Advances in the application of 3D tumor models in precision oncology and drug screening.

Traditional tumor models cannot perfectly simulate the real state of tumors in vivo, resulting in the termination of many clinical trials. 3D tumor models' technology provides new in vitro models that bridge the gap between in vitro and in vivo findings, and organoids maintain the properties of the original tissue over a long period of culture, which enables extensive research in this area. In addition, they can be used as a substitute for animal and in vitro models, and organoids can be established from patients' normal and malignant tissues, with unique advantages in clinical drug development and in guiding individualized therapies. 3D tumor models also provide a promising platform for high-throughput research, drug and toxicity testing, disease modeling, and regenerative medicine. This report summarizes the 3D tumor model, including evidence regarding the 3D tumor cell culture model, 3D tumor slice model, and organoid culture model. In addition, it provides evidence regarding the application of 3D tumor organoid models in precision oncology and drug screening. The aim of this report is to elucidate the value of 3D tumor models in cancer research and provide a preclinical reference for the precise treatment of cancer patients.

Growth arrest-specific 5 (GAS5) insertion/deletion polymorphism and cancer susceptibility in Asian populations: A meta-analysis.

BACKGROUND: Previous studies have reported the association of an insertion/deletion (Ins/Del) polymorphism (rs145204276 AGGCA/-) in the promoter region of growth arrest-specific 5 (GAS5) with the risk of cancer, such as breast cancer, gastric cancer, and hepatocellular carcinoma. However, the results are still controversial. We aimed to clarify the association of GAS5 rs145204276 polymorphism with cancer risk by meta-analysis. METHODS: PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and Cochrane Library were searched for studies concerning GAS5 and cancer published up to November 25, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate cancer risk. RESULTS: A total of 12 case-control studies with 8729 cases and 10,807 controls were included in this meta-analysis. We found that the GAS5 rs145204276 polymorphism was not significantly associated with cancer risk (Del vs Ins: OR = 0.96, 95% CI: 0.81-1.13; Del/Del vs Ins/Ins: OR = 1.00, 95% CI: 0.70-1.43; Ins/Del vs Ins/Ins: OR = 0.92, 95% CI: 0.78-1.08; Ins/Del and Del/Del vs Ins/Ins: OR = 0.93, 95% CI: 0.76-1.13; Del/Del vs Ins/Del and Ins/Ins: OR = 1.04, 95% CI: 0.78-1.38). In the stratified analyses, significant effects on gastric cancer were found (Del vs Ins: OR = 0.79, 95% CI: 0.72-0.86; Del/Del vs Ins/Ins: OR = 0.65, 95% CI: 0.52-0.82; Ins/Del vs Ins/Ins: OR = 0.76, 95% CI: 0.68-0.86; Ins/Del + Del/Del vs Ins/Ins: OR = 0.74, 95% CI: 0.66-0.83; Del/Del vs Ins/Ins + Ins/Del: OR = 0.74, 95% CI: 0.59-0.91). CONCLUSION: Our meta-analysis showed that GAS5 rs145204276 polymorphisms were not related to overall cancer risk. However, the GAS5 rs145204276 polymorphism may be a protective factor for gastric cancer in the stratification analyses.

Efficacy of circulating microRNA-130b and blood routine parameters in the early diagnosis of gastric cancer.

Patients with gastric cancer (GC) have a poor prognosis, which is mainly due to the low rate of early diagnosis. The present study aimed to evaluate whether circulating microRNA-130b (miR-130b) and blood routine parameters [neutrophil count (N#), lymphocyte count (L#), monocyte count (M#), neutrophil percentage (N%), lymphocyte percentage (L%), monocyte percentage (M%), hemoglobin (Hb) level, hematocrit (Hct), red blood cell distribution width (RDW), platelet count, platelet distribution width (PDW), mean platelet volume (MPV), MPV to platelet count ratio (MPV/PC), monocyte to lymphocyte ratio (MLR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR)] are useful biomarkers for GC, early stage GC (EGC) and precancerous lesion (Pre) detection, and to identify more effective diagnostic models by combining circulating blood markers. Circulating levels of M#, M%, RDW-coefficient of variation (RDW-CV), MPV, PDW, MLR and NLR were significantly higher, and the levels of Hb and L% were significantly lower in patients with GC and Pre compared with those in healthy controls (NCs) (all P<0.05). The N#, N% and PLR in patients with GC were significantly higher and the Hct was significantly lower than those in the NCs (all P<0.05). The values of MPV/PC were significantly higher in the Pre cohort compared with those in the NCs. The area under the curve (AUC) of the receiver operating characteristic curve of potential biomarkers for GC was 0.634-0.887 individually, and this increased to 0.978 in the combination model of miR-130b-PDW-MLR-Hb. Additionally, the values for RDW-CV, PLR, NLR, N# and N% were positively correlated with cancer stage, while the values for MPV, L#, L%, Hb and Hct were negatively correlated with cancer stage. Furthermore, the circulating levels of miRNA-130b, and the values for NLR, RDW-CV, PDW, M%, red blood cell count, Hct, Hb and MLR differed between the EGC and NC groups. The AUC values of these biomarkers were 0.6491-0.911 individually in the diagnosis of EGC, and these increased to 0.960 in combination. In addition, the AUC values for miR-130b, RDW-CV, MPV/PC ratio, MLR, NLR, PDW, L%, M%, M# and Hb in the diagnosis of Pre were 0.638-0.811 individually. The dual-model of miR-130b-PDW manifested the largest AUC of 0.896 in the diagnosis of Pre, and the sensitivity and accuracy were increased when miR-130b and PDW were combined. All these results suggested that circulating miR-130b and blood routine parameters might be potential biomarkers, and combinations of measurements of these biomarkers may improve the GC, EGC and Pre diagnostic accuracy.

Combined effects of berberine and evodiamine on colorectal cancer cells and cardiomyocytes in vitro.

Chemotherapy induces inevitable adverse effects, while complementary and alternative medicine employs many chemical substances. Herb pairs normally contain two herbal medicines, and they have satisfactory effects on cancer therapy. Zuojinwan, a well-known herb pair, is composed of Coptidis Rhizoma and Euodiae Fructus. Berberine and evodiamine are considered the most important compounds in the Zuojinwan herb pair. Previous reports have shown that combined use of evodiamine and berberine displays synergistic anticancer activities in various types of cancers, but this combination has not been tested in colorectal cancer. Hence, this study aimed to explore the combined effects of evodiamine and berberine on colorectal cancer cell lines and cardiomyocytes. We found that the combination of berberine and evodiamine showed synergistic anticancer activity in P-glycoprotein (P-gp)-positive colorectal cancer cells through attenuating the overexpression of P-gp mRNA independent of cell cycle arrest and cell apoptosis. However, berberine did not increase the cytotoxicity of evodiamine in normal human colon mucosal epithelial cells. Furthermore, berberine attenuated evodiamine-induced cardiotoxicity by regulating extrinsic apoptosis via nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent and reactive oxygen species-independent pathways. Therefore, we suggest that the combination of berberine and evodiamine displays high anticancer activity while reducing the side effects in specific cell lines.

High Prevalence of Vitamin D Deficiency in Pregnant Women in South China.

Objective: To investigate the vitamin D status of pregnant women in the Liuzhou area and assess the effects of maternal vitamin D status on the cord blood of their newborns. Subjects and methods: This study included 8852 pregnant women and 2000 newborns. The serum 25-hydroxyvitamin D [25(OH)D] levels of the 8852 pregnant women and the cord blood of 2000 newborns were measured. Results: The results showed that the average level of 25(OH)D in pregnant women in this area was 76.55 nmol/L, and women in different trimesters had different vitamin D levels (p < 0.001). The overall prevalence of vitamin D deficiency (<75 nmol/L) in pregnant women was 62.34%, and the proportion of severe deficiency (<25 nmol/L) was 0.25%. Vitamin D deficiency was more prevalent in the winter and spring than in the summer and autumn (p < 0.001). Pregnant women who had regular vitamin D supplementation had higher levels of 25(OH)D than the women with discontinuous supplementation or no supplementation (p < 0.001). Conclusions: Vitamin D deficiency was prevalent in pregnant women in the Liuzhou area. There were differences in vitamin D levels between the three trimesters and different seasons. For pregnant women with vitamin D deficiency, it is important to scientifically determine the appropriate level of vitamin D supplementation to ensure the health of mothers and babies.

Comparison of Architect i2000sr and Cobas e601 Systems for Determining Serum Human Chorionic Gonadotropin-Beta.

BACKGROUND: Human chorionic gonadotropin-beta (ß-hCG) is an important index used to monitor embryonic development following embryo transfer. Architect i2000sr and Cobas e601 are widely used automated immunoassay systems used to measure serum ß-hCG concentrations; however, the correlations between serum ß-hCG levels measured with these two immunoassays and the accuracy of the immunoassays have not been fully evaluated. METHODS: Serum ß-hCG levels were measured in 133 serum samples using the Architect i2000sr and Cobas e601 automated immunoassay systems. Passing-Bablok regression analysis was used to compare the correlation in serum ß-hCG levels obtained using the two immunoassays. A Bland-Altman plot analysis was used to identify mean ratios and 95% CIs of the mean ratios of the ß-hCG results between the two immunoassays. In this graphical method the mean ratios between the two techniques were plotted against the averages of the two techniques. RESULTS: The total coefficients of variations (CVs) of serum ß-hCG ranged from 3.12 - 4.66% for Cobas e601 and 3.18 - 4.99% for Architect i2000sr. The measured value of serum ß-hCG detected by the two immunoassays was statistically significant (p < 0.001). The Passing-Bablok regression analysis showed good correlation between the serum ß-hCG values measured using the two systems. At a low concentration of serum ß-hCG (< 10000 IU/L, n = 52), the correlation coefficient r was 0.9628. At a high concentration of serum ß-hCG (> 10000 IU/L, n = 81), the correlation coefficient r was 0.8076. The Bland-Altman plot analysis showed that the measured value of serum ß-hCG detected by Architect i2000sr was about 1.25 times higher than that of Cobas e601. The mean ratio was 1.12 at a low concentration of serum ß-hCG, and it was 1.33 at a high concentration. CONCLUSIONS: Architect i2000sr and Cobas e601 have good concordance for determining serum ß-hCG. However, the ß-hCG values measured with Architect i2000sr were 25% higher than those obtained using Cobas e601.