Summary Advanced hepatocellular carcinoma has a poor therapeutic outcome and treatment options are limited. Sorafenib, an orally active multikinase inhibitor, is the only systemic drug that has been shown to provide survival benefits in randomized control studies. However, the gains in survival are modest and new treatment strategies are needed. We report here the case of a patient with advanced hepatocellular carcinoma who had an impressive response to a combination of sorafenib and radiotherapy. The treatment was well tolerated with no unexpected toxicities. Post‐treatment imaging showed a satisfactory partial response with regression of the tumor by more than 50%.
Chronic hepatitis B (CHB) leads to liver inflammation and dysfunction, resulting in liver fibrosis and cancer. Nucleos(t)ide analogues (NAs), inhibitors of hepatitis B virus (HBV), specifically suppress HBV replication. We proposed that immune modulation benefits seroconversion by HBsAg loss. However, activation of T lymphocytes also deteriorates hepatic inflammation. Therefore, we intended to investigate the T cell status and its relationship with hepatic functions in CHB patients treated with NAs. Serum markers, including liver function markers AST, ALT, and HBV-infected markers HBV DNA, HBsAg, HBeAg, and HBsAb were measured in the clinical routine. The T cell levels and markers, including CD69, CD107a, CXCR3, and PD-1 were investigated using flow cytometry. Meanwhile, IFNγ, IL-2, and CXCL10 as immune activation markers in the PBMCs were investigated using qPCR. To validate the effects of NAs on T cell status, qPCR and flow cytometry were used to investigate the gene expression in the HepG2 and PLC5 cells treated with NAs, and in the healthy PBMCs treated with the cell-cultured supernatant. We found that NAs significantly suppressed HBV DNA and reduced AST and ALT levels in the CHB patients. Meanwhile, AST and ALT were both positively correlated with activation marker CD107a in CD8
Abstract STAT3 is a transcriptional factor involved in tumorigenesis and the initiation of cancer stemness property. However, the STAT3‐downstream regulatory gene expressions in the formation of colorectal cancer (CRC)‐derived tumorsphere is obscure. In this study, RNAseq was used to uncover the potential genes involved in the formation of colorectal HCT116‐ and HT29‐derived stem‐like tumorspheres, whereas HCT116 and HT29 overexpressed CD133. Furthermore, STAT3 was knockdowned and analyzed consequently by RNAseq for picking up the STAT3‐mediated genes associated with tumorspheres formation. Then, quantitative polymerase chain reaction was used for validating the expressions of selected driver genes in epidermal growth factor (EGF) treated‐ and in STAT3‐knockdowned HT29 cells. We found that 654 genes and 646 genes were upregulated in HCT116‐ and HT29‐derived tumorspheres, respectively. There were 103 genes simultaneously increased in both CRC tumorspheres, including, STAT3 selected as a driver gene by NetworkAnalyst ( https://www.networkanalyst.ca/ ). Moreover, there were 139 genes downregulated in HT29shSTAT3 cells compared to HT29shLuc cells, 12 of the genes were overlapped with the overexpressed 103 genes from tumorspheres, including, NDRG1 , ALDOC , BHLHE40 , ATF3 , C6orf223 , JUND , ERRFI1 , HK2 , ITPKA , PLOD2 , IDI1 , and S100A14 . Among them, BHLHE40 , ATF3 , ERRFI1 , ITPKA , and S100A14 were validated and induced by EGF treatment, that were, otherwise, decreased in HT29shSTAT3 cells. We found and validated that STAT3 mediated the formation of CRC stemness tumorspheres, and STAT3‐downstram BHLHE40 , ATF3 , ERRFI1 , ITPKA , and S100A14 may be involved in the stemness property.
In the past 12 years, 12 patients with histologically proven ectopic pancreas were detected in the Tri-Service General Hospital. Distribution of the ectopic pancreatic tissue were 7 in the stomach, 1 in duodenal bulb, 1 in the 2nd portion of duodenum, 2 in the jejunum and 1 in the mesentery. There were seven males and five females. Their ages ranged from 3 days to 71 years old with a mean age of 36.1 years. Preoperative upper gastrointestinal (UGI) panendoscopy were performed in 9 cases. Characteristic central umbilicated submucosal lesion were found in 4 cases, while the other 5 cases presented with a submucosal tumor without central umbilication. The remaining three patients were incidentally found during laparotomy. Although endoscopic ultrasonography may differentiate submucosal tumor from external compression, it cannot differentiate the nature of various submucosa tumors, such as adenomyoma, carcinoid, neurofibroma and ectopic pancreas. Our analysis showed that ectopic pancreas might be correctly diagnosed preoperatively by UGI panendoscopic study when it presented with a characteristic central umbilication. On the other hand, if the lesion presented without central umbilication, definite preoperative diagnosis may be difficult.
Abstract We proposed that cancer stem cells (CSCs) survived and presented resistance to radiotherapy (RT) in hepatocellular carcinoma (HCC) cells. Interleukin 6 (IL‐6) has been reported to be particularly involved in HCC tumorigenesis. Therefore, we intended to validate that IL‐6 downstream STAT3‐mediated CSCs formation and immune checkpoint PD‐L1 expression in HCC, thus contributing to radioresistance. HBV‐positive HCC tumorspheres were formed and exposed with X‐ray irradiation, cell viability of which was measured consequently. Specific inhibitors targeting EGFR (by gefitinib), STAT3 (by BBI608), and HCC‐targeted therapy sorafenib were investigated to suppress tumorsphere formation. Reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) was used for detecting STAT3‐downstream PD‐L1 and anti‐apoptosis MCL1 and BCL2 gene expression in the PLC5‐derived tumorspheres and STAT3‐knockdown PLC5. We found that RT significantly inhibited HBV‐positive Hep3B and PLC5 cell viability but not for HCC‐derived stem‐like tumorspheres cultured by EGF, IL‐6, bFGF, and HGF. It revealed that tumorspheres presented radioresistance compared with the parental cells. Specifically, RT induces IFNs, EGF, and IL‐6 expression, resulting in STAT3 phosphorylation. Kaplan–Meier plotter indicated that highly EGF ( p = .0024), IL‐6 ( p = .12), and FGF2 ( p = .0041) were associated with poor survival probability in patients with HBV‐positive HCC. We further demonstrated that BBI608 and sorafenib significantly suppressed PLC5 cell viability and PLC5‐derived tumorsphere formation. To investigate the mechanism of CSC‐presented radioresistance, STAT3 and STAT3‐downstream genes, including PD‐L1 and anti‐apoptosis MCL1 and BCL2, were detected using qPCR. We demonstrated higher STAT3, PD‐L1, MCL1, and BCL2 in Hep3B‐ and PLC5‐derived CSCs compared to PLC5. In addition, knockdown of STAT3 reduced cell proliferation in PLC5 cells, resulting in down‐regulation of IL‐6‐mediated PD‐L1 and BCL‐2. Meanwhile, we found that knockdown of STAT3 significantly improved RT‐mediated suppression of tumorsphere formation. In conclusion, we found that CSCs presented radioresistance and figured out which may be mediated by STAT3 in HBV‐positive HCC.
The aim of this study was to investigate whether Hirsutella sinensis mycelium (HSM) has any antifatigue effect, using a forced swimming model in rats. Forty rats were randomly divided into five groups, each containing eight animals. The control group received 2 ml/kg body weight of distilled water and a positive control group was administered 1.13 ml/kg Quaker Essence of Chicken. The treated swimming groups were administered HSM powder manufactured by Chang Gung Biotechnology Corporation, Ltd., at doses of 63 mg/kg, 189 mg/kg or 378 mg/kg body weight/day, respectively for a period of six weeks. The above experiment was repeated with another 40 rats but for a period of eight weeks. At the end of the experiments, rats were placed in a swimming apparatus and the total swimming time until exhaustion was recorded. Pre-/post-exercise concentrations of serum urea nitrogen (BUN) and lactic acid were also determined. There were no deaths during the study. Physical and behavioral examinations did not reveal any treatment-related adverse effects after dosing. Changes in lactate levels were dose-dependent for the 8- but not the 6-week treatment. BUN levels were more affected by the 8-week treatment of HSM but not significantly altered in the 6-week treatment groups. The 8-week treatment groups showed a significant increase in swimming time to exhaustion compared to the control groups, which was not dose-dependent. For the 6-week treatment, only the middle and high doses increased swimming time to exhaustion. Conjugated diene contents were significantly higher in rats treated at any HSM dose for 8-weeks than the control groups. Swimming did not alter levels of liver glycogen when compared to the control sub-groups. Results of this study demonstrate that HSM improves physical endurance, which may be beneficial in treating conditions where fatigue is a factor and other antifatigue treatments are contraindicated.
Background Fetuin-A and leukocyte cell-derived chemotaxin-2 (LECT-2) are liver-derived proteins. Fetuin-A is an independent risk factor for type 2 diabetes (T2D) and obese patients with T2D have higher plasma fetuin-A levels than those without T2D. LECT-2 has positive correlation with the severity of both obesity and insulin resistance. The changes in plasma fetuin-A are not consistent after bariatric surgery and no studies have investigated the changes in LECT-2 on the obese patients with T2D after bariatric surgery. Methods Overall, 18 patients undergoing gastric bypass (GB) and 16 patients undergoing sleeve gastrectomy (SG) were enrolled. The fasting plasma fetuin-A and LECT-2 levels were measured at baseline, one week, three months, and one year after surgery. Results Both the GB and SG groups significantly decreased the body mass index (BMI), waist-to-hip ratio, a body shape index; the triglyceride, fasting blood sugar (FBS), hemoglobin A1c, C-peptide levels; and homeostatic model assessment (HOMA-IR) one year after surgery. The SG group showed a decreasing trend in plasma fetuin-A levels one year after SG surgery. There are no significant changes in LECT-2 one year after either GB or SG. Fetuin-A had a near significant negative relationship with insulin ( P = 0.056) and HOMA-IR ( P = 0.050) in the SG group. Changes in fetuin-A had a significant positive relationship with changes in BMI ( P = 0.031) and waist-to-hip ratio ( P = 0.031) in the GB group and had a near significant positive correlation with FBS ( P = 0.051) in the SG group. Discussion Neither GB nor SG modifies plasma levels of plasma fetuin-A or LECT-2 in T2D patients after surgery. The changes in plasma fetuin-A have a positive correlation with those of the BMI and waist-to-hip ratio 12 months after GB.
Background The promising postsurgical weight loss and remission of type 2 diabetes (T2D) from bariatric surgery can be attributed to modified eating physiology after surgical procedures. We sought to investigate the changes in the parameters of consumption behaviors and appetite sensations induced by a mixed meal tolerance test, and to correlate these alterations with age, body mass index, C-peptide levels, and duration of T2D 1 year after bariatric surgery. Methods A total of 16 obese patients with T2D who underwent mini-gastric bypass (GB) and 16 patients who underwent sleeve gastrectomy (SG) were enrolled in this study and evaluated using a mixed meal tolerance test one year after surgery. A visual analogue scale was used for scoring appetite sensation at different time points. The area under the curve (AUC) and the incremental or decremental AUC (ΔAUC) were compared between the two groups. Results One year after surgery, a decreasing trend in the consumption time was observed in the GB group compared to the SG group, while the duration of T2D before surgery was negatively correlated with the post-operative consumed time in those after GB. Patients who underwent GB had significantly higher fasting scores for fullness and desire to eat, higher AUC 0′–180′ of scores for desire to eat, as well as more effective post-meal suppression of hunger and desire to eat compared with those undergoing SG one year after surgery. Post-operative C-peptide levels were negatively correlated with ΔAUC 0′–180′ for hunger and ΔAUC 0′–180′ for desire to eat in the GB group, while negatively correlated with ΔAUC 0′–180′ for fullness in the SG group. Discussion Patients with T2D after either GB or SG exhibit distinct nutrient-induced consumption behaviors and appetite sensations post-operatively, which may account for the differential effects on weight loss and glycemic control after different surgery.
Background: Hepassocin is a liver-derived protein and its serum concentrations significantly increase in diabetes and fatty liver patients. Hepassocin is also a biomarker for diabetes and fatty liver; therefore, we aimed to investigate the impacts of different types of bariatric surgery on hepassocin plasma levels in obese patients with diabetes, and to determine if hepassocin could be a potential new marker for monitoring the effects of bariatric surgery and a treatment target. Methods: Overall, 12 patients undergoing gastric bypass (GB), 10 patients undergoing sleeve gastrectomy (SG) and 11 patients undergoing duodeno-jejunal bypass with sleeve gastrectomy (DJB-SG) were enrolled. Fasting hepassocin levels were measured at baseline, three, 12, and 24 months after surgery. Results: All the three groups significantly decreased their body mass index, waist-to-hip ratio, a body shape index (ABSI), triglycerides, fasting blood sugar, hemoglobin A1c, C-peptide levels and homeostasis model assessment of insulin resistance 24 months after surgery. There were no significant changes in hepassocin levels, even 24 months after the three surgeries. Hepassocin had a significant negative relationship with the ABSI (p< 0.001) 24 months after the SG. Conclusions: Neither GB, SG, nor DJB-SG altered plasma hepassocin levels in diabetic patients up to 24 months after surgery. The use of hepassocin in clinical settings requires more investigation.
Benign pancreatic hyperenzymemia, or Gullo's syndrome, is an uncommon syndrome characterized by a long-term increase of serum pancreatic enzyme in the absence of pancreatic diseases. It is primarily discovered incidentally and occurs in either sporadic or familial form. Herein, we report the first case of benign pancreatic hyperenzymemia in Taiwan. A 57-year-old Chinese male was incidentally noted with elevated serum amylase and lipase levels during a health check-up and was diagnosed with benign pancreatic hyperenzymemia using a series of image and serological tests. Although this is the first case of benign pancreatic hyperenzymemia in Taiwan, its prevalence may be underestimated due to the diagnostic difficulties. Correct diagnosis of this disease is important to avoid costly test duplication, unfounded anxieties, and multiple consultations.
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