Cytokine-induced killer cells: new insights for therapy of hematologic malignancies.

BACKGROUND: Cytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC-unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment-related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies. MAIN BODY: CIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3-/CD56+ NK cells, and CD3+/CD56- cytotoxic T cells. In this regard, the CD3+/CD56+ NK T cells are the primary effectors. Compared with the previously reported antitumor immune cells, CIK cells are characterized by improved in vitro proliferation and amplification, enhanced migration and invasive capacity to tumor region, more significant antitumor activity, and a broader antitumor spectrum. CIK cells can also induce death in tumor cells via numerous pathways and mechanisms. Hence, CIKs-based therapy has been used in various clinical trials and has shown efficacy with a very low graft versus host disease (GVHD) against several cancers, such as hematologic malignancies, even in relapsing cases, or cases not responding to other therapies. Despite the high content of T cells, CIK cells induce low alloreactivity and, thus, pose a restricted threat of GVHD induction even in MHC-mismatched transplantation cases. Phase 1 and 2 clinical trials of CIK cell therapy have also highlighted satisfactory therapeutic advantages against hematologic cancers, indicating the safety of CIK cells even in haploidentical transplantation settings. CONCLUSION: CIK cells have shown promising results in the treatment of hematologic malignancies, especially in combination with other antitumor strategies. However, the existing controversies in achieving desired clinical responses underscore the importance of future studies.

Self-Management among Stroke Survivors in the United States, 2016 to 2021.

Background: Self-management among stroke survivors is effective in mitigating the risk of a recurrent stroke. This study aims to determine the prevalence of self-management and its associated factors among stroke survivors in the United States. Methods: We analyzed the Behavioral Risk Factor Surveillance System (BRFSS) data from 2016 to 2021, a nationally representative health survey. A new outcome variable, stroke self-management (SSM = low or SSM = high), was defined based on five AHA guideline-recommended self-management practices, including regular physical activity, maintaining body mass index, regular doctor checkups, smoking cessation, and limiting alcohol consumption. A low level of self-management was defined as adherence to three or fewer practices. Results: Among 95,645 American stroke survivors, 46.7% have low self-management. Stroke survivors aged less than 65 are less likely to self-manage (low SSM: 56.8% vs. 42.3%; p < 0.0001). Blacks are less likely to self-manage than non-Hispanic Whites (low SSM: 52.0% vs. 48.6%; p < 0.0001); however, when adjusted for demographic and clinical factors, the difference was dissipated. Higher education and income levels are associated with better self-management (OR: 2.49, [95%CI: 2.16-2.88] and OR: 1.45, [95%CI: 1.26-1.67], respectively). Further sub-analysis revealed that women are less likely to be physically active (OR: 0.88, [95%CI: 0.81-0.95]) but more likely to manage their alcohol consumption (OR: 1.57, [95%CI: 1.29-1.92]). Stroke survivors residing in the Stroke Belt did not self-manage as well as their counterparts (low-SSM: 53.1% vs. 48.0%; p < 0.001). Conclusions: The substantial diversity in self-management practices emphasizes the need for tailored interventions. Particularly, multi-modal interventions should be targeted toward specific populations, including younger stroke survivors with lower education and income.

Imaging the post-treatment pelvis with gynecologic cancers.

Gynecological malignancies, such as ovarian cancers, cervical cancers, and endometrial cancers, have a significant global impact. Women with gynecologic malignancies may receive a single or a combination of treatments, including surgery, chemotherapy, and radiation-based therapies. Radiologists utilize various diagnostic imaging modalities to provide the surgeon with relevant information about the diagnosis, prognosis, optimal surgical strategy, and prospective post-treatment imaging. Computerized Tomography (CT) and magnetic resonance imaging (MRI) may be used initially to evaluate and detect post-treatment complications. Although CT is primarily used for staging, MRI is commonly used for a more accurate evaluation of a tumor's size and detection of local invasion. Complications such as hematoma, abscess, inclusion cyst, seroma, tumor thrombosis, anorectovaginal fistula, and gossypiboma may occur after the three primary treatments, and systems such as the genitourinary, gastrointestinal, neurological, and musculoskeletal may be affected. In order to distinguish between early-onset and late-onset complications following gynecological treatment, radiological findings of the most common post-treatment complications will be presented in this review.

Modulatory Effects of Hydatid Cyst Fluid on a Mouse Model of Experimental Autoimmune Encephalomyelitis.

The reduced burden of helminth parasites in industrialized countries is probably one of the reasons for the increased prevalence of autoimmune disorders such as multiple sclerosis (MS). The current study aimed to evaluate the potential preventive effects of hydatid cyst fluid (HCF) on the disease severity in an EAE mouse model of MS. EAE-induced mice were treated with HCF before and after EAE induction. An RT-PCR-based evaluation of IFN-γ, IL-1ß, TNF, T-bet, IL-4, GATA3, IL-17, RoRγ, TGF-ß, and FOXP3 expression levels in splenocytes and an ELISA-based analysis of IFN-γ and IL-4 levels in cell culture supernatant of splenocytes were performed. Histopathological examinations of mice during the study were also conducted. The expression levels of T-bet, IL-4, GATA3, TGF-ß, and FOXP3 in EAE + HCF mice were significantly higher compared to EAE + PBS mice. In the EAE + HCF group, the expression levels of IFN-γ, IL-1ß, and TNF were significantly lower than in the EAE + PBS group. The histopathological results showed significantly reduced inflammation and demyelination in EAE + HCF mice compared to EAE + PBS mice. Our study provides proof-of-concept in the EAE mouse model of MS that helminth-derived products such as HCF have a potential prophylactic effect on MS development and present a novel potential therapeutic strategy.

Targeted Silencing of NRF2 by rituximab-conjugated nanoparticles increases the sensitivity of chronic lymphoblastic leukemia cells to Cyclophosphamide.

BACKGROUND: Targeting influential factors in resistance to chemotherapy is one way to increase the effectiveness of chemotherapeutics. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway overexpresses in chronic lymphocytic leukemia (CLL) cells and appears to have a significant part in their survival and chemotherapy resistance. Here we produced novel nanoparticles (NPs) specific for CD20-expressing CLL cells with simultaneous anti-Nrf2 and cytotoxic properties. METHODS: Chitosan lactate (CL) was used to produce the primary NPs which were then respectively loaded with rituximab (RTX), anti-Nrf2 Small interfering RNA (siRNAs) and Cyclophosphamide (CP) to prepare the final version of the NPs (NP-Nrf2_siRNA-CP). All interventions were done on both peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMNCs). RESULTS: NP-Nrf2_siRNA-CP had satisfying physicochemical properties, showed controlled anti-Nrf2 siRNA/CP release, and were efficiently transfected into CLL primary cells (both PBMCs and BMNCs). NP-Nrf2_siRNA-CP were significantly capable of cell apoptosis induction and proliferation prevention marked by respectively decreased and increased anti-apoptotic and pro-apoptotic factors. Furthermore, use of anti-Nrf2 siRNA was corresponding to elevated sensitivity of CLL cells to CP. CONCLUSION: Our findings imply that the combination therapy of malignant CLL cells with RTX, CP and anti-Nrf2 siRNA is a novel and efficient therapeutic strategy that was capable of destroying malignant cells. Furthermore, the use of NPs as a multiple drug delivery method showed fulfilling properties; however, the need for further future studies is undeniable. Video Abstract.

The role of SF3B1 and NOTCH1 in the pathogenesis of leukemia.

The discovery of new genes/pathways improves our knowledge of cancer pathogenesis and presents novel potential therapeutic options. For instance, splicing factor 3b subunit 1 (SF3B1) and NOTCH1 genetic alterations have been identified at a high frequency in hematological malignancies, such as leukemia, and may be related to the prognosis of involved patients because they change the nature of malignancies in different ways like mediating therapeutic resistance; therefore, studying these gene/pathways is essential. This review aims to discuss SF3B1 and NOTCH1 roles in the pathogenesis of various types of leukemia and the therapeutic potential of targeting these genes or their mutations to provide a foundation for leukemia treatment.