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Background and Objective: Immune checkpoint inhibitors (ICIs) have been widely applied and studied in the treatment of gastrointestinal (GI) cancers, and have achieved good results. However, in clinical practice, it has been observed that only some patients respond well to ICIs, and some patients may experience various degrees of adverse reactions during the treatment. Timely evaluation of the potential therapeutic effects and adverse reactions of ICIs for patients has important clinical significance. This review aimed to summarize recent progress regarding efficacy-associated biomarkers for ICIs in GI cancer. Methods: The literature on ICI treatment in GI cancers was searched in the PubMed, Embase, and Cochrane Library databases for publications up to April 2023. Key Content and Findings: Clinical practice and research has gradually revealed some biomarkers related to the treatment of GI cancers with ICIs, which can be roughly divided into three types: biomarkers that predict the effectiveness of ICIs treatment, biomarkers associated with resistance to ICIs, and biomarkers associated with immune related adverse events (irAEs). This review article provides a literature review on biomarkers related to the efficacy of ICIs in the treatment of GI cancers. Conclusions: According to existing clinical research results, there are multiple biomarkers that can be used for predicting and monitoring the efficacy and risk of adverse events of ICIs in the treatment of digestive system malignant tumors.
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BACKGROUND: The main causes of intracerebral hemorrhage differ between young adults and older adults. Data regarding potential targets for early intervention in young adult patients with intracerebral hemorrhage are lacking. METHODS: We retrospectively analysed data for 196 young adult patients with intracerebral hemorrhage who were admitted to Tianjin Huanhu Hospital and died within 30 days of admission between June 2005 and June 2015. The Kaplan-Meier method was used to calculate survival rate, and the log-rank test was used to determine survival rate significance. A Cox proportional hazards regression model was used for univariate and multivariate analyses. RESULTS: Univariate analysis revealed a statistically significant association of age, disturbance of consciousness, National Institutes of Health Stroke Scale and Glasgow Coma Scale scores, seizure occurrence, infratentorial hemorrhage, intraventricular extension, hernia, glucose level, white blood cell count, albumin level, creatinine level, uric acid level, and surgical treatment with early mortality (P<0.05). However, multivariate regression analysis revealed that only infratentorial hemorrhage (P=0.003) and intraventricular extension (P=0.003) were significant risk factors for early mortality. CONCLUSIONS: Our results suggest that young adult patients who exhibit infratentorial hemorrhage and intraventricular extension in the early stages of intracerebral hemorrhage onset exhibit an increased risk of early mortality.
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Epidemiological studies indicate that there is a gender difference in the susceptibility to tobacco and environmental carcinogens, and this gender difference is suspected to result in a higher risk for lung cancer among women. However, the molecular mechanisms underlying this sexual dimorphism remain unclear. In the present study, we have evaluated the roles of CYP1A1 and dihydrodiol dehydrogenase (DDH) in the formation of benzo[a]pyrene (BaP) DNA adducts in various lung cancer cell lines. Among six lung cancer cell lines tested, higher adduct levels were observed in CL-3 and CL1-1 cells, which had relatively high expression of both CYP1A1 and DDH isoform 1 (DHH1). To determine whether a reduction in DDH expression changed the adduct levels, an siRNA was used to knock down DDH1 expression in CL-3 cells. The BaP adduct levels in siDDH-CL-3 cells increased 1.4-2.2-fold relative to that of the parental CL-3 cells. We also examined BaP-like DNA adducts, and CYP1A1 and DDH1 expression by immunohistochemistry in 120 lung tumors. Detection of DNA adducts correlated with CYP1A1-positive tumors (P = 0.023), but not with DDH1-positive tumors. In addition, 28 of 33 tumors (85%) that were CYP1A1-positive and DDH1-negative contained detectable levels of DNA adducts, a proportion that was higher than for tumors from the other three categories of CYP1A1 and DDH1 expression (P = 0.012). Finally, a greater proportion of adduct-positive tumors from females were CYP1A1-positive/DDH1-negative (45.3%) than were tumors from males (27.3%). These results suggest that the reduction of DDH expression in lung tumors may contribute to an increase in DNA adduct levels, which may be partly responsible for the higher susceptibility of female lung cancer patients to DNA damage.