Efficacy and Safety of Programmed Cell Death 1 Inhibitor Monotherapy Versus Chemotherapy as Second-Line Treatment for Advanced Esophageal Cancer: A Meta-analysis and Systematic Review.

PURPOSE: With programmed cell death 1 (PD-1) inhibitors approved for second-line treatment of advanced esophageal cancer, immunotherapy and chemotherapy have gradually become the main treatments for second-line treatment of patients with advanced esophageal cancer (AEC). This meta-analysis and systematic review were conducted to evaluate the efficacy and safety of PD-1 inhibitors monotherapy versus chemotherapy in second-line treatment of AEC. METHODS: Eligible randomized controlled trials were searched in PubMed, Embase, and the Cochrane Library and abstracts presented at the American Society of Clinical Oncology or European Society of Medical Oncology were reviewed to assess the efficacy and tolerability of PD-1/programmed cell death ligand 1 (PD-L1) inhibitors relative to chemotherapy for AEC from January 2016 to October 2020. Patients diagnosed with AEC and progressing after first-line therapy were included in this study. Hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) of objective response rate (ORR), and the odds ratios (ORs) of adverse effects (AEs) were calculated. FINDINGS: The study included 4 randomized controlled trials with 1683 patients. The results indicated that PD-1 inhibitors prolonged the OS (HR = 0.79; 95% CI, 0.71-0.88; P < 0.01) and improved the ORR (RR = 3.00; 95% CI, 2.36-3.82; P = 0.01) but did not improve the PFS (HR = 0.96; 95% CI, 0.76-1.20; P = 0.692) compared with chemotherapy in the second-line treatment of AEC. PD-1 inhibitors alone were associated with a lower incidence of all treatment-related AEs (OR = 0.29; 95% CI, 0.09-0.89; P = 0.03) and grade 3 to 5 treatment-related AEs (OR = 0.26; 95% CI, 0.16-0.44; P < 0.01) versus chemotherapy. PD-1 inhibitors prolonged OS mainly in the following patient groups: male, age <65 years, Eastern Cooperative Oncology Group performance status of 1, or PD-L1 tumor proportion score ≥10%. Asian patients had a longer OS than non-Asian patients (P = 0.01). IMPLICATIONS: The available evidence indicates that the efficacy and tolerability of PD-1 inhibitors were better than chemotherapy in the second-line treatment of AEC, and the benefiting population of these patients was limited to males, those <65 years of age, those with a Eastern Cooperative Oncology Group performance status of 1, or those with a PD-L1 tumor proportion score ≥10%. Notably, Asian patients receiving immune monotherapy had longer OS than non-Asian patients.

Effect of CD44st and HER2 expression on the postoperative prognosis of breast cancer patients.

OBJECTIVE: CD44st is a member of the CD44 family; abnormal expression of some CD44 isoforms are closely associated with axillary lymph node metastasis, cancer progression, and patients' prognosis. The objective of this study is to investigate the correlation between the expression of CD44st and HER2 in breast cancer and the effect on patients' prognosis. METHODS: Primers were designed to target the CD44st mRNA (Gene Bank No FJ216964) which has been newly identified in a drug-resistant breast cancer cell line. The expression of CD44st and HER2 mRNA and proteins in cancerous and paracancerous tissue of postoperative breast cancer patients was detected and compared. Tissue samples were obtained from 102 cases of invasive ductal carcinoma, 19 cases of intraductal carcinoma, and 11 cases of medullary carcinoma. The correlation between CD44st and HER2 expression and clinical pathological features was examined. RESULTS: The expression rate of CD44st mRNA and protein in breast cancer tissue was 64.4% (85/132), while HER2 mRNA and protein was expressed in 22.0% (29/106) of the samples. The expression of CD44st and HER2 were low in paracancerous tissue. In breast cancer tissue, the expression rate of HER2 mRNA and protein in the CD44st-positive group was 28.2% (24/85), and 10.6% (5/47) in the CD44st-negative group. This difference was statistically significant (P=0.015). Sequencing analysis showed that the amplified CD44st gene in this study was the same as that which was previously discovered in the drug-resistant breast cancer cell line. A linear correlation was found between the expression of CD44st and HER2 (r=0.972, r2=0.945, F=2,213.51, P<0.001). The expression of CD44st and HER2 was also closely associated with luminal cancer subtypes, lymph node metastasis, and TNM stage (P<0.05), but not associated with age, pathological type, or tumor size (P>0.05). The median overall survival in the CD44st high-expression group was 51.85 months (95% CI: 48.48-55.22), which was significantly shorter than that in the CD44st low-expression group (57.61 months; 95% CI: 55.54-59.68, P=0.032). CONCLUSION: CD44st is closely related to the expression of HER2. The expression of CD44st affects patient prognosis and is associated with lymph node metastasis, TNM staging, and molecular subtyping.

Research progress in the radioprotective effect of the canonical Wnt pathway.

Irradiation from diverse sources is ubiquitous and closely associated with human activities. Radiation therapy (RT), an important component of multiple radiation origins, is a common therapeutic modality for cancer. More importantly, RT provides significant contribution to oncotherapy by killing tumor cells. However, during the course of therapy, irradiation of normal tissues can result in a wide range of side effects, including self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. Although numerous promising radioprotective agents have emerged, only a few have successfully entered the market because of various limitations. At present, the widely accepted hypothesis for protection against radiation-caused injury involves the Wnt canonical pathway. Activating the Wnt/ß-catenin signaling pathway may protect the salivary gland, oral mucosa, and gastrointestinal epithelium from radiation damage. The underlying mechanisms include inhibiting apoptosis and preserving normal tissue functions. However, aberrant Wnt signaling underlies a wide range of pathologies in humans, and its various components contribute to cancer. Moreover, studies have suggested that Wnt/ß-catenin signaling may lead to radioresistance of cancer stem cell. These facts markedly complicate any definition of the exact function of the Wnt pathway.