Efficacy and safety of multikinase inhibitors for patients with refractory thyroid cancer: Systematic review and network meta-analysis.

CONTEXT: Multikinase inhibitors (MKIs) improve the treatment of refractory thyroid cancer, included radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) and advanced medullary thyroid carcinoma (aMTC). OBJECTIVE: This study aims to compare the efficacy of MKIs in improving survival outcomes and safety. DATA SOURCES: Comprehensive database searches of MEDLINE via PubMed, EMBASE and Cochrane performed from inception to December 2023. STUDY SELECTION: Three independent authors selected these studies. Randomised-controlled trials that compared the use of a MKI to other MKIs or placebo were included. DATA EXTRACTION AND SYNTHESIS: This review followed PRISMA guidelines. Risk of bias was analyzed using the Cochrane RoB 2 tool. Bayesian network meta-analysis was performed. Treatments were grouped into common nodes based on the type of MKI. MAIN OUTCOMES AND MEASURES: Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate, disease control rate, clinical benefit rate, and adverse events. RESULTS: Cabozantinib 60 mg/d (CAB60) was associated with the highest prolonged PFS in RAIR-DTC patients, followed by lentivatinib 18 or 24 mg/d (LEN18 or LEN24), and apatinib. PFS was also improved in in aMTC patients received CAB 140 mg/d (CAB140), CAB60, or anlotinib. A significantly greater improvement on the performance of OS was seen in CAB60, LEN24, anlotinib, and sorafenib in RAIR-DTC patients, but which in aMTC patients were lack of statistical differences. Compared with the low-dose of MKIs, high-dose of MKIs such as CAB, LEN, and vandetanib increased the incidence of adverse events. CONCLUSION: CAB60, LEN, and apatinib are promising topical MKIs with statistically significant primary outcomes in RAIR-DTC patients, while CAB and anlotinib are effective in prolonging PFS in aMTC patients.

Baicalein suppresses the growth of the human thyroid cancer cells by inducing mitotic catastrophe, apoptosis and autophagy via NF-kB signalling pathway

The Editors of JBUON issue an Expression of Concern to 'Baicalein suppresses the growth of the human thyroid cancer cells by inducing mitotic catastrophe, apoptosis and autophagy via NF-kB signalling pathway', by Shijian Yi, Guowen Liu, Yang Wu, Qiankun Liang, Lanlan Li; JBUON 2020;25(1):389-394; PMID: 32277659. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Circular RNA circUBE2D2 functions as an oncogenic factor in hepatocellular carcinoma sorafenib resistance and glycolysis.

Circular RNAs (circRNAs) have been reported to regulate the hepatocellular carcinoma (HCC) chemoresistance and tumor progression by regulating gene expression. However, the underlying molecular mechanisms of HCC sorafenib resistance regulated by circRNAs remain unclear. Here, higher expression of circUBE2D2 was directly associated with low survival rate in HCC patients. Functional experiments showed that circUBE2D2 promoted the glycolysis (Warburg effect) and sorafenib resistance in vitro, and knockdown of circUBE2D2 repressed the tumor growth in vivo. Mechanistically, circUBE2D2 was predominantly localized in the cytoplasm and sponged miR-889-3p, which in turn targeted the 3'-UTR of LDHA mRNA. Therefore, circUBE2D2 exerted an oncogenic role through miR-889-3p/LDHA axis. In conclusion, these findings demonstrate that circUBE2D2 accelerated the HCC glycolysis and sorafenib resistance via circUBE2D2/miR-889-3p/LDHA axis, which provides a novel approach for HCC treatment.

Social capital, depressive symptoms, and perceived quality of care among hypertensive patients in primary care.

BACKGROUND: Depression is an important issue in the management of hypertension. However, little attention has been paid to addressing such aspects of psychological health among patients with hypertension. We aimed to estimate the prevalence of depressive symptoms among patients with hypertension in primary care settings and to identify the potential role of social capital in predicting depressive symptoms. The influence of psychological well-being on the perceived quality of hypertensive care was also examined. METHODS: In Shenzhen, China, an on-site cross-sectional study was conducted from March to September 2017. In total, 1046 respondents completed a face-to-face survey interview. We examined the associations between social capital, depressive symptoms, and perceived quality of care. RESULTS: The results showed that 10.7% of patients with hypertension who attended primary care facilities had depressive symptoms. Two components of social capital-social ties (9.63 vs. 10.67; OR = 1.314, 95% CI 1.165-1.483; P < .001) and trust (3.46 vs. 3.89; OR = 2.535, 95% CI 1.741-3.691; P < .001)-were protective factors for depression among patients with hypertension in primary care settings. We also found that depressive symptoms were negatively associated with perceived quality of care (30.5 vs. 32.5; ß = 1.341, 95% CI 0.463-2.219; P = .003).. CONCLUSIONS: We found inverse associations between depressive symptoms and perceived quality of care and between social capital and the occurrence of symptoms of depression. Our findings suggest that strategies addressing both hypertension and depressive symptoms should be implemented to better manage hypertension. Appropriate social interventions should be designed and implemented.

Compound amino acid combined with high-dose vitamin B6 attenuate traumatic coagulopathy via inhibiting inflammation by HMGB1/TLR4/NF-κB pathway.

BACKGROUND: Traumatic coagulopathy (TC) arises primarily from coagulation system failure to maintain adequate hemostasis after serious blood loss or trauma. Circulatory homeostasis restoration is the mainstay of the therapeutic approach to TC, but the effects are significantly inhibited by coagulopathy. OBJECTIVE: To identify the therapeutic effects and underlying mechanism of compound amino acid (CAA) combined with high-dosage of vitamin B6 (VB6) on TC. METHODS: Rabbit traumatic model and cellular model were used to evaluate the effect of CAA combined with high-dosage of VB6 in TC. Blood concentrations of AST and ALT were measured using the Vitros 250 device while blood APTT, PT and TT concentrations were measured using commercial diagnostics kits. Furthermore, qRT-PCR, ELISA and Western blotting were used to determine the expression of clotting factor (II, VII, IX, X and XI), inflammatory factors (TNF-α, IL-6 and IL-1ß) and HMGB1/TLR4/NF-κB signaling-related proteins, respectively. RESULTS: In the rabbit traumatic model, CAA combined with high-dosage of VB6 therapy inhibited the high expression of AST and ALT, but increased the expression of coagulation factors. Additionally, in both the rabbit trauma model and cellular injury model, CAA combined with high-dosage of VB6 inhibited the expression of inflammatory factors (IL-6, TNF-α and IL-1ß) and proteins (HMGB1, TLR4 and p-p65) in HMGB1/TLR4/NF-κB pathway. Most importantly, over-expression of HMGB1 reversed the effect of CAA and VB6 in HUVECs and EA.hy926 cells injury model. CONCLUSION: CAA combined with high-dosage of VB6 alleviated TC and inhibited the expression and secretion of inflammatory factors by inhibiting HMGB1-mediated TLR4/NF-κB pathway.

Baicalein suppresses the growth of the human thyroid cancer cells by inducing mitotic catastrophe, apoptosis and autophagy via NF-kB signalling pathway.

PURPOSE: The current study aimed at investigating the anticancer effects of plant-based flavone Baicalein against the thyroid cancer. METHODS: Cell viability was assessed using MTT assay. Flow cytometric-based estimation of cell cycle analysis was done for determining the cancer cell phase distribution. DAPI staining method followed by fluorescent microscope examination was used for inferring the cancer cell apoptosis. Transmission electron microscopy (TEM) was used for detection of autophagosomes. Western blotting was done for protein concentration estimation. RESULTS: Baicalein induced dose-dependent decline in proliferation of MDA-T68 thyroid cancer cells, while the reduction of cell proliferation was surprisingly lower for normal thyrocytes. IC50 of 10µM was estimated against cancer cells. Baicalein induced cell apoptosis in a concentration-dependent manner. Induction of apoptosis was attributed to increase in apoptotic protein concentration and signal was mediated through change Bax/Bcl-2 ratio. The autophagic cell death occurred in cancer cells when treated with Baicalein. The mechanism of cell death was inferred as modulation of NF-kB signaling pathway. Baicalein was also seen to induce mitotic cell cycle arrest in thyroid cancer cells by reducing the concentration of Cyclin B1 mitotic protein. CONCLUSION: The results of current study suggest Baicalein as an important anticancer agent against thyroid cancer. Future research to further investigate and enhance the effects of Baicalein against thyroid cancer is needed.

Glucose Oxidase-Instructed Traceable Self-Oxygenation/Hyperthermia Dually Enhanced Cancer Starvation Therapy.

Cancer theranostics based on glucose oxidase (GOx)-induced starvation therapy has got more and more attention in cancer management. Herein, GOx armed manganese dioxide nanosheets (denoted as MNS-GOx) were developed as cancer nanotheranostic agent for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided self-oxygenation/hyperthermia dually enhanced starvation cancer therapy. The manganese dioxide nanomaterials with different morphologies (such as nanoflowers, nanosheets and nanowires) were synthesized by a biomimetic approach using melanin as a biotemplate. Afterwards, the manganese dioxide nanosheets (MNS) with two sides and large surface area were selected as the vehicle to carry and deliver GOx. The as-prepared MNS-GOx can perform the circular reaction of glucose oxidation and H2O2 decomposition for enhanced starvation therapy. Moreover, the catalytic activity of GOx could be further improved by the hyperthermia of MNS-GOx upon near-infrared laser irradiation. Most intriguingly, MNS-GOx could achieve "turn-on" MR imaging and "turn-off" PA imaging simultaneously. The theranostic capability of MNS-GOx was evaluated on A375 tumor-bearing mice with all tumor elimination. Our findings integrated molecular imaging and starvation-based synergistic cancer therapy, which provided a new platform for cancer nanotheranostics.

MR diffusion-weighted imaging of rabbit liver VX-2 tumor.

AIM: To investigate the implanting method of rabbit liver VX-2 tumor and its MR diffusion-weighted imaging (DWI) characteristics. METHODS: Thirty-five New Zealand rabbits were included in the study. VX-2 tumor was implanted subcutaneously in 14 rabbits and intrahepatically in 6 for pre-experiments. VX-2 tumor was implanted intrahepatically in 12 rabbits for experiment and three were used as the control group. DWI, T1- and T2-weighted of MRI were performed periodically in 15 rabbits for experiment before and after implantation. The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance was calculated by analysis of variance (ANOVA) of the randomized block design using SPSS10.0 software. RESULTS: The successful rate of subcutaneous implantation of VX-2 tumor was 29% (4/14) while that of intrahepatic implantation of it was 33% (2/6) in the pre-experiment. The successful rate of intrahepatic implantation of VX-2 tumor in the experiment was 83% (10/12) and 15 tumors grew in 10 successfully implanted rabbits. The DWI signal of VX-2 tumor was high and became lower when the b value increased step by step. The signal of VX-2 tumor on the map of ADC was low. When the b value was 100 or 300 s/mm2, the ADC value of normal group and VX-2 tumor group was respectively 2.57+/-0.26, 1.73+/-0.31, 1.87+/-0.25 and 1.57+/-0.23 mm2/s. Their distinction was significant (F = 43.26, P<0.01), the tumor ADC value between b values 100 and 300 s/mm2 was significant (Tukey HSP, P<0.05) and the ADC value between VX-2 tumor and normal liver was also significant (Tukey HSP, P<0.01). VX-2 tumor developed quickly and metastasized early to all body, especially to the lung, liver, lymph nodes of mediastinum, etc. CONCLUSION: The DWI signal of rabbit VX-2 tumor has its characteristics on MR DWI and DWI plays an important role in diagnosing and discovering VX-2 tumor.