrome | Year: 2011

Insulin is one of the major metabolic hormones regulating glucose homeostasis in the organism and a key growth factor for normal and neoplastic cells. Work conducted primarily over the past 3 decades has unravelled the presence of insulin in human breast cancer tissues and, more recently, in human non-small cell lung carcinomas (NSCLC). These findings have suggested that intracellular insulin is involved in the development of these highly prevalent human tumors. A potential mechanism for such involvement is insulin's binding and inactivation of the retinoblastoma tumor suppressor protein (RB) which in turn is likely controlled by insulin-degrading enzyme (IDE). This model and its supporting data are collectively covered in this survey in order to provide further insight into insulin-driven oncogenesis and its reversal through future anticancer therapeutics. © 2011 Radulescu; licensee BioMed Central Ltd.


Radulescu R.T.,Molecular Concepts Research MCR
Journal of Experimental and Clinical Cancer Research | Year: 2010

The past two decades have witnessed an increasing appreciation of the role of the tumor microenvironment, of genetic and epigenetic alterations in normal cells adjacent to tumors and of the migration of normal cells with aberrant intrinsic properties in cancer pathophysiology. Aside from these insights, a novel concept termed "oncoprotein metastasis" (OPM) has recently been advanced and proposed to reflect protein-based neoplastic phenomena that might occur even before any modifications relating to the morphology, location or (epi)genetic outfit of cells during the malignant process. Here, evidence is presented that supports the OPM perception and thus should contribute not only to further rethink the definition of a normal cell, but also the treatment of cancer disease in the years to come. © 2010 Radulescu; licensee BioMed Central Ltd.


Radulescu R.T.,Molecular Concepts Research MCR
Protein and Peptide Letters | Year: 2014

About twenty years ago, the search for a peptide mimetic of the crucial 928-amino acid human retinoblastoma tumor suppressor protein (RB) has led to the identification of a potential active site in RB spanning 6 amino acids. Subsequent studies revealed that this hexapeptide needs to be coupled to a cellular internalization sequence in order to be biologically active. The prototype molecule resulting therefrom has been the synthetic 22-amino acid peptide MCR-4 that was proven through several investigations to exert both in vitro and in vivo anti-cancer activity both resembling and going beyond the antiproliferative effects of its template RB. This was followed by the elaboration of a distinct series of MCR peptides designed to also interfere with target structures located on the surface of cells and known to be involved in triggering cell proliferation such as the insulin receptor. For this second generation group, the prototype peptide has been another 22-amino acid peptide coined MCR-14 and equally demonstrated to display in vitro and in vivo anti-tumor effects. Finally, a miniaturization of the structure-function relationships intrinsic to the already small MCR-4 peptide has led to the development of the third generation 17-amino acid peptide MCR-15 which in turn was also shown to inhibit in vitro and in vivo malignant cell reproduction. Given more recent conceptual advances, it is warranted to claim that MCR peptides are likely candidate therapeutics not only for the treatment of neoplasias, but also of viral and bacterial infections, type 2 diabetes as well as hypertension. © 2014 Bentham Science Publishers.


PubMed | Molecular Concepts Research MCR
Type: Journal Article | Journal: Protein and peptide letters | Year: 2014

About twenty years ago, the search for a peptide mimetic of the crucial 928-amino acid human retinoblastoma tumor suppressor protein (RB) has led to the identification of a potential active site in RB spanning 6 amino acids. Subsequent studies revealed that this hexapeptide needs to be coupled to a cellular internalization sequence in order to be biologically active. The prototype molecule resulting therefrom has been the synthetic 22-amino acid peptide MCR-4 that was proven through several investigations to exert both in vitro and in vivo anti-cancer activity both resembling and going beyond the antiproliferative effects of its template RB. This was followed by the elaboration of a distinct series of MCR peptides designed to also interfere with target structures located on the surface of cells and known to be involved in triggering cell proliferation such as the insulin receptor. For this second generation group, the prototype peptide has been another 22-amino acid peptide coined MCR-14 and equally demonstrated to display in vitro and in vivo anti-tumor effects. Finally, a miniaturization of the structure-function relationships intrinsic to the already small MCR-4 peptide has led to the development of the third generation 17-amino acid peptide MCR-15 which in turn was also shown to inhibit in vitro and in vivo malignant cell reproduction. Given more recent conceptual advances, it is warranted to claim that MCR peptides are likely candidate therapeutics not only for the treatment of neoplasias, but also of viral and bacterial infections, type 2 diabetes as well as hypertension.


Radulescu R.T.,Molecular Concepts Research MCR
Romanian Journal of Morphology and Embryology | Year: 2013

In this survey, the initial insights on the sub-and transcellular process of oncoprotein metastasis (OPM) are linked to recent observations and advances in related fields. The six proteins described here, i.e. insulin, osteopontin, interleukin-6, anterior gradient-2 protein, cellular apoptosis susceptibility protein and hepatoma-derived growth factor, as well as distinct peptide fragments thereof might henceforth serve as pivotal biomarkers for OPM in clinical chemistry, molecular morphology, pathology and oncology and, as a result, guide as potential targets future structure-based interventions in cancer treatment.

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