Unveiling the promise of PD1/PD-L1: A new dawn in immunotherapy for cholangiocarcinoma.

Cholangiocarcinoma (CCA), a rare yet notably aggressive cancer, has experienced a surge in incidence in recent years. Presently, surgical resection remains the most effective curative strategy for CCA. Nevertheless, a majority of patients with CCA are ineligible for surgical removal at the time of diagnosis. For advanced stages of CCA, the combination of gemcitabine and cisplatin is established as the standard chemotherapy regimen. Despite this, treatment efficacy is often hindered by the development of resistance. In recent times, immune checkpoint inhibitors, particularly those that block programmed death 1 and its ligand (PD1/PD-L1), have emerged as promising strategies against a variety of cancers and are being increasingly integrated into the therapeutic landscape of CCA. A growing body of research supports that the use of PD1/PD-L1 monoclonal antibodies in conjunction with chemotherapy may significantly improve patient outcomes. This article seeks to meticulously review the latest studies on PD1/PD-L1 involvement in CCA, delving into their expression profiles, prognostic significance, contribution to oncogenic processes, and their potential clinical utility.

miR-101-3p-mediated role of PDZK1 in hepatocellular carcinoma progression and the underlying PI3K/Akt signaling mechanism.

BACKGROUND: The molecular targets and associated mechanisms of hepatocellular carcinoma (HCC) have been widely studied, but the roles of PDZK1 in HCC are unclear. Therefore, the aim of this study is to explore the role and associated mechanisms of PDZK1 in HCC. RESULTS: It was found that the expression of PDZK1 in HCC tissues was higher than that in paired paracancerous tissues. High expression of PDZK1 was associated with lymph node metastasis, degree of differentiation, and clinical stage. Upregulation of PDZK1 in HCC cells affected their proliferation, migration, invasion, apoptosis, and cell cycle, and also induced PI3K/AKT activation. PDZK1 is a downstream target gene of miR-101-3p. Accordingly, increase in the expression of miR-101-3p reversed the promotive effect of PDZK1 in HCC. Moreover, PDZK1 was found to accelerate cell proliferation and promote the malignant progression of HCC via the PI3K/AKT pathway. CONCLUSION: Our study indicated that the miR-101-3p/PDZK1 axis plays a role in HCC progression and could be beneficial as a novel biomarker and new therapeutic target for HCC treatment.

PCSK6 mediates Th1 differentiation and promotes chronic colitis progression and mucosal barrier injury via STAT1.

This study was aimed at investigating the expression and role of proprotein convertase subtilisin/kexin type (PCSK6) in inflammatory bowel disease (IBD). DSS induced mouse colitis and mucosal barrier injury, down-regulation of TJ proteins, improvement of permeability, and increases of the proportions of Th1 and M1 macrophages. After PCSK6 knockdown, the colitis in KO mice was improved relative to WT mice, the TJ protein levels increased, and the proportions of Th1 and M1 macrophages decreased. STAT1 inhibitor treatment also inhibited chronic colitis in mice. As revealed by in-vitro experiments, PCSK6 overexpression promoted the transformation of Th0 into Th1, while PCSK6 silencing suppressed the transfection. COPI assay results revealed the presence of targeted binding relation between PCSK6 and STAT1. PCSK6 binds to STAT1 to promote STAT1 phosphorylation and regulate Th1 cell differentiation, thus promoting the M1 polarization of macrophages and aggravating colitis progression. PCSK6 is promising as the new target for the treatment of colitis.

Clinical prognostic value of circulating tumor cells in the treatment of pancreatic cancer with gemcitabine chemotherapy.

Pancreatic cancer (PC) is a highly malignant tumor type with a high early metastasis rate and no obvious symptoms. Gemcitabine is a first-line chemotherapeutic drug for PC. Since there is no distinct method to determine the efficacy of chemotherapy with gemcitabine in patients with PC, the purpose of the present study was to determine whether positivity for circulating tumor cells (CTCs) in patients with advanced PC is associated with response to gemcitabine chemotherapy and to explore whether CTCs may be used as a predictor of prognosis of patients with advanced PC undergoing chemotherapy. First, immunomagnetic microspheres (magnetic beads; MIL) were prepared to detect CTCs. The patients' clinical characteristics and survival data, as well as efficacy and adverse effects of chemotherapy, were prospectively obtained and their association with CTCs was analyzed. The results indicated that CTC-positive patients with advanced PC had a higher probability of developing resistance to gemcitabine chemotherapy than CTC-negative patients. Survival in the CTC-negative group was significantly higher than in the CTC-positive group (χ2=14.58, P<0.001). CTC-positive patients with advanced PC also had shorter progression-free survival (PFS) after chemotherapy with gemcitabine (P=0.01). In conclusion, CTC-positive patients with PC are more likely to develop gemcitabine resistance, have poor PFS and low incidence of thrombocytopenia. CTCs are expected to become a prognostic indicator for chemotherapy response in patients with PC.

Hepatitis B Virus Reactivation Potential Risk Factors in Hepatocellular Carcinoma via Transcatheter Arterial Chemoembolization: A Retrospective Research.

Background: To explore the clinical characteristics of reactivation of hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The pathological correlation of prognosis and hepatitis B virus reactivation has been given detailed analyses in our research. Methods: A total of 108 related TACE-treated HCC clinical data from January 2008 to January 2016 was gleaned and involved in this retrospective analysis. To lucubrate the nuance of survival rates between HBV reactivated group and HBV nonreactivated group, clinical data of each patient was analyzed in detail and refined the retrospective studies. Results: HBV reactivation occurred in 42 patients with a proportion of 38.9%. The detected HBV DNA level ≥104 in patients showed a reactivation rate of 65.8% (25/38), which was significantly higher than the HBV DNA < 104 cases (24.3%, 17/70). Research data revealed a conspicuous lower cellular immunity (P < 0.01) and better 2-year survival rate (P=0.03) in the HBV-reactivated group when compared to the nonreactivated group. Conclusion: Some of the patients with primary hepatocellular carcinoma possibly had HBV reactivation at post-TACE-therapy. And the predominant risk factors of HBV reactivation are positive HBV test and immunosuppression. Our study suggested that HBV reactivation at post-TACE-therapy is an independent predictor of poor prognosis and low survival rate as well as a crucial reason for poor prognosis and lower survival rate, which indirectly proved that it is urgent to necessitate the antiviral therapy and immune enhancer in improving the curative effect and prognosis of HCC patients.

AMP­activated protein kinase family member 5 is an independent prognostic indicator of pancreatic adenocarcinoma: A study based on The Cancer Genome Atlas.

Pancreatic adenocarcinoma (PAAD) is a common and highly malignant tumor. The identification of prognostic biomarkers for PAAD could provide invaluable information for clinical treatment. AMP­activated protein kinase family member 5 (ARK5) is a member of the AMPK family that mediates the migration of PAAD cells. In the present study, ARK5 expression was evaluated using bioinformatics analysis in public datasets from The Cancer Genome Atlas. The expression levels of ARK5 in PAAD tumor tissue were significantly increased, compared with matched non­cancerous tissues. ARK5 target genes were then predicted and Gene Ontology Biological Processes, Kyoto Encyclopedia of Genes and Genomes pathway analysis and Reactome gene sets were used to determine the functions associated with the target genes. A protein­protein interaction network was also constructed to find out the node genes and observe their association with the overall survival rate of PAAD. A total of nine node genes were identified in the PPI network, of which six were significantly upregulated in PAAD tissue, compared with matched normal tissue. The prognostic value of each node gene was evaluated by comparing the overall survival in patients with PAAD stratified according to the expression levels of these genes. Overall survival was significantly reduced in patients with high polo­like kinase­1 (PLK1) or protein phosphatase 1 catalytic subunit ß (PPP1CB) expression, compared with patients with low expression of these genes. To further evaluate the relationship between PAAD and ARK5, ARK5 immunohistochemical staining was performed in a tissue microarray consisting of 112 tumor samples from patients with PAAD and adjacent normal tissue samples. ARK5 protein expression in PAAD tissue was markedly increased, compared with non­cancerous tissue (P=7.631x10­11). Moreover, ARK5 protein levels were associated with N stage (P=0.018). The overall survival of patients with PAAD with high ARK5 protein expression levels was reduced (P=0.014), compared with patients with low expression. In conclusion, these findings suggested that ARK5 may represent an independent prognostic indicator of PAAD.

Clinicopathologic features and surgical outcome of solid pseudopapillary tumor of the pancreas: analysis of 17 cases.

BACKGROUND: We summarize our experience of the diagnosis, surgical treatment, and prognosis of solid pseudopapillary tumors (SPTs). METHODS: We carried out a retrospective study of clinical data from a series of 17 patients with SPT managed in two hospitals between October 2001 and November 2011. RESULTS: All of the 17 patients were female and the average age at diagnosis was 26.6 years (range 11 years to 55 years). The tumor was located in the body or tail in ten patients, the head in five patients, and the neck in two patients. The median tumor size was 5.5 cm (range 2 cm to 10 cm). All 17 patients had curative resections, including seven distal pancreatectomies, five local resections, four pancreaticoduodenectomies, and one central pancreatectomy. Two patients required concomitant splenic vein resection due to local tumor invasion. All patients were alive and disease-free at a median follow-up of 48.2 months (range 2 to 90 months). There were no significant associations between clinicopathologic factors and malignant potential of SPT. Ki-67 was detected in three patients with pancreatic parenchyma invasion. CONCLUSIONS: The SPT is an infrequent tumor, typically affecting young women without notable symptoms. Surgical resection is justified even in the presence of local invasion or metastases, as patients demonstrate excellent long-term survival. Positive immunoreactivity for Ki-67 may predict the malignant potential of SPTs.