PD-L1 and miR-34a are Prognostic Factors for Primary Gastric Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP.

INTRODUCTION: Primary gastric diffuse large B-cell lymphoma (GDLBCL) is a heterogeneous disease in clinicopathological features and prognosis. Programmed death ligand-1 (PD-L1) and microRNA-34a (miR-34a) play crucial roles in GDLBCL progress. The purpose of this research is to explore the clinical significance of PD-L1 and miR-34a expression in GDLBCL. PATIENTS AND METHODS: The expressions of PD-L1 and miR-34a were examined by IHC and qRT-PCR in 109 patients who were diagnosed with GDLBCL and were treated with rituximab plus cyclophosphamide, doxorubicin, prednisone vincristine and prednisone chemotherapy (R-CHOP) from January 2010 to December 2018. RESULTS: PD-L1 level was significantly higher in tumor tissues than adjacent non-tumor tissues (60.5%, P<0.001), while the miR-34a level was just reversed (50.5%, P<0.001), which was negatively correlated (r=-0.524, P<0.001). Notably, PD-L1-positive and miR-34a-negative expressions were significantly correlated with the advanced Lugano stage of IIE-IV stage (P<0.001 and P<0.01), elevated serumal LDH levels (P<0.001 and P<0.05), B symptoms present (P<0.001 and P<0.001), non-GCB subtype (P<0.001 and P<0.001) and negative Bcl-2 expression (P<0.05 and P<0.001). PD-L1 high and miR-34a low expression groups had more patients with IPI scores of 2 or greater (P<0.001 and P<0.05) and poor R-IPI (P<0.01 and P<0.01). The complete response rate was upregulated in patients with negative PD-L1 and positive miR-34a expression after R-CHOP treatment. DISCUSSION: PD-L1 expression and miR-34a expression were significantly associated with clinicopathological characteristics and survival prognosis; they may serve as novel prognostic markers in GDLBCL patients who were treated with R-CHOP. Immunotherapies targeting PD-L1 and miR-34a pathway may have therapeutic potential in GDLBCL.

Cobimetinib-induced "dropped head syndrome" and subsequent disease management in an Erdheim-Chester patient.

Our rechallenge of cobimetinib in an Erdheim-Chester Disease (ECD) patient for the rare adverse effect, "dropped head syndrome," with a previously unexplored cobimetinib regimen was successful. Similar to other experiences with targeted agents in ECD, dosing of cobimetinib may vary to mitigate toxicity without impairing efficacy.

The effect of preoperative smoking cessation and smoking dose on postoperative complications following radical gastrectomy for gastric cancer: a retrospective study of 2469 patients.

BACKGROUND: To investigate whether smoking adversely affects the short-term outcomes and the potential effects of cigarette dose and preoperative smoking cessation, in patients who underwent gastric cancer (GC) surgery. METHODS: Two thousand, four hundred sixty-nine consecutive patients who underwent radical gastrectomy from November 2010 to July 2018 were included in the present study. Smokers (current or former smokers) were divided into 3 groups in accordance with the duration of smoking cessation preoperatively (≤ 2, 2 to 4, or ≥ 4 weeks) and the cigarette dose (≤ 20, 20 to 40, and ≥ 40 pack-years). The primary endpoint was postoperative complications (surgical site infection, pulmonary problems, bleeding, and others). RESULTS: A total of 1056 patients (42.8%) were smokers. Compared with non-smokers, smokers had significantly higher overall postoperative complications (11.3% vs 7.5%, P = 0.001), and in particular pulmonary problems. Smokers also had more major complications, needing intensive care unit care, and longer postoperative hospital stays. Multivariate analysis confirmed that smoking (odds ratio = 1.506, 95% confidence interval 1.131-2.004, P = 0.005) was an independent risk factor for postoperative complications. Further subgroup analysis identified that there was a positive relationship between the incidence of complications and cigarette dose, and > 20 pack-years was demonstrated to have increased significantly the risk of complications. Smokers who stopped smoking ≥ 4 weeks before surgery had lower pulmonary problems than those with a shorter period of smoking cessation. CONCLUSIONS: Preoperative smoking cessation should be encouraged to reduce postoperative complications in GC patients, especially for heavy smokers.

LncRNAs in DNA damage response and repair in cancer cells.

In order to maintain integrity of the genome, eukaryotic cells develop a complex DNA damage/repair response network, which can induce cell cycle arrest, apoptosis, or DNA repair. Chemo- and radiation therapies, which act primarily through the induction of DNA damage, are the most commonly used therapies for cancer. Impairment in the DNA damage response and repair system that protect cells from persistent DNA damage can affect the therapeutic efficacy of cancer. To date, accumulating evidence has suggested that long non-coding RNAs (lncRNAs) are involved in the regulation of the DNA damage/repair network. LncRNAs have been demonstrated to be master regulators of the genome at the transcriptional and post-transcriptional levels and play a key role in many physiological and pathological processes of cells. In this review, we will discuss the function of lncRNAs in regulating the cellular response to DNA damage.

ISG15 in the tumorigenesis and treatment of cancer: An emerging role in malignancies of the digestive system.

The interferon-stimulated gene 15 ubiquitin-like modifier (ISG15) encodes an IFN-inducible, ubiquitin-like protein. The ISG15 protein forms conjugates with numerous cellular proteins that are involved in a multitude of cellular functions, including interferon-induced immune responses and the regulation of cellular protein turnover. The expression of ISG15 and ISG15-mediated conjugation has been implicated in a wide range of human tumors and cancer cell lines, but the roles of ISG15 in tumorigenesis and responses to anticancer treatments remain largely unknown. In this review, we discuss the findings of recent studies with regard to the role of ISG15 pathways in cancers of the digestive system.