Purpose: Immunotherapy has become the standard treatment for advanced tumors so that many biomarkers play parts in predicting prognosis and clinical outcome. Use of FARI is increasing, but there are no studies on its use prior to immunotherapy. Patients and Methods: A retrospective study prior to immunotherapies in advanced carcinoma used FARI and other biomarkers as clinical parameters from which to analyse data from January 2014 to November 2020. Data were presented in GraphPad Prism 7 and X-Tile and analyzed using IBM SPSS. Results: A total of 146 patients were enrolled in our study. FARI (with an optimal cut-off value of 11.1%) was divided into a high group, in connection with shorter OS mainly in patients with bone metastasis (120m vs 11.5m, 95% Cl: 12.17-23.83, SE: 2.974, p=0.03), and a low group with a longer PFS (11.0m vs 5.0m, 95% Cl: 3.303-12.697, SE: 2.397, p=0.03) in NSCLC but a shorter PFS (3.5m vs 5.5m, 95% Cl: 3.757-6.243, SE: 0.634, p=0.01) in liver metastasis. FARI was not determined as an independent predictor of OS in patients undergoing medical therapies (>11.1% vs ≤11.1%, HR: 1.296, 95% Cl: 0.687-2.032, p=0.314). ECOG (HR: 2.892, 95% Cl: 1.911-4.378, p<0.001) can be an independent predictor for PFS and OS in advanced carcinoma. Conclusion:Our findings highlight certain potential values for predicting prognosis but no outstanding biomarkers prior to immunotherapy according to FARI.
There is growing evidence that estrogen receptors (ER) are expressed in lung cancer cells, and are able to interact with the epidermal growth factor receptor (EGFR) signaling pathway. However, data on the association between cytoplasmic ER expression and the response to EGFR-tyrosine kinase inhibitors (TKI) treatment are limited. The aim of the present study was to investigate the associations between ERα/ERβ expression and EGFR mutational status and response to TKI treatment in metastatic lung adenocarcinoma. A retrospective study of 126 consecutive patients with lung adenocarcinoma who were diagnosed with stage IV disease and had received EGFR-TKI treatment was conducted. ER expression was detected by immunohistochemistry. EGFR and GTPase KRas (KRAS) mutational statuses were evaluated by denaturing high performance liquid chromatography and PCR-restriction fragment length polymorphism, respectively. In the overall cohort of 126 lung adenocarcinoma samples analyzed, ERα expression in the nucleus of tumor cells was identified in 17 (18.9%) patients, whereas ERβ expression was identified in the nucleus (22/126, 17.5%) and cytoplasm (17/126, 13.5%). The nuclear expression of ERβ was positively associated with the degree of tumor differentiation (P=0.010). EGFR-sensitizing mutations were significantly associated with improved objective response rates (ORR), disease control rates (DCR), median progression-free survival (mPFS) and median overall survival (mOS) (P<0.001; P<0.001; P=0.003; and P=0.026, respectively). Patients with cytoplasmic ERβ expression exhibited non-significant poorer ORR, DCR, mPFS and mOS compared with patients without cytoplasmic ERβ expression (P=0.082; P=0.106; P=0.084; and P=0.119, respectively). However, the significant decrease of ORR, DCR and mPFS was observed in patients with coexisting cytoplasmic ERβ expression and EGFR-sensitizing mutations (P=0.030; P=0.009; and P=0.018, respectively) in comparison with the subgroup with EGFR sensitizing mutations but negative expression of cytoplasmic ERβ. A trend towards shorter mOS was also observed in patients with coexisting cytoplasmic ERβ expression and EGFR-sensitizing mutations (P=0.071). No KRAS mutations were identified in patients with cytoplasmic ERβ expression. Subsequent to adjusting for sex, smoking status and EGFR mutation status, the Cox repression analysis indicated that cytoplasmic expression of ERβ was a negative independent predictor for mPFS in the whole patient cohort (HR=1.870; 95% confidence interval 1.058–3.305; P=0.031). Cytoplasmic ERβ expression was negatively correlated with the efficacy of EGFR-TKI treatment for metastatic lung adenocarcinoma, particularly for patients with coexisting cytoplasmic ERβ expression and EGFR-sensitizing mutations. Cytoplasmic ERβ may be a promising marker to predict the outcome of EGFR-TKI treatment.
Introduction Lipid metabolism and endoplasmic reticulum (ER) stress play an important role in the progression and metastasis of hepatocellular carcinoma (HCC). We aimed to establish lipid droplet (LD)-associated and ER stress-related gene risk signature as prognostic indicators. Materials and methods Literature searches for LD-associated proteins was screened and validated in The Cancer Genome Atlas (TCGA) and International Cancer Genome Collaboratory (ICGC) databases. A total of 371 samples were enrolled from the TCGA RNA-seq dataset (training cohort) and 240 samples from IGGC RNA-seq dataset (validation cohort). A 10-gene risk signature was established by the last absolute shrinkage and selection operator (LASSO) regression analysis. The prognostic value of the risk signature was evaluated by Cox regression, Kaplan–Meier and ROC Curve analyses. Biological features associated with LD and ER stress-related factors were explored by functional analysis and in vitro experiment. Results Based on the medical literatures, 124 lipid droplet-associated proteins were retrieved, and three genes failed to establish a valid prognostic model. ER stress was considered as an important component by functional analysis. A 10-gene risk signature compared the clinicopathology characteristics, immunosuppressive events and a nomogram in HCC patients. Conclusion LD-associated and ER stress-related gene risk signatures highlighted poor prognosis for clinicopathological features, positively correlate with macrophages and T cell immunoglobulin and mucin-3 (TIM-3) expression in the tumor microenvironment, and might act as independent prognostic factors.
The outcome of small cell lung cancer (SCLC) patients is poor because rapid metastasis develops after first‐line chemotherapy and few drugs are available for second‐line chemotherapy. The median survival rate has not significantly changed in recent years. In this report, we discuss the case of a 71‐year‐old Chinese female non‐smoker diagnosed with extensive‐stage SCLC who was treated with nivolumab for a short period and obtained a prolonged clinical benefit. We report the clinical history, clinical features, potential mechanism, benefits, and the best therapeutic window. The patient was treated with transcatheter arterial chemoembolization because of liver metastasis and then with four doses of nivolumab as third‐line systemic treatment. There was no disease progression for 15 months. The lesions became larger than before, suggesting disease progression, thus nivolumab treatment was ceased. Immunotherapy has the capacity to turn combined therapy into a feature that may be exploited for clinical benefit. Further research is required to evaluate whether combined treatment is beneficial for patients, affecting the efficacy of immunotherapy, and to determine the best therapeutic window for clinical treatment.
Introduction Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect the lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of Male C57BL/6 mice and reveal the potential underlying mechanisms. Methods A total of 60 male C57BL/6 mice were randomly divided into 4 groups. They were exposed to the fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/ml of nicotine and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. Results Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. Conclusions The findings of the present study indicate that the safety of E-cig should be further evaluated. Implications Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.
In cancer, the incidence of ESCA is the eighth and the mortality is the sixth worldwide. Copper is one of race metal elements in human body, which may play an important role in apoptosis in cancer. In recent years, Cuproptosis was proposed and studied as a less explored form of apoptosis. The main apoptotic mechanism is that copper binding to lipidated components, which are producted in the tricarboxylic acid cycle (TCA) directly, causes protein lipidation and subsequently leads to the lack of Fe-S cluster proteins, triggering proteotoxic stress and eventually apoptosis. Our study explored the role of cuproptosis in ESCA and built a risk model by using TCGA-ESCA date, named cuproptosis-related risk score model (CRRS). This model obtained cuproptosis-related risk scores to assess patient survival and prognosis. We also explored the differential expressed gene function enrichment, immune characteristics, and the tumor mutational load (TMB) between the two risk groups. Besides, we predicted the drug sensitivity of ESCA in the CRRS.
increasing large population has become consumers of e-cigarettes 4,5. Therefore, it is of great importance to fully understand the potential hazards of e-cigarettes. Nevertheless, the information about potential hazards is insufficient, especially the effects on body metabolism. Many studies have indicated that the levels of blood lipid and chronic inflammatory indexes are closely related to insulin sensibility. ApoE gene knockout mice are frequently used to investigate ABSTRACT INTRODUCTION The current study aimed to investigate the effects of electronic cigarettes on insulin sensibility in ApoE gene knockout mice. METHODS In total, 48 male ApoE gene knockout mice were randomly divided into four exposure groups: 1) electronic cigarette (e-cigarette) containing 12 mg/ mL of nicotine, 2) e-cigarette without nicotine (0mg), 3) traditional cigarette (cigarette), and 4) fresh air (control). The first three groups were exposed to the associated smoke for 18 weeks. The body weight was recorded regularly in the four groups. After the last exposure, the concentrations of lipids, hs-CRP and TNF-α in serum were detected and the effect of electronic cigarettes on insulin tolerance was measured. RESULTS The levels of serum lipid, hs-CRP and TNF-α in the e-cigarette, 0mg and cigarette groups were significantly increased compared with those in the control group (p<0.05). Also, the insulin tolerance in the e-cigarette, 0mg and cigarette groups was significantly decreased compared to that in the control group (p<0.05). CONCLUSIONS Electronic cigarettes showed comparable effects to traditional cigarettes in influencing the metabolic functions in ApoE gene knockout mice.
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