scholarly journals Biochemistry, Not Oncogenes, may Demystify and Defeat Cancer

2021 ◽  
Author(s):  
Jay Kulsh
Keyword(s):  
Active Site ◽  
Epidemiological Studies ◽  
The Cancer Genome Atlas ◽  
Causative Gene ◽  
Principal Role ◽  
Cervical Cancers ◽  
Cancer Genome Atlas ◽  
A Cell ◽  
Rate Limiting ◽  
Insight Into

The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.

scholarly journals Biochemistry, Not Oncogenes, may Demystify and Defeat Cancer

2021 ◽  
Author(s):  
Jay Kulsh
Keyword(s):  
Epidemiological Studies ◽  
The Cancer Genome Atlas ◽  
Causative Gene ◽  
Experimental Proof ◽  
Principal Role ◽  
Cervical Cancers ◽  
Cancer Genome Atlas ◽  
A Cell ◽  
Rate Limiting ◽  
Insight Into

Presence of mutated genes strongly correlates with incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprit, we need to look at the biochemistry of cancer, with focus on enzymes which carry out any and all transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) which is tightly linked to tumor growth. Beside the circumstantial evidence that cancer is induced at its vulnerable active-site by various carcinogens, there exists experimental proof of its role in initiating retinoblastoma and HPV-related cervical cancers. Blocking the activity of RnR is a certain way to arrest cancer.

scholarly journals Biochemistry, Not Oncogenes, may Demystify and Defeat Cancer

2021 ◽  
Author(s):  
Jay Kulsh
Keyword(s):  
Epidemiological Studies ◽  
The Cancer Genome Atlas ◽  
Causative Gene ◽  
Experimental Proof ◽  
Principal Role ◽  
Cervical Cancers ◽  
Cancer Genome Atlas ◽  
A Cell ◽  
Rate Limiting ◽  
Insight Into

Presence of mutated genes strongly correlates with incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprit, we need to look at the biochemistry of cancer, with focus on enzymes which carry out any and all transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) which is tightly linked to tumor growth. Beside the circumstantial evidence that cancer is induced at its vulnerable active-site by various carcinogens, there exists experimental proof of its role in initiating retinoblastoma and HPV-related cervical cancers. Blocking the activity of RnR is a certain way to arrest cancer.

scholarly journals High expression levels of pyrimidine metabolic rate–limiting enzymes are adverse prognostic factors in lung adenocarcinoma: a study based on The Cancer Genome Atlas and Gene Expression Omnibus datasets

2020 ◽  
Vol 16 (3) ◽  
pp. 347-366 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Lung Cancer ◽  
Metabolic Rate ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Pyrimidine Metabolism ◽  
Expression Levels ◽  
Cancer Genome Atlas ◽  
Rate Limiting ◽  
Genome Atlas

Abstract Reprogramming of metabolism is described in many types of cancer and is associated with the clinical outcomes. However, the prognostic significance of pyrimidine metabolism signaling pathway in lung adenocarcinoma (LUAD) is unclear. Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, we found that the pyrimidine metabolism signaling pathway was significantly enriched in LUAD. Compared with normal lung tissues, the pyrimidine metabolic rate–limiting enzymes were highly expressed in lung tumor tissues. The high expression levels of pyrimidine metabolic–rate limiting enzymes were associated with unfavorable prognosis. However, purinergic receptors P2RX1, P2RX7, P2RY12, P2RY13, and P2RY14 were relatively downregulated in lung cancer tissues and were associated with favorable prognosis. Moreover, we found that hypo-DNA methylation, DNA amplification, and TP53 mutation were contributing to the high expression levels of pyrimidine metabolic rate–limiting enzymes in lung cancer cells. Furthermore, combined pyrimidine metabolic rate–limiting enzymes had significant prognostic effects in LUAD. Comprehensively, the pyrimidine metabolic rate–limiting enzymes were highly expressed in bladder cancer, breast cancer, colon cancer, liver cancer, and stomach cancer. And the high expression levels of pyrimidine metabolic rate–limiting enzymes were associated with unfavorable prognosis in liver cancer. Overall, our results suggested the mRNA levels of pyrimidine metabolic rate–limiting enzymes CAD, DTYMK, RRM1, RRM2, TK1, TYMS, UCK2, NR5C2, and TK2 were predictive of lung cancer as well as other cancers.

scholarly journals CAPRI: Efficient Inference of Cancer Progression Models from Cross-sectional Data

2014 ◽  
Author(s):  
Daniele Ramazzotti ◽  
Giulio Caravagna ◽  
Loes Olde Loohuis ◽  
Alex Graudenzi ◽  
Ilya Korsunsky ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Directed Acyclic Graphs ◽  
The Cancer Genome Atlas ◽  
Scoring Method ◽  
Cross Sectional ◽  
Progression Model ◽  
Acyclic Graphs ◽  
Cancer Genome Atlas ◽  
Atypical Chronic Myeloid Leukemia ◽  
Insight Into

We devise a novel inference algorithm to effectively solve the cancer progression model reconstruction problem. Our empirical analysis of the accuracy and convergence rate of our algorithm, CAncer PRogression Inference (CAPRI), shows that it outperforms the state-of-the-art algorithms addressing similar problems. Motivation: Several cancer-related genomic data have become available (e.g., The Cancer Genome Atlas, TCGA) typically involving hundreds of patients. At present, most of these data are aggregated in a cross-sectional fashion providing all measurements at the time of diagnosis. Our goal is to infer cancer ?progression? models from such data. These models are represented as directed acyclic graphs (DAGs) of collections of ?selectivity? relations, where a mutation in a gene A ?selects? for a later mutation in a gene B. Gaining insight into the structure of such progressions has the potential to improve both the stratification of patients and personalized therapy choices. Results: The CAPRI algorithm relies on a scoring method based on a probabilistic theory developed by Suppes, coupled with bootstrap and maximum likelihood inference. The resulting algorithm is efficient, achieves high accuracy, and has good complexity, also, in terms of convergence properties. CAPRI performs especially well in the presence of noise in the data, and with limited sample sizes. Moreover CAPRI, in contrast to other approaches, robustly reconstructs different types of confluent trajectories despite irregularities in the data. We also report on an ongoing investigation using CAPRI to study atypical Chronic Myeloid Leukemia, in which we uncovered non trivial selectivity relations and exclusivity patterns among key genomic events.

scholarly journals miRNA-144-5p/ITGA3 Suppressed the Tumor-Promoting Behaviors of Thyroid Cancer Cells by Downregulating ITGA3

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jizong Zhang ◽  
Yan Zhong ◽  
Yiming Sang ◽  
Guanghui Ren
Keyword(s):  
Thyroid Cancer ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Luciferase Assay ◽  
Cell Behaviors ◽  
Protein Levels ◽  
Related Cell ◽  
Cancer Genome Atlas ◽  
Thyroid Cancer Cells ◽  
Insight Into

Objective. To ascertain the mechanism of miRNA-144-5p and ITGA3 in thyroid cancer (TC). Methods. From The Cancer Genome Atlas (TCGA), RNA expression profiles were obtained for the expression analysis of miRNAs and mRNAs in TC. qRT-PCR and western blot were utilized to measure the expression of miRNA-144-5p and ITGA3 at RNA and protein levels, respectively. The association between miRNA-144-5p and ITGA3 was validated by the dual-luciferase assay. CCK-8, scratch healing, transwell, and flow cytometry assays were employed to evaluate tumor-related cell behaviors. Results. Low-expressed miRNA-144-5p and high-expressed ITGA3 were found in TC cells relative to normal cells. miRNA-144-5p expression was positively associated with suppressive effects on proliferative, invasive, and migratory ability of TC cells while negatively associated with cell apoptosis. miRNA-144-5p inhibited ITGA3 expression in TC, and its overexpression remarkably reversed the tumor-promoting effects of overexpressed ITGA3 on the biological functions of TC. Conclusion. It is verified in our study that cell growth of TC is inhibited by the miRNA-144-5p/ITGA3 axis, which represents an underlying target for TC. This research proposed a new insight into the strategy of TC treatment.

scholarly journals Examining the interaction between TGFBR3 and ESRRA in ovarian cancer prognosis

2016 ◽  
Author(s):  
Alun Passey ◽  
Robert Brown ◽  
Charlotte S. Wilhelm-Benartzi
Keyword(s):  
Ovarian Cancer ◽  
Conflicts Of Interest ◽  
The Cancer Genome Atlas ◽  
Cancer Prognosis ◽  
Serous Ovarian Cancer ◽  
Cancer Genome Atlas ◽  
A Cell ◽  
Funding Support ◽  
Functional Investigation ◽  
Ovarian Cancer Prognosis

ABSTRACTThe authors found that ESRRA when co-expressed at high levels with TGFβR3 may be prognostic for serous ovarian cancer overall survival in data from the Cancer Genome Atlas; however, this result was not validated in further datasets. A cell line was also identified in this study for future functional investigation of interactions between ESRRA and TGFβR3 in the context of oestrogen signaling in order to further elucidate their potential roles as prognostic biomarkers for serous ovarian cancer.FUNDING SUPPORTThis work was supported by Cancer Research UK program A6689 (RB and CSWB) and the Medical Research Council (AP)CONFLICT OF INTEREST DISCLOSURESThe authors have declared no conflicts of interest.AUTHOR CONTRIBUTIONSCSWB designed the study. AP, CSWB, and RB developed the methodology. AP and CSWB collected the data. AP, CSWB, and RB wrote the manuscript. CSWB is responsible for the overall content.

The new world of poly-(ADP)-ribose polymerase inhibitors (PARPi) used in the treatment of gynecological cancers

2020 ◽  
Vol 30 (10) ◽  
pp. 1608-1618
Author(s):  
Anca Chelariu-Raicu ◽  
Graziela Zibetti Dal Molin ◽  
Robert L Coleman
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Recurrent Ovarian Cancer ◽  
The Cancer Genome Atlas ◽  
Gynecological Cancers ◽  
Cervical Cancers ◽  
Polymerase Inhibitors ◽  
New Concepts ◽  
Cancer Genome Atlas ◽  
Cancer Types

The clinical development of poly-(ADP)-ribose polymerase inhibitors (PARPi) began with the treatment of ovarian cancer patients harboring BRCA1/2 mutations and continues to be expanded to other gynecological cancers. Furthermore, The Cancer Genome Atlas (TCGA) analysis of endometrial and cervical cancers offered rationale that PARPi may be an option for treatment based on the molecular profiles of these cancer types. This review summarizes the current indications of PARPi, such as its role in the treatment and maintenance of recurrent ovarian cancer and for first-line maintenance therapy in advanced ovarian cancer. We also outline new concepts for PARPi therapy in other gynecological cancers such as endometrial and cervical cancers based on recent clinical data. Finally, we present potential future directions to continue exploring the world of PARPi resistance and combining PARPi with other therapies.

scholarly journals Dynamics and predicted drug response of a gene network linking dedifferentiation with β-catenin dysfunction in hepatocellular carcinoma

2018 ◽  
Author(s):  
Claude Gérard ◽  
Mickaël Di-Luoffo ◽  
Léolo Gonay ◽  
Stefano Caruso ◽  
Gabrielle Couchy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
The Cancer Genome Atlas ◽  
Pharmacological Agents ◽  
Distinct Cell ◽  
Cancer Genome Atlas ◽  
Gene Regulatory ◽  
Using Data ◽  
Insight Into

AbstractAlterations of individual genes variably affect development of hepatocellular carcinoma (HCC), prompting the need to characterize the function of tumor-promoting genes in the context of gene regulatory networks (GRN). Here, we identify a GRN which functionally links LIN28B-dependent dedifferentiation with dysfunction of CTNNB1 (β-CATENIN). LIN28B and CTNNB1 form a functional GRN with SMARCA4 (BRG1), Let-7b, SOX9, TP53 and MYC. GRN activity is detected in HCC and gastrointestinal cancers; it negatively correlates with HCC prognosis and contributes to a transcriptomic profile typical of the proliferative class of HCC. Using data from The Cancer Genome Atlas and from transcriptomic, transfection and mouse transgenic experiments, we generated and validated a quantitative mathematical model of the GRN. The model predicts how the expression of GRN components changes when the expression of another GRN member varies or is inhibited by a pharmacological drug. The dynamics of GRN component expression reveal distinct cell states that can switch reversibly in normal condition, and irreversibly in HCC. We conclude that identification and modelling of the GRN provides insight into prognosis, mechanisms of tumor-promoting genes and response to pharmacological agents in HCC.

ErbB4 acts as a suppressor in colitis and its associated carcinoma by negatively regulating cholesterol metabolism

2018 ◽  
Vol 40 (5) ◽  
pp. 680-686
Author(s):  
Hengli Ni ◽  
Lin Chen ◽  
Liming Song ◽  
Lina Sun ◽  
Hongxia Cui ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Significant Negative Correlation ◽  
Protective Role ◽  
The Cancer Genome Atlas ◽  
Clinical Samples ◽  
Cancer Genome Atlas ◽  
In Vitro Cell Lines ◽  
Rate Limiting

AbstractPreviously we reported that ErbB4 played a protective role in chronic liver injury and hepatocellular carcinoma. Herein, we examined the role of ErbB4 in the development of colitis-associated cancer (CAC) in ErbB4 knockout mice models, in vitro cell lines and clinical samples. We found that ErbB4 deficiency may lead to more severe inflammation, slower recovery and the development of CAC. Further, loss of ErbB4 could activate Kras by upregulating rate-limiting enzymes in cholesterol metabolism pathway through interacting with the transcription factor Srebf1. In clinic samples, ErbB4 is downregulated in colonic tissues from patients with Crohn’s disease. And data from The Cancer Genome Atlas also showed significant negative correlation between ErbB4 and several cholesterol metabolic enzymes. In summary, our study uncovers ErbB4 as a protector in the development of CAC, for its loss could activate Kras by upregulating cholesterol metabolism.

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