Curcumin inhibits colon cancer malignant progression and promotes T cell killing by regulating miR-206 expression.

Colon cancer is a great threat to human health. Curcumin, as a traditional Chinese medicine extract with anti-tumor and anti-inflammatory effects, can affect the development of diverse human diseases including cancer. The aim of this research was to probe the mechanism by which curcumin regulates colon cancer progression. Colon cancer cells were processed with graded concentrations of curcumin. The proliferation and apoptosis of the treated cells were determined by MTT, colony formation assay and flow cytometry. Expression of signaling pathway-related proteins and programmed death-ligand 1 (PD-L1) was measured by western blotting. The effect of curcumin on tumor cell growth was verified through T cell-mediated killing and ELISA assays. The relationship between target gene expression and the survival rate of colon cancer patients was analyzed by a survival curve. Curcumin treatment restrained proliferation and accelerated apoptosis of colon cancer cells. It elevated miR-206 expression, which in turn affected colon cancer cell function. miR-206 enhanced colon cancer cell apoptosis and inhibited PD-L1 expression; thus, curcumin enhanced the killing effect of T cells on tumor cells by suppressing PD-L1 through inhibiting the JAK/STAT3 pathway. Patients with high expression of miR-206 had better survival rates than those with low expression. Curcumin can regulate miR-206 expression and inhibit the malignant behavior of colon cancer cells and enhance T cell killing through the JAK/STAT3 pathway.

Triamcinolone acetonide suppressed scar formation in mice and human hypertrophic scar fibroblasts in a dose-dependent manner.

A hypertrophic scar is a complex medical problem. The study of triamcinolone acetonide for the treatment of scars is necessary. The 7mm full-thickness skin wounds were created on the back of BALA/c mice to construct the animal scar model. The different doses of triamcinolone acetonide injection or normal saline were injected into the wound on the 15th, 30th and 45th day after the operation. The skin histopathological changes of mice were observed by Hematoxylin-Eosin (H&E) staining. The proteins and mRNA expression level of scar-biomarkers (COL1, COL3, α-SMA) in mice scar tissue were detected by western blot and qRT-PCR. Besides, the effect of triamcinolone acetonide on the proliferation, invasion, and migration of human hypertrophic scar fibroblast (hHSFs) in vitro was also explored by cck-8, transwell and wound healing assays. After triamcinolone acetonide was injected into the wound, the proportion of scar was significantly reduced, and the treatment effect was concentration-dependently. H&E staining showed that the skin histopathological of mice was improved dose-dependently after injecting the low/middle/high-dosage of triamcinolone acetonide. The proteins and mRNA expression levels of COL1, COL3, and α-SMA were reduced dose-dependently in mice scar tissue. Furthermore, triamcinolone acetonide dose-dependently suppressed the proliferation, invasion, and migration of hHSFs in vitro. Together, triamcinolone acetonide suppressed scar formation in mice and human hypertrophic scar fibroblasts in a dose-dependent manner, phenotypically and mechanistically. The research and further exploration of triamcinolone acetonide in treating scar formation may find new effective treatment methods for the scar.

[Prediction model of mid-term fatality risk after radical resection in patients with hepatocellular carcinoma based on ALBI-grade].

OBJECTIVE: To establish a clinical prediction model of the mid-term fatality risk after radical resection in patients with primary hepatocellular carcinoma (HCC) based on the albumin-bilirubin (ALBI) grade and to assess its prediction value. METHODS: Clinical data of 533 patients who received HCC radical resection in Jinhua Hospital of Zhejiang University, Jinhua People's Hospital, Jinhua Hospital of Traditional Chinese Medicine and Jinhua Guangfu Hospital from January 2010 to August 2016 were retrospectively reviewed. In the training group ( n=407), Cox model was used to screen the clinical risk factors of postoperative death, and a predictive model based on ALBI grade was established and then examined in the validation group ( n=126). The value of the prediction model was assessed by ROC curve and calibration curve; the prediction results of the model were visualized by the nomogram for the convenience of clinical use. RESULTS: Cox model showed that ALT ≥ 80 U/L, tumor maximum diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 were independent risk factors for the prognosis of patients with HCC radical resection. The prognosis index (PI) was 0.550×ALT+0.512×ALBI grade+0.872×maximum tumor diameter+1.377×portal vein tumor thrombus. The AUCs for predicting the risk of death in 12, 36 and 60 months were 0.872, 0.814 and 0.810, respectively (all P < 0.01), and the goodness of fit ( r 2) of the established model were 0.953, 0.976 and 0.994. AUC of the established model for predicting risk of death in 36 months after resection was 0.814, which was higher than those of ALBI (AUC=0.683), BCLC (AUC=0.713), CLIP (AUC=0.689), Child-Pugh (AUC=0.645), TNM (AUC=0.612) ( P < 0.05 or P < 0.01). CONCLUSIONS: ALT ≥ 80 U/L, maximum tumor diameter ≥ 5 cm, portal vein tumor thrombus and ALBI grade 2 are independent risk factors of patients after HCC resection, and ALBI grade-based prediction model is satisfactory in prediction of mid-term death risk of the patients.

Activation of Glycolysis by MCM10 Increases Stemness and Paclitaxel Resistance in Gastric Cancer Cells.

BACKGROUND/AIMS: Chemotherapy is an essential avenue for curing malignancies; however, tumor cells acquire resistance to chemotherapeutic agents, eventually leading to chemotherapy failure. At present, paclitaxel (PTX) resistance seriously hinders the therapeutic efficacy of gastric cancer (GC). Investigating the molecular mechanism of PTX resistance in GC is critical. This study attempted to delineate the impact of MCM10 on GC resistance to PTX and its mechanism in GC. MATERIALS AND METHODS: The expression of minichromosome maintenance complex component 10 (MCM10) in GC tissues, its enrichment pathways, and its correlation with glycolysis marker genes and stemness index (mRNAsi) were analyzed in a bioinformatics effort. Real-time quantitative polymerase chain reaction was used to assay the expression of MCM10 in cells. Cell counting kit-8 (CCK-8) was used to analyze cell viability and calculate the 50% inhibitor concentration (IC50) value. Western blot was used to measure the expression of MCM10, Hexokinase 2 (HK2) and stemness-related factors in cells. Sphere-forming assay was performed to study cell sphere-forming ability. Seahorse XF 96 was utilized to measure cell extracellular acidification and oxygen consumption rates. The content of glycolysisrelated products was tested with corresponding kits. RESULTS: MCM10 was significantly upregulated in GC and enriched in the glycolysis pathway, and it was positively correlated with both glycolysis-related genes and stemness index. High expression of MCM10 increased sphere-forming ability of drug-resistant cells and GC resistance to PTX. The stimulation of PTX resistance and drug-resistant cell stemness in GC by high MCM10 expression was mediated by the glycolysis pathway. CONCLUSION: MCM10 was upregulated in GC and drove stemness and PTX resistance in GC cells by activating glycolysis. These findings generated new insights into the development of PTX resistance in GC, implicating that targeting MCM10 may be a novel approach to improve GC sensitivity to PTX chemotherapy.

Predictive Value of Preoperative Dynamic Contrast-Enhanced MRI Imaging Features in Breast Cancer Patients with Postoperative Recurrence Time.

Although the implementation of surgery has reduced the mortality of breast cancer, postoperative recurrence is still an important problem bothering patients. DCE-GMRI can not only clearly display the morphological characteristics of breast lesions but also dynamically observe the blood perfusion of the lesions. On account of this, we explored the predictive value of preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) imaging features in breast cancer patients on postoperative recurrence time of breast cancer. The results showed that DCE-MRI images can clearly show the hemodynamic characteristics and morphological characteristics of tumor lesions, and have important value in predicting the recurrence time of breast cancer after surgery. The prognosis of early recurrence of breast cancer is worse. DCE-MRI can predict the time of postoperative recurrence and provide important clinical references.

Primary ascending colon cancer accompanying skip metastases in left shoulder skin and left neck lymph node: A case report.

BACKGROUND: Lymph node skip metastases are common in lung, breast, and thyroid cancer patients, but are rare in colon cancer patients. Specifically, lymph node skip metastases occur in 1%-3% of colon cancer patients. Previous reports have demonstrated colon cancer skip metastases involving the retropancreatic and portocaval lymph nodes and Virchow's node; however, reports involving skip metastases into the left neck lymph nodes and left shoulder skin are extremely rare, as are related reports of clinical treatment and prognosis. CASE SUMMARY: A 44-year-old Chinese man was admitted to the hospital for evaluation of persistent shoulder pain for 3 d and a cutaneous mass (3.0 cm × 2.0 cm) on the left shoulder. The left shoulder cutaneous mass was excised and bisected, revealing tissues with a fish-like appearance. The pathologic diagnosis of the cutaneous mass suggested a signature [CDX-2 (++), CK20 (++), Ki-67 (+) > 50%] of infiltrating or metastatic colorectal adenocarcinoma. An enhanced computed tomography scan of the abdomen revealed chronic appendicitis with fecal stone formation, cecal edema, and a pelvic effusion. A colonoscopy revealed a cauliflower-like mass within the ascending colon area that involved the lumen. The surface of the ascending colon mass was eroded and bleeding; a biopsy was performed. The pathologic diagnosis of the colonoscopy biopsy was an ascending colon mucinous adenocarcinoma. The patient underwent a laparoscopic radical resection of the right colon based on the pathological diagnosis. The tumor was 5.0 cm × 4.5 cm × 1.8 cm in size and infiltrated the entire thickness of the intestinal wall with vascular tumor thrombi. No nerve tissue involvement was noted. The ileum and colon resection margins were negative. The postoperative pathologic analysis revealed non-metastatic involvement of ileocecal, pericolic, or peri-ileal lymph nodes. The postoperative medical examination revealed palpably enlarged lymph nodes in the left neck, and the following color Doppler ultrasound examination of the neck confirmed enlarged lymph nodes in the left neck. After surgical resection and pathologic diagnosis, a common pathologic signature consistent with resected cutaneous mass and right colon was identified, suggesting skip metastasis of left cervical lymph nodes. The patient was then treated with eight courses of chemotherapy and under follow-up evaluations for 4 years; currently, no tumor recurrences or metastases have been noted. CONCLUSION: We report an abnormal skip metastasis involving the left shoulder skin and left neck lymph node in a patient with ascending colon adenocarcinoma. Specifically, we observed non-metastatic involvement of the lymph nodes around the tumor site but with metastases to the cervical lymph nodes. The standard surgical operations were performed to resect the cutaneous mass, tumor tissue, and cervical lymph nodes, followed by chemotherapy for eight courses. The patient is healthy with no tumor recurrences or metastases for 4 years. This clinical case will contribute to future research about the abnormal skip metastasis in colon cancers and a better clinical treatment design.

Clinical outcomes of laparoscopic versus open right hepatectomy for liver tumors: A meta-analysis.

BACKGROUND: Laparoscopic right hepatectomy (LRH) is one of the most challenging procedures. Right liver resections have been always performed in open procedure and open right hepatectomy (ORH) was initially considered as routine way. Moreover, it is unclear how beneficial the minimally invasive technique is to patients; thus, we conducted a meta-analysis to acquire a more reliable conclusion about the feasibility and safety of LRH compared with ORH. METHODS: We comprehensively searched the electronic databases of PubMed, Embase, and the Cochrane Library using the key words. Meta-analysis was performed using the Review Manager, with results expressed as odds ratio and weighted mean difference with 95% confidence intervals. The fixed-effect model was selected initially if high heterogeneity was not present between the studies; otherwise, the randomized-effect model was used. Subgroup analysis was performed based on different surgical methods of pure laparoscopic operation or hand-assisted operation. RESULTS: Seven studies with 467 patients were included. In the overall analysis, less intraoperative blood loss (MD = -155.17; 95% CI, -238.89, -71.45; P = .0003) and a shorter length of stay (MD = -4.45; 95% CI, -5.84, -3.07; P < .00001) were observed in the LRH group compared to the ORH group. There were fewer overall complications (OR = 0.30; 95% CI, 0.10, 0.90; P = 0.03) and severe complications (OR = 0.24; 95% CI, 0.10, 0.58; P = .002;) in the LRH group than in the ORH group. The disadvantage of LRH was the longer operative time (MD = 49.39; 95% CI, 5.33, 93.45; P = .03). No significant difference was observed between the 2 groups in portal occlusion, rate of R0 resection, transfusion rate, mild complications, and postoperative mortality. In the subgroup analysis, intraoperative blood loss was significantly lower in the pure LRH group and hand-assist LRH group compared with ORH group. Length of stay was shorter by use of pure LRH and hand-assisted LRH manners than ORH. The incidence rate of complications was lower in the pure LRH group than in the ORH group. In contrast, there was no significant difference between hand-assisted LRH group and ORH group. CONCLUSION: Compared to ORH, LRH has short-term surgical advantages and leads to a shorter recovery time in selected patients. We speculate that the operative time of LRH is closer with ORH. Overall, LRH can be considered a feasible choice in routine clinical practice with experienced surgeons, although more evidence is needed to make a definitive conclusion.