The process of carcinogenesis described by mathematical formulas

The paper presents neoplasms as dissipative structures formed de novo in the host organism under conditions far from thermodynamic equilibrium. The neoplastic process has also been described as a form of random ”blastoid regeneration” (Fig. 2), and the use of information theory elements in this process has been shown to be expedient. The dissipative (precancerous) state may regress, or a thermodynamic branch may develop, and from it – as a result of neoplastic transformation – neoplasm, as illustrated in Figure 4, in the form of an ontogenetic ”tree”. Structures dissipative with fluctuating changes can probably create more and more organized formations, and thus the molecular level would explain Darwin’s theory of evolution and selection. Neoplasms are emergent structures created in the creative process and as disordered and unstable systems, they tend to the state of thermodynamic equilibrium, i.e. death. Their death can be accelerated by anti-cancer therapy or they die with the death of the macro-organism.

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Structural insights into the role of the Chl4–Iml3 complex in kinetochore assembly

Acta Crystallographica Section D Biological Crystallography ◽

10.1107/s0907444913022397 ◽

2013 ◽

Vol 69 (12) ◽

pp. 2412-2419 ◽

Cited By ~ 5

Author(s):

Qiong Guo ◽

Yuyong Tao ◽

Hejun Liu ◽

Maikun Teng ◽

Xu Li

Keyword(s):

De Novo ◽

Molecular Level ◽

Structural Information ◽

Binding Activity ◽

Intramolecular Interactions ◽

Exact Role ◽

Dna Binding Activity ◽

Kinetochore Assembly ◽

Structural Insights

Human CENP-N and CENP-L have been reported to selectively recognize the CENP-A nucleosome and to contribute to recruiting other constitutive centromere-associated network (CCAN) complexes involved in assembly of the inner kinetochore. As their homologues, Chl4 and Iml3 from budding yeast function in a similar way inde novoassembly of the kinetochore. A lack of biochemical and structural information precludes further understanding of their exact role at the molecular level. Here, the crystal structure of Iml3 is presented and the structure shows that Iml3 adopts an elongated conformation with a series of intramolecular interactions. Pull-down assays revealed that the C-terminal domain of Chl4, which forms a dimer in solution, is responsible for Iml3 binding. Acting as a heterodimer, the Chl4–Iml3 complex exhibits a low-affinity nonspecific DNA-binding activity which may play an important role in the kinetochore-assembly process.

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Targeting de novo lipogenesis as a novel approach in anti-cancer therapy

British Journal of Cancer ◽

10.1038/bjc.2017.374 ◽

2017 ◽

Vol 118 (1) ◽

pp. 43-51 ◽

Cited By ~ 26

Author(s):

Katharina Stoiber ◽

Olga Nagło ◽

Carla Pernpeintner ◽

Siwei Zhang ◽

Andreas Koeberle ◽

...

Keyword(s):

Cancer Therapy ◽

De Novo ◽

De Novo Lipogenesis ◽

Novel Approach ◽

Anti Cancer

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De novo assembly and inferred functional annotation of the transcriptome of Heterosigma akashiwo

10.22541/au.164112034.43396317/v1 ◽

2022 ◽

Author(s):

Masanao Sato ◽

Masahide Seki ◽

Yutaka Suzuki ◽

Shoko Ueki

Keyword(s):

Functional Annotation ◽

De Novo ◽

Molecular Level ◽

Transcriptome Assembly ◽

Practical Interest ◽

Heterosigma Akashiwo ◽

Sequence Information ◽

Biological Characterization ◽

Nucleotide Database

Heterosigma akashiwo is a eukaryotic, cosmopolitan, and unicellular alga (class: Raphidophyceae), and produces fish-killing blooms. There is a substantial scientific and practical interest in its ecophysiological characteristics that determine bloom dynamics and its adaptation to broad climate zones. A well-annotated genomic/genetic sequence information enables researchers to characterize organisms using modern molecular technology. The Chloroplast and the mitochondrial genome sequences and transcriptome sequence assembly (TSA) datasets with limited sizes for H. akashiwo are available in NCBI nucleotide database on December 2021: there is no doubt that more genetic information of the species will greatly enhance the progress of biological characterization of the species. Here, we conducted H. akashiwo RNA sequencing, a de novo transcriptome assembly (NCBI TSA ICRV01) of a large number of high-quality short-read sequences, and the functional annotation of predicted genes. Based on our transcriptome, we confirmed that the organism possesses genes that were predicted to function in phagocytosis, supporting the earlier observations of H. akashiwo bacterivory. Along with its capability for photosynthesis, the mixotrophy of H. akashiwo may partially explain its high adaptability to various environmental conditions. Our study here will provide an important toehold to decipher H. akashiwo ecophysiology at a molecular level.

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13′‐Carboxychromanol, a long‐chain metabolite of delta‐tocopherol, has potent anti‐cancer effects by interrupting de novo sphingolipid synthesis in human cancer cells

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.639.14 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Yumi Jang ◽

Soo Yee Kuah ◽

Qing Jiang

Keyword(s):

Cancer Cells ◽

De Novo ◽

Human Cancer ◽

Human Cancer Cells ◽

Anti Cancer ◽

Long Chain

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De novo assembly and inferred functional annotation of the transcriptome of Heterosigma akashiwo

10.22541/au.164112034.43396317/v2 ◽

2022 ◽

Author(s):

Masanao Sato ◽

Masahide Seki ◽

Yutaka Suzuki ◽

Shoko Ueki

Keyword(s):

Functional Annotation ◽

De Novo ◽

Molecular Level ◽

Transcriptome Assembly ◽

Practical Interest ◽

Heterosigma Akashiwo ◽

Sequence Information ◽

Biological Characterization ◽

Nucleotide Database

Heterosigma akashiwo is a eukaryotic, cosmopolitan, and unicellular alga (class: Raphidophyceae), and produces fish-killing blooms. There is a substantial scientific and practical interest in its ecophysiological characteristics that determine bloom dynamics and its adaptation to broad climate zones. A well-annotated genomic/genetic sequence information enables researchers to characterize organisms using modern molecular technology. The Chloroplast and the mitochondrial genome sequences and transcriptome sequence assembly (TSA) datasets with limited sizes for H. akashiwo are available in NCBI nucleotide database on December 2021: there is no doubt that more genetic information of the species will greatly enhance the progress of biological characterization of the species. Here, we conducted H. akashiwo RNA sequencing, a de novo transcriptome assembly (NCBI TSA ICRV01) of a large number of high-quality short-read sequences, and the functional annotation of predicted genes. Based on our transcriptome, we confirmed that the organism possesses genes that were predicted to function in phagocytosis, supporting the earlier observations of H. akashiwo bacterivory. Along with its capability for photosynthesis, the mixotrophy of H. akashiwo may partially explain its high adaptability to various environmental conditions. Our study here will provide an important toehold to decipher H. akashiwo ecophysiology at a molecular level.

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Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms20163960 ◽

2019 ◽

Vol 20 (16) ◽

pp. 3960 ◽

Cited By ~ 1

Author(s):

Yi-Ta Hsieh ◽

Yi-Fen Chen ◽

Shu-Chun Lin ◽

Kuo-Wei Chang ◽

Wan-Chun Li

Keyword(s):

Head And Neck ◽

Metabolic Pathways ◽

Cancer Metabolism ◽

Molecular Level ◽

Review Article ◽

Metabolic Reprogramming ◽

Prognostic Indicators ◽

Normal Cells ◽

Anti Cancer ◽

Great Energy

Considering the great energy and biomass demand for cell survival, cancer cells exhibit unique metabolic signatures compared to normal cells. Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. Recent findings have shown that environmental challenges, as well as intrinsic metabolic manipulations, could modulate HNSCC experimentally and serve as clinic prognostic indicators, suggesting that a better understanding of dynamic metabolic changes during HNSCC development could be of great benefit for developing adjuvant anti-cancer schemes other than conventional therapies. However, the following questions are still poorly understood: (i) how does metabolic reprogramming occur during HNSCC development? (ii) how does the tumorous milieu contribute to HNSCC tumourigenesis? and (iii) at the molecular level, how do various metabolic cues interact with each other to control the oncogenicity and therapeutic sensitivity of HNSCC? In this review article, the regulatory roles of different metabolic pathways in HNSCC and its microenvironment in controlling the malignancy are therefore discussed in the hope of providing a systemic overview regarding what we knew and how cancer metabolism could be translated for the development of anti-cancer therapeutic reagents.

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Biotechnological Approaches for Production of Anti-Cancerous Compounds Resveratrol, Podophyllotoxin and Zerumbone

Current Medicinal Chemistry ◽

10.2174/0929867324666170404145656 ◽

2018 ◽

Vol 25 (36) ◽

pp. 4693-4717 ◽

Cited By ~ 16

Author(s):

Krishnadas Nandagopal ◽

Mihir Halder ◽

Biswabhusan Dash ◽

Sanghamitra Nayak ◽

Sumita Jha

Keyword(s):

Plant Pathogens ◽

De Novo ◽

Higher Plants ◽

Toxicity Testing ◽

Cell Suspension Cultures ◽

Stilbene Synthase ◽

Callus Cultures ◽

Suspension Cultures ◽

Precursor Feeding ◽

Anti Cancer

Secondary metabolites from numerous plant sources have been developed as anti- cancer reagents and compounds such as resveratrol, podophyllotoxin and zerumbone are of particular importance in this regard. Since their de novo chemical synthesis is both arduous and commercially expensive, there has been an impetus to develop viable, biotechnological methods of production. Accordingly, this review focuses on the recent developments in the field, highlighting the use of micropropagation, cell suspension cultures, callus cultures, hairy root cultures, recombinant microbes and genetically modified higher plants. Optimization of media and culture conditions, precursor feeding, immobilization and the use of chemical or physical elicitation in various protocols has led to an increase in resveratrol and podophyllotoxin production. Heterologous gene transformation of higher plants with stilbene synthase derived from Arachis hypogaea or Vitis vinifera lead to resveratrol production with the concomitant increase in resistance to plant pathogens. Interestingly, genetic transformation of Podophyllum hexandrum and Linum flavum with Agrobacterium rhizogenes resulted in Ri-T-DNA gene(s)-mediated enhancement of podophyllotoxin production. Zerumbone yields from tissue cultured plantlets or from suspension cultures are generally low and these methods require further optimization. In microbes lacking the native resveratrol or zerumbone biosynthesis pathway, metabolic engineering required not only the introduction of several genes of the pathway, but also precursor feeding and optimization of gene expression to increase their production. Data pertaining to safety and toxicity testing are needed prior to use of these sources of anti-cancer compounds in therapy.

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Anti-Tumor Potential of IMP Dehydrogenase Inhibitors: A Century-Long Story

Cancers ◽

10.3390/cancers11091346 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1346 ◽

Cited By ~ 13

Author(s):

Naffouje ◽

Grover ◽

Yu ◽

Sendilnathan ◽

Wolfe ◽

...

Keyword(s):

Cancer Treatment ◽

Cancer Progression ◽

De Novo ◽

Malignant Tumors ◽

Inosine Monophosphate Dehydrogenase ◽

Variable Response ◽

Purine Nucleotides ◽

Proliferating Cells ◽

Anti Cancer ◽

Impdh Inhibitors

The purine nucleotides ATP and GTP are essential precursors to DNA and RNA synthesis and fundamental for energy metabolism. Although de novo purine nucleotide biosynthesis is increased in highly proliferating cells, such as malignant tumors, it is not clear if this is merely a secondary manifestation of increased cell proliferation. Suggestive of a direct causative effect includes evidence that, in some cancer types, the rate-limiting enzyme in de novo GTP biosynthesis, inosine monophosphate dehydrogenase (IMPDH), is upregulated and that the IMPDH inhibitor, mycophenolic acid (MPA), possesses anti-tumor activity. However, historically, enthusiasm for employing IMPDH inhibitors in cancer treatment has been mitigated by their adverse effects at high treatment doses and variable response. Recent advances in our understanding of the mechanistic role of IMPDH in tumorigenesis and cancer progression, as well as the development of IMPDH inhibitors with selective actions on GTP synthesis, have prompted a reappraisal of targeting this enzyme for anti-cancer treatment. In this review, we summarize the history of IMPDH inhibitors, the development of new inhibitors as anti-cancer drugs, and future directions and strategies to overcome existing challenges.

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