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  1. Article: Intravital tumor decellularization as a new approach to cancer treatment.

    Kakabadze, Zurab / Paresishvili, Teona

    American journal of cancer research

    2023  Volume 13, Issue 9, Page(s) 4192–4207

    Abstract: This study demonstrates the possibility of tumor decellularization in living animals. Subcutaneous Ehrlich tumor induced by isolated Ehrlich ascitic carcinoma cells in mice was used as a model. The study also presents methods for ex vivo ... ...

    Abstract This study demonstrates the possibility of tumor decellularization in living animals. Subcutaneous Ehrlich tumor induced by isolated Ehrlich ascitic carcinoma cells in mice was used as a model. The study also presents methods for ex vivo decellularization of human gastric adenocarcinoma (HGA) and hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in rat. Sodium dodecyl sulfate (SDS) and Triton X-100 were used as detergents for tumor decellularization. The detergents for HGA and HCC were administered through organ vessels. For intravital decellularization of Ehrlich's subcutaneous tumor, detergents were injected directly into the tumor parenchyma. The results of the study showed that the effectiveness of tumor decellularization using SDS and Triton X-100 depended on the size, structure, stiffness and density of the tumor, as well as on the concentration, route and speed of detergent administration. The study also showed that an hour after the initiation of decellularization, the central part of Ehrlich's tumor changed the color, and after three hours, it completely acquired a translucent white color. Chemical contamination of tissues surrounding the tumor with the detergents was not observed. Histological studies showed the complete absence of all cellular components of Ehrlich's tumor and a slightly deformed extracellular matrix (ECM). There were no loco-regional recurrences or metastases of Ehrlich's tumor within 150 days after decellularization. The developed intravital decellularization method allows the effective removal of the cellular components and the DNA content of Ehrlich's subcutaneous tumor without compromising animal health. Additionally, this method can destroy tumor ECM, which will significantly improve the delivery of anticancer drugs to the tumor cells. However, more detailed and extensive studies are needed to develop an in vivo technique for isolated decellularization of the tumor or a part of the organ with the tumor. It is also necessary to identify less toxic decellularization agents and to develop the most efficient route for their delivery to the tumor cells.
    Language English
    Publishing date 2023-09-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2589522-9
    ISSN 2156-6976
    ISSN 2156-6976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Challenges and Opportunities Associated With Drug Delivery for the Treatment of Solid Tumors.

    Paresishvili, Teona / Kakabadze, Zurab

    Oncology reviews

    2023  Volume 17, Page(s) 10577

    Abstract: In this review, we discuss the effectiveness of drug delivery system based on metal nanoparticles, and also, describe the problems associated with their delivery to tumor cells. Throughout recent years, more reports have appeared in the literature that ... ...

    Abstract In this review, we discuss the effectiveness of drug delivery system based on metal nanoparticles, and also, describe the problems associated with their delivery to tumor cells. Throughout recent years, more reports have appeared in the literature that demonstrate promising results for the treatment of various types of cancer using metal-based nanoparticles. Due to their unique physical and chemical properties, metal nanoparticles are effectively being used for the delivery of drug to the tumor cells, for cancer diagnosis and treatment. They can also be synthesized allowing the control of size and shape. However, the effectiveness of the metal nanoparticles for cancer treatment largely depends on their stability, biocompatibility, and ability to selectively affect tumor cells after their systemic or local administration. Another major problem associated with metal nanoparticles is their ability to overcome tumor tissue barriers such as atypical blood vessel structure, dense and rigid extracellular matrix, and high pressure of tumor interstitial fluid. The review also describes the design of tumor drug delivery systems that are based on metal nanoparticles. The mechanism of action of metal nanoparticles on cancer cells is also discussed. Considering the therapeutic safety and toxicity of metal nanoparticles, the prospects for their use for future clinical applications are being currently reviewed.
    Language English
    Publishing date 2023-08-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2390302-8
    ISSN 1970-5565 ; 1970-5565 ; 1970-5557
    ISSN (online) 1970-5565
    ISSN 1970-5565 ; 1970-5557
    DOI 10.3389/or.2023.10577
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Freeze-Dried Mesenchymal Stem Cells: From Bench to Bedside. Review.

    Paresishvili, Teona / Kakabadze, Zurab

    Advanced biology

    2023  Volume 8, Issue 2, Page(s) e2300155

    Abstract: This review describes the freeze-dried mesenchymal stem cells (MSCs) and their ability to restore damaged tissues and organs. An analysis of the literature shows that after the lyophilization MSCs retain >80% of paracrine factors and that the mechanism ... ...

    Abstract This review describes the freeze-dried mesenchymal stem cells (MSCs) and their ability to restore damaged tissues and organs. An analysis of the literature shows that after the lyophilization MSCs retain >80% of paracrine factors and that the mechanism of their action on the restoration of damaged tissues and organs is similar to the mechanism of action of paracrine factors in fresh and cryopreserved mesenchymal stem cells. Based on the own materials, the use of paracrine factors of freeze-dried MSCs in vivo and in vitro for the treatment of various diseases of organs and tissues has shown to be effective. The study also discusses about the advantages and disadvantages of freeze-dried MSCs versus cryopreserved MSCs. However, for the effective use of freeze-dried MSCs in clinical practice, a more detailed study of the mechanism of interaction of paracrine factors of freeze-dried MSCs with target cells and tissues is required. It is also necessary to identify possible other specific paracrine factors of freeze-dried MSCs. In addition, develop new therapeutic strategies for the use of freeze-dried MSCs in regenerative medicine and tissue bioengineering.
    MeSH term(s) Mesenchymal Stem Cells ; Regenerative Medicine ; Cryopreservation ; Freeze Drying
    Language English
    Publishing date 2023-11-21
    Publishing country Germany
    Document type Journal Article ; Review
    ISSN 2701-0198
    ISSN (online) 2701-0198
    DOI 10.1002/adbi.202300155
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Multifunctional hybrid hydrogel for the prevention of post-surgery tumor recurrence.

    Paresishvili, Teona / Janelidze, Merab / Kakabadze, Zurab

    American journal of cancer research

    2023  Volume 13, Issue 6, Page(s) 2504–2516

    Abstract: In this study, we present a multifunctional hybrid hydrogel (MFHH) for the prevention of postoperative tumor recurrence. MFHH consists of two components; component A - containing a gelatin-based cisplatin, which destroys the residual cancer after surgery, ...

    Abstract In this study, we present a multifunctional hybrid hydrogel (MFHH) for the prevention of postoperative tumor recurrence. MFHH consists of two components; component A - containing a gelatin-based cisplatin, which destroys the residual cancer after surgery, and component B - containing macroporous gelatin microcarriers (CultiSpher) loaded with freeze-dried bone marrow stem cells (BMSCs), which activates the wound healing process. We also evaluated the effects of MFHH in a subcutaneous Ehrlich tumor mouse model. MFHH acted as a local delivery system by directly supplying cisplatin to the tumor environment, resulting in excellent anti-cancer effects and minimal side effects. MFHH released cisplatin gradually to destroy the residual tumors, thereby preventing loco-regional recurrence. We have also demonstrated that BMSCs are able to inhibit residual tumor growth. Moreover, CultiSpher loaded with BMSCs acted as an injection 3D scaffold and easily filled the wound defect formed by tumor removal, and the paracrine factors of the freeze-dried BMSCs accelerated the wound healing process. The components of the MFHH can be used both separately and together. However, for the successful application of MFHH in clinical practice, it is necessary to study in more detail the role of paracrine factors of freeze-dried BMSCs in the inhibition or proliferation of residual cancer. These questions will be the focus of our future research.
    Language English
    Publishing date 2023-06-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2589522-9
    ISSN 2156-6976
    ISSN 2156-6976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Human Placental Mesenchymal Stem Cells for the Treatment of ARDS in Rat.

    Kakabadze, Zurab / Kipshidze, Nicholas / Paresishvili, Teona / Kipshidze, Nodar / Vadachkoria, Zurab / Chakhunashvili, David

    Stem cells international

    2022  Volume 2022, Page(s) 8418509

    Abstract: The acute respiratory distress syndrome (ARDS) is one of the main causes of high mortality in patients with coronavirus (COVID-19). In recent years, due to the coronavirus pandemic, the number of patients with ARDS has increased significantly. ... ...

    Abstract The acute respiratory distress syndrome (ARDS) is one of the main causes of high mortality in patients with coronavirus (COVID-19). In recent years, due to the coronavirus pandemic, the number of patients with ARDS has increased significantly. Unfortunately, until now, there are no effective treatments for ARDS caused by COVID-19. Many drugs are either ineffective or have a low effect. Currently, there have been reports of efficient use of mesenchymal stem cells (MSCs) for the treatment of ARDS caused by COVID-19. We investigated the influence of freeze-dried human placenta-derived mesenchymal stem cells (HPMSCs) in ARDS rat model. All animals have received intratracheal injection of 6 mg/kg of lipopolysaccharide (LPS). The rats were randomly divided into five groups: I: LPS, II: LPS+dexamethasone, III: LPS+HPMSCs, IV: HPMSC, and V: saline. ARDS observation time was short-term and amounted to 168 hours. The study has shown that HPMSCs are able to migrate and attach to damaged lung tissue, contributing to the resolution of pathology, restoration of function, and tissue repair in the alveolar space. Studies have also shown that the administration of HPMSCs in animals with ARDS model significantly reduced the levels of key cytokines such as IL-1
    Language English
    Publishing date 2022-06-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2573856-2
    ISSN 1687-9678 ; 1687-966X
    ISSN (online) 1687-9678
    ISSN 1687-966X
    DOI 10.1155/2022/8418509
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: A novel therapeutic vaccine targeting the soluble TNFα receptor II to limit the progression of cardiovascular disease: AtheroVax™.

    Iversen, Patrick L / Kipshidze, Nicholas / Kipshidze, Nodar / Dangas, George / Ramacciotti, Eduardo / Kakabadze, Zurab / Fareed, Jawed

    Frontiers in cardiovascular medicine

    2023  Volume 10, Page(s) 1206541

    Abstract: The burden of atherosclerotic cardiovascular disease contributes to a large proportion of morbidity and mortality, globally. Vaccination against atherosclerosis has been proposed for over 20 years targeting different mediators of atherothrombosis; ... ...

    Abstract The burden of atherosclerotic cardiovascular disease contributes to a large proportion of morbidity and mortality, globally. Vaccination against atherosclerosis has been proposed for over 20 years targeting different mediators of atherothrombosis; however, these have not been adequately evaluated in human clinical trials to assess safety and efficacy. Inflammation is a driver of atherosclerosis, but inflammatory mediators are essential components of the immune response. Only pathogenic forms of sTNFR2 are acted upon while preserving the membrane-bound (wild-type) TNFR2 contributions to a non-pathogenic immune response. We hypothesize that the inhibition of sTNRF2 will be more specific and offer long-term treatment options. Here we describe pre-clinical findings of an sTNFR2-targeting peptide vaccine (AtheroVax™) in a mouse model. The multiple pathways to synthesis of the soluble TNFRII receptor (sTNFRII) were identified as sTNFRII(PC), sTNFRII(Δ7), and sTNFRII(Δ7,9). The sTNFRII(Δ7) peptide, NH2-DFALPVEKPLCLQR-COOH is specific to sTNFR2 based on an mRNA splice-variant in which exon 6 is joined to exon 8. The role of sTNFRII(Δ7) as a mediator of prolonged TNFα activity by preventing degradation and clearance was investigated. Inflammation is a critical driver of onset, progression and expansion of atherosclerosis. The TNFα ligand represents a driver of inflammation that is mediated by a splice variant of TNFR2, referred to as sTNFRII(Δ7). The multiple forms of TNFRII, both membrane bound and soluble, are associated with distinctly different phenotypes. sTNFRII(PC) and sTNFRII(Δ7) are not equivalent to etanercept because they lack a clearance mechanism. The unique peptide associated with sTNFRII(Δ7) contains a linear B-cell epitope with amino acids from both exon 6 and exon 8 supporting the vaccine design. Animal studies to evaluate the vaccine are ongoing, and results will be forthcoming. We describe a peptide vaccine targeting sTNFR2 in limiting the progression of atherosclerosis. A therapeutic vaccine limiting the progression of atherosclerosis will greatly contribute to the reduction in morbidity and mortality from cardiovascular disease. It is likely the vaccine will be used in combination with the current standards of care and lifestyle modifications.
    Language English
    Publishing date 2023-07-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2023.1206541
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  7. Article ; Online: Challenges and perspectives of surgical treatment of liver failure. Current status and last achievements in Georgia.

    Inauri, Nina / Tsomaia, Keti / Ghirdaladze, Avtandil / Chkhaidze, Zurab / Khodeli, Nodar / Chanukvadze, Ilia / Kakabadze, Zurab / Kordzaia, Dimitri / Kiladze, Merab

    Annali italiani di chirurgia

    2022  Volume 92, Page(s) 595–603

    Abstract: Liver transplantation is considered to be the last hope of treatment for irreversible liver failure caused by different diffuse and/or space-occupying lesions of this organ. The strict limitation of the donor organs stipulates for development of ... ...

    Abstract Liver transplantation is considered to be the last hope of treatment for irreversible liver failure caused by different diffuse and/or space-occupying lesions of this organ. The strict limitation of the donor organs stipulates for development of alternative approaches for the solving this problem. The presented review of literature and our experience aims to discuss the modern aspects of management of different hepatic pathologies causing liver failure with the view of creation of the auxiliary, bioengineer-based functional tissues and/or organs and innovative surgical interventions allowing to conduct the operations in cases, which were up to date considered as inoperable. There are highlighted the last achievements of the experimental and translational studies performed in four University research centers of Georgia, which, on the one hand, provoke the specific professional interest, and on the other hand, require the international cooperation and collaboration for further progress and advances in this field of surgery. KEY WORDS: Artificial liver, Bio-Artificial organs, Liver failure, Innovative surgery, Tissue engineering.
    MeSH term(s) Humans ; Liver Failure/surgery ; Liver Transplantation ; Tissue Engineering ; Georgia (Republic)
    Language English
    Publishing date 2022-02-16
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 418927-9
    ISSN 2239-253X ; 0003-469X
    ISSN (online) 2239-253X
    ISSN 0003-469X
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  8. Article: Oral microbiota and oral cancer: Review.

    Kakabadze, Mariam Z / Paresishvili, Teona / Karalashvili, Lia / Chakhunashvili, David / Kakabadze, Zurab

    Oncology reviews

    2020  Volume 14, Issue 2, Page(s) 476

    Abstract: In this review, we draw attention and discuss the risk factors and causes of the development of oral squamous cell carcinoma (OSCC) focusing on oral microbiota. Recently, a breakthrough in the study of cancer has been the discovery of the relationship ... ...

    Abstract In this review, we draw attention and discuss the risk factors and causes of the development of oral squamous cell carcinoma (OSCC) focusing on oral microbiota. Recently, a breakthrough in the study of cancer has been the discovery of the relationship between the presence of certain types of bacteria and the development of cancer in the human body. Studies have shown that,
    Language English
    Publishing date 2020-07-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2390302-8
    ISSN 1970-5565 ; 1970-5565 ; 1970-5557
    ISSN (online) 1970-5565
    ISSN 1970-5565 ; 1970-5557
    DOI 10.4081/oncol.2020.476
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  9. Article ; Online: Bone Marrow Stem Cell and Decellularized Human Amniotic Membrane for the Treatment of Nonhealing Wound After Radiation Therapy.

    Kakabadze, Zurab / Chakhunashvili, David / Gogilashvili, Ketevan / Ediberidze, Ketevan / Chakhunashvili, Konstantine / Kalandarishvili, Konstantine / Karalashvili, Lia

    Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation

    2019  Volume 17, Issue Suppl 1, Page(s) 92–98

    Abstract: Objectives: In this study, our aim was to create a bioactive wound dressing that combined decellularized and lyophilized human amniotic membrane and freeze-dried rat bone marrow stem cells for the treatment of nonhealing wounds.: Materials and methods! ...

    Abstract Objectives: In this study, our aim was to create a bioactive wound dressing that combined decellularized and lyophilized human amniotic membrane and freeze-dried rat bone marrow stem cells for the treatment of nonhealing wounds.
    Materials and methods: For the decellularized human amniotic membrane, sodium dodecyl sulfate and 1% Triton X-100 were used. The mononuclear fraction of bone marrow stem cells was isolated by density gradient centrifugation using Ficoll Paque Plus (GE Healthcare Bio-Sciences, Pittsburgh, PA, USA). Investigations were conducted on Lewis inbred rats with the radiation wound model (dose of 60 Gy). On day 20 after application of radiation, the skin was excised around the radiation burn. The wound was treated with decellularized human amniotic membrane seeded with and without freeze-dried bone marrow stem cells.
    Results: The use of a decellularized amniotic membrane for closing the burn wound increased the rate of healing by 2.5 times; the use of a decellularized amniotic membrane seeded with bone marrow stem cells or freeze-dried bone marrow stem cells increased the rate of wound healing by approximately 4 times.
    Conclusions: Administration of freeze-dried bone marrow stem cell may represent a novel therapeutic approach in the treatment of nonhealing wounds and other conditions. We observed no evidence of local or systemic complications related to the procedure. However, further efforts with better protocol design for future studies are needed.
    MeSH term(s) Amnion ; Animals ; Biological Dressings ; Cells, Cultured ; Disease Models, Animal ; Female ; Freeze Drying ; Humans ; Male ; Pregnancy ; Radiodermatitis/pathology ; Radiodermatitis/therapy ; Rats, Inbred Lew ; Skin/pathology ; Skin/radiation effects ; Stem Cells/physiology ; Time Factors ; Tissue Scaffolds ; Wound Healing
    Language English
    Publishing date 2019-02-19
    Publishing country Turkey
    Document type Journal Article
    ZDB-ID 2396778-X
    ISSN 2146-8427 ; 1304-0855
    ISSN (online) 2146-8427
    ISSN 1304-0855
    DOI 10.6002/ect.MESOT2018.O29
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: A three-dimensional scaffold from decellularized human umbilical artery for bile duct reconstruction.

    Chakhunashvili, Konstantine / Kiladze, Merab / G Chakhunashvili, David / Karalashvili, Lia / Kakabadze, Zurab

    Annali italiani di chirurgia

    2018  Volume 90, Page(s) 165–173

    Abstract: Aim: The main purpose of the study was to create in vitro bile duct equivalent out of decellularized human umbilical cord artery and use it to reconstruct common bile duct obstruction with preservation of sphincter of Oddi.: Material and methods: SDS ...

    Abstract Aim: The main purpose of the study was to create in vitro bile duct equivalent out of decellularized human umbilical cord artery and use it to reconstruct common bile duct obstruction with preservation of sphincter of Oddi.
    Material and methods: SDS and Triton X-100 were used for decellularization of the artery. Allogeneic isolated cholangiocytes were seeded onto the inner surface of the decellularized artery. Experimental study was held and 12 domestic pigs of both sexes, weighing 25-30 kg were used. They were divided in equivalent two groups. Common bile duct obstruction model was created in all animals. Animals of the first group (n=6) received no further treatment and were under observation. Animals of the second group (n=6) underwent relaparotomy after two days of initial intervention, lesion site (2 cm) was incised and defect was reconstructed with the bile duct equivalent with the size of 2-2,5 cm. Maximum observation period was 84 days.
    Results: Laboratory, morphologic and radiologic investigations showed good integration with the host organism.
    Discussion: Bile duct reconstruction is still a major of HPB surgery. This fact prompted this study to assess the efficacy of the novel method for bile duct reconstruction the experimental study by using appropriate laboratory, morphologic and radiologic investigations.
    Conclusion: Preliminary results obtained with the described method allows us to say that bile duct equivalent created by us with decellularized human umbilical artery and cholangiocytes can be successfully used for bile duct reconstruction with inclusion of the sphincter of oddi.
    Key words: Bile Duct Obstruction, Bile Duct Reconstruction, Decellularization, Human Umbilical Artery.
    MeSH term(s) Animals ; Cells, Cultured ; Cholestasis/surgery ; Common Bile Duct/surgery ; Cytological Techniques ; Disease Models, Animal ; Female ; Humans ; Male ; Organ Sparing Treatments ; Sphincter of Oddi ; Swine ; Tissue Scaffolds ; Umbilical Arteries
    Language English
    Publishing date 2018-12-04
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 418927-9
    ISSN 2239-253X ; 0003-469X
    ISSN (online) 2239-253X
    ISSN 0003-469X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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