Metformin synergizes with gilteritinib in treating FLT3-mutated leukemia via targeting PLK1 signaling.

Fms-like tyrosine kinase 3 (FLT3) mutations, present in over 30% of acute myeloid leukemia (AML) cases and dominated by FLT3-internal tandem duplication (FLT3-ITD), are associated with poor outcomes in patients with AML. While tyrosine kinase inhibitors (TKIs; e.g., gilteritinib) are effective, they face challenges such as drug resistance, relapse, and high costs. Here, we report that metformin, a cheap, safe, and widely used anti-diabetic agent, exhibits a striking synergistic effect with gilteritinib in treating FLT3-ITD AML. Metformin significantly sensitizes FLT3-ITD AML cells (including TKI-resistant ones) to gilteritinib. Metformin plus gilteritinib (low dose) dramatically suppresses leukemia progression and prolongs survival in FLT3-ITD AML mouse models. Mechanistically, the combinational treatment cooperatively suppresses polo-like kinase 1 (PLK1) expression and phosphorylation of FLT3/STAT5/ERK/mTOR. Clinical analysis also shows improved survival rates in patients with FLT3-ITD AML taking metformin. Thus, the metformin/gilteritinib combination represents a promising and cost-effective treatment for patients with FLT3-mutated AML, particularly for those with low income/affordability.

Advances of research of Fc-fusion protein that activate NK cells for tumor immunotherapy.

The rapid development of bioengineering technology has introduced Fc-fusion proteins, representing a novel kind of recombinant protein, as promising biopharmaceutical products in tumor therapy. Numerous related anti-tumor Fc-fusion proteins have been investigated and are in different stages of development. Fc-fusion proteins are constructed by fusing the Fc-region of the antibody with functional proteins or peptides. They retain the bioactivity of the latter and partial properties of the former. This structural and functional advantage makes Fc-fusion proteins an effective tool in tumor immunotherapy, especially for the recruitment and activation of natural killer (NK) cells, which play a critical role in tumor immunotherapy. Even though tumor cells have developed mechanisms to circumvent the cytotoxic effect of NK cells or induce defective NK cells, Fc-fusion proteins have been proven to effectively activate NK cells to kill tumor cells in different ways, such as antibody-dependent cell-mediated cytotoxicity (ADCC), activate NK cells in different ways in order to promote killing of tumor cells. In this review, we focus on NK cell-based immunity for cancers and current research progress of the Fc-fusion proteins for anti-tumor therapy by activating NK cells.

The expression of cancer-testis antigen in ovarian cancer and the development of immunotherapy.

Ovarian cancer is a relatively common tumor in women with the highest mortality among female reproductive system tumors. The lack of apparent early symptoms and effective screening strategies often leads to ovarian cancer being diagnosed at an advanced stage. Immunotherapy relying on tumor-associated antigens might improve the treatment of ovarian cancer. Cancer-testis antigens (CTAs) are ideal tumor-associated antigens, and MAGE-A, NY-ESO-1, CT45, and Sp17 are classic CTAs highly expressed in ovarian cancer. Here, we review the research on CTAs in ovarian cancer, including prognostic value and advances in immunotherapy, all of which are essential for developing a theoretical basis for targeted therapy strategies.

Integrated microenvironment-associated genomic profiles identify LRRC15 mediating recurrent glioblastoma-associated macrophages infiltration.

Glioblastoma (GBM) is the most common malignant intracranial tumour with intrinsic infiltrative characteristics, which could lead to most patients eventually relapse. The prognosis of recurrent GBM patients remains unsatisfactory. Cancer cell infiltration and their interaction with the tumour microenvironment (TME) could promote tumour recurrence and treatment resistance. In our study, we aimed to identify potential tumour target correlated with rGBM microenvironment based on the gene expression profiles and clinical information of rGBM patients from The Cancer Genome Atlas (TCGA) database. LRRC15 gene with prognostic value was screened by univariate and multivariate analysis, and the correlation between macrophages and LRRC15 was identified as well. Furthermore, the prognosis correlation and immune characteristics of LRRC15 were validated using the Chinese Glioma Genome Atlas (CGGA) database and our clinical tissues by immunochemistry assay. Additionally, we utilized the transwell assay and carboxy fluorescein succinimidyl ester (CFSE) tracking to further confirm the effects of LRRC15 on attracting microglia/macrophages and tumour cell proliferation in the TME. Gene profiles-based rGBM microenvironment identified that LRRC15 could act in collusion with microglia/macrophages in the rGBM microenvironment to promote the poor prognosis, especially in mesenchymal subtype, indicating the strategies of targeting LRRC15 to improve macrophages-based immunosuppressive effects could be promising for rGBM treatments.

Eastern perspectives on roles, responsibilities and filial piety: A case study.

INTRODUCTION: Broad issues relating to filial piety and ethical dilemmas of families and care practitioners in residential care were discussed as part of an international networking project. It is meaningful to explore the different roles and responsibilities of participants in residential care in the context of China's filial piety. Older residents and their children are part of this caring process, which might be significantly different from that in Western countries. However, only a little amount of research related to this topic has been conducted. OBJECTIVE: This study aimed to identify and describe the roles and responsibilities of a nursing professional, manager, older person, and her children, as well as other mutual contacts in residential care, based on the context of Chinese filial piety culture. METHODS: The study was conducted as a case study. The product of the analysis, themes, or categories that describe the phenomenon, content analysis method was applied. After a consultation with a group of experts on research on older adults, a specific nursing home was selected in Xiamen City, China. This case study emphasized the roles and responsibilities of a nursing professional, manager, the older resident, and her children as they related to the care of older adult. The data, which consisted of interviews with four participants, were collected using a semi-structured interview method. Inductive content analysis was applied to analyze data. ETHICAL CONSIDERATIONS: Permission to conduct the interviews received ethical approval from the participating organization based on national standards. The elements of voluntary participation, anonymity, and confidentiality on the part of the respondent were explained. FINDINGS: The analysis resulted in four participants, with some variation of roles and responsibilities, describing staffing level and competence and their behavior for reducing the accident of the older adult, and the children of older adult influencing the quality of taking care of the older adult, based on the filial piety. The nursing home residents were described as becoming increasingly complex with a subsequent demand for increased spiritual support. There was variation in roles and responsibilities among four participants, but their contributions adjusting was an overall focus. Manager plays a considerable role in the future development of the institution, as a resource allocator, and decision-maker. Nursing professional is the main personnel serving as a link among staffs. The older adult herself adjust mentally and actively with the aging process, and some of them can be able to burden in taking care of her grandchildren or can be rehired and still have a distinct role in society. Children are required to fulfill their obligations to their parents, which involves supports of care, spiritual and economy. Several factors such as managers and nursing professional competence and their cooperation, various aspects of supports from their children based on the filial piety, and adequate communication and self-adjusting of the older adult, were recognized as factors affecting the process of taking care of the older adult. DISCUSSION: New information was produced to serve as theoretical guidelines in managing nursing homes, the training of nursing staff, preservation of the filial piety culture, and encouraging self-care among older people in the new era. CONCLUSION: A variety of roles and responsibilities for a nursing professional, manager, MrsWang and her children was identified in the older adult care process. Several factors to manager's and nursing professional's experience of the resource situation and competence level, and also adequate communication and self-adjusting of the older adult were suggested to affect the effect of taking care of the older adult. The older adults were perceived as more complex with more physical and mental problems but inadequate care from family members forcing the older adult from home care to a nursing home. A nursing home seems to have a higher nursing competence and be well-suited for the needs of the older adult, on the other hand, filial piety and self-care are also needed to play an important role in taking care of the older adult.

Sequential combination of laccase pretreatment and acid extraction for high-yield pectin production from pomelo peels.

A sequential combination of laccase pretreatment and acid extraction of pectin from pomelo peels was performed in this study. By using a laccase dose of 10 U/g, the yield and galacturonic acid content of the extracted pectin were 21.67% and 75.74%, respectively, which reflected an improvement by nearly 30% and 44% relative to the extraction process without laccase. Moreover, the degree of esterification of the extracted pectin was significantly improved as the laccase concentration was increased from 0 to 10 U/g but did not affect the molecular weight. Besides, the enzyme-treated sample displayed more than 29% loss of total lignin, in which the acid soluble lignin and the acid insoluble lignin were removed by over 15% and 33%, respectively. Scanning electron microscopy indicated that the penetration and partial destruction of the pomelo peel cell wall due to laccase might be one of the main reasons why laccase pretreatment could release pectin from cell wall complexes and increase the pectin yield in subsequent acid extraction processes.

TEX19 promotes ovarian carcinoma progression and is a potential target for epitope vaccine immunotherapy.

AIMS: Testis Expressed 19 (TEX19) is one of cancer/testis antigens identified in recent years and is related to the oncogenesis and progress of several cancers. This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application. MAIN METHODS: TEX19 levels were evaluated by immunohistochemistry (IHC) in 98 human ovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), and loss-of-function assays were used to determine the biological effects of TEX19 on the proliferation, migration, and invasion of OC cells. Subsequently, candidate epitope peptides from TEX19 were predicted and verified by the IEDB database, pepsite2 website, MOE software, and T2 cell binding assay. KEY FINDINGS: TEX19 was significantly upregulated in OC which correlated to higher TNM stage, lymph node involvement, and invasiveness. Knockdown of TEX19 inhibited proliferation, migration, and invasion of OC cells. Additionally, we screened four peptides derived from TEX19 and found TL to be the dominant peptide with the greatest affinity with HLA-A*0201. SIGNIFICANCE: Our data indicated a cancer-promoting effect of TEX19 in OC and demonstrated that TL could be a potential candidate for an anti-tumor epitope vaccine of OC, suggesting that TEX19 is a promising biomarker and immunotherapeutic target for OC.