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  • Frontiers Media SA  (12)
  • 1
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    DataSheet_1.xlsx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-10-25)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-10-25)
    Abstract: Bilateral multiple ground glass opacities (GGOs) are observed in quite a part of patients with early-stage lung adenocarcinoma. For this so-called synchronous multiple primary lung cancer (sMPLC), targeting immune checkpoint is a favorable option in addition to surgical resection. The purpose of this study is to reveal the safety and efficacy of performing immune checkpoint inhibitors (ICIs) on patients with sMPLC and to explore the biomarkers of the efficacy. Methods A total of 21 patients with sMPLC were enrolled and all included cases were pathologically confirmed adenocarcinoma after conducting surgical treatment for unilateral GGOs. ICIs of Sintilimab were then used to target programmed death 1 (200mg i.v., Q3W) for up to 10 cycles. Seven patients of them received the other surgery for contralateral GGOs, and multiomics assessments, including neoantigens, somatic mutations, and methylated loci, were further performed to investigate potential biomarkers. Results Grade 1 or 2 treatment-related adverse events (AEs) occurred in most of the patients (12/21, 57.1%), and one subject withdrawn for grade 3 AEs. For the seven patients underwent twice surgeries, twelve and thirteen GGOs were achieved before and after the use of ICIs separately, and a favorable efficacy was observed among six lesions after immunotherapy ( & gt; 50% pathologic tumor regression). Tumor infiltration T-cell and B-cell were further shown to be associated with the biological activity of ICIs. According to mechanism-based multiomics analyses, MUC19 - and PCDHB5 - mutations were indicated to correlate with a favorable prognosis of sMPLC underwent immunotherapy, and our results suggested that immunogenetic mutation and associated promoter methylation could provide a quantitative explanation for the pathologic response of GGOs. Conclusion Our study provides evidence that the use of ICIs contributed favorable efficacy and safety to patients with sMPLC. Immune infiltration and immunogenic biomarkers are revealed to be implications of performing ICIs on sMPLC. These preliminary findings exhibit the prospects in performing neoadjuvant or adjuvant immunotherapies on patients with sMPLC. Clinical Trial Registration https://www.chictr.org.cn/showproj.aspx?proj=36878 , identifier ChiCTR1900022159.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1009621
    DOI: 10.3389/fimmu.2022.1009621.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 2
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    Table9.xlsx
    Frontiers Media SA ; 2021
    In:  Frontiers in Molecular Biosciences Vol. 8 ( 2021-5-26)
    Details
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 8 ( 2021-5-26)
    Abstract: Background: Hepatocellular carcinoma (HCC) is a tumor with high morbidity and high mortality worldwide. DNA methylation, one of the most common epigenetic changes, might serve a vital regulatory role in cancer. Methods: To identify categories based on DNA methylation data, consensus clustering was employed. The risk signature was yielded by systematic bioinformatics analyses based on the remarkably methylated CpG sites of cluster 1. Kaplan–Meier analysis, variable regression analysis, and ROC curve analysis were further conducted to validate the prognosis predictive ability of risk signature. Gene set enrichment analysis (GSEA) was performed for functional annotation. To uncover the context of tumor immune microenvironment (TIME) of HCC, we employed the ssGSEA algorithm and CIBERSORT method and performed TIMER database exploration and single-cell RNA sequencing analysis. Additionally, quantitative real-time polymerase chain reaction was employed to determine the LRRC41 expression and preliminarily explore the latent role of LRRC41 in prognostic prediction. Finally, mutation data were analyzed by employing the “maftools” package to delineate the tumor mutation burden (TMB). Results: HCC samples were assigned into seven subtypes with different overall survival and methylation levels based on 5′-cytosine-phosphate-guanine-3′ (CpG) sites. The risk prognostic signature including two candidate genes (LRRC41 and KIAA1429) exhibited robust prognostic predictive accuracy, which was validated in the external testing cohort. Then, the risk score was significantly correlated with the TIME and immune checkpoint blockade (ICB)–related genes. Besides, a prognostic nomogram based on the risk score and clinical stage presented powerful prognostic ability. Additionally, LRRC41 with prognostic value was corroborated to be closely associated with TIME characterization in both expression and methylation levels. Subsequently, the correlation regulatory network uncovered the potential targets of LRRC41 and KIAA1429. Finally, the methylation level of KIAA1429 was correlated with gene mutation status. Conclusion: In summary, this is the first to identify HCC samples into distinct clusters according to DNA methylation and yield the CpG-based prognostic signature and quantitative nomogram to precisely predict prognosis. And the pivotal player of DNA methylation of genes in the TIME and TMB status was explored, contributing to clinical decision-making and personalized prognosis monitoring of HCC.
    Type of Medium: Online Resource
    ISSN: 2296-889X
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    DOI: 10.3389/fmolb.2021.683240
    DOI: 10.3389/fmolb.2021.683240.s001
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    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2814330-9
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  • 3
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    Image_1.tif
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 12 ( 2023-1-18)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2023-1-18)
    Abstract: Radiotherapy (RT) is one of the most important treatments for patients with colorectal cancer (CRC). Radioresistance is the crucial cause of poor therapeutic outcomes in colorectal cancer. However, the underlying mechanism of radioresistance in colorectal cancer is still poorly defined. Herein we established a radioresistant colorectal cancer cell line and performed transcriptomics analyses to search for the underlying genes that contribute to radioresistance and investigate its association with the prognosis of CRC patients. Methods The radioresistant cell line was developed from the parental HCT116 cell by a stepwise increased dose of irradiation. Differential gene analysis was performed using cellular transcriptome data to identify genes associated with radioresistance, from which extracellular matrix (ECM) and cell adhesion-related genes were screened. Survival data from a CRC cohort in the TCGA database were used for further model gene screening and validation. The correlation between the risk score model and tumor microenvironment, clinical phenotype, drug treatment sensitivity, and tumor mutation status were also investigated. Results A total of 493 different expression genes were identified from the radioresistant and wild-type cell line, of which 94 genes were associated with ECM and cell adhesion-related genes. The five model genes TNFRSF13C , CD36 , ANGPTL4 , LAMB3 , and SERPINA1 were identified for CRC radioresistance via screening using the best model. A ROC curve indicated that the AUC of the resulting prognostic model (based on the 5-gene risk score and other clinical parameters, including age, sex, and tumor stages) was 0.79, 0.77, and 0.78 at 1, 2, and 3 years, respectively. The calibration curve showed high agreement between the risk score prediction and actual survival probability. The immune microenvironment, drug treatment sensitivity, and tumor mutation status significantly differed between the high- and low-risk groups. Conclusions The risk score model built with five radioresistance genes in this study, including TNFRSF13C , CD36 , ANGPTL4 , LAMB3 , and SERPINA1 , showed favorable performance in prognosis prediction after radiotherapy for CRC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
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    URL: Article
    DOI: 10.3389/fonc.2022.1100481
    DOI: 10.3389/fonc.2022.1100481.s001
    DOI: 10.3389/fonc.2022.1100481.s002
    DOI: 10.3389/fonc.2022.1100481.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 4
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    DataSheet_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-7-11)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-7-11)
    Abstract: Tientsin albino 2 (TA2) mice can develop spontaneous breast cancer (SBC), which is associated with multiple pregnancies and infection with the mouse mammary tumor virus (MMTV). In this study, we sought to elucidate the molecular mechanisms underlying the development of SBC in TA2 mice induced by MMTV. Methods The integration site of MMTV in TA2 SBC was identified using whole-genome sequencing. The expression of fibroblast growth factor 3 (FGF3) in SBCs and normal breast tissues was compared. The primary cell line, TA-1106, derived from SBC, was cultured. The proliferation, cell cycle, migration, invasion, and tumorigenicity abilities, as well as the expression of epithelial-mesenchymal transition-related proteins, phosphorylated STAT3, and phosphorylated Akt, were assessed in MA-891cell line from TA2 and TA-1106 cells after FGF3 knockdown. The binding of FGF3 to FGF receptor 1 (FGFR1) was determined by co-immunoprecipitation. Additionally, the relationship between STAT3 and Akt phosphorylation was investigated using a small molecule inhibitor and STAT3 knockdown. Results MMTV integrated upstream of the FGF3 gene, and the FGF3 protein was highly expressed in TA2 SBCs. FGF3 knockdown in MA-891 and TA-1106 decreased their proliferation, migration, and invasion abilities, affected the cell cycle and expression of epithelial-mesenchymal transition-related proteins, and inhibited the growth of animal xenografts. FGF3 binds to FGFR1, and either FGF3 or FGFR1 knockdown decreases STAT3 and Akt phosphorylation levels. Inhibition of phosphorylation or expression of STAT3 resulted in decreased Akt phosphorylation levels. Inhibition of Akt phosphorylation also resulted in decreased STAT3 phosphorylation levels. Furthermore, treatment of MA-891 and TA-1106 cells with Wortmannin or Stattic caused FGFR1 upregulation in addition to inhibiting Akt or STAT3 phosphorylation. Conclusion The results of this study demonstrate that FGF3 plays a significant role in the development of SBC through the FGF3/FGFR1/STAT3 signaling pathway. There is a reciprocal activation between STAT3 and Akt. Inhibition of STAT3 or Akt phosphorylation promoted the expression of FGFR1. Validating the conclusions obtained in this study in human breast cancer (HBC) may contribute to targeted therapy and it is worth exploring whether the homologous sequences of MMTV in HBC have a similar oncogenic effect.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2023.1161410
    DOI: 10.3389/fonc.2023.1161410.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 5
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    Colorectal Cancer Screening With High Risk-Factor Questionnaire and Fecal Immunochemical Tests Among 5, 947, 986 Asymptomatic Population: A Population-Based Study
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-5-30)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-5-30)
    Abstract: The recent uptrend in colorectal cancer (CRC) incidence in China is causing an increasingly overwhelming social burden. And its occurrence can be effectively reduced by sensitizing CRC screening for early diagnosis and treatment. However, a large number of people in China do not undergo screening due to multiple factors. To address this issue, since 2012, a CRC screening program has been initiated in Tianjin. Methods Residents aged 40-74 years were eligible for CRC screening. The first was to complete the high-risk factor questionnaire (HRFQ) and undergo fecal immunochemical test (FIT). Then those with a positive result in any of the two screening methods were recommended for a free colonoscopy. Results The detection rate of intestinal diseases increased with age, had a male predominance, and was higher in residents from central urban areas and those with primary school above education level. The sensitivity of predicting CRC after colonoscopy in the high-risk group was 76.02%; the specificity was 25.33%.A significant decrease in the detection rate of intestinal disease, CRC and advanced adenoma was observed from positive FIT, the high-risk group and positive HRFQ, 47.13%, 44.79%, 42.30%; 3.15%, 2.44%, 1.76%; 7.72%, 6.42%, 5.08%, in that order, while no inter-group difference was found for the detection of polyps. In addition, the different combinations of HRFQ and FIT can enroll more high-risk population than FIT or (and) HRFQ only, and thus detect more intestinal diseases (include CRC/AA/Polyp). Conclusion The superimposition of different screening method for HRFQ and FIT is an effective strategy for the detection of CRC, AA, and Polyp, compared to HRFQ or FIT alone. However, further improvements in screening and interventions are needed to promote colonoscopy compliance.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2022.893183
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 6
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    Study of unripe and inferior banana flours pre-gelatinized by four different physical methods
    Frontiers Media SA ; 2023
    In:  Frontiers in Nutrition Vol. 10 ( 2023-6-19)
    Details
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 10 ( 2023-6-19)
    Abstract: This study aimed to prepare the pre-gelatinized banana flours and compare the effects of four physical treatment methods (autoclaving, microwave, ultrasound, and heat-moisture) on the digestive and structural characteristics of unripe and inferior banana flours. After the four physical treatments, the resistant starch (RS) content values of unripe and inferior banana flours were decreased from 96.85% (RS2) to 28.99–48.37% (RS2 + RS3), while C∞ and k values were increased from 5.90% and 0.039 min −1 to 56.22–74.58% and 0.040–0.059 min −1 , respectively. The gelatinization enthalpy (ΔHg) and I 1047/1022 ratio (short-range ordered crystalline structures) were decreased from 15.19 J/g and 1.0139 to 12.01–13.72 J/g, 0.9275–0.9811, respectively. The relative crystallinity decreased from 36.25% to 21.69–26.30%, and the XRD patterns of ultrasound (UT) and heat-moisture (HMT) treatment flours maintained the C-type, but those samples pre-gelatinized by autoclave (AT) and microwave (MT) treatment were changed to C + V-type, and heat-moisture (HMT) treatment was changed to A-type. The surface of pre-gelatinized samples was rough, and MT and HMT showed large amorphous holes. The above changes in structure further confirmed the results of digestibility. According to the experimental results, UT was more suitable for processing unripe and inferior banana flours as UT had a higher RS content and thermal gelatinization temperatures, a lower degree and rate of hydrolysis, and a more crystalline structure. The study can provide a theoretical basis for developing and utilizing unripe and inferior banana flours.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    URL: Article
    DOI: 10.3389/fnut.2023.1201106
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2776676-7
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  • 7
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    Data_Sheet_1.DOCX
    Frontiers Media SA ; 2022
    In:  Frontiers in Ecology and Evolution Vol. 9 ( 2022-2-2)
    Details
    In: Frontiers in Ecology and Evolution, Frontiers Media SA, Vol. 9 ( 2022-2-2)
    Abstract: Momilactones are diterpenoid phytoalexins with allelopathic functions, which have been found in the widely distributed bryophyte Calohypnum plumiforme . Clustered genes containing CpDTC1/HpDTC1 , CpCYP970A14 , CpCYP964A1 , and CpMAS are involved in momilactone biosynthesis. Besides, momilactone concentration in C. plumiforme is affected by heavy metal treatment such as CuCl 2 . However, transcription factors which might regulate momilactone biosynthesis are unclear. WRKY transcription factors (TFs) regulate phytoalexin biosynthesis in many plant species. In this study, a systematic analysis of the WRKY TFs was performed according to the C. plumiforme genome. A total of 19 CpWRKY genes were identified and categorized into five subgroups based on their phylogenetic relationship. Conserved domain and motif analysis suggested that the WRKY domain was highly conserved, but there were some variations. Cis -acting elements and binding sites analysis implied that CpWRKY genes might be induced by stress and further regulate the biosynthesis of momilactones. Our study lays a foundation for further functional characterization of the candidate CpWRKY genes involved in the regulation of momilactone biosynthesis, and provides new strategies for increasing momilactone production.
    Type of Medium: Online Resource
    ISSN: 2296-701X
    URL: Article
    URL: Article
    DOI: 10.3389/fevo.2021.809729
    DOI: 10.3389/fevo.2021.809729.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2745634-1
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  • 8
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    Lipid Droplets, the Central Hub Integrating Cell Metabolism and the Immune System
    Frontiers Media SA ; 2021
    In:  Frontiers in Physiology Vol. 12 ( 2021-12-3)
    Details
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 12 ( 2021-12-3)
    Abstract: Lipid droplets (LDs) are commonly found in various biological cells and are organelles related to cell metabolism. LDs, the number and size of which are heterogeneous across cell type, are primarily composed of polar lipids and proteins on the surface with neutral lipids in the core. Neutral lipids stored in LDs can be degraded by lipolysis and lipophagocytosis, which are regulated by various proteins. The process of LD formation can be summarized in four steps. In addition to energy production, LDs play an extremely pivotal role in a variety of physiological and pathological processes, such as endoplasmic reticulum stress, lipid toxicity, storage of fat-soluble vitamins, regulation of oxidative stress, and reprogramming of cell metabolism. Interestingly, LDs, the hub of integration between metabolism and the immune system, are involved in antitumor immunity, anti-infective immunity (viruses, bacteria, parasites, etc.) and some metabolic immune diseases. Herein, we summarize the role of LDs in several major immune cells as elucidated in recent years, including T cells, dendritic cells, macrophages, mast cells, and neutrophils. Additionally, we analyze the role of the interaction between LDs and immune cells in two typical metabolic immune diseases: atherosclerosis and Mycobacterium tuberculosis infection.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    URL: Article
    DOI: 10.3389/fphys.2021.746749
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2564217-0
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  • 9
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    Screening and Prognostic Value of Methylated Septin9 and its Association With Clinicopathological and Molecular Characteristics in Colorectal Cancer
    Frontiers Media SA ; 2021
    In:  Frontiers in Molecular Biosciences Vol. 8 ( 2021-5-20)
    Details
    In: Frontiers in Molecular Biosciences, Frontiers Media SA, Vol. 8 ( 2021-5-20)
    Abstract: Screening of CRC continues to show poor compliance of endoscopy examination. The detection of mSEPT9 in peripheral blood is among the safe and simple early screening methods for CRC. The issue of how to elucidate whether detection of mSEPT9 in peripheral blood can effectively improve compliance of endoscopy and increase the early diagnosis rate of CRC and the relationship between levels of mSEPT9 in the peripheral blood and clinical stage, pathological classification, and expression of characteristic molecules in CRC remains unsolved. A total of 7759 individuals participated in the study that was performed using a questionnaire for screening of high-risk CRC. The endoscopic detection compliance of individuals with high-risk CRC who underwent the fecal occult blood test (FOBT) or mSEPT9 test was compared based on the results of the questionnaire. Additionally, correlation of mSEPT9 levels in the peripheral blood with clinicopathological features, mutation status of TP53 , mismatch repair deficiency (dMMR), and KRAS / NRAS / BRAF / PIK3CA genotype was analyzed, and association of biomarkers with cancer-specific survival (CSS) and time to recurrence (TTR) was compared. We also detected levels of mSEPT9 in the peripheral blood of patients with CRC 7 days after surgery and compared the prognostic value of mSEPT9 with CEA. Results of our study showed that the mSEPT9 test could improve compliance of endoscopy and indicated a higher percentage of patients with positive mSEPT9 willing to undergo endoscopy detection than in those with positive FOBT. The specificity and sensitivity of mSEPT9 were better than that of FOBT for the detection of CRC. mSEPT9 was associated with the TNM stage, dMMR, and mutations in TP53 , BRAF, and PIK3CA . A Ct value of mSEPT9 ≤ 37.5 was significantly related to poor CSS. mSEPT9 could affect association of dMMR and BRAF and PIK3CA mutations with CSS in a specific stage of CRC. The positive rate of mSEPT9 after surgery was found to correlate with poor TTR, and sensitivity was higher than CEA. The combination of mSEPT9 with CEA had a better prognostic value than that of mSEPT9 alone. The level of mSEPT9 was related to dMMR, mutations in TP53 , BRAF , and PIK3CA , and was an effective biomarker for the prognosis of patients with CRC.
    Type of Medium: Online Resource
    ISSN: 2296-889X
    URL: Article
    DOI: 10.3389/fmolb.2021.568818
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 10
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    Intestinal Immune System and Amplification of Mouse Mammary Tumor Virus
    Frontiers Media SA ; 2022
    In:  Frontiers in Cellular and Infection Microbiology Vol. 11 ( 2022-1-13)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 11 ( 2022-1-13)
    Abstract: Mouse mammary tumor virus (MMTV) is a virus that induces breast cancer in mice. During lactation, MMTV can transmit from mother to offspring through milk, and Peyer’s patches (PPs) in mouse intestine are the first and specific target organ. MMTV can be transported into PPs by microfold cells and then activate antigen-presenting cells (APCs) by directly binding with Toll-like receptors (TLRs) whereas infect them through mouse transferrin receptor 1 (mTfR1). After being endocytosed, MMTV is reversely transcribed and the cDNA inserts into the host genome. Superantigen (SAg) expressed by provirus is presented by APCs to cognate CD4 + T cells via MHCII molecules to induce SAg response, which leads to substantial proliferation and recruitment of related immune cells. Both APCs and T cells can be infected by MMTV and these extensively proliferated lymphocytes and recruited dendritic cells act as hotbeds for viral replication and amplification. In this case, intestinal lymphatic tissues can actually become the source of infection for the transmission of MMTV in vivo , which results in mammary gland infection by MMTV and eventually lead to the occurrence of breast cancer.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    DOI: 10.3389/fcimb.2021.807462
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2619676-1
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