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.

The effect of the earliest COVID-19 outbreak on survival in uninfected advanced NSCLC patients receiving chemotherapy in Jiangsu Province, China: A retrospective cohort study.

Coronavirus disease 2019 (COVID-19) is still rampant and uncontrolled across the globe. China's strict epidemic prevention measures have had an impact on the treatment in patients with non-small cell lung cancer (NSCLC). The aim of this study is to explore the impact of the COVID-19 outbreak on the uninfected NSCLC patients. The chemotherapeutic efficacy and survival of 89 uninfected advanced NSCLC patients were retrospectively analyzed. The endpoints were overall survival (OS), progression-free survival (PFS), and response rate. Forty and forty-nine patients with advanced NSCLC received chemotherapy during the COVID-19 outbreak and nonoutbreak periods, respectively. Mean delay time was 12.8 months for COVID-19 outbreak stage versus 5.68 months for nonoutbreak stage (P = .003). There was no significant difference in the rates of chemotherapy delay and discontinuation between the 2 groups (P = .055 and .239). Significant difference was not detected in median OS (15.8 months) for COVID-19 outbreak stage versus 16.0 months for nonoutbreak stage (adjusted hazard ratio, 1.058; 95% confidence interval, 0.593-1.888; P = .849); Median PFS was 7.9 months for COVID-19 outbreak stage versus 10.3 months for nonoutbreak stage (adjusted hazard ratio, 0.878; 95% confidence interval 0.513-1.503; P = .634). There was also no statistical difference in the disease control rate between the 2 groups (P = .137). The earliest COVID-19 outbreak had no significant impact on the PFS and OS in uninfected advanced NSCLC patients receiving chemotherapy. However, the mean delay time of receiving chemotherapy was prolonged during the COVID-19 outbreak.

LINC00839/miR-144-3p/WTAP (WT1 Associated protein) axis is involved in regulating hepatocellular carcinoma progression.

The present work aimed to explore LINC00839 expression level and its function in hepatocellular carcinoma (HCC), and identify the downstream molecular mechanisms. qRT-PCR (Real-Time Quantitative Reverse Transcription PCR) and western blot were employed to detect mRNA and protein levels. Functional investigations were performed by flow cytometric-based apoptosis assay, CCK8 (Cell Counting Kit-8) assay, clone formation assay, Transwell migration and invasion assay. Functional interactions between LINC00839 and miR-144-3p or miR-144-3p and WTAP were validated by dual luciferase reporter assay. siRNA (small interfering RNA) was used for LINC00839 silencing, and microRNA mimic or inhibitor were employed to modulate miR-144-3p activity. LINC00839 was upregulated in HCC cells and tissues. Silencing LINC00839 suppressed the proliferation, invasion, migration of HCC cells and induced apoptosis. Additionally, LINC00839 served as a sponge to negatively impact on miR-144-3p activity, which contributed to the high expression of WTAP (WT1 Associated Protein) and the malignant phenotype of HCC cells. Our study revealed an oncogenic role of LINC00839 in HCC, and identified miR-144-3p/WTAP axis as downstream effectors mediating the oncogenic function of LINC00839. LINC00839 might serve as a potential therapeutic target and prognostic marker for HCC.

Efficacy of gecko polysaccharide on suppressed immune response induced by cyclophosphamide in mice.

OBJECTIVE: To evaluate the efficacy of gecko polysaccharide on the cyclophosphamide-induced suppressed immune response in mice. METHODS: Polysaccharides were extracted from fresh gecko for the first time using an orthogonal method and protein was removed using Sevag reagent (chloroform:N-butanol, 5:1, v/v). The gecko polysaccharide (GPCE) content was determined by the phenol-concentrated sulfuric acid method. An immunocompromised mouse model was established by intraperitoneally injecting cyclophosphamide at 100 mg/kg into 48 mice. The effects of GPCE on immune regulation in mice were assessed by a thymus-spleen index, serum hemolysin levels, and the proliferation of splenic lymphocytes. Spleen cell CD4+, CD8+, and the CD4+/CD8+ ratio were evaluated by flow cytometry and the tumor necrosis factor-α (TNF-α) levels were measured by ELISA. RESULTS: The optimal extraction process for gecko polysaccharide included a 1:20 ratio of material to liquid (v/v), an extraction temperature of 60 ℃ and a time of 2 h. The polysaccharide content of the extract was 65.74%. GPCE was analyzed by HPLC and primarily contained glucose and small amounts of mannose, rha, and gal. Compared with the model, the thymus index, the spleen index were indices for GPCE increased with dose, whereas the high and medium groups exhibited significant differences (P < 0.05, P < 0.01). Higher doses of GPCE increased serum TNF-α levels and there was a significant difference between the medium and high GPCE doses and the model (P < 0.05, P < 0.01); The number of CD4+ cells and the CD4+/CD8+ ratio in the gecko polysaccharide group were increased (P < 0.05) and there was no statistical difference in the number of CD8+ cells in the gecko polysaccharide group (P > 0.05); The high GPCE dose significantly increased the level of serum hemolysin (P < 0.01). CONCLUSIONS: Gecko polysaccharide significantly improved the suppressed immune response induced by cyclophosphamide in mice and promoted the secretion of tumor necrosis factor. The mechanism of gecko polysaccharide as an antitumor agent warrants further study.

Clinical Benefit of Therapeutic Drug Monitoring in Colorectal Cancer Patients Who Received Fluorouracil-Based Chemotherapy.

BACKGROUND The impact of therapeutic drug management (TDM) on reducing toxicity and improving efficacy in colorectal cancer (CRC) patients receiving fluorouracil-based chemotherapy is still unclear. MATERIAL AND METHODS A total of 207 patients (Study Group n=54, Historical Group n=153) with metastatic colorectal cancer were enrolled. All of them received 6 administrations of the 5-FU based regimens. Initial 5-FU dosing of all patients was calculated using body surface area (BSA). In the Study Group, individual exposure during each cycle was measured using a nanoparticle immunoassay, and the 5-FU blood concentration was calculated using the area under the curve (AUC). We adjusted the 5-FU infusion dose of the next cycle based on the AUC data of the previous cycle to achieve the target of 20-30 mg×h/L. RESULTS In the fourth cycle, patients in the target concentration range (AUC mean, 26.3 mg×h/L; Median, 28 mg×h/L; Range, 14-38 mg×h/L; CV, 22.4%) accounted for 46.8% of all patients, which were more than the ones in the first cycle (P<0.001). 5-FU TDM significantly reduced the toxicity of chemotherapy and improved its efficacy. The Study Group (30/289) showed a lower percentage of severe adverse events than that in the Historical Group (185/447) (P<0.001). The incidences of complete response and partial response in the Study Group were higher than those in the Historical Group (P=0.032). CONCLUSIONS TDM in colorectal cancer can reduce toxicity, improve efficacy and clinical outcome, and can be routinely used in 5-FU-based chemotherapy.

The effect of TKI therapy and chemotherapy treatment delivery sequence on total progression-free survival in patients with advanced EGFR-mutated NSCLC.

The present study aimed to evaluate the total progression-free survival (PFS) time of the 1st-line chemotherapy (CHT)/2nd-line tyrosine kinase inhibitor (TKI) and 1st-line TKI/2nd-line CHT therapeutic regimens. Data from patients with non-small-cell lung cancer (NSCLC) harboring sensitizing epidermal growth factor receptor (EGFR) mutations, who had received both TKI and platinum CHT were retrieved from the Shandong Cancer Hospital (Jinan, China) database. A total of 89 patients were included, 50 of whom were treated with the 1st-line CHT/2nd-line TKI regimen and the remaining 39 patients underwent a 1st-line TKI/2nd-line CHT regimen. The differences in total PFS time between the two regimens were analyzed. The median total PFS time was 14.28 months with the 1st-line CHT/2nd-line TKI regimen and 17.77 months with the 1st-line TKI/2nd-line CHT regimen (adjusted hazard ratio, 0.96; 95% confidence interval (CI), 0.56-1.66; P=0.886). A significant difference in PFS time was revealed between the two strategies when comparing only the 1st-line or 2nd-line treatments (all P<0.001). The objective response rate (RR) was 52.0% for those treated with 1st-line CHT/2nd-line TKI and 38.5% for the reverse regimen. After adjusting for associated factors, the odds ratio for the RR was 2.77 (95% CI: 0.77-9.90; P=0.117). The current results revealed that there was no significant difference between the total PFS time of patients with NSCLC undergoing the 1st-line CHT/2nd-line TKI regimen compared with patients with NSCLC undergoing the 1st-line TKI/2nd-line CHT regimen.

DTX3L is upregulated in glioma and is associated with glioma progression.

Gliomas are the most common primary brain tumors of the central nervous system (CNS). Due to the poor prognosis of glioma patients, it is urgent to develop more effective therapies. Deltex-3-like (DTX3L), also known as B-lymphoma and BAL-associated protein (BBAP), has been reported to play an important role in the progression of many tumors. This study aimed to investigate the clinical significance and biological function of DTX3L in human glioma. Clinically, the protein expression level of DTX3L is increased in glioma tissues compared with that observed in normal brain tissues. Immunohistochemical analysis demonstrated that DTX3L was highly expressed in the glioma tissues and its level was correlated with the grade of malignancy. Multivariate analysis revealed the association between high expression of DTX3L and the poor prognosis of glioma patients. In addition, knockdown of DTX3L by siRNA transfection increased glioma cell apoptosis. Moreover, suppression of DTX3L expression was shown to significantly inhibit the migration and invasion of glioma cells. These data indicate that DTX3L plays an important role in the pathogenic process of glioma, suggesting that DTX3L could be a potential prognostic biomarker for glioma.

Upregulated expression of Nucleostemin/GNL3 is associated with poor prognosis and Sorafenib Resistance in Hepatocellular Carcinoma.

Nucleostemin (NS)/GNL3 protein has been recently documented to be a nucleolar protein that was abundantly expressed in stem cells and cancer cells. Herein, we showed that NS was upregulated in HCC tissues and the expression of NS was inversely correlated with that of p53. Overexpression of NS predicted significantly worsened prognosis in HCC patients, suggesting that NS might serve as a prognostic marker of HCC. In addition, we found that depletion of NS sensitized HCC cells to sorafenib-induced apoptosis. Moreover, we found that the mechanism underlying NS-mediated sorafenib resistance involved dysregulated expression of p53, and downstream Bax and Bcl-2 proteins. NS interacted with p53 in HCC cells. Depletion of NS increased the expression of p53 and Bax, whereas impaired the level of cellular Bcl-2. Interference of NS enhanced the cytotoxic effects of sorafenib in HCC cells. Furthermore, ectopic expression of NS impaired the apoptosis of HCC cells following sorafenib exposure. Therefore, NS may contribute to sorafenib resistance in HCC cells through the modulation of p53 pathway and Bcl-2 proteins. These findings indicated that the combination of silencing NS expression and sorafenib treatment is a promising therapeutic strategy in treatment of HCC.

High Expression of BCCIP ß Can Promote Proliferation of Esophageal Squamous Cell Carcinoma.

BACKGROUND: BCCIP was originally identified as a BRCA2 interacting protein in humans and Ustilago maydis. It had low expression in some human cancer tissues. However, recent research indicated that many caretaker genes are also necessary for cell viability and their expression could contribute to tumor progression. AIM: To characterize whether BCCIP is a caretaker gene in esophageal squamous cell carcinoma (ESCC). METHODS: Western blotting and immunohistochemistry were used to measure the expression of BCCIP ß. In vitro studies were used to verify the effects of BCCIP ß in Eca109 cells. RESULTS: Expression of BCCIP ß was notably higher in tumor tissues of ESCC and Eca 109 cells. Meanwhile, the immunohistochemistry stain revealed that BCCIP ß was positively correlated with clinical pathologic variables such as tumor size and tumor grade, as well as Ki-67, and prompted poor prognosis. In vitro studies such as starvation and refeeding assay along with BCCIP ß-shRNA transfection assay demonstrated that BCCIP ß expression promoted proliferation of ESCC cells. In addition, BCCIP ß downregulation by silencing RNA significantly decreased the rate of colony formation, alleviated cellular apoptosis and increased the chemosensitivity of cisplatin. CONCLUSIONS: This research first put forward that BCCIP ß is an oncogene in human ESCC and contributes to the poor outcome of the deadly disease.

IGFBP6 Regulates Cell Apoptosis and Migration in Glioma.

The insulin-like growth factor binding protein 6 (IGFBP6), as an inhibitor of IGF-II actions, plays an important role in inhibiting survival and migration of tumor cells. In our study, we intended to demonstrate the biological function of IGFBP6 in the development of glioma and its clinical significance. Firstly, Western blot and immunohistochemistry revealed that the expression of IGFBP6 inversely correlated with glioma grade. Secondly, multivariate analysis with the Cox proportional hazards model and Kaplan-Meier analysis indicated that IGFBP6 could be an independent prognostic factor for the survival of glioma patients. In addition, overexpression of IGFBP6 induced glioma cell apoptosis, and depletion of IGFBP6 had the opposite action. Finally, overexpression of IGFBP6 inhibited migration of glioma cells, and depletion of IGFBP6 had the opposite action. Together our findings suggest that IGFBP6 might be an important regulator and prognostic factor for glioma.

Knockdown of DIXDC1 Inhibits the Proliferation and Migration of Human Glioma Cells.

DIX domain containing 1 (DIXDC1), the human homolog of coiled-coil-DIX1 (Ccd1), is a positive regulator of Wnt signaling pathway. Recently, it was found to act as a candidate oncogene in colon cancer, non-small-cell lung cancer, and gastric cancer. In this study, we aimed to investigate the clinical significance of DIXDC1 expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that DIXDC1 was overexpressed in glioma tissues and glioma cell lines. The expression level of DIXDC1 was evidently linked to glioma pathological grade and Ki-67 expression. Kaplan-Meier curve showed that high expression of DIXDC1 may lead to poor outcome of glioma patients. Serum starvation and refeeding assay indicated that the expression of DIXDC1 was associated with cell cycle. To determine whether DIXDC1 could regulate the proliferation and migration of glioma cells, we transfected glioma cells with interfering RNA-targeting DIXDC1; investigated cell proliferation with Cell Counting Kit (CCK)-8, flow cytometry assays, and colony formation analyses; and investigated cell migration with wound healing assays and transwell assays. According to our data, knockdown of DIXDC1 significantly inhibited proliferation and migration of glioma cells. These data implied that DIXDC1 might participate in the development of glioma, suggesting that DIXDC1 can become a potential therapeutic strategy for glioma.

The role of ubiquitin-specific protease 14 (USP14) in cell adhesion-mediated drug resistance (CAM-DR) of multiple myeloma cells.

OBJECTIVE: Cell adhesion-mediated drug resistance (CAM-DR) is one of the mechanisms underlying the drug resistance in multiple myeloma (MM). Ubiquitin-specific protease 14 (USP14) is downregulated in the apoptotic model and upregulated in the adhesive model of MM. This study was undertaken to determine the role of USP14 in CAM-DR of MM cells. METHODS: We examined the expression of USP14 in the apoptotic model of MM. The mechanism of USP14 in the process of apoptosis was further explored by flow cytometry assay and co-immunoprecipitation. We then performed the cell co-culture and adhesion assay and cell viability assay to investigate the effect of USP14 on adhesive rate and drug resistance in MM. RESULTS: We discovered that USP14 played a negative role in cell apoptosis, which is correlated with Bcl-xl. Moreover, overexpression of USP14 in MM cell adhesion model could enhance the ability of cell adhesion by regulating Wnt-signaling pathways, thereby promoting the CAM-DR in MM. CONCLUSION: USP14 participates in CAM-DR of MM through acting as a bridge between Bcl-xl apoptotic pathway and Wnt-signaling pathways and may be represented as a good candidate for pursuing clinical trials in MM.

Protein phosphatase 1γ regulates the proliferation of human glioma via the NF-κB pathway.

Protein phosphatase 1γ (PP1γ), a member of mammalian protein phosphatases, serine/threonine phosphatases, catalyzes the majority of protein dephosphorylation events and regulates diverse cellular processes, such as neuronal signaling, muscle contraction, glycogen synthesis, and cell proliferation. However, its expression and potential functions in human glioma is unclear. In this study, we detected the high expression of PP1γ and phosphorylated p65 (p-p65) in human glioma tissues. Besides, we demonstrated that upregulation of PP1γ was tightly related to poor 5-year survival via systemic statistical analysis. Employing serum-starved and re-feeding models of U251 and U87MG, we observed the increasing expression of PP1γ and p-p65 were accompanied by the cell proliferation markers cyclin D1 and proliferating cell nuclear antigen (PCNA). Employing depletion-PP1γ models, we found downregulated PP1γ and p-p65 compared with upregulated IκBα, which indicates the inhibition of NF-κB pathway, and flow cytometry analysis confirmed the weakened cell proliferation. Moreover, we found that the translocation of p65 into the nucleus was impaired. Collectively, we identified the positive correlation between upregulation of PP1γ and human glioma cell proliferation and that knock-down of PP1γ alleviated the glioma proliferation by reducing p65 transportation into the nucleus. The results showed that PP1γ could accelerate human glioma proliferation via the NF-κB pathway.

Nucleostemin promotes the proliferation of human glioma via Wnt/ß-Catenin pathway.

Nucleostemin, nucleolar guanosine triphosphate (GTP)-binding protein 3, is a member of the MMR1/HSR1 GTP-binding protein family. The important roles of nucleostemin in self-renewal, cell cycle regulation, apoptosis, and cell proliferation of various cancer types as been shown. Nevertheless, its expression and potential functions in human glioma is still unclear. In the present study, we demonstrated that up-regulation of nucleostemin was tightly related to poor 5-year-survival ratios. In serum-starved and re-feeding models of U251 and U373MG, we observed the rising expression of nucleostemin and p-ß-Catenin (p-Tyr645) were accompanied with cell proliferation markers (cyclin D1 and proliferating cell nuclear antigen (PCNA)). Employing nucleostemin-depletion models, we found down-regulated nucleostemin and p-ß-Catenin. The flow cytometry analysis proved the weakened cell proliferation. Moreover, we detected the translocation of ß-Catenin into the nucleus was impaired, meaning the inhibition of the Wnt/ß-Catenin pathway. Taken together, we identified a positive correlation between up-regulation of nucleostemin and human glioma cell proliferation and that knocking-down nucleostemin alleviated glioma proliferation by reducing ß-Catenin transportation into the nucleus. All results suggested that nucleostemin might accelerate human glioma proliferation via the Wnt/ß-Catenin pathway.

CHD1L Regulates Cell Cycle, Apoptosis, and Migration in Glioma.

Chromodomain helicase/ATPase DNA binding protein 1-like (CHD1L) gene is a newly identified oncogene located at Chr1q21 and it is amplified in many solid tumors. In this study, we intended to investigate the clinical significance of CHD1L expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that CHD1L was overexpressed in glioma tissues and glioma cell lines. In addition, the expression level of CHD1L was positively correlated with glioma pathological grade and Ki-67 expression. Kaplan-Meier curve indicated that high expression of CHD1L may result in poor prognosis of glioma patients. Accordingly, suppression of CHD1L in glioma cells was shown to induce cell cycle arrest and increase apoptosis. In addition, knockdown of CHD1L significantly accelerated migration and invasion ability of glioma cells. Together our findings suggest that CHD1L is involved in the progression of glioma and may be a novel target for further therapy.

Expression and clinical role of RBQ3 in gliomas.

RBQ3, also known as RBBP5 (RB-binding protein 5), was an RB-binding protein. Besides, it was one of core components of MLL1 (mixed lineage leukemia 1), which were required for H3K4 methyltransferase activity. MLL1 dysfunction was found to be associated with the progression of some cancers such as acute leukemias. However, the precise role of RBQ3 in tumor progression remains obscure. In this study, we explored the expression and clinical role of RBQ3 in gliomas. Our results showed that RBQ3 was significantly upregulated in clinical glioma specimens by Western blot and immunohistochemistry. Moreover, its level was significantly associated with the pathology grades. High RBQ3 expression was suggested to be an independent prognostic factor for glioma patients' survival by univariate and multivariate analyses. Serum starvation and refeeding assay indicated that the expression of RBQ3 increased 8h after serum-stimulation, together with percentage of cells at S phase. In addition, knockdown of RBQ inhibited U87-MG cell proliferation with CCK8 kit, flow cytometry assays and colony formation analyses; while the depletion of RBQ3 induced the apoptosis of U87-MG cells. All the findings suggested that RBQ3 might play an important role in glioma, and RBQ3 inhibitors might be novel anti-tumor agents.

Effects of Traditional Chinese Medicine in Treatment of Breast Cancer Patients After Mastectomy: A Meta-Analysis.

The purpose of the present study is to investigate the clinical efficacy of traditional Chinese medicine (TCM) in treating breast cancer patients after mastectomy. We searched EMBASE, CENTRAL, MEDLINE, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP), and PubMed to collect randomized controlled trials of TCM in treatment of breast cancer patients after mastectomy. Quality of the methodology was assessment in accordance with Cochrane 4.2.2 Handbook. All patients were divided into two groups: TCM group (TCM only or TCM plus conventional treatment) and control group (conventional treatment only). Effects of TCM on short-term clinical outcome, long-term survival rate, and incidence of adverse reaction were compared between the two groups. Twenty-nine studies were included in this meta-analysis, involving a total of 3142 breast cancer patients. Meta-analyses showed that TCM could improve short-term treatment efficacy (Z = 7.67, RR = 1.59, 95% cl [1.41-1.80], P < 0.00001), extend 3-year (Z = 5.47, RR = 1.26, 95% cl [1.16-1.37], P < 0.00001) and 5-year (Z = 5.53, RR = 1.17, 95% cl [1.11-1.24], P < 0.00001) survival, reduce the incidence of adverse reactions in breast cancer patients after mastectomy. TCM provides beneficial and complementary effects in the treatment of breast cancer patients after mastectomy.