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  1. Article: Clinical Significance of ABCG2/BCRP Quantified by Fluorescent Nanoparticles in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy.

    Tada, Hiroshi / Gonda, Kohsuke / Kitamura, Narufumi / Ishida, Takanori

    Cancers

    2023  Volume 15, Issue 8

    Abstract: Breast cancer resistance protein (BCRP), also known as ATP-binding cassette transporter G2 (ABCG2), is associated with chemotherapy resistance. BCRP is also implicated in breast cancer stem cells, and is reported as a poor prognostic factor. However, the ...

    Abstract Breast cancer resistance protein (BCRP), also known as ATP-binding cassette transporter G2 (ABCG2), is associated with chemotherapy resistance. BCRP is also implicated in breast cancer stem cells, and is reported as a poor prognostic factor. However, the relationship of BCRP levels in breast cancer tissues with chemotherapy resistance and prognosis has not been clarified. We aimed to evaluate the correlation between BCRP expression and prognosis in breast cancer using immunohistochemistry with fluorescent phosphor-integrated dots (IHC-PIDs). A total of 37 breast cancer patients with residual cancer in the primary tumor and axillary lymph nodes were evaluated. BCRP levels in breast cancer tissue and metastatic lymph nodes were quantitatively detected after neoadjuvant chemotherapy (NAC). Among these 37 patients, 24 had corresponding core needle biopsies obtained before NAC. Biomarker assay with IHC-PIDs showed high accuracy for the quantitative assessment of BCRP with low expression. High BCRP expression in the primary tumor and metastatic lymph nodes after preoperative chemotherapy was associated with worse overall survival. In conclusion, high BCRP levels may be associated with poor prognosis in patients with breast cancer, having residual tumors within the primary tumor and lymph nodes after preoperative chemotherapy. These findings provide a basis for further appropriate adjuvant therapy in these patients.
    Language English
    Publishing date 2023-04-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15082365
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  2. Article ; Online: Prospect of immunotherapy in neoadjuvant/adjuvant treatment for early breast cancer.

    Miyashita, Minoru / Ishida, Takanori

    Chinese clinical oncology

    2020  Volume 9, Issue 3, Page(s) 28

    Abstract: Immunotherapy is revolutionary and changing the cancer therapy of multiple solid tumors. Immunotherapy began with discovering the proteins of immune checkpoints such as programmed death-1 (PD-1), programmed death ligand-1 (PD-L1) and cytotoxic T- ... ...

    Abstract Immunotherapy is revolutionary and changing the cancer therapy of multiple solid tumors. Immunotherapy began with discovering the proteins of immune checkpoints such as programmed death-1 (PD-1), programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte associated antigen-4 (CTLA-4). Breast cancer, unlike cancers with high tumor mutation burden, is generally considered to be of intermediate immunogenicity; therefore, the efficacy of checkpoint monotherapy is limited. Among breast cancer subtypes, triple negative breast cancer (TNBC) is considered to be the most immunogenic and is mainly evaluated in clinical trials. Some trials have demonstrated that checkpoint inhibitors when combined with chemotherapy improve the survival of TNBC patients. When investigating new drugs, a neoadjuvant setting is preferred because drug efficacy can be evaluated earlier using pathological complete response (pCR) as an alternative endpoint for survival. The strategy is based on the accumulated results that pCR after neoadjuvant therapy significantly correlates with both progression free survival (PFS) and overall survival (OS). We aimed to review relevant articles, and discuss the current position of immunotherapy and future prospects of immunotherapy as neoadjuvant/adjuvant therapy in breast cancer based on our conclusions from the findings in the current literature.
    MeSH term(s) Breast Neoplasms/drug therapy ; Breast Neoplasms/immunology ; Female ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy/methods ; Neoadjuvant Therapy/methods
    Chemical Substances Immune Checkpoint Inhibitors
    Language English
    Publishing date 2020-04-17
    Publishing country China
    Document type Journal Article ; Review
    ZDB-ID 2828547-5
    ISSN 2304-3873 ; 2304-3865
    ISSN (online) 2304-3873
    ISSN 2304-3865
    DOI 10.21037/cco.2020.04.01
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study.

    Tanda, Naoko / Tada, Hiroshi / Washio, Jumpei / Takahashi, Nobuhiro / Ishida, Takanori / Koseki, Takeyoshi

    PloS one

    2022  Volume 17, Issue 6, Page(s) e0269335

    Abstract: Background: Bone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse ...

    Abstract Background: Bone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients.
    Methods: We retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model.
    Results: The median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268-5.841, P = 0.010).
    Conclusion: Alcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.
    MeSH term(s) Aldehyde Dehydrogenase, Mitochondrial ; Bone Neoplasms/secondary ; Bone and Bones/pathology ; Breast Neoplasms/pathology ; Diphosphonates/therapeutic use ; Docetaxel/therapeutic use ; Female ; Humans ; Retrospective Studies
    Chemical Substances Diphosphonates ; Docetaxel (15H5577CQD) ; ALDH2 protein, human (EC 1.2.1.3) ; Aldehyde Dehydrogenase, Mitochondrial (EC 1.2.1.3)
    Language English
    Publishing date 2022-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0269335
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  4. Article ; Online: SGLT1 as an adverse prognostic factor in invasive ductal carcinoma of the breast.

    Tsunokake, Satoko / Iwabuchi, Erina / Miki, Yasuhiro / Kanai, Ayako / Onodera, Yoshiaki / Sasano, Hironobu / Ishida, Takanori / Suzuki, Takashi

    Breast cancer research and treatment

    2023  Volume 201, Issue 3, Page(s) 499–513

    Abstract: Purpose: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained ... ...

    Abstract Purpose: Sodium/glucose cotransporter (SGLT) 1 and 2 expression in carcinoma cells was recently examined, but their association with the clinicopathological factors of the patients and their biological effects on breast carcinoma cells have remained remain virtually unknown. Therefore, in this study, we explored the expression status of SGLT1 and SGLT2 in breast cancer patients and examined the effects of SGLT1 inhibitors on breast carcinoma cells in vitro.
    Methods: SGLT1 and SGLT2 were immunolocalized and we first correlated the findings with clinicopathological factors of the patients. We then administered mizagliflozin and KGA-2727, SGLT1 specific inhibitors to MCF-7 and MDA-MB-468 breast carcinoma cell lines, and their growth-inhibitory effects were examined. Protein arrays were then used to further explore their effects on the growth factors.
    Results: The SGLT1 high group had significantly worse clinical outcome including both overall survival and disease-free survival than low group. SGLT2 status was not significantly correlated with clinical outcome of the patients. Both mizagliflozin and KGA-2727 inhibited the growth of breast cancer cell lines. Of particular interest, mizagliflozin inhibited the proliferation of MCF-7 cells, even under very low glucose conditions. Mizagliflozin downregulated vascular endothelial growth factor receptor 2 phosphorylation.
    Conclusion: High SGLT1 expression turned out as an adverse clinical prognostic factor in breast cancer patient. This is the first study demonstrating that SGLT1 inhibitors suppressed breast carcinoma cell proliferation. These results indicated that SGLT1 inhibitors could be used as therapeutic agents for breast cancer patients with aggressive biological behaviors.
    MeSH term(s) Humans ; Female ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Sodium-Glucose Transporter 2/metabolism ; Prognosis ; Vascular Endothelial Growth Factor A/metabolism ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Glucose/metabolism ; Carcinoma, Ductal
    Chemical Substances Sodium-Glucose Transporter 2 Inhibitors ; Sodium-Glucose Transporter 2 ; Vascular Endothelial Growth Factor A ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-07-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 604563-7
    ISSN 1573-7217 ; 0167-6806
    ISSN (online) 1573-7217
    ISSN 0167-6806
    DOI 10.1007/s10549-023-07024-9
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  5. Article ; Online: Maternal lifestyle and nutrient intakes during pregnancy and exclusive breastfeeding in relation to risk factors for breast cancer: The Japan Environment and Children's Study.

    Minami, Yuko / Miyashita, Minoru / Ishida, Takanori / Fujita, Megumi / Hamada, Hirotaka / Saito, Masatoshi / Arima, Takahiro / Yaegashi, Nobuo

    Preventive medicine

    2023  Volume 168, Page(s) 107446

    Abstract: Breastfeeding has many benefits for infant growth and maternal health, such as reducing breast cancer risk. However, data on maternal factors influencing breastfeeding are insufficient. To clarify the associations between maternal lifestyle and diet ... ...

    Abstract Breastfeeding has many benefits for infant growth and maternal health, such as reducing breast cancer risk. However, data on maternal factors influencing breastfeeding are insufficient. To clarify the associations between maternal lifestyle and diet during pregnancy and exclusive breastfeeding (EBF), we conducted a prospective study of pregnant women within the framework of the Japan Environment and Children's Study (a nationwide birth cohort study). Of 97,413 pregnant women recruited between January 2011 and March 2014, 27,775 with a singleton first live birth whose dietary data during pregnancy and lactation data were complete were eligible. Using logistic regression, we evaluated the associations between lifestyle factors including smoking and prepregnancy body mass index and intake of nutrients (macronutrients, isoflavones, and dietary fiber), some of which are known risk factors of breast cancer, and EBF for one month postpartum (initiation of EBF). To investigate the associations of these factors with EBF for 6 months (continuation of EBF), 9582 women who had successfully completed one-month EBF were further followed up. Smoking and prepregnancy obesity were inversely associated with the initiation and continuation of EBF. Intakes of protein, fat, isoflavone, and dietary fiber were positively associated (p
    MeSH term(s) Infant ; Female ; Humans ; Pregnancy ; Child ; Breast Feeding ; Cohort Studies ; Prospective Studies ; Japan ; Breast Neoplasms ; Risk Factors ; Eating ; Dietary Fiber ; Life Style ; Mothers
    Chemical Substances Dietary Fiber
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 184600-0
    ISSN 1096-0260 ; 0091-7435
    ISSN (online) 1096-0260
    ISSN 0091-7435
    DOI 10.1016/j.ypmed.2023.107446
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  6. Article ; Online: Mitochondrial dynamics as a novel treatment strategy for triple-negative breast cancer.

    Wang, Yuechen / Harada-Shoji, Narumi / Kitamura, Narufumi / Yamazaki, Yuto / Ebata, Akiko / Amari, Masakazu / Watanabe, Mika / Miyashita, Minoru / Tada, Hiroshi / Abe, Takaaki / Suzuki, Takashi / Gonda, Kohsuke / Ishida, Takanori

    Cancer medicine

    2024  Volume 13, Issue 2, Page(s) e6987

    Abstract: Introduction: Triple-negative breast cancer (TNBC), recognized as the most heterogeneous type of breast cancer (BC), exhibits a worse prognosis than other subtypes. Mitochondria dynamics play a vital role as mediators in tumorigenesis by adjusting to ... ...

    Abstract Introduction: Triple-negative breast cancer (TNBC), recognized as the most heterogeneous type of breast cancer (BC), exhibits a worse prognosis than other subtypes. Mitochondria dynamics play a vital role as mediators in tumorigenesis by adjusting to the cell microenvironments. However, the relationship between mitochondrial dynamics and metabophenotype exhibits discrepancies and divergence across various research and BC models. Therefore, this study aims to explore the role of mitochondrial dynamics in TNBC drug resistance and tumorigenesis.
    Methods: The Wst-8 test was conducted to assess doxorubicin sensitivity in HCC38, MDA-MB-231 (TNBC), and MCF-7 (luminal). Confocal microscopy and FACS were used to quantify the mitochondrial membrane potential (ΔφM), mitophagy, and reactive oxygen species (ROS) production. Agilent Seahorse XF Analyzer was utilized to measure metabolic characteristics. Dynamin-related protein-1 (DRP1), Parkin, and p62 immunohistochemistry staining were performed using samples from 107 primary patients with BC before and after neoadjuvant chemotherapy (NAC).
    Results: MDA-MB-231, a TNBC cell line with reduced sensitivity to doxorubicin, reduced ΔφM, and enhanced mitophagy to maintain ROS production through oxidative phosphorylation (OXPHOS)-based metabolism. HCC38, a doxorubicin-sensitive cell line, exhibited no alterations in ΔφM or mitophagy. However, it demonstrated an increase in ROS production and glycolysis. Clinicopathological studies revealed that pretreatment (before NAC) expression of DRP1 was significant in TNBC, as was pretreatment expression of Parkin in the hormone receptor-negative group. Furthermore, low p62 levels seem to be a risk factor for recurrence-free survival.
    Conclusion: Our findings indicated that the interplay between mitophagy, linked to a worse clinical prognosis, and OXPHOS metabolism promoted chemotherapy resistance in TNBC. Mitochondrial fission is prevalent in TNBC. These findings suggest that targeting the unique mitochondrial metabolism and dynamics in TNBC may offer a novel therapeutic strategy for patients with TNBC.
    MeSH term(s) Humans ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/pathology ; Mitochondrial Dynamics ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Ubiquitin-Protein Ligases/genetics ; Carcinogenesis ; Tumor Microenvironment
    Chemical Substances Reactive Oxygen Species ; Doxorubicin (80168379AG) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
    Language English
    Publishing date 2024-02-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2659751-2
    ISSN 2045-7634 ; 2045-7634
    ISSN (online) 2045-7634
    ISSN 2045-7634
    DOI 10.1002/cam4.6987
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  7. Article ; Online: Evaluating homologous recombination activity in tissues to predict the risk of hereditary breast and ovarian cancer and olaparib sensitivity.

    Motonari, Tokiwa / Yoshino, Yuki / Haruta, Moe / Endo, Shino / Sasaki, Shota / Miyashita, Minoru / Tada, Hiroshi / Watanabe, Gou / Kaneko, Toshiro / Ishida, Takanori / Chiba, Natsuko

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 7519

    Abstract: Homologous recombination (HR) repairs DNA damage including DNA double-stranded breaks and alterations in HR-related genes results in HR deficiency. Germline alteration of HR-related genes, such as BRCA1 and BRCA2, causes hereditary breast and ovarian ... ...

    Abstract Homologous recombination (HR) repairs DNA damage including DNA double-stranded breaks and alterations in HR-related genes results in HR deficiency. Germline alteration of HR-related genes, such as BRCA1 and BRCA2, causes hereditary breast and ovarian cancer (HBOC). Cancer cells with HR deficiency are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors and DNA-damaging agents. Thus, accurately evaluating HR activity is useful for diagnosing HBOC and predicting the therapeutic effects of anti-cancer agents. Previously, we developed an assay for site-specific HR activity (ASHRA) that can quantitatively evaluate HR activity and detect moderate HR deficiency. HR activity in cells measured by ASHRA correlates with sensitivity to the PARP inhibitor, olaparib. In this study, we applied ASHRA to lymphoblastoid cells and xenograft tumor tissues, which simulate peripheral blood lymphocytes and tumor tissues, respectively, as clinically available samples. We showed that ASHRA could be used to detect HR deficiency in lymphoblastoid cells derived from a BRCA1 pathogenic variant carrier. Furthermore, ASHRA could quantitatively measure the HR activity in xenograft tumor tissues with HR activity that was gradually suppressed by inducible BRCA1 knockdown. The HR activity of xenograft tumor tissues quantitatively correlated with the effect of olaparib. Our data suggest that ASHRA could be a useful assay for diagnosing HBOC and predicting the efficacy of PARP inhibitors.
    MeSH term(s) Humans ; Female ; Homologous Recombination ; BRCA1 Protein/genetics ; Phthalazines/pharmacology ; Phthalazines/therapeutic use ; Antineoplastic Agents/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Poly(ADP-ribose) Polymerases/genetics ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; DNA/therapeutic use ; Piperazines
    Chemical Substances olaparib (WOH1JD9AR8) ; BRCA1 Protein ; Phthalazines ; Antineoplastic Agents ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; DNA (9007-49-2) ; Piperazines
    Language English
    Publishing date 2024-04-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-57367-6
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  8. Article ; Online: Heterogeneous Nuclear Ribonucleoprotein K Is Involved in the Estrogen-Signaling Pathway in Breast Cancer.

    Iwabuchi, Erina / Miki, Yasuhiro / Suzuki, Takashi / Hirakawa, Hisashi / Ishida, Takanori / Sasano, Hironobu

    International journal of molecular sciences

    2021  Volume 22, Issue 5

    Abstract: Heterogeneous nuclear ribonucleoprotein K (hnRNPK) transcripts are abundant in estrogen receptor (ER)- or progesterone receptor (PR)-positive breast cancer. However, the biological functions of hnRNPK in the ER-mediated signaling pathway have remained ... ...

    Abstract Heterogeneous nuclear ribonucleoprotein K (hnRNPK) transcripts are abundant in estrogen receptor (ER)- or progesterone receptor (PR)-positive breast cancer. However, the biological functions of hnRNPK in the ER-mediated signaling pathway have remained largely unknown. Therefore, this study analyzes the functions of hnRNPK expression in the ER-mediated signaling pathway in breast cancer. We initially evaluated hnRNPK expression upon treatment with estradiol (E2) and ICI 182,780 in the ERα-positive breast carcinoma cell line MCF-7. The results revealed that E2 increased hnRNPK; however, hnRNPK expression was decreased with ICI 182,780 treatment, indicating estrogen dependency. We further evaluated the effects of hnRNPK knockdown in the ER-mediated signaling pathway in MCF-7 cells using small interfering RNAs. The results revealed that hnRNPK knockdown decreased ERα expression and ERα target gene pS2 by E2 treatment. As hnRNPK interacts with several other proteins, we explored the interaction between hnRNPK and ERα, which was demonstrated using immunoprecipitation and proximity ligation assay. Subsequently, we immunolocalized hnRNPK in patients with breast cancer, which revealed that hnRNPK immunoreactivity was significantly higher in ERα-positive carcinoma cells and significantly lower in Ki67-positive or proliferative carcinoma cells. These results indicated that hnRNPK directly interacted with ERα and was involved in the ER-mediated signaling pathway in breast carcinoma. Furthermore, hnRNPK expression could be an additional target of endocrine therapy in patients with ERα-positive breast cancer.
    MeSH term(s) Breast Neoplasms/metabolism ; Carcinoma/metabolism ; Cell Line, Tumor ; Cell Proliferation/physiology ; Estrogens/metabolism ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Heterogeneous-Nuclear Ribonucleoprotein K/metabolism ; Humans ; MCF-7 Cells ; RNA, Small Interfering/metabolism ; Receptors, Estrogen/metabolism ; Signal Transduction/physiology
    Chemical Substances Estrogens ; Heterogeneous-Nuclear Ribonucleoprotein K ; RNA, Small Interfering ; Receptors, Estrogen ; HNRNPK protein, human (146410-60-8)
    Language English
    Publishing date 2021-03-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22052581
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  9. Article ; Online: FE65 in breast cancer and its clinicopathological significance.

    Xu, Junyao / Iwabuchi, Erina / Miki, Yasuhiro / Kanai, Ayako / Ishida, Takanori / Sasano, Hironobu

    Breast cancer (Tokyo, Japan)

    2021  Volume 29, Issue 1, Page(s) 144–155

    Abstract: Background: Transcription coregulator adapter protein FE65 is well known to play pivotal roles in pathogenesis of Alzheimer's disease by regulating amyloid precursor protein (APP) expression and processing. APP was recently reported to be also involved ... ...

    Abstract Background: Transcription coregulator adapter protein FE65 is well known to play pivotal roles in pathogenesis of Alzheimer's disease by regulating amyloid precursor protein (APP) expression and processing. APP was recently reported to be also involved in development of human malignancies. Therefore, in this study, we studied FE65 status in different subtypes of human breast cancer and correlated the results with cell proliferation and migration of carcinoma cells and clinicopathological features of breast cancer patients to explore its biological and clinical significance in breast cancer.
    Methods: We first immunolocalized FE65 and APP in 138 breast cancer patients and correlated the results with their tumor grade. Then, we did further exploration by proximity ligation assay, WST-8, and wound-healing assay.
    Results: FE65 immunoreactivity in carcinoma cells was significantly associated with lymph-node metastasis, ERα, and high pathological N factor. APP immunoreactivity was significantly positively correlated with high pathological N factor. FE65, APP, and p-APP were all significantly correlated with shorter disease-free survival of breast cancer patients. In addition, the status of FE65 was significantly associated with overall survival. Results of in vitro analysis revealed that FE65 promoted the migration and proliferation of T-47D and ZR-75-1 breast carcinoma cells. In situ proximity ligation assay revealed that FE65 could bind to APP in the cytoplasm. FE65 was also associated with APP and ERα in carcinoma cells, suggesting their cooperativity in promoting carcinoma cell proliferation and migration. APP was also significantly associated with adverse clinical outcome of the patients.
    Conclusions: This is the first study to explore the clinical significance of FE65 in human breast cancer. The significant positive correlation of FE65 with poor clinical outcome, direct binding to APP, and promotion of carcinoma cell proliferation and migration indicated that FE65-APP pathway could serve as the potential candidate of therapeutic intervention in breast cancer patients.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Amyloid beta-Protein Precursor/metabolism ; Breast Neoplasms/metabolism ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Disease-Free Survival ; Estrogen Receptor alpha/metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Nerve Tissue Proteins/metabolism ; Nuclear Proteins/metabolism
    Chemical Substances APBB1 protein, human ; Amyloid beta-Protein Precursor ; Estrogen Receptor alpha ; Nerve Tissue Proteins ; Nuclear Proteins
    Language English
    Publishing date 2021-09-08
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2052429-8
    ISSN 1880-4233 ; 1340-6868
    ISSN (online) 1880-4233
    ISSN 1340-6868
    DOI 10.1007/s12282-021-01291-4
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  10. Article ; Online: Value of ultrafast and standard dynamic contrast-enhanced magnetic resonance imaging in the evaluation of the presence and extension of residual disease after neoadjuvant chemotherapy in breast cancer.

    Kato, Erina / Mori, Naoko / Mugikura, Shunji / Sato, Satoko / Ishida, Takanori / Takase, Kei

    Japanese journal of radiology

    2021  Volume 39, Issue 8, Page(s) 791–801

    Abstract: Purpose: To evaluate the diagnostic performance of ultrafast and standard dynamic contrast-enhanced (DCE)-MRI in evaluating the residual disease after neoadjuvant chemotherapy (NAC) for breast cancer.: Materials and methods: Sixty-seven consecutive ... ...

    Abstract Purpose: To evaluate the diagnostic performance of ultrafast and standard dynamic contrast-enhanced (DCE)-MRI in evaluating the residual disease after neoadjuvant chemotherapy (NAC) for breast cancer.
    Materials and methods: Sixty-seven consecutive patients underwent MRI after NAC. Visual analysis of enhancement was performed on ultrafast and standard DCE-MRI, and compared between no residual disease and residual disease groups. The lesion diameters measured on the last phase of ultrafast DCE-MRI and early and delayed phases of standard DCE-MRI were compared with pathological diameter of entire residual cancer and residual invasive ductal carcinoma (IDC).
    Results: The visual analysis in the delayed phase of standard DCE-MRI exhibited the highest sensitivity (90%), whereas ultrafast DCE-MRI revealed the highest positive predictive value (92%). There were no significant differences between the diameters in the delayed phase of the standard DCE-MRI and the pathological entire residual cancer (p = 0.97), and the diameters in ultrafast DCE-MRI and the pathological residual IDC (p = 0.97).
    Conclusion: The delayed phase of standard DCE-MRI may be effective for detecting the residual disease and evaluating the extension of entire residual cancer. Enhancement in ultrafast DCE-MRI may be strongly suggestive of the presence of residual disease, and effective for evaluating the extension of residual IDC.
    MeSH term(s) Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Contrast Media ; Female ; Humans ; Magnetic Resonance Imaging ; Neoadjuvant Therapy ; Neoplasm, Residual/diagnostic imaging ; Time Factors
    Chemical Substances Contrast Media
    Language English
    Publishing date 2021-03-20
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2488907-6
    ISSN 1867-108X ; 1867-1071
    ISSN (online) 1867-108X
    ISSN 1867-1071
    DOI 10.1007/s11604-021-01110-y
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