<b><i>Background:</i></b> Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. Most HCC patients are first diagnosed at an advanced stage, and systemic treatments are the mainstay of treatment. <b><i>Summary:</i></b> In recent years, immune checkpoint inhibitors have made a breakthrough in the systemic treatment of middle-advanced HCC, breaking the single therapeutic pattern of molecular-targeted agents. To better guide the clinical treatment for effective and safe use of immunotherapeutic drugs, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Clinical Expert Consensus on Immunotherapy for Hepatocellular Carcinoma (2021)” based on current clinical studies and clinical medication experience for reference in China. <b><i>Key Messages:</i></b> The consensus contained 17 recommendations, including the preferred regimen for first- and second-line immunotherapy, evaluation and monitoring before/during/after treatment, management of complications, precautions for special patients, and potential population for immunotherapy.
122 Background: The efficacy of laparoscopic D2 gastrectomy for the treatment of advanced gastric cancer (AGC) with curative intent is still controversial. Thus, the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) group conducted a multicenter prospective randomized controlled trial, aiming to evaluate the surgical safety and long-term outcomes of laparoscopic D2 gastrectomy compared with conventional open surgery for AGC. (NCT01609309) Methods: The patients with tumor located at distal stomach at clinical T2-4a, N0-3, M0 stage were eligible for enrollment, treated by either laparoscopic D2 distal subtotal gastrectomy (LG) or open D2 gastrectomy (OG) after randomization. Seventeen institutions currently participated in the study. The morbidity and mortality within postoperative 30 days were compared between the two groups. Results: A total of 607 consecutive eligible patients were randomly assigned to either LG group (n=308) or OG group (n=299) between September 2012 and January 2014. The compliance rates of D2 lymphadenectomy in the LG group and OG group were similar (97.4% vs. 98.3%; P=0.591). Open conversion rate was 4.5%. There was no significant differences between the LG group and OG group in the incidence of intraoperative complication (5.8% vs. 4.3%; P=0.402), postoperative morbidity (18.8% vs. 14.7%; P=0.175), and mortality (0.6% vs. 0; P=0.499). The severity grade pattern was also similar according to the Clavien-Dindo classification (P=0.372). Conclusions: Laparoscopic D2 distal subtotal gastrectomy for AGC could be safely performed by experienced surgeons. Thus, our multicenter prospective study on long-term outcomes can be ongoing. Clinical trial information: NCT01609309.
Six new compounds, penicitrinols L-O (1-4), penicillenols D1 (9) and D2 (10), together with six known compounds were isolated from the marine--derived fungus Penicillium citrinum.Their structures were elucidated on the basis of comprehensive spectral analysis and chemical methods.All the new compounds were evaluated for their cytotoxic effects on the A-549, HL-60 and SW-620 cell lines by the MTT method.Penicitrinols L (1) and M (2) showed weak cytotoxicities against SW-620 cell line, while penicillenols D1 (9) and D2 (10) showed weak cytotoxicities against A-549 and HL-60 cell lines, respectively.Penicillium citrinum is a rich source of various anticancer compounds. 1Our previous chemical investigation of P. citrinum resulted in the isolation of seven new citrinin derivatives, penicitrinols C-I, 1a,1f two new tumonoic acids (K and L), 1g and a new benzene derivative, 1g which showed different degrees of cytotoxicities against the P388, HL-60 and A-375 cell lines.Our continuing search for bioactive compounds from this organism has further resulted in the isolation of another four new citrinin derivatives, namely, penicitrinols L-O (1-4), along with two new tetramic acid analogues, namely, penicillenols D1 and D2 (9, 10).Additional, six known compounds, including penicitrinol J (5), 2 citrinin (6), 2 dihydrocitrinone (7), 1g 2, 4-dihydroxy-3, 5, 6-trimethylbenzaldehyde (8), 3 penicillenol B1 (11), 4 and penicillenol B2 (12), 4 were purified together.In this paper, we report the isolation, structural elucidation and bioactivities of these metabolites.
The existence of cancer stem cells (CSCs) is considered as a direct reason for the failure of clinic treatment in hepatocellular carcinoma (HCC). Growing evidences have demonstrated that miRNAs play an important role in regulation of stem cell proliferation, differentiation and self-renewal and their aberrances cause the formation of CSCs and eventually result in carcinogenesis. We recently identified miRNA-148b as one of the miRNAs specifically down-regulated in side population (SP) cells of PLC/PRF/5 cell line. However, it remains elusive how miRNA-148b regulates CSC properties in HCC. In the present study, we observed that overexpression or knockdown of miR-148b through lentiviral transfection could affect the proportion of SP cells as well as CSC-related gene expression in HCC cell lines. In addition, miR-148b blocking could stimulate cell proliferation, enhance chemosensitivity, as well as increase cell metastasis and angiogenesis in vitro. More importantly, miR-148b could significantly suppress tumorigenicity in vivo. Further studies revealed that Neuropilin-1 (NRP1), a transmembrane co-receptor involved in tumour initiation, metastasis and angiogenesis, might be the direct target of miRNA-148b. Taking together, our findings define that miR-148b might play a critical role in maintenance of SP cells with CSC properties by targeting NRP1 in HCC. It is the potential to develop a new strategy specifically targeting hepatic CSCs (HCSCs) through restoration of miR-148b expression in future therapy.
Negative lymph node (NLN) count has been validated as a protective predictor in various cancers after radical resection. However, the prognostic value of NLN count in the setting of stage IV gastric cancer patients who have received palliative resection has not been investigated. Surveillance, Epidemiology, and End Results Program (SEER)-registered gastric cancer patients were used for analysis in this study. Kaplan-Meier survival curves and multivariate Cox proportional hazards model were used to assess the risk factors for patients' survivals. The results showed that NLN count and N stage were independently prognostic factors in patients with stage IV gastric cancer after palliative surgery (P< 0.001). X-tile plots identified 2 and 11 as the optimal cutoff values to divide the patients into high, middle and low risk subsets in term of cause-specific survival (CSS). And NLN count was proved to be an independently prognostic factor in multivariate Cox analysis (P< 0.001). The risk score of NLN counts demonstrated that the plot of hazard ratios (HRs) for NLN counts sharply increased when the number of NLN counts decreased. Collectively, our present study revealed that NLN count was an independent prognostic predictor in stage IV gastric cancer after palliative resection. Standard lymph node dissection, such as D2 lymphadectomy maybe still necessary during palliative resection for patients with metastatic gastric cancer.
Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complications of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment, and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient’s general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements, and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.
BACKGROUND Aberrant expression of lncRNA has been suggested to have an association with tumorigenesis. Our study was designed to reveal the underlying connection between lncRNA SNHG1 and hepatocellular carcinoma (HCC) pathogenesis. MATERIAL AND METHODS A total of 122 pairs of HCC tissues (case group) and matched adjacent non-tumor liver tissues (control group) were collected for this study. RT-PCR and in situ hybridization were conducted to investigate differences in lncRNA SNHG1 expression between the case and control group. The expression levels of lncRNA SNHG1 and miR-195 in HepG2 cells transfected with SNHG1-mimic and SNHG1-inhibitor were measured by RT-PCR. The proliferation, invasion, and migration status of HepG2 cells after transfection were assessed through MTT assay, wound healing assay, and Transwell assay, respectively. Whether miR-195 is a direct downstream target of lncRNA SNHG1 was verified by both bioinformatics target gene prediction and dual-luciferase report assay. RESULTS The expression level of lncRNA SNHG1 was remarkably upregulated in HCC tissues and cell lines compared with normal tissues and cell lines. High expression of lncRNA SNHG1 contributed to the downregulation of miR-195 in HepG2 cells. Also, lncRNA SNHG1 exacerbated HCC cell proliferation, invasion, and migration in vitro through the inhibition of miR-195. This suggests that miR-195 is a direct downstream target of lncRNA SNHG1. CONCLUSIONS lncRNA SNHG1 may contribute to the aggravation of HCC through the inhibition of miR-195.
Galectin-3 serves an important function in cancer development and progression. The present study aimed to explore the association between single nucleotide polymorphisms in galectin-3, and the susceptibility to chemotherapy drug resistance of gastric carcinoma. The present study was a case-control study including 479 patients with gastric carcinoma and 458 cancer-free controls in a population from the Fujian province in Southeast China. Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry was used to determine the genotype of rs4644 and rs4652, and immunohistochemistry was used to identify the expression level of various proteins associated with chemotherapeutic drug resistance. The results revealed that individuals exhibiting the rs4652 CA/AA genotype had a significantly increased risk of developing gastric carcinoma compared with the rs4652 CC genotype (adjusted odds ratio, 1.51; 95% confidence interval, 1.05-2.18; adjusted P=0.03). In addition, it was demonstrated that there were significant differences in the P-glycoprotein expression level depending on rs4652 genotypic distributions (χ2=9.063; P=0.028). Therefore, the present study demonstrated that rs4652 single nucleotide polymorphisms of the galectin-3 gene contribute to the susceptibility to and chemotherapeutic drug resistance of gastric carcinoma.