Bibliometric Analysis of γδ T Cells as Immune Regulators in Cancer Prognosis.

γδ T cells are one of only three immune cell types that express antigen receptors that undergo somatic recombination, and they contribute to immune responses to infection, cellular transformation, and tissue damage. As a "bridge" between the innate and adaptive immune systems, γδ T cells have been noted to be involved in various immune responses during cancer progression. The purpose of our study was to review current published information on γδ T cells and investigate their functions in different types of malignancy using bibliometric and bioinformatic methods. Our results indicated that studies on γδ T cells and cancer progression increased from 2014, and the number had peaked by 2021. We discovered that there is international cooperation in the performance of studies among 26 countries, where China was identified as the most productive with the highest citations. Using keyword co-occurrence analysis, we found that among all the cancer types investigated, gastric and breast cancers were most closely related to γδ T cells. Furthermore, interleukin (IL)-17 and IL-2 were the most common cytokines linked to γδ T cells and our investigation of their potential involvement in the prognosis of gastric and breast cancers, identified their different roles in various malignancies. Thus, we concluded that γδ T cells might influence the progression of different cancers in diverse ways.

Single-Agent versus Combination Doxorubicin-Based Transarterial Chemoembolization in the Treatment of Hepatocellular Carcinoma: A Single-Blind, Randomized, Phase II Trial.

OBJECTIVES: It was the aim of this study to find an optimal therapeutic regimen of transarterial chemoembolization (TACE) by comparing the efficacy of chemoembolization with different anticancer agents in hepatocellular carcinoma (HCC) patients. METHODS: A single-blind, three-group parallel, randomized trial was conducted in Guangdong General Hospital, Guangzhou, China, with patients with biopsy-confirmed HCC. Group 1 received single-drug (doxorubicin) chemoembolization, while group 2 received double-drug (doxorubicin and mitomycin C) chemoembolization. Patients in group 3 were treated with triple-drug (doxorubicin, mitomycin C, and gemcitabine) chemoembolization. Lipiodol was used as embolization agent in all protocols. We compared the overall survival (OS), time to progression (TTP), and objective response rate (ORR) between groups. Response assessment was performed according to modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria. RESULTS: Between January 2008 and January 2011, 162 patients (group 1, n = 50; group 2, n = 59; group 3, n = 53) were recruited. The OS and TTP in groups 1, 2, and 3 were 14.9 and 6.4, 13.2 and 6.4, and 20.5 and 6.8 months, respectively. OS and TTP were statistically significant among groups (p = 0.002 and p = 0.037). The ORR was 22.0, 40.7, and 56.6%, respectively. The ORR was significantly different across the three groups (p < 0.002). CONCLUSIONS: TACE with multiple chemotherapeutic agents might significantly increase survival and tumor response; additionally, gemcitabine was likely to have an advantage in improving the prognosis of HCC patients. © 2015 S. Karger AG, Basel.

Arsenic trioxide transarterial chemoembolization with and without additional intravenous administration of arsenic trioxide in unresectable hepatocellular carcinoma with lung metastasis: a single-blind, randomized trial.

AIM: To evaluate the efficacy and safety of arsenic trioxide transarterial chemoembolization and intravenous administration in unresectable hepatocellular carcinoma with lung metastasis. METHODS: A single-blind, two-parallel group, randomized trial was conducted at three medical centers (Guangzhou, China), including patients with both biopsy-confirmed hepatocellular carcinoma and lung metastasis. The experimental group received arsenic trioxide transarterial chemoembolization and intravenous administration of arsenic trioxide, while the control group only received arsenic trioxide transarterial chemoembolization. We compared overall survival (OS), time to progression (TTP), disease control rate (DCR), and objective response rate (ORR) between the groups. RESULTS: Between April 2013 and June 2014, 139 patients received the allocated intervention, 70 of whom were in the experimental group and 69 of whom were in the control group. No patient was lost to follow-up. The median OS was 7.3 (95 % CI = 6.8-7.8) months in the experimental group and 2.9 (95 % CI = 2.6-3.1) months in the control group (P < 0.001). The median TTP was 2.7 (95 % CI = 1.9-3.3) months in the experimental group and 1.2 (95 % CI = 1.0-1.9) months in the control group (P = 0.023). In the experimental group, the DCR was 72.85 % and the ORR was 7.14 %, while in the control group, the DCR was 7.24 % and the ORR was 0.00 %. DCR and ORR differed significantly between the two groups (P < 0.001 and P = 0.024, respectively). CONCLUSIONS: Arsenic trioxide transarterial chemoembolization and intravenous administration were safe and effective in unresectable hepatocellular carcinoma with lung metastasis.

The relationship of kinase insert domain receptor gene polymorphisms and clinical outcome in advanced hepatocellular carcinoma patients treated with sorafenib.

Kinase insert domain receptor (KDR) is the principal receptor that promotes the pro-angiogenic action of vascular endothelial growth factor and has been the principal target of anti-angiogenic therapies. Our aim was to determine whether single-nucleotide polymorphisms (SNPs) in KDR gene are associated with clinical outcomes after first-line sorafenib therapy in advanced hepatocellular carcinoma (HCC). The SNPs in KDR were tested in 78 advanced HCC patients receiving first-line sorafenib. Correlations with clinicopathological features and survival were analyzed. Patients with AA genotype of rs1870377 and AA genotype of rs2305948 were significantly associated with a better response and longer time to progression (TTP) (5.8 vs 4.0 months, P=0.001; 5.8 vs 4.5 months, P=0.016, respectively). Patients harboring AA genotype in rs1870377 and TT/TC genotype in rs2071559 had a longer overall survival (OS) (15.0 vs 9.6 months, P=0.001; 13.0 vs 9.0 months, P=0.007, respectively). At multivariate analysis, major vascular invasion and rs1870377 were independent factors in TTP and performance status, rs1870377, and rs2071559 were independent factors in OS. Our results suggest that SNPs in KDR gene can predict clinical outcome in advanced HCC patients receiving first-line sorafenib.

Genetic variants in the KDR gene is associated with the prognosis of transarterial chemoembolization treated hepatocellular carcinoma.

Kinase insert domain receptor (KDR) is the principal receptor that promotes the proangiogenic action of vascular endothelial growth factor and is involved in the tumorigenesis and progression of many malignancies, including hepatocellular carcinoma (HCC). Single-nucleotide polymorphisms (SNPs) of KDR have been reported to be with the risk and prognosis of several malignancies. Our aim was to determine whether SNPs in KDR gene are associated with clinical outcomes in HCC patients treated with transcatheter arterial chemoembolization. A total of 192 HCC patients were tested for KDR SNPs, and the SNP results were correlated with progression-free survival (PFS) and overall survival (OS). The association of the SNPs with the overall survival (OS) of patients was assessed by Kaplan-Meier method, and then Cox proportional hazards model was used to assess the variables resulted significant at univariate analysis. No significant differences were found in correlation between KDR SNPs and patients' PFS. Our data showed that genotype AA+TA of rs1870377 and genotype CC+TC of rs2071559 were significantly associated with overall survival of HCC patients (P<0.001 and P<0.001, respectively) and remained as significant predictors for OS adjusting for high level of serum AFP (>400 µg/L), existence of portal vein tumor thrombus, and high BCLC stage (HR=0.61; 95% CI, 0.36-0.88; P=0.003 and HR=0.54; 95% CI, 0.40-0.94; P=0.002, respectively). Our results suggest that SNPs rs1870377 and rs2071559 in the KDR gene may serve as independent prognosis biomarkers for unresectable HCC patient, which warranted further validating investigation.

Clinical value of circulating tumor cells for the prognosis of postoperative transarterial chemoembolization therapy.

The aim of this study was to clarify circulating tumor cells (CTCs) count could reflect the effect of postoperative transarterial chemoembolization therapy. A single-blind, two-parallel group, randomized trial was conducted in Guangdong General Hospital, Guangzhou, China, with patients: (1) with biopsy-confirmed hepatocellular carcinoma (HCC) and (2) undergoing partial resection. Patients in transarterial chemoembolization (TACE) group received TACE 1 month after resection, while control group received no managements. The time points for blood collection to count CTCs were as follows: (1) 1 month after resection (also 1 day before TACE); (2) 1 month after TACE; (3) 2 months after TACE; (4) 3 months after TACE; (5) 6 months after TACE; and (6) 1 year after TACE. A diagnosis of recurrence was based on computed tomography scans, magnetic resonance imaging, or digital subtraction angiography. We compared recurrence rate (RR) and CTC counts between groups. Between July 2010 and July 2012, 171 patients (TACE group: n = 81; control group: n = 90) were recruited. After TACE, mean CTC count in TACE group was 1.32 (CI 2.59-3.34), compared with 3.65 (CI 3.43-3.88) in control group (F = 200.89, P<0.05). CTCs counts were statistically significantly between groups at post-TACE time points. In addition, RR of TACE group was 25.9 % (21/81), while the number was 56.7 % (51/90) in control group. RR was statistically significantly between groups (P = 0.031). CTCs count was an important prognostic parameter for postoperative TACE on HCC recurrence.

Prognostic value of serum vascular endothelial growth factor receptor 2 response in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

We aimed to elucidate whether serum VEGFR2 concentration before and after transarterial chemoembolization (TACE) can predict survival in patients with unresectable hepatocellular carcinoma (HCC). Serum VEGFR2 concentrations were serially measured in 169 patients with advanced HCC before and after TACE. We defined a decrease in the serum VEGFR2 level>10% from the pretreatment level as response. Serum VEGFR2 concentrations decreased in 44 (26.0%) patients at week 4. Patients who had a VEGFR2 response at week 4 had a longer median survival than those who did not have a VEGFR2 decrease (19.0 vs. 9.8 months, p<0.001). Clinical variables associated with OS in addition to VEGFR2 response also included extrahepatic metastases (p=0.005) and vascular invasion (p=0.035). VEGFR2 decrease after TACE (p=0.012) and presence of extrahepatic metastases (p=0.02) were independently associated with OS by multivariate analysis. A serum VEGFR2 concentration decrease at 4 weeks after TACE may predict favorable overall survival in patients with advanced HCC.

The blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced hepatocellular carcinoma receiving sorafenib.

BACKGROUND AND AIM: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the prognostic significance of the blood neutrophil-to-lymphocyte ratio (NLR) in patients with advanced HCC who received sorafenib monotherapy. METHODS: A total of sixty-five patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib were enrolled. Potential prognostic factors such as age, gender, tumoral characteristics, performance status and NLR were analyzed. RESULTS: Median OS and TTP for the entire cohort were 10.0 months (95%CI, 7.6-12.3 months) and 4.5 months (95% CI, 4.0-4.9 months). The mean NLR at baseline was 2.89. The median OS of patients with a high NLR (>4) was 6.5 months (95%CI, 5.2-7.7 months) compared with 12.5 months (95%CI, 9.9-15.0) for patients with a normal NLR (≤ 4) (P = 0.01). Age ≤ 65, NLR >4, extrahepatic metastases and vascular invasion were all predictors of poorer overall survival. Multivariate analysis showed that NLR > 4, vascular invasion and extrahepatic metastases were independent predictors of poorer overall survival. The median TTP of patients with a high NLR was 2.5 months (95%CI, 1.4-3.6 months) compared with 4.5 months (95%CI, 3.9-5.1 months) for patients with a normal NLR (P=0.012). CONCLUSIONS: High baseline NLR was associated with worse OS and TTP for patients with advanced HCC treated with sorafenib.

Sorafenib in combination with transarterial chemoembolization and radiofrequency ablation in the treatment for unresectable hepatocellular carcinoma.

The purpose of this study is to assess clinical efficacy and safety of sorafenib combined with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) on patients with unresectable hepatocellular carcinoma (HCC). Efficacy and safety profiles of sorafenib in combination with TACE and RFA were evaluated based on retrospective data for thirty patients with unresectable HCC. Patients were treated with TACE initially when admitted to hospital, followed by RFA 3 days after TACE. All TACE and RFA were performed by the same team of doctors. Seven days after the first TACE, patients started taking continuous sorafenib 400 mg bid without breaks until unacceptable toxicities or disease progression. The response to treatment, overall survival (OS), time to progression (TTP), and adverse effects were evaluated. The disease control rate was 33.3% by RECIST criteria. The median TTP was 15.3 months (95% CI 4.8-23.5). The median OS was 28.8 months (95% CI 12.8-39.6). At the time of data record, 13 patients (43.3%) were dead. Median OS in patients with or without portal vein thrombosis was 12.3 months (95% CI 7.6-14.5) and 30.2 months (95% CI 24.2-34.5), respectively, P = 0.018. The most common adverse events related to sorafenib were hand-foot skin reaction (53.3%) and diarrhea (33.3%). The combination of sorafenib, TACE, and RFA proved both safe and effective in the treatment for unresectable hepatocellular carcinoma patients.