Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012-2023).

CAR-T cell therapy has emerged as a significant approach for the management of hematological malignancies. Over the past few years, the utilization of CAR-T cells in the investigation and treatment of solid tumors has gained momentum, thereby establishing itself as a prominent area of research. This descriptive study involved the retrieval of articles about CAR-T cell therapy for solid tumors from the Web of Science Core Collection (WoSCC) database. Subsequently, bibliometric analysis and knowledge map analysis were conducted on these articles. The field under consideration is currently experiencing a period of swift advancement, as evidenced by the escalating number of publications in this domain each year. The United States holds an indisputable position as the foremost leader in this particular field, with the University of Pennsylvania emerging as the most active institution. The authors with the highest citation frequency and co-citation frequency are Carl H. June and Shannon L. Maude, respectively. The research hotspots in this field mainly focus on five aspects. Additionally, 10 emerging themes were identified. This study undertakes a comprehensive, systematic, and objective analysis and exploration of the field of CAR-T cell treatment for solid tumors, utilizing bibliometric methods. The findings of this study are expected to serve as a valuable reference and enlightenment for future research endeavors in this particular domain.

BRCA1 overexpression attenuates breast cancer cell growth and migration by regulating the pyruvate kinase M2-mediated Warburg effect via the PI3K/AKT signaling pathway.

This work explored the mechanism of the effect of breast-cancer susceptibility gene 1 (BRCA1) on the metabolic characteristics of breast cancer cells, including the Warburg effect and its specific signaling. We transfected MCF-7 cells with a BRCA1-encoding LXSN plasmid or PKM2 siRNA and examined cancer cell metabolism using annexin V staining, inhibitory concentration determination, Western blotting, glucose uptake and lactic acid content measurements, and Transwell assays to assess glycolytic activity, cell apoptosis, and migration, and sensitivity to anti-cancer treatment. The BRCA1-expressing MCF-7 cells demonstrated low PKM2 expression and decreased glycolytic activity (downregulated hexokinase 2 (HK2) expression, upregulated isocitrate dehydrogenase 1 (IDH1) expression, and reduced O2 and glucose consumption and lactate production) via regulation of PI3K/AKT pathway compared with the empty LXSN group. BRCA1 transfection slightly increased apoptotic activity, decreased cell migration, and increased the IC50 index for doxorubicin, paclitaxel, and cisplatin. Inhibiting PKM2 using siRNA attenuated the IC50 index for doxorubicin, paclitaxel, and cisplatin compared with the control. Inhibiting PKM2 activated PI3K/AKT signaling, increased apoptosis, and decreased MCF-7 cell migration. Our data suggest that BRCA1 overexpression reverses the Warburg effect, inhibits cancer cell growth and migration, and enhances the sensitivity to anti-cancer treatment by decreasing PKM2 expression regulated by PI3K/AKT signaling. These novel metabolic findings represent a potential mechanism by which BRCA1 exerts its inhibitory effect on breast cancer.

LncRNA HEIH regulates cell proliferation and apoptosis through miR-4458/SOCS1 axis in triple-negative breast cancer.

Hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA (HEIH) is a newly discovered lncRNA and has been suggested to be dysregulated in human cancers. However, the role of HEIH in triple-negative breast cancer (TNBC) was still unknown. Thus, the aim of our study was to investigate the clinical significance and biological function of HEIH in TNBC. In our study, we found that HEIH was overexpressed in TNBC tissues and cell lines compared with adjacent normal mammary tissues and normal mammary epithelial cell line, respectively. In addition, we conducted bioinformatic analysis, and found that HEIH harbors a potential miR-4458-binding site. Furthermore, we observed that HEIH and miR-4458 had a high correlation score in TNBC tissues, and HEIH directly binds to miR-4458, and negatively regulates miR-4458 expression in TNBC cells. The in vitro cell proliferation and apoptosis assays suggested down-regulation of HEIH inhibited TNBC cell proliferation and promoted apoptosis through regulating miR-4458/SOCS1 axis. Finally, we found that TNBC patients with tumor size ≥ 5 cm or advanced clinical stage had higher levels of HEIH expression than patients with tumor size < 5 cm or early clinical stage. In conclusion, HEIH functions as an oncogenic lncRNA that is overexpressed in TNBC and associated with clinical progression, and regulates TNBC cell proliferation and apoptosis through miR-4458/SOCS1 axis.

miR-29a inhibits proliferation, invasion, and migration of papillary thyroid cancer by targeting DPP4.

Purpose: The purpose of this study was to investigate the effects of miR-29a on papillary thyroid cancer (PTC) and its underlying mechanisms. Methods: Primary tumor tissues and adjacent tissues of 69 patients with PTC were obtained. Human thyroid cell line Nthy-ori3-1 and PTC cell lines K1, BCPAP, TPC-1 were cultured. K1 cells were transfected and divided into following groups: blank group (without any treatment), miR-29a mimics group, control mimics group, miR-29a inhibitor group, control inhibitor group, DPP4 siRNA group, control siRNA group and miR-29a inhibitor + DPP4 siRNA group. qRT-PCR and Western blot were used to detect miR-29a and DPP4 expression. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assay were performed to detect cells proliferation, migration, and invasion. A nude mice xenograft experiment was performed. Results: miR-29a was significantly downregulated in PTC tissues, K1 and TPC-1 cells (P<0.01). DPP4 was significantly upregulated in the miR-29a inhibitor group and significantly downregulated in the miR-29a mimics group (P<0.01). DPP4 was the target gene of miR-29a. miR-29a significantly inhibited K1 cell proliferation, invasion, migration and PTC growth in nude mice by targeting DPP4 (P<0.01). Conclusion: miR-29a inhibits proliferation, migration, and invasion of PTC by targeting DPP4, which might provide a new target for clinical treatment of PTC.

Correlation of SOCS-1 gene with onset and prognosis of breast cancer.

The aim of the present study is to study the expressions of suppressor of cytokine signaling (SOCS)-1 in the tumor tissues and adjacent normal tissues of patients with breast cancer. The study was also planned to investigate the association of SOCS-1 gene expression with patients' clinical pathology, molecular subtype and prognosis. A total of 60 cases of frozen and paraffin-embedded specimens of tumor tissues and corresponding adjacent normal tissues of patients with breast cancer were selected. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of SOCS-1 messenger RNA (mRNA) in the patients' tumor tissues and adjacent normal tissues. The immunohistochemical method was applied to detect the expressions of SOCS-1 proteins in the patients' breast cancer tissues and adjacent normal tissues. Moreover, the correlations of SOCS-1 protein expressions in breast cancer tissues with patients' pathological parameters, molecular subtypes and prognosis were analyzed in combination with the clinical data. The results of RT-qPCR showed that the SOCS-1 mRNA expression in breast cancer tissues was significantly lower than that in adjacent normal tissues (p<0.01). The immunohistochemical results indicated that the positive expression rate of the SOCS-1 proteins in breast cancer tissues (23.33%) was remarkably lower than that in adjacent normal tissues (88.33%) (p<0.01). The low expression of SOCS-1 in breast cancer tissues was related to lymph node metastasis and clinical staging. The positive expression rates of the luminal A SOCS-1 proteins were the highest (47.62%) (p<0.01). The 5-year overall survival rate of the breast cancer patients was 63.33% (38/60). The univariate survival analysis revealed that the patients with low expression of SOCS-1 had poorer prognosis. In conclusion, the low expression of SOCS-1 plays a key role in the pathogenesis of breast cancer; in particular, it is associated with the lymph node metastasis and clinical staging of the tumor; so, the SOCS-1 expression in breast cancer tissues can be regarded as an important reference for the prognostic estimation of breast cancer.

SOCS1 is associated with clinical progression and acts as an oncogenic role in triple-negative breast cancer.

Suppressors of cytokine signaling 1 (SOCS1) is a member of SOCS family and acts as negative regulators of cytokine signaling by direct inhibition of receptor-associated janus kinases. The clinical significance and biological function of SOCS1 in variant tumor tissues and at variant tumor stages is still controversial. The aim of our study is to confirm the expression status of SOCS1 in triple-negative breast cancer (TNBC) tissues and cell lines, and explore the clinical value and biological function of SOCS1 in TNBC. In microarray data sets (GDS2250 and GDS817), we observed SOCS1 was overexpressed in TNBC tissues and cell line compared with normal mammary tissues and mammary epithelial cell line, or non-TNBC tissues and cell line. Furthermore, SOCS1 mRNA and protein overexpression were confirmed in TNBC tissues and cell lines compared with normal mammary tissues and mammary epithelial cell lines or non-TNBC tissues and cell lines. SOCS1 protein overexpression was obviously associated with advanced clinical stage, large tumor size, more lymph node metastasis, present distant metastasis, and malign histological grade. Downregulation of SOCS1 expression suppressed TNBC cells proliferation and promoted cell apoptosis. In conclusion, SOCS1 is associated with clinical progression in TNBC patients and acts as an oncogenic role in regulating TNBC cells proliferation and apoptosis. © 2018 IUBMB Life, 70(4):320-327, 2018.