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  1. Article ; Online: Elucidating shape-mediated drug carrier mechanics of hematite nanomaterials for breast cancer therapeutics.

    Babunagappan, Kaviya Vijayalakshmi / Raj, Thilak / Seetharaman, Abirami / Ariraman, Subastri / Sudhakar, Swathi

    Journal of materials chemistry. B

    2024  

    Abstract: Metallic nanomaterials have gained significant attention in cancer therapy as potential nanocarriers due to their unique properties at the nanoscale. However, nanomaterials face several drawbacks, including biocompatibility, stability, and cellular ... ...

    Abstract Metallic nanomaterials have gained significant attention in cancer therapy as potential nanocarriers due to their unique properties at the nanoscale. However, nanomaterials face several drawbacks, including biocompatibility, stability, and cellular uptake. Hematite (α-Fe
    Language English
    Publishing date 2024-03-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2702241-9
    ISSN 2050-7518 ; 2050-750X
    ISSN (online) 2050-7518
    ISSN 2050-750X
    DOI 10.1039/d4tb00052h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Doxorubicin loaded thermostable nanoarchaeosomes: a next-generation drug carrier for breast cancer therapeutics.

    Babunagappan, Kaviya Vijayalakshmi / Seetharaman, Abirami / Ariraman, Subastri / Santhosh, Poornima Budime / Genova, Julia / Ulrih, Natasa Poklar / Sudhakar, Swathi

    Nanoscale advances

    2024  Volume 6, Issue 8, Page(s) 2026–2037

    Abstract: Breast cancer has a poor prognosis due to the toxic side effects associated with high doses of chemotherapy. Liposomal drug encapsulation has resulted in clinical success in enhancing chemotherapy tolerability. However, the formulation faces severe ... ...

    Abstract Breast cancer has a poor prognosis due to the toxic side effects associated with high doses of chemotherapy. Liposomal drug encapsulation has resulted in clinical success in enhancing chemotherapy tolerability. However, the formulation faces severe limitations with a lack of colloidal stability, reduced drug efficiency, and difficulties in storage conditions. Nanoarchaeosomes (NA) are a new generation of highly stable nanovesicles composed of the natural ether lipids extracted from archaea. In our study, we synthesized and characterized the NA, evaluated their colloidal stability, drug release potential, and anticancer efficacy. Transmission electron microscopy images have shown that the NA prepared from the hyperthermophilic archaeon
    Language English
    Publishing date 2024-01-02
    Publishing country England
    Document type Journal Article
    ISSN 2516-0230
    ISSN (online) 2516-0230
    DOI 10.1039/d3na00953j
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  3. Article: Optimization and Validation of a Harmonized Protocol for Generating Therapeutic-Grade Dendritic Cells in a Randomized Phase II Clinical Trial, Using Two Varied Antigenic Sources.

    Seetharaman, Abirami / Christopher, Vasanth / Dhandapani, Hemavathi / Jayakumar, Hascitha / Dhanushkodi, Manikandan / Bhaskaran, Narmadha / Rajaraman, Swaminathan / Ranganathan, Rama / Sunder Singh, Shirley / Vijayakumar, Varalakshmi / Rajamanickam, Arivazhagan / Suri, Anil / Jagadish, Nirmala / Rajkumar, Thangarajan / Ramanathan, Priya

    Vaccines

    2024  Volume 12, Issue 2

    Abstract: Autologous dendritic cell (DC)-based immunotherapy is a cell-based advanced therapy medicinal product (ATMP) that was first introduced more than three decades ago. In the current study, our objective was to establish a harmonized protocol using two ... ...

    Abstract Autologous dendritic cell (DC)-based immunotherapy is a cell-based advanced therapy medicinal product (ATMP) that was first introduced more than three decades ago. In the current study, our objective was to establish a harmonized protocol using two varied antigenic sources and a good manufacturing practice (GMP)-compliant, manual method for generating clinical-grade DCs at a limited-resource academic setting. After obtaining ethical committee-approved informed consent, the recruited patients underwent leukapheresis, and single-batch DC production was carried out. Using responder-independent flow cytometric assays as quality control (QC) criteria, we propose a differentiation and maturation index (DI and MI, respectively), calculated with the QC cut-off and actual scores of each batch for comparison. Changes during cryopreservation and personnel variation were assessed periodically for up to two to three years. Using our harmonized batch production protocol, the average DI was 1.39 and MI was 1.25. Allogenic responder proliferation was observed in all patients, while IFN-gamma secretion, evaluated using flow cytometry, was detected in 10/36 patients and significantly correlated with CD8+ T cell proliferation (
    Language English
    Publishing date 2024-01-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines12020112
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  4. Article ; Online: Immunotherapy for cervical cancer: Can it do another lung cancer?

    Ramanathan, Priya / Dhandapani, Hemavathi / Jayakumar, Hascitha / Seetharaman, Abirami / Thangarajan, Rajkumar

    Current problems in cancer

    2018  Volume 42, Issue 2, Page(s) 148–160

    Abstract: Cervical cancer, although preventable, is still the second most common cancer among women worldwide. In developing countries like India, where screening for cervical cancer is virtually absent, most women seek treatment only at advanced stages of the ... ...

    Abstract Cervical cancer, although preventable, is still the second most common cancer among women worldwide. In developing countries like India, where screening for cervical cancer is virtually absent, most women seek treatment only at advanced stages of the disease. Although standard treatment is curative in more than 90% of women during the early stages, for stage IIIb and above this rate drops to 50% or less. Hence, novel therapeutic adjuvants are required to improve survival at advanced stages. Lung cancer has shown the way forward with the use of Immunotherapeutic interventions as standard line of treatment in advanced stages. In this review, we provide an overview of mechanisms of immune evasion, strategies that can be employed to boost the immune system in order to improve the overall survival of the patients and summarize briefly the clinical trials that have been completed or that are underway to bring therapeutic vaccines for cervical cancer to the clinics.
    MeSH term(s) Cancer Vaccines/therapeutic use ; Female ; Humans ; Immunotherapy/methods ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Lung Neoplasms/virology ; Papillomaviridae/immunology ; Papillomavirus Infections/complications ; Papillomavirus Infections/pathology ; Papillomavirus Infections/therapy ; Uterine Cervical Neoplasms/pathology ; Uterine Cervical Neoplasms/therapy ; Uterine Cervical Neoplasms/virology
    Chemical Substances Cancer Vaccines
    Language English
    Publishing date 2018-01-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 441816-5
    ISSN 1535-6345 ; 0147-0272
    ISSN (online) 1535-6345
    ISSN 0147-0272
    DOI 10.1016/j.currproblcancer.2017.12.004
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  5. Article: Dendritic cells matured with recombinant human sperm associated antigen 9 (rhSPAG9) induce CD4

    Dhandapani, Hemavathi / Jayakumar, Hascitha / Seetharaman, Abirami / Singh, Shirley Sunder / Ganeshrajah, Selvaluxmy / Jagadish, Nirmala / Suri, Anil / Thangarajan, Rajkumar / Ramanathan, Priya

    Cancer cell international

    2021  Volume 21, Issue 1, Page(s) 473

    Abstract: Background: Dendritic cell (DC)-based immunotherapy is capable of activating the immune system and in particular tumor-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumor. However, major limitations are the availability of autologous tumor ... ...

    Abstract Background: Dendritic cell (DC)-based immunotherapy is capable of activating the immune system and in particular tumor-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumor. However, major limitations are the availability of autologous tumor cells as antigenic source and the selection of antigen that may have potential to activate both CD4
    Methods: Human monocytes derived DCs were pulsed with different concentrations (250 ng/ml to 1000 ng/ml) of recombinant human SPAG9 (rhSPAG9) and evaluated for their phenotypic and functional ability. The efficacy of DCs primed with 750 ng/ml of rhSPAG9 (SPDCs) was compared with DCs primed with autologous tumor lysates (TLDCs), to induce CD4
    Results: Phenotypic and functional characterization of DCs pulsed with 750 ng/ml rhSPAG9 was found to be optimal and effective for priming DCs. SPDCs were also capable of stimulating allogeneic T cells similar to TLDCs. SPDCs showed a statistically insignificant increase in the expression of maturation marker CD83 and migration towards CCL19 and CCL21 compared with TLDCs (CD83; P = 0.4; migration; P = 0.2). In contrast, although TLDCs showed better proliferation and secretion of Th1 cytokines (IL12p40, IL12p70 and IFNγ) compared to SPDCs, this difference was not statistically significant (IL12p40, P = 0.06). Further we also observed that clinical dose of cisplatin (200 µM) treated SPDCs were able to stimulate the proliferation of cytotoxic T lymphocytes without increasing the FOXP3
    Conclusions: In summary, in order to overcome the limitation of the availability of autologous tumor cells as antigenic sources, our present strategy provides an insight to consider rhSPAG9 as a strong immunogen for DC-based immunotherapy for cervical cancer trials and warrants further studies. This is the first report to suggest that rhSPAG9 is an effective antigen for pulsing DCs that are capable of eliciting a potent Th1 response which, in turn, may help in decreasing the tumor burden when used along with a cisplatin based combinatorial regimen for therapeutic intervention.
    Language English
    Publishing date 2021-09-07
    Publishing country England
    Document type Journal Article
    ISSN 1475-2867
    ISSN 1475-2867
    DOI 10.1186/s12935-021-01951-7
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  6. Article ; Online: Autologous cervical tumor lysate pulsed dendritic cell stimulation followed by cisplatin treatment abrogates FOXP3+ cells in vitro.

    Dhandapani, Hemavathi / Seetharaman, Abirami / Jayakumar, Hascitha / Ganeshrajah, Selvaluxmy / Singh, Shirley Sunder / Thangarajan, Rajkumar / Ramanathan, Priya

    Journal of gynecologic oncology

    2021  Volume 32, Issue 4, Page(s) e59

    Abstract: Objective: Dendritic cells (DCs) are administered as immunotherapeutic adjuvants after the completion of standard treatment in most settings. However, our Phase I trial indicated that one patient out of four, who received autologous tumor lysate-pulsed ... ...

    Abstract Objective: Dendritic cells (DCs) are administered as immunotherapeutic adjuvants after the completion of standard treatment in most settings. However, our Phase I trial indicated that one patient out of four, who received autologous tumor lysate-pulsed dendritic cell (TLDC) also received cisplatin chemotherapy and experienced complete regression of her lung lesion, continuing to be disease free till date. Hence, the objective of our current study is to evaluate the sustenance or augmentation of immune responses when autologous human papillomavirus positive cervical tumor lysate pulsed DC- are combined with cisplatin, using co-culture assays in vitro.
    Methods: Before treatment, peripheral blood and punch biopsy samples were collected from 23 cervical cancer patients after obtaining an informed consent. DC functionality was confirmed through phenotypic and functional assays using autologous peripheral blood mononuclear cells as responders. For cisplatin experiments, the drug was added at 150, 200 (clinical dose equivalent), and 400 μM concentrations to DCs alone or DC-T cell co-cultures. Phenotypic assessment and functional characterization of DCs was done using flow cytometry. Cytokine enzyme-linked immunosorbent assay and interferon (IFN)-γ enzyme-linked immune absorbent spot assays were also performed.
    Results: The functionality of TLDCs was not compromised upon cisplatin treatment in vitro even at the highest (400 μM) concentration. Even though cisplatin treatment reduced the secretion of IFN-γ and interleukin (IL)-12p40 in co-cultures stimulated with TLDCs, this effect was not significant (p>0.05). A doubling of IFN-γ secretion following cisplatin treatment was observed in at least one of three independent experiments. Additional experiments showed a reduction in both FOXP3+ regulatory T cells and IL-10 levels.
    Conclusion: Our results provide evidence that cisplatin treatment may be given after autologous TLDC administration to maintain or improve a productive anti-tumor response in vaccinated patients.
    MeSH term(s) Cisplatin ; Dendritic Cells ; Female ; Forkhead Transcription Factors ; Humans ; Interferon-gamma ; Leukocytes, Mononuclear ; Pharmaceutical Preparations ; Uterine Cervical Neoplasms/therapy
    Chemical Substances FOXP3 protein, human ; Forkhead Transcription Factors ; Pharmaceutical Preparations ; Interferon-gamma (82115-62-6) ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2021-04-06
    Publishing country Korea (South)
    Document type Clinical Trial, Phase I ; Journal Article
    ZDB-ID 2478405-9
    ISSN 2005-0399 ; 2005-0380
    ISSN (online) 2005-0399
    ISSN 2005-0380
    DOI 10.3802/jgo.2021.32.e59
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    Zs.A 6484: Show issues Location:
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  7. Article ; Online: Combination of IDO1

    Jayakumar, Hascitha / Seetharaman, Abirami / Sunder Singh, Shirley / Dhandapani, Hemavathi / Subramani, Jayavelu / Ganeshrajah, Selvaluxmy / Thangarajan, Rajkumar / Ramanathan, Priya

    Journal of reproductive immunology

    2021  Volume 149, Page(s) 103454

    Abstract: The over expression of Indoleamine 2, 3-Dioxygenase (IDO1), an immune checkpoint inhibitor, is well known in cervical cancer. However, its association with chemokine signals promoting cellular infiltration in the cervical tumor microenvironment, is ... ...

    Abstract The over expression of Indoleamine 2, 3-Dioxygenase (IDO1), an immune checkpoint inhibitor, is well known in cervical cancer. However, its association with chemokine signals promoting cellular infiltration in the cervical tumor microenvironment, is unknown. In the current study, we evaluated the expression and enzymatic activity of IDO1. We also profiled the expression of chemokine ligand-receptors- CCR4-CCL22, CXCR3-CXCL10, CXCR4-CXCL12, and CCR7-CCL19 using immunohistochemistry (IHC), and studied their association with IDO1, statistically. After getting an informed consent, punch biopsy samples were obtained from 105 patients diagnosed with cervical cancer. HPV typing by Sanger sequencing, realtime PCR for quantifying IDO1 mRNA expression, HPLC for determining the K/T ratio and IHC for all the above chemokine receptor-ligand pairs along with IDO1 were performed. We found a significant increase in the expression of IDO1 and K/T levels in early and locally advanced stages when compared to Stage IV disease. Among the chemokine ligand -receptor pairs profiled, we found that high CCL19 marker expression was a good prognostic indicator of patients' disease-free (p = 0.013) and overall survival (p = 0.043). Although we could not identify IDO1 as an independent prognostic factor, we found that high levels of IDO1 expression may further reduce survival outcomes in patients with low CCL19 expression. This could be vital for designing immuno therapeutic interventions targeting IDO1.
    MeSH term(s) Adult ; Aged ; Cervix Uteri/metabolism ; Cervix Uteri/pathology ; Chemokine CCL19/genetics ; Chemokine CCL19/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism ; Middle Aged ; Neoplasm Staging ; Papillomaviridae/physiology ; Papillomavirus Infections/diagnosis ; Papillomavirus Infections/metabolism ; Papillomavirus Infections/mortality ; Predictive Value of Tests ; Prognosis ; Survival Analysis ; Tumor Microenvironment ; Uterine Cervical Neoplasms/diagnosis ; Uterine Cervical Neoplasms/metabolism ; Uterine Cervical Neoplasms/mortality
    Chemical Substances Chemokine CCL19 ; IDO1 protein, human ; Indoleamine-Pyrrole 2,3,-Dioxygenase
    Language English
    Publishing date 2021-11-23
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 424421-7
    ISSN 1872-7603 ; 0165-0378
    ISSN (online) 1872-7603
    ISSN 0165-0378
    DOI 10.1016/j.jri.2021.103454
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