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Biomedicine & Pharmacotherapy =... Oct 2023BCL6 is a transcriptional repressor that regulates multiple genes involved in immune cell differentiation, DNA damage repair, cell cycle, and apoptosis, and is a...
BCL6 is a transcriptional repressor that regulates multiple genes involved in immune cell differentiation, DNA damage repair, cell cycle, and apoptosis, and is a carcinogenic factor in acute myeloid leukemia (AML). AML is one of the four major types of leukemia with the 5-year survival rate of patients is less than 20% and chemotherapy resistance remains the major obstacle to the treatment failure of AML. We identified WK499, a small molecule compound that can bind to BCL6 structure. Treatment with WK499 hinders the interactions between BCL6 with its corepressor proteins, resulting in a remarkable change of BCL6 downstream genes and anti-proliferative effects in AML cells, and inducing cell cycle arrest and apoptosis. We verified that AraC and DOXo could induce BCL6 expression in AML cells, and found that WK499 had a synergistic effect when combined with chemotherapeutic drugs. We further proved that WK499 and AraC could achieve a better result of inhibiting the growth of AML in vivo. These findings indicate that WK499, a small molecule inhibitor of BCL6, not only inhibits the proliferation of AML, but also provides an effective therapeutic strategy for increasing AML sensitivity to chemotherapy.
Topics: Humans; Leukemia, Myeloid, Acute; Carcinogens; Apoptosis; Carcinogenesis; Cell Cycle; Cytarabine; Proto-Oncogene Proteins c-bcl-6
PubMed: 37634473
DOI: 10.1016/j.biopha.2023.115358 -
Biomolecules Dec 2023Signaling by calcium ion (Ca) plays a prominent role in cell physiology, and these mechanisms are frequently altered in tumor cells. In this review, we consider the... (Review)
Review
Signaling by calcium ion (Ca) plays a prominent role in cell physiology, and these mechanisms are frequently altered in tumor cells. In this review, we consider the interplay of Ca signaling and the functions of the proto-oncogene non-receptor tyrosine kinase c-Src in tumor cells, and the viral oncogenic variant v-Src in transformed cells. Also, other members of the Src-family kinases are considered in this context. The role of Ca in the cell is frequently mediated by Ca-binding proteins, where the Ca-sensor protein calmodulin (CaM) plays a prominent, essential role in many cellular signaling pathways. Thus, we cover the available information on the role and direct interaction of CaM with c-Src and v-Src in cancerous cells, the phosphorylation of CaM by v-Src/c-Src, and the actions of different CaM-regulated Ser/Thr-protein kinases and the CaM-dependent phosphatase calcineurin on v-Src/c-Src. Finally, we mention some clinical implications of these systems to identify mechanisms that could be targeted for the therapeutic treatment of human cancers.
Topics: Humans; Phosphorylation; src-Family Kinases; Signal Transduction; Calmodulin; Oncogenes
PubMed: 38136610
DOI: 10.3390/biom13121739 -
Apoptosis : An International Journal on... Apr 2024CCDC58, a member of the CCDC protein family, has been primarily associated with the malignant progression of hepatocellular carcinoma (HCC) and breast cancer, with...
CCDC58, a member of the CCDC protein family, has been primarily associated with the malignant progression of hepatocellular carcinoma (HCC) and breast cancer, with limited research conducted on its involvement in other tumor types. We aimed to assess the significance of CCDC58 in pan-cancer. We utilized the TCGA, GTEx, and UALCAN databases to perform the differential expression of CCDC58 at both mRNA and protein levels. Prognostic value was evaluated through univariate Cox regression and Kaplan-Meier methods. Mutation and methylation analyses were conducted using the cBioPortal and SMART databases. We identified genes interacting with and correlated to CCDC58 through STRING and GEPIA2, respectively. Subsequently, we performed GO and KEGG enrichment analyses. To gain insights into the functional status of CCDC58 at the single-cell level, we utilized CancerSEA. We explored the correlation between CCDC58 and immune infiltration as well as immunotherapy using the ESTIMATE package, TIMER2.0, TISIDB, TIDE, TIMSO, and TCIA. We examined the relationship between CCDC58 and tumor heterogeneity, stemness, DNA methyltransferases, and MMR genes. Lastly, we constructed a nomogram based on CCDC58 in HCC and investigated its association with drug sensitivity. CCDC58 expression was significantly upregulated and correlated with poor prognosis across various tumor types. The mutation frequency of CCDC58 was found to be increased in 25 tumors. We observed a negative correlation between CCDC58 expression and the methylation sites in the majority of tumors. CCDC58 showed negative correlations with immune and stromal scores, as well as with NK T cells, Tregs, CAFs, endothelial cells, and immunomodulators. Its value in immunotherapy was comparable to that of tumor mutational burden. CCDC58 exhibited positive correlations with tumor heterogeneity, stemness, DNA methyltransferase genes, and MMR genes. In HCC, CCDC58 was identified as an independent risk factor and demonstrated potential associations with multiple drugs. CCDC58 demonstrates significant clinical value as a prognostic marker and indicator of immune response across various tumor types. Its comprehensive analysis provides insights into its potential implications in pan-cancer research.
Topics: Humans; Carcinogens; Carcinoma, Hepatocellular; Endothelial Cells; Liver Neoplasms; Apoptosis; Carcinogenesis; DNA
PubMed: 38066393
DOI: 10.1007/s10495-023-01919-0 -
Nutrients Dec 2023The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a... (Review)
Review
The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a strong relationship between the recommended daily dose of selected B vitamins and a functional immune system. Regarding specific B vitamins: (1) Riboflavin is necessary for the optimization of reactive oxygen species (ROS) in the fight against bacterial infections caused by and . (2) Niacin administered within normal doses to obese rats can change the phenotype of skeletal fibers, and thereby affect muscle metabolism. This metabolic phenotype induced by niacin treatment is also confirmed by stimulation of the expression of genes involved in the metabolism of free fatty acids (FFAs) and oxidative phosphorylation at this level. (3) Vitamin B5 effects depend primarily on the dose, thus large doses can cause diarrhea or functional disorders of the digestive tract whereas normal levels are effective in wound healing, liver detoxification, and joint health support. (4) High vitamin B6 concentrations (>2000 mg per day) have been shown to exert a significant negative impact on the dorsal root ganglia. Whereas, at doses of approximately 70 ng/mL, sensory symptoms were reported in 80% of cases. (5) Chronic increases in vitamin B12 have been associated with the increased incidence of solid cancers. Additionally, glucuronolactone, whose effects are not well known, represents a controversial compound. (6) Supplementing with D-glucarates, such as glucuronolactone, may help the body's natural defense system function better to inhibit different tumor promoters and carcinogens and their consequences. Cumulatively, the present review aims to evaluate the relationship between the selected B vitamins group, glucuronolactone, and the immune system and their associations to bioavailability, doses, and efficiency.
Topics: Animals; Rats; Vitamin B Complex; Niacin; Biological Availability; Glucuronates; Vitamin A; Vitamin K; Carcinogens
PubMed: 38201854
DOI: 10.3390/nu16010024 -
JAMA Aug 2023
Topics: Aspartame; Carcinogens; Dipeptides; Sweetening Agents; Dissent and Disputes
PubMed: 37494077
DOI: 10.1001/jama.2023.13132 -
Annals of Medicine Dec 2023Occupational-related cancers are a substantial global health issue. The largest proportion of occupational-related cancers is tracheal, bronchus, and lung (TBL) cancer....
Global burden of tracheal, bronchus, and lung cancer attributable to occupational carcinogens in 204 countries and territories, from 1990 to 2019: results from the global burden of disease study 2019.
BACKGROUND
Occupational-related cancers are a substantial global health issue. The largest proportion of occupational-related cancers is tracheal, bronchus, and lung (TBL) cancer. This study aimed to explore the geographical and temporal trends in occupational carcinogens related to TBL cancer.
METHODS
Data on TBL cancer attributable to occupational carcinogens were collected from the Global Burden of Disease Study 2019. Numbers and age-standardized rates (ASRs) of deaths, disability-adjusted life years (DALYs), and corresponding average annual percentage change (AAPC) were evaluated and stratified by geographic location, socio-demographic index (SDI) quintiles, age, and sex.
RESULTS
Globally, ASRs of deaths and DALYs in TBL cancer attributable to occupational carcinogens showed a downward trend (AAPC = - 0.69%, - 1.01%) while increases were observed in the low, low-middle, and middle SDI quintiles. Although males accounted for 82.4% and 81.5% of deaths and DALYs in 2019, respectively, it showed an upward trend of ASRs in females (AAPC = 0.33%, 0.02%). Occupational exposure to asbestos, silica and diesel engine exhaust were the top three causes of age-standardized TBL cancer deaths and DALYs. Over the past three decades, the percentage of age-standardized TBL cancer deaths and DALYs attributable to occupational asbestos and silica exposure decreased by 18.24, 6.71 and 20.52%, 4.00% globally, but increased significantly in lower SDI regions, while the burden attributable to occupational diesel engine exhaust exposure increased by 32.76, 37.23% worldwide.
CONCLUSIONS
Occupational exposure remains an important risk factor for TBL cancer. The burden of TBL cancer attributable to occupational carcinogens showed obvious heterogeneity which decreased in higher SDI but increased in lower SDI regions. The burden of males was significantly higher than females, but the females showed an increasing trend. Occupational exposure to asbestos was the main causes of the burden. Therefore, effective prevention and control measures tailored to local conditions are necessary.
Topics: Male; Female; Humans; Quality-Adjusted Life Years; Global Burden of Disease; Vehicle Emissions; Risk Factors; Lung Neoplasms; Asbestos; Global Health; Carcinogens; Bronchi
PubMed: 37155297
DOI: 10.1080/07853890.2023.2206672 -
Scientific Reports Dec 2023The recently discovered APRO (anti-proliferative protein) family encodes a group of trans-membrane glycoproteins and includes 6 members: TOB1, TOB2, BTG1, BTG2, BTG3 and...
The recently discovered APRO (anti-proliferative protein) family encodes a group of trans-membrane glycoproteins and includes 6 members: TOB1, TOB2, BTG1, BTG2, BTG3 and BTG4. The APRO family is reportedly associated with the initiation and progression of cancers. This study aims to undertake a comprehensive investigation of the APRO family of proteins as a prognostic biomarker in various human tumors. We performed a pan-cancer analysis of the APRO family based on The Cancer Genome Atlas (TCGA). With the bioinformatics methods, we explored the prognostic value of the APRO family and the correlation between APRO family expression and tumor mutation burden (TMB), microsatellite instability (MSI), drug sensitivity, and immunotherapy in numerous cancers. Our results show that the APRO family was primarily down-regulated in cancer samples. The expression of APRO family members was linked with patient prognosis. In addition, APRO family genes showed significant association with immune infiltrate subtypes, tumor microenvironment, and tumor cell stemness. Finally, our study also demonstrated the relationship between APRO family genes and drug sensitivity. This study provides comprehensive information to understand the APRO family's role as an oncogene and predictor of survival in some tumor types.
Topics: Humans; Oncogenes; Immunotherapy; Cognition; Computational Biology; Neoplasms; Tumor Microenvironment; Immediate-Early Proteins; Tumor Suppressor Proteins
PubMed: 38062199
DOI: 10.1038/s41598-023-48961-1 -
Cold Spring Harbor Perspectives in... Mar 2024Rodent models of breast cancer have played critical roles in our understanding of breast cancer development and progression as well as preclinical testing of cancer... (Review)
Review
Rodent models of breast cancer have played critical roles in our understanding of breast cancer development and progression as well as preclinical testing of cancer prevention and therapeutics. In this article, we first review the values and challenges of conventional genetically engineered mouse (GEM) models and newer iterations of these models, especially those with inducible or conditional regulation of oncogenes and tumor suppressors. Then, we discuss nongermline (somatic) GEM models of breast cancer with temporospatial control, made possible by intraductal injection of viral vectors to deliver oncogenes or to manipulate the genome of mammary epithelial cells. Next, we introduce the latest development in precision editing of endogenous genes using in vivo CRISPR-Cas9 technology. We conclude with the recent development in generating somatic rat models for modeling estrogen receptor-positive breast cancer, something that has been difficult to accomplish in mice.
Topics: Mice; Rats; Animals; Disease Models, Animal; Neoplasms; Oncogenes; Epithelial Cells
PubMed: 37217281
DOI: 10.1101/cshperspect.a041328 -
Apoptosis : An International Journal on... Apr 2024This analysis covers 4494 anoikis-related publications (2003-2022). It explores annual trends, top countries, core journals, leading institutions, keywords, references,...
This analysis covers 4494 anoikis-related publications (2003-2022). It explores annual trends, top countries, core journals, leading institutions, keywords, references, authors, and collaborations. Key findings include the United States leading in publications, Chulalongkorn University as the top institution, and Oncogene as the most prolific journal. The Journal of Biological Chemistry holds the highest influence. Burst keywords like "signal transduction," "apoptosis resistance," "metabolism," and "tumor microenvironment" highlight emerging research areas. This study offers a comprehensive overview, aiding researchers in grasping anoikis research trends, contributors, and prospects.
Topics: Humans; Anoikis; Oncogenes; Bibliometrics; Signal Transduction; Tumor Microenvironment
PubMed: 38001344
DOI: 10.1007/s10495-023-01910-9 -
British Journal of Cancer Nov 2023It has been acknowledged that the tumour immune microenvironment (TIME) plays a critical role in determining therapeutic responses and clinical outcomes in breast cancer...
BACKGROUND
It has been acknowledged that the tumour immune microenvironment (TIME) plays a critical role in determining therapeutic responses and clinical outcomes in breast cancer (BrCa). Thus, the identification of the TIME features is essential for guiding therapy and prognostic assessment for BrCa.
METHODS
The heterogeneous cellular composition of the TIME in BrCa by single-cell RNA sequencing (scRNA-seq). Two subtype-special genes upregulated in the tumour-rich subtype and the immune-infiltrating subtype were extracted, respectively. The CRABP2/CD69 signature was established based on CRABP2 and CD69 expression, and its predictive values for the clinical outcome and the neoadjuvant chemotherapy (NAT) responses were validated in multiple cohorts. Moreover, the oncogenic role of CRABP2 was explored in BrCa cells.
RESULTS
Based on the heterogeneous cellular composition of the TIME in BrCa, the BrCa samples could be divided into the tumour-rich subtype and the immune-infiltrating subtype, which exhibited distinct prognosis and chemotherapeutic responses. Next, we extracted CRABP2 as the biomarker for the tumour-rich subtype and CD69 as the biomarker for the immune-infiltrating subtype. Based on the CRABP2/CD69 signature, BrCa samples were re-divided into three subtypes, and the CRABP2CD69 subtype exhibited the worst prognosis and the lowest chemotherapeutic response, while the CRABP2CD69 subtype showed the opposite results. Furthermore, CARBP2 functioned as a novel oncogene in BrCa, which promoted tumour cell proliferation, migration, and invasion, and CRABP2 inhibition triggered the activation of cytotoxic T lymphocytes (CTLs).
CONCLUSION
The CRABP2/CD69 signature is significantly associated with the TIME features and could effectively predict the clinical outcome. Also, CRABP2 is determined to be a novel oncogene, which could be a therapeutic target in BrCa.
Topics: Female; Humans; Biomarkers; Breast Neoplasms; Cell Proliferation; Neoadjuvant Therapy; Oncogenes; Prognosis; Tumor Microenvironment
PubMed: 37715025
DOI: 10.1038/s41416-023-02432-6