Displaying publications 81 - 100 of 108 in total

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  1. Fulltext Molecular Signatures of Human Regulatory T Cells in Colorectal Cancer and Polyps
    Johdi NA, Ait-Tahar K, Sagap I, Jamal R
    Front Immunol, 2017;8:620.
    PMID: 28611777 DOI: 10.3389/fimmu.2017.00620
    Regulatory T cells (Tregs), a subset of CD4(+) or CD8(+) T cells, play a pivotal role in regulating immune homeostasis. An increase in Tregs was reported in many tumors to be associated with immune suppression and evasion in cancer patients. Despite the importance of Tregs, the molecular signatures that contributed to their pathophysiological relevance remain poorly understood and controversial. In this study, we explored the gene expression profiles in Tregs derived from patients with colorectal cancer [colorectal carcinoma (CRC), n = 15], colorectal polyps (P, n = 15), and in healthy volunteers (N, n = 15). Tregs were analyzed using CD4(+)CD25(+)CD127(low)FoxP3(+) antibody markers. Gene expression profiling analysis leads to the identification of 61 and 66 immune-related genes in Tregs derived from CRC and P patients, respectively, but not in N-derived Treg samples. Of these, 30 genes were differentially expressed both in CRC- and P-derived Tregs when compared to N-derived Tregs. Most of the identified genes were involved in cytokine/chemokine mediators of inflammation, chemokine receptor, lymphocyte activation, and T cell receptor (TCR) signaling pathways. This study highlights some of the molecular signatures that may affect Tregs' expansion and possible suppression of function in cancer development. Our findings may provide a better understanding of the immunomodulatory nature of Tregs and could, therefore, open up new avenues in immunotherapy.
    Matched MeSH terms: Immunotherapy
  2. Naturally occurring immunomodulators with antitumor activity: An insight on their mechanisms of action
    Mohamed SIA, Jantan I, Haque MA
    Int Immunopharmacol, 2017 Sep;50:291-304.
    PMID: 28734166 DOI: 10.1016/j.intimp.2017.07.010
    Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities. The anticancer activity of these immunomodulators is due to their anti-inflammatory, antioxidant, and induction of apoptosis, anti-angiogenesis, and anti-metastasis effect. These natural immunomodulators such as genistein, curcumin, and resveratrol can be used as prophylaxis against the initiation of cancer besides the inhibition of tumor growth and proliferation. Whereas, immunostimulants can elicit and activate humoral and cell-mediated immune responses against the tumor that facilitate the recognition and destruction of the already existing tumor. This review represents the recent studies on various natural immunomodulators with antitumor effects. We have focused on the relationship between their anticancer activity and immunomodulatory mechanisms. The mechanisms of action of various immunomodulators such as polyphenolic compounds, flavonoids, organosulfur compounds, capsaicin, vinca alkaloids, bromelain, betulinic acid and zerumbone, the affected cancerous cell lines in addition to the targeted molecules and transcriptional pathways have been review and critically analyzed.
    Matched MeSH terms: Immunotherapy
  3. Characterisation and immunosuppressive activity of human cartilage-derived mesenchymal stem cells
    Sandrasaigaran P, Algraittee SJR, Ahmad AR, Vidyadaran S, Ramasamy R
    Cytotechnology, 2018 Jun;70(3):1037-1050.
    PMID: 29497876 DOI: 10.1007/s10616-017-0182-4
    Mesenchymal stem cells (MSCs) exert potent immuno-regulatory activities on various immune cells and also differentiate into various mesodermal lineages besides retaining a distinct self-renewal ability. Such exclusive characteristics had enabled MSCs to be recognised as an ideal source for cell-based treatment in regenerative medicine and immunotherapy. Thus, considering MSCs for treating degenerative disease of organs with limited regenerative potential such as cartilage would serve as an ideal therapy. This study explored the feasibility of generating human cartilage-derived MSCs (hC-MSCs) from sports injured patients and characterised based on multipotent differentiation and immunosuppressive activities. Cartilage tissues harvested from a non-weight bearing region during an arthroscopy procedure were used to generate MSCs. Despite the classic morphology of fibroblast-like cells and a defined immunophenotyping, MSCs expressed early embryonic transcriptional markers (SOX2, REX1, OCT4 and NANOG) and differentiated into chondrocytes, adipocytes and osteocytes when induced accordingly. Upon co-culture with PHA-L activated T-cells, hC-MSCs suppressed the proliferation of the T-cells in a dose-dependent manner. Although, hC-MSCs did not alter the activation profile of T cells significantly, yet prevented the entering of activated T cells into S phase of the cell cycle by cell cycle arrest. The present study has strengthened the evidence of tissue-resident mesenchymal stem cells in human cartilage tissue. The endogenous MSCs could be an excellent tool in treating dysregulated immune response that associated with cartilage since hC-MSCs exerted both immunosuppressive and regenerative capabilities.
    Matched MeSH terms: Immunotherapy
  4. Fulltext Why is there an emerging need to look for a suitable drug delivery platform in targeting and regulating microbiota?
    Dua K, Gupta G, Awasthi R, Chellappan DK
    Panminerva Med, 2018 09;60(3):136-137.
    PMID: 30176703 DOI: 10.23736/S0031-0808.18.03446-8
    Matched MeSH terms: Immunotherapy
  5. Fulltext Epithelial-to-mesenchymal transition (EMT) causing acquired resistance to afatinib in a patient with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma
    Poh ME, Liam CK, Rajadurai P, Chai CS
    J Thorac Dis, 2018 Jul;10(7):E560-E563.
    PMID: 30174934 DOI: 10.21037/jtd.2018.06.122
    We report the first case of epithelial-to-mesenchymal transition (EMT) as the cause of acquired resistance to the second-generation EGFR-tyrosine kinase inhibitor (TKI), afatinib in a patient with advanced non-small cell lung cancer (NSCLC) harboring a sensitizing EGFR mutation. Patients with EGFR-mutant NSCLC inevitably develop acquired resistance while on EGFR-TKI treatment. EMT which renders cancer cells more invasive and migratory is one of the mechanisms of acquired resistance to EGFR-TKIs and correlates with a poor prognosis. Possible therapeutic strategies in patients with EMT include blocking M2 muscarinic receptor signalling, targeting EMT with histone deacetylase inhibitors such as entinostat and MEK-inhibitors such as selumetinib, inhibition of microRNAs, immunotherapy and inhibiting fibroblast growth factor receptor-1.
    Matched MeSH terms: Immunotherapy
  6. Fulltext Gene therapy and type 1 diabetes mellitus
    Chellappan DK, Sivam NS, Teoh KX, Leong WP, Fui TZ, Chooi K, et al.
    Biomed Pharmacother, 2018 Dec;108:1188-1200.
    PMID: 30372820 DOI: 10.1016/j.biopha.2018.09.138
    BACKGROUND: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet β cells. Management of T1DM is challenging and complicated especially with conventional medications. Gene therapy has emerged as one of the potential therapeutic alternatives to treat T1DM. This review primarily focuses on the current status and the future perspectives of gene therapy in the management of T1DM. A vast number of the studies which are reported on gene therapy for the management of T1DM are done in animal models and in preclinical studies. In addition, the safety of such therapies is yet to be established in humans. Currently, there are several gene level interventions that are being investigated, notably, overexpression of genes and proteins needed against T1DM, transplantation of cells that express the genes against T1DM, stem-cells mediated gene therapy, genetic vaccination, immunological precursor cell-mediated gene therapy and vectors.

    METHODS: We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review.

    FINDINGS: Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.

    Matched MeSH terms: Immunotherapy
  7. Relapsing encephalopathy with dancing eyes and jerky limbs
    Mohd Fauzi NA, Abdullah S, Tan AH, Mohd Ramli N, Tan CY, Lim SY
    Parkinsonism Relat Disord, 2020 06;75:110-113.
    PMID: 30846242 DOI: 10.1016/j.parkreldis.2019.02.025
    We report a case of relapsing-remitting opsoclonus-myoclonus-ataxia syndrome (OMAS) in a patient with Hashimoto's encephalopathy, diagnosed after comprehensive evaluation. OMAS as a manifestation of Hashimoto's encephalopathy has been reported once previously. It is hoped that recognition of this entity and early initiation of immunotherapy will improve clinical outcomes for patients.
    Matched MeSH terms: Immunotherapy
  8. Fulltext Cytotoxicity, regulation of apoptotic and anti-apoptotic gene expression by IL-27 in MCF-7 and MDA-MB-231 breast cancer cell lines
    Yap Wei Boon, Shaktypreya Nadarajah, Nadiah Shidik, Noorjahan Banu Mohammed Alitheen
    Jurnal Sains Kesihatan Malaysia, 2018;16(101):15-22.
    MyJurnal
    Breast cancer is one of the commonest cancers among women. Conventional therapies cause adverse side effects in patients. Cytokine immunotherapy such as interleukin-27 (IL-27) has been sought as an alternative cancer treatment in recent years. IL-27 has been shown to improve anticancer immunity and anti-angiogenesis in cancers, however, its effect on apoptotic and anti-apoptotic gene expression especially in breast cancers is yet to be explored. Cytotoxicity of IL-27 in non-cancerous (184b5) and cancerous (MCF-7 and MDA-MB-231) breast cell lines was first determined for 24-72 h in this study. The results indicated that IL-27 treatment did not retard 184b5 cell growth, however, did inhibit MCF-7 (48 h) and MDA-MB-231 (72 h) cell growth with IC50 at 442 and 457 ng/ml, respectively. Apoptotic (TRAIL, FADD, FAS, caspase-3 and caspase-8) and anti-apoptotic (BCL-2, AKT, and COX-2) genes were then amplified from untreated (control) and treated breast cancer cells and studied. TRAIL, caspase-3, caspase-8 gene expression was significantly (p < 0.05) upregulated in treated MCF-7 (442 ng/ml) and MDA-MB-231 (457 ng/ml) cells. Expression of FADD and FAS genes was not detected in both control and treated MCF-7 and MDA-MB-231 cells. COX-2 gene was also not expressed by MCF-7 cells, but reduced significantly (p < 0.05) in treated MDA-MB-231 cells. In MDA-MB-231 cells, IL-27 treatment seemed to slightly enhance the expression of AKT and BCL-2 genes which, on the other hand, was downregulated in treated MCF-7 cells. Conclusively, IL-27 is able to inhibit breast cancer cell growth and regulate apoptotic and anti-apoptotic gene expression in breast cancer cells.
    Matched MeSH terms: Immunotherapy
  9. IAPSO-AIRS: A novel improved machine learning-based system for wart disease treatment
    Abdar M, Wijayaningrum VN, Hussain S, Alizadehsani R, Plawiak P, Acharya UR, et al.
    J Med Syst, 2019 Jun 07;43(7):220.
    PMID: 31175462 DOI: 10.1007/s10916-019-1343-0
    Wart disease (WD) is a skin illness on the human body which is caused by the human papillomavirus (HPV). This study mainly concentrates on common and plantar warts. There are various treatment methods for this disease, including the popular immunotherapy and cryotherapy methods. Manual evaluation of the WD treatment response is challenging. Furthermore, traditional machine learning methods are not robust enough in WD classification as they cannot deal effectively with small number of attributes. This study proposes a new evolutionary-based computer-aided diagnosis (CAD) system using machine learning to classify the WD treatment response. The main architecture of our CAD system is based on the combination of improved adaptive particle swarm optimization (IAPSO) algorithm and artificial immune recognition system (AIRS). The cross-validation protocol was applied to test our machine learning-based classification system, including five different partition protocols (K2, K3, K4, K5 and K10). Our database consisted of 180 records taken from immunotherapy and cryotherapy databases. The best results were obtained using the K10 protocol that provided the precision, recall, F-measure and accuracy values of 0.8908, 0.8943, 0.8916 and 90%, respectively. Our IAPSO system showed the reliability of 98.68%. It was implemented in Java, while integrated development environment (IDE) was implemented using NetBeans. Our encouraging results suggest that the proposed IAPSO-AIRS system can be employed for the WD management in clinical environment.
    Matched MeSH terms: Immunotherapy
  10. Fulltext Treatment of spinal cord injury with mesenchymal stem cells
    Liau LL, Looi QH, Chia WC, Subramaniam T, Ng MH, Law JX
    Cell Biosci, 2020;10:112.
    PMID: 32983406 DOI: 10.1186/s13578-020-00475-3
    Background: Spinal cord injury (SCI) is the damage to the spinal cord that can lead to temporary or permanent loss of function due to injury to the nerve. The SCI patients are often associated with poor quality of life.

    Results: This review discusses the current status of mesenchymal stem cell (MSC) therapy for SCI, criteria to considering for the application of MSC therapy and novel biological therapies that can be applied together with MSCs to enhance its efficacy. Bone marrow-derived MSCs (BMSCs), umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (ADSCs) have been trialed for the treatment of SCI. Application of MSCs may minimize secondary injury to the spinal cord and protect the neural elements that survived the initial mechanical insult by suppressing the inflammation. Additionally, MSCs have been shown to differentiate into neuron-like cells and stimulate neural stem cell proliferation to rebuild the damaged nerve tissue.

    Conclusion: These characteristics are crucial for the restoration of spinal cord function upon SCI as damaged cord has limited regenerative capacity and it is also something that cannot be achieved by pharmacological and physiotherapy interventions. New biological therapies including stem cell secretome therapy, immunotherapy and scaffolds can be combined with MSC therapy to enhance its therapeutic effects.

    Matched MeSH terms: Immunotherapy
  11. Merkel cell carcinoma: Preparing to go the distance
    Arumugam M, Jamil A, Amiseno RA, Rosli N, Abdul Shukor N
    Malays J Pathol, 2020 Aug;42(2):277-281.
    PMID: 32860382
    INTRODUCTION: Merkel cell carcinoma (MCC) is a rare and aggressive malignancy of the skin, with poor clinical outcomes. Typical conditions include a rapidly growing, solitary dome-shaped, violaceous nodule. Several root causes have been identified - sun exposure, age, lighter skin, immunocompromised state, and polyomavirus infection. Wide local excision is the best treatment. The tumour is radiotherapy-responsive. However, the success rate of the treatment with chemotherapy is rather limited. Immunotherapy has shown promising results. Early detection is important to prevent morbidity and mortality.

    CASE REPORT: In this literature work, we reported on a particular case of MCC, as exhibited by an 84-year-old Chinese woman, and discussed the clinical features and management of MCC.

    DISCUSSION: We highlighted that MCC cases have a link to the polyomavirus 5. Patients who were identified with the Polyomavirus 5, and underwent immunotherapy, were seen to depict much better prognosis.

    Matched MeSH terms: Immunotherapy
  12. Recent progress in small molecule agents for the targeted therapy of triple-negative breast cancer
    Islam R, Lam KW
    Eur J Med Chem, 2020 Dec 01;207:112812.
    PMID: 32937283 DOI: 10.1016/j.ejmech.2020.112812
    Triple-negative breast cancer (TNBC) is the most aggressive type of cancer, with a high risk of death on recurrence. To date, there is a lack of approved targeted agents for the treatment of the disease. Patients with TNBC continue to depend on surgery, chemotherapy, and radiotherapy, all of which have a wide side effect profile. In the present review, we highlight the current progress and exciting developments in the small-molecule targeted therapy for the treatment of TNBC. Finally, we also discuss the prospect of combining targeted therapy and immunotherapy for the effective treatment of TNBC.
    Matched MeSH terms: Immunotherapy
  13. Fulltext Hypomethylating Agents and Immunotherapy: Therapeutic Synergism in Acute Myeloid Leukemia and Myelodysplastic Syndromes
    Wong KK, Hassan R, Yaacob NS
    Front Oncol, 2021;11:624742.
    PMID: 33718188 DOI: 10.3389/fonc.2021.624742
    Decitabine and guadecitabine are hypomethylating agents (HMAs) that exert inhibitory effects against cancer cells. This includes stimulation of anti-tumor immunity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients. Treatment of AML and MDS patients with the HMAs confers upregulation of cancer/testis antigens (CTAs) expression including the highly immunogenic CTA NY-ESO-1. This leads to activation of CD4+ and CD8+ T cells for elimination of cancer cells, and it establishes the feasibility to combine cancer vaccine with HMAs to enhance vaccine immunogenicity. Moreover, decitabine and guadecitabine induce the expression of immune checkpoint molecules in AML cells. In this review, the accumulating knowledge on the immunopotentiating properties of decitabine and guadecitabine in AML and MDS patients are presented and discussed. In summary, combination of decitabine or guadecitabine with NY-ESO-1 vaccine enhances vaccine immunogenicity in AML patients. T cells from AML patients stimulated with dendritic cell (DC)/AML fusion vaccine and guadecitabine display increased capacity to lyse AML cells. Moreover, decitabine enhances NK cell-mediated cytotoxicity or CD123-specific chimeric antigen receptor-engineered T cells antileukemic activities against AML. Furthermore, combination of either HMAs with immune checkpoint blockade (ICB) therapy may circumvent their resistance. Finally, clinical trials of either HMAs combined with cancer vaccines, NK cell infusion or ICB therapy in relapsed/refractory AML and high-risk MDS patients are currently underway, highlighting the promising efficacy of HMAs and immunotherapy synergy against these malignancies.
    Matched MeSH terms: Immunotherapy
  14. Fulltext The Potential Benefits of Nanotechnology in Treating Alzheimer's Disease
    Ling TS, Chandrasegaran S, Xuan LZ, Suan TL, Elaine E, Nathan DV, et al.
    Biomed Res Int, 2021;2021:5550938.
    PMID: 34285915 DOI: 10.1155/2021/5550938
    Alzheimer's disease is a neurodegenerative disorder that is caused by the accumulation of beta-amyloid plaques in the brain. Currently, there is no definitive cure available to treat Alzheimer's disease. The available medication in the market has the ability to only slow down its progression. However, nanotechnology has shown its superiority that can be applied for medical usage and it has a great potential in the therapy of Alzheimer's disease, specifically in the disease diagnosis and providing an alternative approach to treat Alzheimer's disease. This is done by increasing the efficiency of drug delivery by penetrating and overcoming the blood-brain barrier. Having said that, there are limitations that need to be further investigated and researched in order to minimize the adverse effects and potential toxicity and to improve drug bioavailability. The recent advances in the treatment of Alzheimer's disease using nanotechnology include the regeneration of stem cells, nanomedicine, and neuroprotection. In this review, we will discuss the advancement of nanotechnology which helps in the diagnosis and treatment of neurodegenerative disorders such as Alzheimer's disease as well as its challenges.
    Matched MeSH terms: Immunotherapy
  15. Biocompatible ionic liquids assisted transdermal co-delivery of antigenic protein and adjuvant for cancer immunotherapy
    Chowdhury MR, Moshikur RM, Wakabayashi R, Moniruzzaman M, Goto M
    Int J Pharm, 2021 May 15;601:120582.
    PMID: 33872711 DOI: 10.1016/j.ijpharm.2021.120582
    Human skin contains numerous antigen-presenting cells that are a potential target for several immune-based therapies, including vaccination and cancer immunotherapy. However, the outermost layer of the skin-the stratum corneum-acts as a major physical barrier against the permeation of antigens that have a molecular weight > 500 Da. In this study, an ionic liquid-assisted delivery system (ILDS) was developed, which enabled the successful transdermal delivery of an antigenic protein, ovalbumin (OVA), with a toll-like receptor agonist, imiquimod, as an adjuvant, to stimulate a specific immune response. Both the ionic liquids and ILDS were completely biocompatible for topical or transdermal application for therapeutic purposes. The skin permeation of the antigenic protein and adjuvant was found to be significantly enhanced because of the incorporation of a surface-active ionic liquid in the ILDS. An in vivo immunization study showed that there was a high level of OVA-specific IgG antibody production because of the enhanced permeation of the antigen and adjuvant across and into the skin. In a preclusive anticancer study, vaccination through ILDS showed stronger tumor-growth inhibition compared to control group. These results indicated that the ILDS could be a promising strategy for transdermal immunization as future therapeutics.
    Matched MeSH terms: Immunotherapy
  16. Fulltext The COVID-19/Tuberculosis Syndemic and Potential Antibody Therapy for TB Based on the Lessons Learnt From the Pandemic
    Dass SA, Balakrishnan V, Arifin N, Lim CSY, Nordin F, Tye GJ
    Front Immunol, 2022;13:833715.
    PMID: 35242137 DOI: 10.3389/fimmu.2022.833715
    2020 will be marked in history for the dreadful implications of the COVID-19 pandemic that shook the world globally. The pandemic has reshaped the normality of life and affected mankind in the aspects of mental and physical health, financial, economy, growth, and development. The focus shift to COVID-19 has indirectly impacted an existing air-borne disease, Tuberculosis. In addition to the decrease in TB diagnosis, the emergence of the TB/COVID-19 syndemic and its serious implications (possible reactivation of latent TB post-COVID-19, aggravation of an existing active TB condition, or escalation of the severity of a COVID-19 during TB-COVID-19 coinfection), serve as primary reasons to equally prioritize TB. On a different note, the valuable lessons learnt for the COVID-19 pandemic provide useful knowledge for enhancing TB diagnostics and therapeutics. In this review, the crucial need to focus on TB amid the COVID-19 pandemic has been discussed. Besides, a general comparison between COVID-19 and TB in the aspects of pathogenesis, diagnostics, symptoms, and treatment options with importance given to antibody therapy were presented. Lastly, the lessons learnt from the COVID-19 pandemic and how it is applicable to enhance the antibody-based immunotherapy for TB have been presented.
    Matched MeSH terms: Immunotherapy
  17. Early expression of local cytokines during systemic Candida albicans infection in a murine intravenous challenge model
    Chin VK, Foong KJ, Maha A, Rusliza B, Norhafizah M, Chong PP
    Biomed Rep, 2014 Nov;2(6):869-874.
    PMID: 25279161
    Local cytokine production is a significant indicator for disease pathogenesis or progression. Previous studies on cytokine production during systemic Candida albicans (C. albicans) infection were solely on kidney or single cell type interaction with C. albicans. Therefore, the present study aimed to assess the early cytokine expression of various target organs (kidney, spleen and brain) over a 72-h time course during systemic C. albicans infection. The local cytokine profiles of the target organs during systemic C. albicans infection were measured by cytometric bead array and ELISA analysis. The results demonstrated that interleukin-6 (IL-6) and IL-2 were statistically significant (P<0.05) in the spleen at 24 and 72 h post-infection, whereas in the kidney, IL-6 and tumor necrosis factor-α (TNF-α) were statistically significant (P<0.05) at 24 and 72 h post-infection and CXCL-1 and transforming growth factor-β (TGF-β) were statistically significant (P<0.05) at 72 h post-infection. In the brain, IL-6 and TNF-α were statistically significant (P<0.05) at 24 and 72 h post-infection, whereas TGF-β was statistically significant (P<0.05) at 72 h post-infection. These findings demonstrate that host immune responses were varied among target organs during systemic C. albicans infection. This could be important for designing targeted immunotherapy against this pathogen through immunomodulatory approaches in future exploratory research.
    Matched MeSH terms: Immunotherapy
  18. The multifaceted role of exosomes in cancer progression: diagnostic and therapeutic implications [corrected]
    Sundararajan V, Sarkar FH, Ramasamy TS
    Cell Oncol (Dordr), 2018 06;41(3):223-252.
    PMID: 29667069 DOI: 10.1007/s13402-018-0378-4
    BACKGROUND: Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming. While exosomes interact with cells within the tumour microenvironment to promote tumour growth, these vesicles can also facilitate the process of distant metastasis by mediating the formation of pre-metastatic niches. Next to their tumour promoting effects, exosomes have been found to serve as potential tools for cancer diagnosis and therapy. The ease of isolating exosomes and their content from different body fluids has led to the identification of diagnostic and prognostic biomarker signatures, as well as to predictive biomarker signatures for therapeutic responses. Exosomes can also be used as cargos to deliver therapeutic anti-cancer drugs, and they can be engineered to serve as vaccines for immunotherapy. Additionally, it has been found that inhibition of exosome secretion, and thus the transfer of oncogenic molecules, holds promise for inhibiting tumour growth. Here we provide recent information on the diverse roles of exosomes in various cellular and systemic processes governing cancer progression, and discuss novel strategies to halt this progression using exosome-based targeted therapies and methods to inhibit exosome secretion and the transfer of pro-tumorigenic molecules.

    CONCLUSIONS: This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel therapeutic strategies, as well as its current and future applications in clinical trials.

    Matched MeSH terms: Immunotherapy
  19. Fulltext Asian Society of Gynecologic Oncology International Workshop 2018
    Kong TW, Ryu HS, Kim SC, Enomoto T, Li J, Kim KH, et al.
    J Gynecol Oncol, 2019 Mar;30(2):e39.
    PMID: 30740961 DOI: 10.3802/jgo.2019.30.e39
    The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.
    Matched MeSH terms: Immunotherapy
  20. Immunotherapeutic Interleukin-6 or Interleukin-6 Receptor Blockade in Cancer: Challenges and Opportunities
    Kampan NC, Xiang SD, McNally OM, Stephens AN, Quinn MA, Plebanski M
    Curr Med Chem, 2018;25(36):4785-4806.
    PMID: 28707587 DOI: 10.2174/0929867324666170712160621
    Interleukin 6 (IL-6), a well-known pro-inflammatory cytokine with pleiotropic activity is a central player in chronic inflammatory diseases including cancers. Therefore, blockade of the IL-6 signalling pathway has become a target for the therapy of diverse cancers such as multicentric Castleman's disease (CD), multiple myeloma and solid tumours including renal, prostate, lung, colorectal and ovarian cancers. Monoclonal antibodies against IL-6 (Siltuximab) and the IL-6 receptor (IL-6R) (Tocilizumab) have emerged as potential immunotherapies, alone or in combination with conventional chemotherapy. Human trials have demonstrated the ability to block IL-6 activity and in multicentric CD lead to durable clinical response and longer disease stabilisation. However, the efficacy of these treatments is still debatable for other cancers. New generation therapeutics in development such as Clazakizumab, Sarilumab, and soluble gp130-Fc have the additional features of improved binding affinity, better specificity with reduced adverse effects. A deeper understanding of the immunological basis of these agents, as well as of the challenges that are faced by immunotherapy-based products in clinical trials, will help select the most promising anti-IL-6/IL-6R therapies for large scale use. Concurrently, current research efforts to personalize treatments may help in the treatment of patients that would greatly benefit from IL-6 blocking therapies.
    Matched MeSH terms: Immunotherapy
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