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  1. Article ; Online: Therapeutic vulnerabilities in triple negative breast cancer: Stem-like traits explored within molecular classification.

    Huang, Peng / Zhang, Xi / Prabhu, Jyothi S / Pandey, Vijay

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2024  Volume 174, Page(s) 116584

    Abstract: Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer (BC). Despite advances in the clinical management of TNBC, recurrence-related mortality remains a challenge. The stem-like phenotype of TNBC plays a significant role in the ...

    Abstract Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer (BC). Despite advances in the clinical management of TNBC, recurrence-related mortality remains a challenge. The stem-like phenotype of TNBC plays a significant role in the persistence of minimal disease residue after therapy. Individuals exhibiting stem-like characteristics are particularly prone to inducing malignant relapse accompanied by strong resistance. Therefore, stem-like traits have been broadly proposed as therapeutic vulnerabilities to treat TNBC and reduce recurrence. However, heterogeneity within TNBC often generally restricts the stability of the therapeutic efficacy. To understand the heterogeneity and manage TNBC more precisely, multiple TNBC subtyping categories have been reported, providing the basis for profile-according therapeutic regimens. To provide more insight into targeting stem-like traits to ablate TNBC and reduce recurrence in the context of heterogeneity, this paper reviewed the molecular subtyping of TNBC, identified the consensus subtypes with distinct stem-like phenotypes, characterized the stemness hierarchy of TNBC, outlined the biological models for stem-like TNBC subtypes, summarized the therapeutic vulnerabilities in stem-like traits of the subtypes, and proposed potential therapeutic regimens targeting stem-like characteristics to improve TNBC prognosis.
    MeSH term(s) Humans ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/classification ; Triple Negative Breast Neoplasms/pathology ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Female ; Phenotype ; Animals ; Neoplasm Recurrence, Local/genetics ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2024-04-12
    Publishing country France
    Document type Journal Article ; Review
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2024.116584
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    Ud II Zs.198: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Gender disparity in COVID-19: Role of sex steroid hormones.

    Lipsa, Anuja / Prabhu, Jyothi S

    Asian Pacific journal of tropical medicine

    2021  Volume 14, Issue 1, Page(s) 5–9

    Abstract: The emerging pandemic of COVID-19 caused by the novel pathogenic human coronavirus SARS-CoV-2 has caused significant morbidity and mortality across the globe, prompting the scientific world to search for preventive measures to interrupt the disease ... ...

    Abstract The emerging pandemic of COVID-19 caused by the novel pathogenic human coronavirus SARS-CoV-2 has caused significant morbidity and mortality across the globe, prompting the scientific world to search for preventive measures to interrupt the disease process. Demographic data indicates gender-based differences in COVID-19 morbidity with better outcome amongst females. Disparity in sex-dependent morbidity and mortality in COVID-19 patients may be attributed to difference in levels of sex steroid hormones -androgens and estrogens. Evidence suggests that apart from the regulation of viral host factors, immunomodulatory and cardioprotective roles exerted by estrogen and progesterone may provide protection to females against COVID-19. Exploring the underlying mechanisms and beneficial effects of these hormones as an adjuvant to existing therapy may be a step towards improving the outcomes. This article aims to review studies demonstrating the role of sex steroidal hormones in modulating SARS-CoV-2 host factors and summarize plausible biological reasons for sex-based differences seen in COVID-19 mortality.
    Language English
    Publishing date 2021-01-05
    Publishing country India
    Document type Journal Article
    ISSN 2352-4146
    ISSN (online) 2352-4146
    DOI 10.4103/1995-7645.304293
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  3. Article ; Online: The dynamic tumor-stromal crosstalk: implications of 'stromal-hot' tumors in the process of epithelial-mesenchymal transition in breast cancer.

    Mavatkar, Apoorva D / Naidu, Chandrakala M / Prabhu, Jyothi S / Nair, Madhumathy G

    Molecular biology reports

    2023  Volume 50, Issue 6, Page(s) 5379–5393

    Abstract: Background: Breast cancer metastatic programming involves an intricate process by which the tumor cell coevolves with the surrounding extracellular niche. The supporting cells from the local host stroma get transformed into cancer-associated stromal ... ...

    Abstract Background: Breast cancer metastatic programming involves an intricate process by which the tumor cell coevolves with the surrounding extracellular niche. The supporting cells from the local host stroma get transformed into cancer-associated stromal cells. This complex crosstalk leads to extracellular matrix remodeling, invasion, and eventually distant metastasis.
    Methods: In this review, we examine the protein-miRNA secretome that is crucial for this crosstalk. We also provide evidence from the literature for the pivotal role played by the various stromal cells like fibroblasts, adipocytes, and immune cells in promoting the process of EMT in breast cancer. Through in-silico analysis, we have also attempted to establish that stromal presence is integral to the process of EMT.
    Results and conclusion: The in-silico analysis delineates the persuasive role of the stroma in mediating epithelial-to-mesenchymal transition. This review elucidates the importance of examining the role of the stromal niche that can yield promising diagnostic markers and pave avenues for formulating tailored anti-cancer therapy. Process of EMT as driven by 'stroma-hot' tumors: The process of EMT is driven by the stromal cells. The stromal cells in the form of  fibroblasts, adipocytes, endothelial cells, mesenchymal stromal cells and tissue associated macrophages secrete the miRNA-protein secretome that modulates the stromal niche and the tumor cells to be become 'tumor associated'. This drives tumor progression and invasion. The 'stromal-hot' tumors eventually get the benefit of the surplus nurturing from the stroma that facilitates EMT leading to distant organ seeding and metastasis.
    MeSH term(s) Humans ; Female ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Epithelial-Mesenchymal Transition/genetics ; Endothelial Cells/pathology ; MicroRNAs/genetics ; Stromal Cells/pathology
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2023-04-12
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 186544-4
    ISSN 1573-4978 ; 0301-4851
    ISSN (online) 1573-4978
    ISSN 0301-4851
    DOI 10.1007/s11033-023-08422-4
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1140: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Cell State Transitions and Phenotypic Heterogeneity in Luminal Breast Cancer Implicating MicroRNAs as Potential Regulators.

    Richard, Vinitha / Nair, Madhumathy G / Jaikumar, Vishnu S / Jones, Sara / Prabhu, Jyothi S / Kerin, Michael J

    International journal of molecular sciences

    2023  Volume 24, Issue 4

    Abstract: Luminal breast cancer subtypes respond poorly to endocrine and trastuzumab treatments due to cellular heterogeneity arising from the phenotype transitions, accounted for mainly by the loss of receptor expression. The origins of basal-like and human ... ...

    Abstract Luminal breast cancer subtypes respond poorly to endocrine and trastuzumab treatments due to cellular heterogeneity arising from the phenotype transitions, accounted for mainly by the loss of receptor expression. The origins of basal-like and human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer subtypes have been attributed to genetic and protein modifications in stem-like cells and luminal progenitor cell populations, respectively. The post-transcriptional regulation of protein expression is known to be influenced by microRNAs (miRNAs) that are deemed to be master regulators of several biological processes in breast tumorigenesis and progression. Our objective was to identify the fractions of luminal breast cancer cells that share stemness potentials and marker profiles and to elucidate the molecular regulatory mechanism that drives transitions between fractions, leading to receptor discordances. Established breast cancer cell lines of all prominent subtypes were screened for the expression of putative cancer stem cell (CSC) markers and drug transporter proteins using a side population (SP) assay. Flow-cytometry-sorted fractions of luminal cancer cells implanted in immunocompromised mice generated a pre-clinical estrogen receptor alpha (ERα+) animal model with multiple tumorigenic fractions displaying differential expression of drug transporters and hormone receptors. Despite an abundance of estrogen receptor 1 (ESR1) gene transcripts, few fractions transitioned to the triple-negative breast cancer (TNBC) phenotype with a visible loss of ER protein expression and a distinct microRNA expression profile that is reportedly enriched in breast CSCs. The translation of this study has the potential to provide novel therapeutic miRNA-based targets to counter the dreaded subtype transitions and the failure of antihormonal therapies in the luminal breast cancer subtype.
    MeSH term(s) Humans ; Animals ; Mice ; Female ; Breast Neoplasms/metabolism ; MicroRNAs/genetics ; Receptor, ErbB-2/metabolism ; Trastuzumab/therapeutic use ; Breast/metabolism ; Phenotype ; Receptors, Progesterone/genetics
    Chemical Substances MicroRNAs ; Receptor, ErbB-2 (EC 2.7.10.1) ; Trastuzumab (P188ANX8CK) ; Receptors, Progesterone
    Language English
    Publishing date 2023-02-09
    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/ijms24043497
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  5. Article ; Online: High expression of ACE2 in HER2 subtype of breast cancer is a marker of poor prognosis.

    Nair, Madhumathy G / Prabhu, Jyothi S / Ts, Sridhar

    Cancer treatment and research communications

    2021  Volume 27, Page(s) 100321

    Abstract: Background: ACE2 a key molecule of the Renin-Angiotensin system has been identified as the receptor for SARS-CoV-2 entry into human cells. In the context of human cancers, there is evidence that ACE2 might function as a tumor suppressor. The expression ... ...

    Abstract Background: ACE2 a key molecule of the Renin-Angiotensin system has been identified as the receptor for SARS-CoV-2 entry into human cells. In the context of human cancers, there is evidence that ACE2 might function as a tumor suppressor. The expression levels of ACE2 among the different subtypes of breast cancer has not been investigated.
    Methods: We have examined the differential expression of ACE2 and its correlation with prognosis in breast cancer subtypes using the METABRIC (n = 1898) and TCGA (n = 832) cohorts. Correlations were evaluated by Pearsons's correlation co-efficient and Kaplan-Meier analysis was used to estimate differences in disease-free survival between the ACE2 high and ACE2 low groups.
    Results: There is minimal expression of ACE2 in the luminal classes, but significantly higher levels in the Basal-like and HER2-enriched subclasses. Metastatic biopsies of these tumor types also show enhanced expression of ACE2. High levels of ACE2 correlated with decreased disease-free survival in the HER2-enriched subtype, and it was positively correlated with EGFR expression.
    Conclusion: These observations suggest ACE2 might function as a context dependent factor driving tumor progression in breast cancer and permit new opportunities for targeted therapy.
    MeSH term(s) Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/therapy ; Cohort Studies ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Multivariate Analysis ; Prognosis ; Receptor, ErbB-2/metabolism
    Chemical Substances Biomarkers, Tumor ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2021-01-23
    Publishing country England
    Document type Journal Article
    ISSN 2468-2942
    ISSN (online) 2468-2942
    DOI 10.1016/j.ctarc.2021.100321
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  6. Article ; Online: Premenopausal women with breast cancer in the early post-partum period show molecular profiles of invasion and are associated with poor prognosis.

    Nimbalkar, Vidya P / Snijesh, V P / Rajarajan, Savitha / Alexander, Annie / Kaluve, Rohini / Ramesh, Rakesh / Srinath, B S / Prabhu, Jyothi S

    Breast cancer research and treatment

    2023  Volume 200, Issue 1, Page(s) 139–149

    Abstract: Purpose: Young premenopausal women develop breast cancer (BC) within 5-10 years of the last childbirth, known as post-partum breast cancers (PPBC), often present with aggressive disease. The exact mechanisms that lead to poor prognosis in these patients ...

    Abstract Purpose: Young premenopausal women develop breast cancer (BC) within 5-10 years of the last childbirth, known as post-partum breast cancers (PPBC), often present with aggressive disease. The exact mechanisms that lead to poor prognosis in these patients are largely unknown.
    Methods: We have evaluated the association of clinical and reproductive factors with BC in a cohort of women ≤ 45 years (N = 155) with long-term follow-up. Based on duration since last childbirth (LCB), grouped patients into PPBC1 (LCB ≤ 5 years), PPBC2 (LCB between 6 and 10 years), PPBC3 (LCB > 10 years), and NPBC (age-matched nulliparous BC patients). We compared disease-free survival and hazard associated with recurrence/metastasis between the groups. RNA sequencing of tumor samples was performed from three parous groups (n = 10), and transcriptomic data were analyzed for differentially expressed genes and altered pathways.
    Results: Women in the PPBC1 group had an early menarche and late age at first and last childbirth compared to other groups. Survival analysis within lymph node-positive tumors showed that PPBC1 tumors had a worse prognosis than PPBC2 and NPBC tumors (p = 0.015 and p = 0.026, respectively). Clustering of the differentially expressed genes between the groups showed distinct expression in early PPBC (E-PPBC) tumors. Pathway analysis revealed upregulation of invasive-related pathways along with T cell exhaustion, extracellular matrix remodeling, angiogenesis, and epithelial-to-mesenchymal transition in E-PPBC tumors.
    Conclusion: Early PPBC is a unique subtype with aggressive clinical features and distinct biology. Further research is needed to accurately project the risk of recurrence and optimal treatment strategies in these young patients.
    MeSH term(s) Pregnancy ; Female ; Humans ; Breast Neoplasms/pathology ; Postpartum Period ; Parturition ; Prognosis ; Reproductive History
    Language English
    Publishing date 2023-05-09
    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/s10549-023-06956-6
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    Zs.A 1655: Show issues Location:
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  7. Article: Differential role of glucocorticoid receptor based on its cell type specific expression on tumor cells and infiltrating lymphocytes.

    Snijesh, V P / Nimbalkar, Vidya P / Patil, Sharada / Rajarajan, Savitha / Anupama, C E / Mahalakshmi, S / Alexander, Annie / Soundharya, Ramu / Ramesh, Rakesh / Srinath, B S / Jolly, Mohit Kumar / Prabhu, Jyothi S

    Translational oncology

    2024  Volume 45, Page(s) 101957

    Abstract: Background: The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature ...

    Abstract Background: The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature (GRsig) independent of ER status was developed. We also investigated cell type-specific GR protein expression in BC tumor epithelial cells and infiltrating lymphocytes.
    Methods: GRsig was derived from Dexamethasone treated cell lines through a bioinformatic pipeline. Immunohistochemistry assessed GR protein expression. Associations between GRsig and tumor phenotypes (proliferation, cytolytic activity (CYT), immune cell distribution, and epithelial-to-mesenchymal transition (EMT) were explored in public datasets. Single-cell RNA sequencing data evaluated context-dependent GR roles, and a cell type-specific prognostic role was assessed in an independent BC cohort.
    Results: High GRsig levels were associated with a favorable prognosis across BC subtypes. Tumor-specific high GRsig correlated with lower proliferation, increased CYT, and anti-tumorigenic immune cells. Single-cell data analysis revealed higher GRsig expression in immune cells, negatively correlating with EMT while a positive correlation was observed with EMT primarily in tumor and stromal cells. Univariate and multivariate analyses demonstrated the robust and independent predictive capability of GRsig for favorable prognosis. GR protein expression on immune cells in triple-negative tumors indicated a favorable prognosis.
    Conclusion: This study underscores the cell type-specific role of GR, where its expression on tumor cells is associated with aggressive features like EMT, while in infiltrating lymphocytes, it predicts a better prognosis, particularly within TNBC tumors. The GRsig emerges as a promising independent prognostic indicator across diverse BC subtypes.
    Language English
    Publishing date 2024-04-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2443840-6
    ISSN 1936-5233
    ISSN 1936-5233
    DOI 10.1016/j.tranon.2024.101957
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  8. Article ; Online: miRNAs: Critical mediators of breast cancer metastatic programming.

    Nair, Madhumathy G / Somashekaraiah, Vidya M / Ramamurthy, Vishakha / Prabhu, Jyothi S / Sridhar, T S

    Experimental cell research

    2021  Volume 401, Issue 1, Page(s) 112518

    Abstract: MicroRNA mediated aberrant gene regulation has been implicated in several diseases including cancer. Recent research has highlighted the role of epigenetic modulation of the complex process of breast cancer metastasis by miRNAs. miRNAs play a crucial ... ...

    Abstract MicroRNA mediated aberrant gene regulation has been implicated in several diseases including cancer. Recent research has highlighted the role of epigenetic modulation of the complex process of breast cancer metastasis by miRNAs. miRNAs play a crucial role in the process of metastatic evolution by facilitating alterations in the phenotype of tumor cells and the tumor microenvironment that promote this process. They act as critical determinants of the multi-step progression starting from carcinogenesis all the way to organotropism. In this review, we focus on the current understanding of the compelling role of miRNAs in breast cancer metastasis.
    MeSH term(s) Biomarkers, Tumor/genetics ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Carcinogenesis/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; MicroRNAs/genetics ; Neoplasm Metastasis/genetics ; Neoplasm Metastasis/pathology ; Tumor Microenvironment/genetics
    Chemical Substances Biomarkers, Tumor ; MicroRNAs
    Language English
    Publishing date 2021-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1493-x
    ISSN 1090-2422 ; 0014-4827
    ISSN (online) 1090-2422
    ISSN 0014-4827
    DOI 10.1016/j.yexcr.2021.112518
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    Zs.A 563: Show issues Location:
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  9. Article: Effect of a Novel Sugar Blend on Weight and Cardiometabolic Health among Healthy Indian Adults: A Randomized, Open-Label Study.

    Aswathiah, Srinath / Prabhu, Sunil Kumar / Lingaiah, Ramanna / Ramanna, Anusha / Prabhu, Jyothi S / Pankaj, Shashi Kishor / Mehta, Arti / Bapna, Arohi / Raghavan, Govindarajan

    Foods (Basel, Switzerland)

    2022  Volume 11, Issue 22

    Abstract: Obesity is one of the major factors contributing to noncommunicable diseases (NCDs), which is associated with a high intake of a sugar-rich diet. Sugar blend (a novel combination of sugar and stevia) has half the calories of sugar with the same sweetness ...

    Abstract Obesity is one of the major factors contributing to noncommunicable diseases (NCDs), which is associated with a high intake of a sugar-rich diet. Sugar blend (a novel combination of sugar and stevia) has half the calories of sugar with the same sweetness at recommended use and offers better compliance. A randomized controlled trial was conducted to evaluate the efficacy and safety of this sugar blend in normal to mildly overweight subjects with a body mass index (BMI) of 23−26 kg/m. Sixty subjects were categorized into Group A: Sugar group (n = 30), and Group B: Sugar blend group (n = 30). The primary outcomes evaluated were weight, waist circumference, hip circumference, waist/hip ratio, BMI, and the secondary outcomes evaluated were lipid profile, random blood sugar, and HbA1c. All these parameters were assessed at baseline, 30 days, 60 days, and 90 days. Group B showed a significantly higher weight loss (p = 0.013) at 90 days compared with Group A. A significant reduction in waist circumference (p < 0.0001) by 4.4 cm was noted at 90 days, in addition to reduction in total cholesterol (p < 0.0001), triglyceride (p = 0.006), LDL cholesterol (p = 0.0490), and VLDL cholesterol (p = 0.006) in Group B compared with the baseline. The study revealed that the sugar blend is an effective formulation in reducing weight, anthropometric factors, and other related metabolic parameters. It has been proven to be well tolerated and promotes weight loss when used in conjunction with a daily balanced diet and exercise plan.
    Language English
    Publishing date 2022-11-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704223-6
    ISSN 2304-8158
    ISSN 2304-8158
    DOI 10.3390/foods11223545
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  10. Article: Estimation of ALU Repetitive Elements in Plasma as a Cost-Effective Liquid Biopsy Tool for Disease Prognosis in Breast Cancer.

    Nair, Madhumathy G / Ramesh, Rakesh S / Naidu, Chandrakala M / Mavatkar, Apoorva D / V P, Snijesh / Ramamurthy, Vishakha / Somashekaraiah, Vidya M / C E, Anupama / Raghunathan, Kiruthiga / Panigrahi, Anuradha / Das, Manjula / Dhar, Sujan K / Prabhu, Jyothi S

    Cancers

    2023  Volume 15, Issue 4

    Abstract: Background: Liquid biopsy is widely recognized as an efficient diagnostic method in oncology for disease detection and monitoring. Though the examination of circulating tumor cells (CTC) is mostly implemented for the assessment of genomic aberrations, ... ...

    Abstract Background: Liquid biopsy is widely recognized as an efficient diagnostic method in oncology for disease detection and monitoring. Though the examination of circulating tumor cells (CTC) is mostly implemented for the assessment of genomic aberrations, the need of complex methodologies for their detection has impeded its acceptance in low-resource settings. We evaluated cell-free DNA (cfDNA) as a liquid biopsy tool and investigated its utility in breast cancer patients.
    Methods: Total cell-free DNA was extracted from the plasma of breast cancer patients (n = 167) with a median follow-up of more than 5 years, at various stages of the disease. Quantitative PCR was performed to estimate the copy numbers of two fractions of ALU repetitive elements (ALU 115 and ALU 247), and DNA integrity (DI) was calculated as the ratio of ALU 247/115. Mutations in TP53 and PIK3CA in the cfDNA were estimated by next-gen sequencing (NGS) in a subset of samples. Associations of the levels of both the ALU fragments with various clinico-pathological factors and disease-free survival at various stages were examined. Nomogram models were constructed with clinical variables and ALU 247 levels to predict disease-free survival and the best performing model was evaluated by decision curve analysis.
    Results: DI and ALU 247 levels were significantly lower (
    Conclusion: Our results confirm the utility of cfDNA as an evolving liquid biopsy tool for molecular analysis. Evaluation of larger fragments of cfDNA estimated through ALU 247 can provide vital information concurrent with the pathological process of disease evolution in breast cancer and warrants expansion to other cancer types.
    Language English
    Publishing date 2023-02-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15041054
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