Neoplastic Transformation Induced by Heavy Ions: Studies on Transformation Efficiencies and Molecular Mechanisms

1993 ◽  
pp. 135-141 ◽  
Author(s):  
Ludwig Hieber ◽  
Jan Smida ◽  
Albrecht M. Kellerer
Keyword(s):  
Heavy Ions ◽  
Molecular Mechanisms ◽  
Neoplastic Transformation

scholarly journals Molecular mechanisms of hemostasis impairment in oncology

2021 ◽  
Vol 20 (4) ◽  
pp. 191-198
Author(s):  
E. M. Koltsova ◽  
G. S. Svidelskaya ◽  
Yu. A. Shifrin ◽  
F. I. Ataullakhanov
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Neoplastic Transformation ◽  
Malignant Neoplasms ◽  
Coagulation Disorders ◽  
Platelet Dysfunction ◽  
Hemostasis System

Malignant neoplasms are characterized by the presence of the hemostasis system pathology, predisposing cancer patients to thrombohemorrhagic complications. The pathogenesis of cancer-associated coagulopathy is complex and involves a variety of mechanisms. Tumor cells have the ability to activate the host’s hemostasis system, and this phenomenon is controlled by the same oncogenes that are responsible for neoplastic transformation. In addition to predisposing factors to impaired hemostasis from the side of the disease, the anticancer drugs themselves carry risks of developing coagulation disorders. The pathophysiological basis of this kind of disorders caused by chemotherapy is associated with damage to the endothelium, imbalance of coagulation and anticoagulant proteins, platelet dysfunction and their deficiency. In this article, the authors set themselves the goal of generalizing and updating the current knowledge of the molecular mechanisms that cause thrombohemorrhagic risk in cancer. 

scholarly journals Loss of p53 protein during radiation transformation of primary human mammary epithelial cells.

1994 ◽  
Vol 14 (4) ◽  
pp. 2468-2478 ◽  
Author(s):  
D E Wazer ◽  
Q Chu ◽  
X L Liu ◽  
Q Gao ◽  
H Safaii ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
P53 Protein ◽  
Neoplastic Transformation ◽  
Mammary Epithelial ◽  
G1 Arrest ◽  
Protein Loss ◽  
The Third ◽  
Human Mammary Epithelial

The causative factors leading to breast cancer are largely unknown. Increased incidence of breast cancer following diagnostic or therapeutic radiation suggests that radiation may contribute to mammary oncogenesis. This report describes the in vitro neoplastic transformation of a normal human mammary epithelial cell strain, 76N, by fractionated gamma-irradiation at a clinically used dose (30 Gy). The transformed cells (76R-30) were immortal, had reduced growth factor requirements, and produced tumors in nude mice. Remarkably, the 76R-30 cells completely lacked the p53 tumor suppressor protein. Loss of p53 was due to deletion of the gene on one allele and a 26-bp deletion within the third intron on the second allele which resulted in abnormal splicing out of either the third or fourth exon from the mRNA. PCR with a mutation-specific primer showed that intron 3 mutation was present in irradiated cells before selection for immortal phenotype. 76R-30 cells did not exhibit G1 arrest in response to radiation, indicating a loss of p53-mediated function. Expression of the wild-type p53 gene in 76R-30 cells led to their growth inhibition. Thus, loss of p53 protein appears to have contributed to neoplastic transformation of these cells. This unique model should facilitate analyses of molecular mechanisms of radiation-induced breast cancer and allow identification of p53-regulated cellular genes in breast cells.

scholarly journals Neoplastic transformation of mouse C3H 10T and Syrian hamster embryo cells by heavy ions

1989 ◽  
Vol 9 (10) ◽  
pp. 141-149 ◽  
Author(s):  
L. Hieber ◽  
G. Ponsel ◽  
K. Trutschler ◽  
S. Fenn ◽  
A.M. Kellerer
Keyword(s):  
Syrian Hamster ◽  
Heavy Ions ◽  
Neoplastic Transformation ◽  
Hamster Embryo Cells ◽  
Embryo Cells

Neoplastic transformation of hamster embryo cells by heavy ions

1998 ◽  
Vol 22 (12) ◽  
pp. 1725-1732 ◽  
Author(s):  
Z Han ◽  
H Suzuki ◽  
F Suzuki ◽  
M Suzuki ◽  
Y Furusawa ◽  
...  
Keyword(s):  
Heavy Ions ◽  
Neoplastic Transformation ◽  
Hamster Embryo Cells ◽  
Embryo Cells

Grapevine habituation: Understanding of factors that contribute to neoplastic transformation and somaclonal variation

2008 ◽  
Vol 56 (4) ◽  
pp. 399-408 ◽  
Author(s):  
V. Repka ◽  
I. Baumgartnerová
Keyword(s):  
Molecular Mechanisms ◽  
Protein Microarray ◽  
Neoplastic Transformation ◽  
Computational Prediction ◽  
Protein Family ◽  
Molecular Evidence ◽  
Family Interactions ◽  
Core Network ◽  
Two Dimensional Gel Electrophoresis ◽  
Differential Expression Pattern

Two-dimensional gel electrophoresis coupled to protein microarray analysis was used to examine for the first time the molecular mechanisms of grapevine habituation ( Vitis vinifera L., cv. Limberger) at both the proteome and the interactome level. The examination of 2-D maps derived from control and habituated cell cultures revealed the presence of 55 protein spots displaying a differential expression pattern. Using computational prediction methods, fundamental differences were found between eukaryotic interactomes. It was confirmed that all the predicted protein family interactomes (the full set of protein family interactions within a proteome) of six species are scale-free networks, and that they share a small core network comprising 16 protein families related to indispensable cellular functions predominantly involved in pathogenesis, apoptosis and plant tumorigenesis. There is molecular evidence suggesting that grapevine cells which have become habituated for one or more essential factors originated from heritable alterations in the pattern of gene expression and that they can, therefore, be used as a model for the study of cell differentiation and/or neoplastic transformation.

Multiple mechanisms account for genomic instability and molecular mutation in neoplastic transformation

1995 ◽  
Vol 41 (5) ◽  
pp. 644-657 ◽  
Author(s):  
W B Coleman ◽  
G J Tsongalis
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Dna Replication ◽  
Genomic Instability ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Neoplastic Transformation ◽  
Molecular Alteration ◽  
Cellular Processes ◽  
Genes Encoding

Abstract Neoplastic cells typically possess numerous genomic mutations and chromosomal aberrations, including point mutations, gene amplifications and deletions, and replication errors. Acquisition of such genomic instability may represent an early step in the process of carcinogenesis. Proteins involved in DNA replication, DNA repair, cell cycle progression, and others are all components of complex overlapping biochemical pathways that function to maintain cellular homeostasis. Therefore, mutational alteration of genes encoding proteins involved in these cellular processes could contribute to genomic instability. Loss of normal cellular mechanisms that guard against genomic mutation and the ensuing genomic instability might lead to accumulation of multiple stable mutations in the genome of affected cells, perhaps resulting in neoplastic transformation when some critical number of transformation-related target genes become damaged. Thus, interactions of fundamental cellular processes play significant roles in sustaining cellular normality, and alteration of any of these homeostatic processes could entrain cells to the progressive genomic instability and phenotypic evolution characteristic of carcinogenesis. Here, we discuss possible molecular mechanisms governing DNA mutation and genomic instability in genetically normal cells that might account for the acquisition of genomic instability in somatic cells, leading to the development of neoplasia. These include (a) molecular alteration of genes encoding DNA repair enzymes, (b) molecular alteration of genes responsible for cell-cycle control mechanisms, and (c) direct molecular alteration of dominantly transforming cellular protooncogenes. We also discuss normal cellular processes involved with DNA replication and repair that can contribute to the mutational alteration of critical genes: e.g., slow repair of damaged DNA in specific genes, and the timing of normal gene-specific replication.

scholarly journals Fibroinflammatory Liver Injuries as Preneoplastic Condition in Cholangiopathies

2018 ◽  
Vol 19 (12) ◽  
pp. 3875 ◽  
Author(s):  
Stefania Cannito ◽  
Chiara Milani ◽  
Andrea Cappon ◽  
Maurizio Parola ◽  
Mario Strazzabosco ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Tumor Development ◽  
Neoplastic Transformation ◽  
Inflammatory Cells ◽  
Biliary Tree ◽  
Signal Pathways ◽  
Murine Models ◽  
Liver Injuries ◽  
Cellular Types ◽  
Liver Response

The cholangipathies are a class of liver diseases that specifically affects the biliary tree. These pathologies may have different etiologies (genetic, autoimmune, viral, or toxic) but all of them are characterized by a stark inflammatory infiltrate, increasing overtime, accompanied by an excess of periportal fibrosis. The cellular types that mount the regenerative/reparative hepatic response to the damage belong to different lineages, including cholagiocytes, mesenchymal and inflammatory cells, which dynamically interact with each other, exchanging different signals acting in autocrine and paracrine fashion. Those messengers may be proinflammatory cytokines and profibrotic chemokines (IL-1, and 6; CXCL1, 10 and 12, or MCP-1), morphogens (Notch, Hedgehog, and WNT/β-catenin signal pathways) and finally growth factors (VEGF, PDGF, and TGFβ, among others). In this review we will focus on the main molecular mechanisms mediating the establishment of a fibroinflammatory liver response that, if perpetuated, can lead not only to organ dysfunction but also to neoplastic transformation. Primary Sclerosing Cholangitis and Congenital Hepatic Fibrosis/Caroli’s disease, two chronic cholangiopathies, known to be prodrome of cholangiocarcinoma, for which several murine models are also available, were also used to further dissect the mechanisms of fibroinflammation leading to tumor development.

Loss of p53 protein during radiation transformation of primary human mammary epithelial cells

1994 ◽  
Vol 14 (4) ◽  
pp. 2468-2478
Author(s):  
D E Wazer ◽  
Q Chu ◽  
X L Liu ◽  
Q Gao ◽  
H Safaii ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
P53 Protein ◽  
Neoplastic Transformation ◽  
Mammary Epithelial ◽  
G1 Arrest ◽  
Protein Loss ◽  
The Third ◽  
Human Mammary Epithelial

The causative factors leading to breast cancer are largely unknown. Increased incidence of breast cancer following diagnostic or therapeutic radiation suggests that radiation may contribute to mammary oncogenesis. This report describes the in vitro neoplastic transformation of a normal human mammary epithelial cell strain, 76N, by fractionated gamma-irradiation at a clinically used dose (30 Gy). The transformed cells (76R-30) were immortal, had reduced growth factor requirements, and produced tumors in nude mice. Remarkably, the 76R-30 cells completely lacked the p53 tumor suppressor protein. Loss of p53 was due to deletion of the gene on one allele and a 26-bp deletion within the third intron on the second allele which resulted in abnormal splicing out of either the third or fourth exon from the mRNA. PCR with a mutation-specific primer showed that intron 3 mutation was present in irradiated cells before selection for immortal phenotype. 76R-30 cells did not exhibit G1 arrest in response to radiation, indicating a loss of p53-mediated function. Expression of the wild-type p53 gene in 76R-30 cells led to their growth inhibition. Thus, loss of p53 protein appears to have contributed to neoplastic transformation of these cells. This unique model should facilitate analyses of molecular mechanisms of radiation-induced breast cancer and allow identification of p53-regulated cellular genes in breast cells.

scholarly journals Iron Metabolism: From Inflammation to Cancer

2021 ◽  
Vol 8 (6) ◽  
Author(s):  
Di Paola A ◽  
◽  
Tortora C ◽  
Argenziano M ◽  
Di Leva C ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Iron Uptake ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Neoplastic Transformation ◽  
Direct Consequence ◽  
Cellular Accumulation ◽  
Cell Functions ◽  
Systemic Level ◽  
Inflammatory Processes

Iron is a trace element essential for several physiological cell functions and any alteration in its metabolism could be associated to the onset of several disorders. Cells normally avoid any dysregulation, activating fine molecular mechanisms to balance iron uptake, utilization, recycling, storage and export. The main “actors” in this event are hepcidin, ferroportin, ferritin and transferrin, both at cell and systemic level. Dysregulation in iron homeostasis is closely related to inflammation onset and perpetuation, osteoporosis and cancer progression. During inflammation, it has been observed a reduction in circulating iron as direct consequence of increase in ferritin levels, aimed to contain inflammatory processes and in many cases to restore the immune response. Iron overload directly promotes bone resorption and inhibits bone formation inducing osteoporosis. Moreover, iron cellular accumulation is responsible for ROS production with consequent DNA damage and neoplastic transformation of cells. In conclusion, even though many molecular mechanisms have to be clarified, targeting iron and also the mediators of its metabolism could be useful to manage a great variety of disorders, such inflammation, immune diseases, osteoporosis and cancer.

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