Effect of Cytokine Genes in the Pathogenesis and on the Clinical Parameters for the Treatment of Multiple Myeloma

Haydaroglu, H.; Balcı, Sibel; Pehlıvan, Sacide; Özdilli, Kürşat; Gündoğan, Ersin; Okan, Vahap; Nursal, Ayşe Feyda; Pehlıvan, Mustafa

doi:10.1080/08820139.2016.1208219

Cited by 8 publications

(9 citation statements)

References 34 publications

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“…An important aspect of the pathogenesis of PCM is the presence of cytokine gene polymorphisms, their role as prognostic factors in the course of the disease was confirmed in a study [10]. The relation ship between polymorphic gene variants of a num ber of cytokines, including TNF α and IFN γ, clin ical characteristics and the prognosis of the disease in patients who received new therapeutic drugs for the first time was studied.…”

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confidence: 86%

“…A sig nificant role in this is due to the disruption of the functioning of the immune system, including the regulation of the cytokine network, which ensures the proliferation, differentiation and functioning of substrate plasma cells. In particular, Tumor necrosis factor α (TNF α) contributes to the expansion of the tumor clone in PCM patients [10]. The biological heterogeneity of substrate cells, which characterizes different phases of the course of PCM, is the result of the presence of dysregulated interconnections of the cytokine network, which gives an advantage TNF α as a promoter of disease progression [11].…”

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confidence: 99%

“…Суттєва роль в цьому належить порушен ням функціонування імунної системи, у тому числі регуляції мережі цитокінів, які забезпечують проліферацію, диференціацію та функціонування субстратних плазматичних клітин. Зокрема, фак тор некрозу пухлини α (TNF α) сприяє експансії пухлинного клону у хворих на ПКМ [10]. Біоло гічна гетерогенність субстратних клітин, яка ха рактерна для різних фаз перебігу ПКМ, обумовле на наявністю дисрегульованих взаємозв'язків ме режі цитокінів, що надає перевагу TNF α як про мотору прогресії захворювання [11].…”

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TNF-α AND IONIZING RADIATION: THE ROLE IN THE PATHOGENESIS AND TREATMENT OF PLASMA CELL MYELOMA (review)

Liubarets

2023

Probl Radiac Med Radiobiol

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The review presents data from the literature on the role of Tumor necrosis factor-α (TNF-α) and ionizing radiation (IR) in the pathogenesis and treatment of plasma cell myeloma (PCM). There was analyzed disturbance of regulation of functioning of this cytokine, which affects the interaction of the immune system with substrate plasma cells under the influence of negative external factors, including ionizing radiation IR. Modern directions of therapy of this disease using the latest technologies are presented, in particular CAR T-cell therapy, which will allow to optimize in the future treatment of this disease and, thus, improve the quality and life expectancy of PCM patients. Key words: plasma cell myeloma, cytokines, TNF-α, CAR T-cell therapy.

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confidence: 86%

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confidence: 99%

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TNF-α AND IONIZING RADIATION: THE ROLE IN THE PATHOGENESIS AND TREATMENT OF PLASMA CELL MYELOMA (review)

Liubarets

2023

Probl Radiac Med Radiobiol

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“…Several mediators are elicited by the bone marrow environment and myeloma cells through paracrine or autocrine loops [ 9 ]. The BM microenvironment derived from MM patients exhibits high degrees of EGF, HGF, IL-2R, IL-16, and those interferon-g (IFN-g)-induced cytokines [ 24 25 ]. Many of these cytokines have been suggested to be the promoting factors in MM development, thereafter triggering cell growth or cellular adhesion for MM cells [ 2 ].…”

Section: Urrent Understanding Of Interleukin-10 In Multiple Myeloma Pathologymentioning

confidence: 99%

The perspectives of interleukin-10 in the pathogenesis and therapeutics of multiple myeloma

Liu

Chang

Huang

2021

Tzu Chi Medical Journal

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Multiple myeloma (MM) is typically featured by the increased levels of inflammatory cytokines in the neoplastic plasma cells (PCs) producing monoclonal immunoglobulin. PCs proliferate in the bone marrow, which will lead to extensive skeletal destruction with osteolytic lesions, osteopenia, or pathologic fractures. The diagnostic biology of MM has progressed from morphology and low-sensitivity protein analysis into multiomics-based high-throughput readout, whereas therapeutics has evolved from single active agent to potential active drug combinations underlying precision medicine. Many studies have focused on the cytokine networks that control growth, progression, and dissemination of the disease. The complexity of cytokines in MM development remains to be elucidated comprehensively. Apart from knowing that interleukin (IL)-6 is important in the pathogenesis of MM, it has been shown that IL-6 is a paracrine factor supplied by the microenvironment comprising of those cells from the myeloid compartment. Due to IL-10 was considered an immunosuppressive cytokine to promote cancer escape from immune surveillance, the role of IL-10 in this regard has been underestimated although recent advances have reported that IL-10 induces both PC proliferation and angiogenesis in MM. In addition, cumulative studies have suggested that IL-10 plays an important role in the induction of chemoresistance in many cancers; a virtual requirement of autocrine IL-10 for MM cells to escape from an IL-6-dependent proliferation loop was implicated. In this review, we summarize the available information to elucidate a new understanding of the molecular and functional roles of IL-10 in MM.

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“…Moreover, Terszowski et al. demonstrated that both KIR/HLA interaction and the FcγR3A V-allele may act synergistically to improve NK cell activation in vitro ( 11 , 22 ). However, the influence of particular KIR haplotypes in the efficiency of neoadjuvant trastuzumab for the treatment of BC remains unaddressed ( 10 ).…”

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confidence: 99%

KIR-HLA Functional Repertoire Influences Trastuzumab Efficiency in Patients With HER2-Positive Breast Cancer

et al. 2022

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Trastuzumab induced a high rate of pathological Complete Response (pCR) in patients affected by locally advanced HER2-positive Breast Cancer (HER2-BC), by exploiting immune-mediated mechanisms as Antibody-Dependent Cell Cytotoxicity (ADCC) involving Natural Killer (NK) cells. Host’s immune genetics could influence the response to therapy, through the expression of variants that characterize NK receptors involved in ADCC effectiveness. Killer cell immunoglobin-like receptors (KIRs) modulate NK cell activity through their binding to class-I Human Leukocyte Antigens (HLA). The impact of the KIR/HLA repertoire in HER2-BC is under study. We characterized KIR genotypes of 36 patients with locally advanced HER2-BC treated with neoadjuvant chemotherapy including trastuzumab. We monitored pCR achievement before surgery and Disease-Free Survival (DFS) and Overall Survival (OS) after adjuvant therapy. HLA, and Fc gamma receptor IIIa (FcγR3A) and IIa (FcγR2A) were genotyped through targeted PCR and Sanger sequencing in 35/36 patients. The KIR-HLA combinations were then described as functional haplotypes and divided in two main categories as inhibitory tel A and stimulatory tel B. Trastuzumab-dependent ADCC activity was monitored with an in vitro assay using a HER2-BC model and patients’ NK cells.We observed a higher frequency of KIR activators in patients who achieved a pCR compared to partial responders. During the study of functional haplotypes, individuals carrying a tel B haplotype showed greater ADCC efficiency than tel A cases. In subjects with the tel A haplotype the presence of the favorite V allele in FcγR3A receptor improved their low ADCC levels. Regardless of the haplotypes detected, the presence of KIR3DL2/HLA-A03 or A11 was always associated with the FcγR3A V allele, and therefore correlated with greater ADCC efficiency. However, this particular KIR receptor appeared to harm DFS and OS. Indeed, patients with tel B haplotype without KIR3DL2/HLA-A03 or A11 showed a better outcome. Our data, although preliminary, suggested a potential predictive role for KIR haplotype tel B, in identifying patients who achieve a pCR after neoadjuvant treatment with trastuzumab, and supported a negative prognostic impact of KIR3DL2/HLA-A03 or A11 in the adjuvant setting.

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Effect of Cytokine Genes in the Pathogenesis and on the Clinical Parameters for the Treatment of Multiple Myeloma

Cited by 8 publications

References 34 publications

TNF-α AND IONIZING RADIATION: THE ROLE IN THE PATHOGENESIS AND TREATMENT OF PLASMA CELL MYELOMA (review)

TNF-α AND IONIZING RADIATION: THE ROLE IN THE PATHOGENESIS AND TREATMENT OF PLASMA CELL MYELOMA (review)

The perspectives of interleukin-10 in the pathogenesis and therapeutics of multiple myeloma

KIR-HLA Functional Repertoire Influences Trastuzumab Efficiency in Patients With HER2-Positive Breast Cancer

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