LC-MS/MS method for the quantification of cortisol of hepatocellular carcinoma.

The imbalance of steroid hormones is closely related to the occurrence and development of hepatocellular carcinoma (HCC). However, most research has focused on steroid hormone receptors, and reports about the relationship between the serum concentration of cortisol and the development of HCC are rare. The aim of this research was to establish a simple, specific, sensitive and reliable liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for the quantitation of cortisol in human serum and to compare the level of cortisol in serum between 221 HCC patients and 183 healthy volunteers. The results showed that the correlation coefficients of the linear regression with a weighing factor of 1/x2 ranged from 0.9933 to 0.9984 over the range of 2-1,000 ng/ml. The inter- and intra-day precision and accuracy were <10%. The matrix effect and recovery of cortisol were 94.9-102.5% and 96.3-99.8%, respectively. The concentration of cortisol in HCC patients was significantly higher than that in healthy volunteers (p < 0.05) and was not affected by sex, age, menopause or α-fetoprotein (AFP) level. The present study reveals that elevated cortisol might promote the progression of HCC.

The efficacy and safety of neoadjuvant immunotherapy in resectable locally advanced esophageal squamous cell carcinoma: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to explore the efficacy and safety of neoadjuvant immunotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). Background: Several studies have reported the outcomes of neoadjuvant immunotherapy in patients with ESCC. However, phase 3 randomized controlled trials (RCTs) with long-term outcomes and the comparison of different therapeutic strategies are lacking. Methods: Studies involving patients with advanced ESCC treated with preoperative neoadjuvant immune checkpoint inhibitors (ICIs) were searched through PubMed, Embase, and Cochrane Library up to July 1, 2022. The outcomes were presented as proportions and pooled respectively by fixed or random effect model depending on the heterogeneity between studies. All analyses were performed using the R packages meta 5.5-0 and meta-for 3.4-0. Results: Thirty trials involving 1406 patients were included in the meta-analysis. The pooled pathological complete response (pCR) rate for neoadjuvant immunotherapy was 0.30 (95% confidence interval [CI]: 0.26-0.33). The pCR rate of neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) was significantly higher than that of neoadjuvant immunotherapy combined with chemotherapy (nICT) (nICRT: 0.48, 95% CI: 0.31-0.65; nICT: 0.29, 95% CI: 0.26-0.33; p=0.03). No significant difference in efficacy was observed between the different chemotherapy agents and treatment cycles. The incidences of grade 1-2 and 3-4 treatment-related adverse events (TRAEs) were 0.71 (95% CI: 0.56-0.84) and 0.16 (95% CI: 0.09-0.25), respectively. Patients treated with nICRT and carboplatin had a higher incidence of grade 3-4 TRAEs compared with those treated with nICT (nICRT: 0.46, 95% CI: 0.17-0.77; nICT: 0.14, 95% CI: 0.07-0.22; p=0.03) and cisplatin (carboplatin: 0.33, 95% CI: 0.15-0.53; cisplatin: 0.04, 95% CI: 0.01-0.09; p<0.01). Conclusion: Neoadjuvant immunotherapy has good efficacy and safety profiles in patients with locally advanced ESCC. Additional RCTs with long-term survival data are warranted.

Complete Response to PD-1 Inhibitor in Primary Hepatocellular Carcinoma Patients Post-Progression on Bi-Specific Antibody Conjugated CIK Cell Treatment: A Report of Two Cases.

BACKGROUND: Programmed death receptor-1 (PD-1) immune checkpoint inhibitors (ICIs) have produced encouraging results in hepatocellular carcinoma (HCC) patients. Cytokine-induced killer (CIK) cells treatment can specifically identify tumor-associated antigens and has encouraging preliminary efficacy for HCC. This study reported two cases of HCC patients achieved complete response (CR) by anti-PD-1 antibody therapy post-progression on bi-specific antibody conjugated CIK immunotherapy. CASE PRESENTATION: Case one, a 75-year-old male, was diagnosed with the intrahepatic cholangiocarcinoma (ICC) in October 2017. After interventional, CIK, ablation and other comprehensive therapy, ICC was gradually cured. When new occurrence of HCC, he was treated with anti-PD-1 antibody therapy and achieved CR. Case two, a 65-year-old female, was diagnosed with HCC in July 2016. After progression on several ablation treatments, she received 8 cycles of CIK treatment and achieved stable disease (SD). After disease progressed on CIK treatment, she received 4 cycles of anti-PD-1 antibody therapy, finally achieved CR. CONCLUSION: Anti-PD-1 antibody therapy after prior progression on bi-specific antibody conjugated CIK immunotherapy may be efficacy and safety for HCC patients.

Antiproliferation of berberine is mediated by epigenetic modification of constitutive androstane receptor (CAR) metabolic pathway in hepatoma cells.

Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, cell cycle arrest, but less ROS production in CAR overexpressed mCAR-HepG2 cells. Moreover, berberine inhibits expressions of CAR and its target genes CYP2B6 and CYP3A4. Furthermore, berberine enhances DNA methylation level in whole genome but reduces that in promoter regions CpG sites of CYP2B6 and CYP3A4 genes under the presence of CAR condition. These results indicated that the antiproliferation of berberine might be mediated by the unique epigenetic modifying mechanism of CAR metabolic pathway, suggesting that berberine is a promising candidate in anticancer adjuvant chemotherapy, due to its distinct pharmacological properties in clinic.

Novel single nucleotide polymorphisms (SNPs) of CYP2W1 gene in Chinese Uygur and Han populations.

Cytochrome P450 2W1 (CYP2W1) is expressed specially in certain cancers and could metabolize some substances into cytotoxic antitumor drugs in Caucasian ethnic population. To investigate the genetic polymorphism of CYP2W1 in Chinese, all the nine exons and exon-intron junctions were sequenced by dideoxy chain termination method among 385 Chinese subjects (including 223 Han and 162 Uygur). The present results showed that 40 single nucleotide polymorphisms (SNPs) were detected (14 in the exons and 26 in the introns), 10 were novel variants of which in Chinese. There were 7 novel SNPs in the exons and other 3 novel SNPs in the introns. Four of the 6 novel non-synonymous variations in exons, 131T > C (Leu44Pro), 1289C > A (Ala88Glu), 2027G > A (Arg187Gln) and 5070C > T (Thr383Met) were computationally predicted to affect CYP2W1 protein function, in spite of these variants were heterozygotes. Moreover, the allele frequencies in 6 known SNPs including CYP2W1*2 (2008G > A) and CYP2W1*3 (173A > C) were analyzed, which were significantly lower in Chinese Han (2.9% and 0.0%, respectively) and Uygur (5.2% and 0.0%, respectively) individuals, than those reported previously in Caucasians (9.1% and 33.1%, respectively, P < 0.05). These data provide useful information on the pharmacogenetic studies of CYP2W1 among Chinese and other ethnic populations.

A prognostic biomarker for gastric cancer with lymph node metastases.

Gastric cancer is one of the leading causes of tumor-related deaths in China. The tumor, node, metastasis (TNM) classification system is useful for predicting clinical prognosis of patients with gastric cancer. However, determining the presence of lymph node involvement in the early stages of gastric cancer is difficult without biopsy. Therefore, it is necessary to identify novel serum biomarkers for TNM cancer staging and prognostic follow-up. In this study, we have reported fibrinopeptide-A (FPA) with alanine truncation at the N-terminal as a novel biomarker to differentiate gastric cancer with and without lymph node metastases. We analyzed 369 individual serum samples including gastric cancer patients without lymph node metastases (n = 33), gastric cancer patients with lymph node metastases (n = 157; confirmed by pathology), and age- and sex-matched healthy individuals (n = 179). The data showed that 85.4% of patients with lymph node metastases were positive for FPA with alanine truncation at the N-terminal (degAla-FPA, 1,465.63 Da), as determined by tandem mass spectrometry (MS). Using degAla-FPA as the biomarker, the sensitivity was 85.4% for gastric cancer patients with lymph node metastases, and the specificity was 100% for gastric cancer patients without lymph node metastases. The high sensitivity and specificity achieved with serum degAla-FPA levels indicated that MS technology could facilitate the discovery of a novel and quantitative prognostic biomarker for gastric cancer with lymph node involvement.