Exosomal miR-27a Derived from Gastric Cancer Cells Regulates the Transformation of Fibroblasts into Cancer-Associated Fibroblasts

Background/Aims: The malignant biological behavior of gastric cancer(GC) is not only determined by cancer cells alone, but also closely regulated by the microenvironment. Fibroblasts represent a large proportion of the components in the tumor microenvironment, and they promote the development of disease. Currently, accumulating evidence suggests that exosomes can function as intercellular transport systems to relay their contents, especially microRNAs(miRNAs). Methods: First, we detected the highly-expressed level of miR-27a in exosomes isolated from gastric cancer cells by qRT-PCR. MiR-27a –over-expressed models in vitro and in vivo were established to investigate the transformation of cancer-associated fibroblasts observed by Western blotting, and the malignant behavior of gastric cancer cells using the methods CCK8 and Transwell. Moreover, the downregulation of CSRP2 in fibroblasts was used to evaluate the promotion of malignancy of gastric cancer using the methods CCK8 and Transwell. Results: In this study, we found a marked high level of miR-27a in exosomes derived from GC cells. miR-27a was found to function an oncogene that not only induced the reprogramming of fibroblasts into cancer-associated fibroblasts(CAFs), but also promoted the proliferation, motility and metastasis of cancer cells in vitro and in vivo. Conversely, CAFs with over-expression of miR-27a could pleiotropically increase the malignant behavior of the GC cells. For the first time, we revealed that CSRP2 is a downstream target of miR-27a. CSRP2 downregulation could increase the proliferation and motility of GC cells. Conclusion: Thus, this report indicates that miR-27a in exosomes derived from GC cells has a crucial impact on the microenvironment and may be used as a potential therapeutic target in the treatment of G

The value of the systematic inflammation-based Glasgow Prognostic Score in patients with gastric cancer: A literature review

The presence of a systemic inflammatory response (SIR) is recognized to occur in the presence of malignancy. And the SIR-Glasgow Prognostic Score (GPS)/modified GPS (mGPS) composed of the C-reactive protein (CRP) and albumin is a tumor stage- and treatment-independent, routinely available and well-standardized prognostic factor, reflects both an ongoing SIR (CRP) and a progressive nutritional decline (albumin) in patients with advanced cancer. Previous studies showed that GPS/mGPS appear to be a superior prognostic factor compared with other cellular components of the SIR and Eastern Cooperative Oncology Group performance status in some aspects. Besides, GPS/mGPS aids at deciding active or palliation treatment and selecting patients with gastric cancer who tolerate platinum-based chemotherapy. Therefore, GPS/mGPS may be incorporated or combined with other factors to improve assessment of prognosis and guide treatment of patients with gastric cancer in a routine clinical work. However, it remains to be determined whether the GPS and mGPS have different prognostic value in each stage of gastric cancer and the necessity of normalization of the GPS/mGPS by anti-inflammation and maintenance of performance status or nutritional status in clinical work

Bevacizumab/PD-1 inhibitor plus chemotherapy as first-line treatment of advanced non-squamous non-small-cell lung cancer

Aim: To compare the effectiveness of PD-1 inhibitor or bevacizumab plus chemotherapy in advanced nonsquamous non-small cell lung cancer (nsNSCLC). Methods: We retrospectively collected data for patients with advanced nsNSCLC who underwent first-line treatment with PD-1 inhibitor or bevacizumab plus chemotherapy (IC and BC groups). Propensity score matching (PSM) was adopted to balance covariates. Results: 278 patients were enrolled, after PSM (n = 104/group), the objective response rate was 45.1% and 24.0% in the IC and BC groups (p = 0.001).Median progression-free survival (PFS) was 13.5 and 8.2 months (p = 0.007), and duration of response was 14.8 versus 8.1 months (p = 0.007), respectively. In subgroup analysis, the PFS for those patients with PD-L1≥1% (16.2 vs 6.8 months, p = 0.000) was significantly longer in the IC group than that in BC group, but not in the PD-L1<1% subgroup (8.9 vs12.7 months, p = 0.719). Conclusion: PD-1 inhibitor plus chemotherapy was superior to bevacizumab plus chemotherapy as firstline treatment for advanced nsNSCLC, which is debatable for patients with PD-L1<1%

The effects of tislelizumab treatment on the health‐related quality of life of patients with advanced non‐small cell lung cancer

Abstract This study examined the health‐related quality of life (HRQoL) of patients with advanced non‐small cell lung cancer (NSCLC) receiving tislelizumab versus docetaxel in the open‐label, multicenter, Phase 3 trial called RATIONALE‐303 (NCT03358875). HRQoL was assessed with the EORTC QLQ‐C30, EORTC QLQ‐LC13, and the EQ‐5D‐5L instruments. A longitudinal analysis of covariance assessed the change from baseline to Week 12 and from baseline to Week 18. A time to deterioration analysis was also performed using the Kaplan–Meier method. Eight hundred and five patients were randomized to either tislelizumab (n = 535) or docetaxel, respectively (535 and 270 to tislelizumab and docetaxel, respectively). The tislelizumab arm improved while the docetaxel arm worsened in the QLQ‐C30 global health status/QoL scale score (difference LS mean change Week 18: 5.7 [95% CI: 2.38, 9.07, p = 0.0008]), fatigue (Week 12: ‐3.2 [95% CI: −5.95, −0.37, p < 0.0266]; Week 18: −4.9 [95% CI: −8.26, −1.61, p = 0.0037]), and QLQ‐LC13 symptom index score (Week 12: −5.5 [95% CI: −6.93, −4.04, P < 0.0001]; Week 18: −6.6 [95% CI: −8.25, −4.95, p < 0.0001]). The tislelizumab arm had improvements in coughing versus the docetaxel arm (Week 12: −4.7 [95% CI: −8.57, −0.78, p = 0.0188]; Week 18: −8.3 [95% CI: −13.02, −3.51, p = 0.0007]). The patients who received tislelizumab were less at risk for clinically meaningful worsening in the overall lung cancer symptom index scale (hazard ratio (HR): 0.24 [95% CI: 0.162, 0.356], p < 0.0001), dyspnea (HR: 0.74 [95% CI: 0.567, 0.958], p = 0.0109), coughing (HR: 0.74 [95% CI: 0.534, 1.019], p = 0.0309), and peripheral neuropathy (HR: 0.55 [95% CI: 0.370, 0.810] p = 0.0011). In general, tislelizumab versus docetaxel was associated with improved HRQoL and symptoms of lung cancer in patients who previously failed treatment with platinum‐containing chemotherapy

Effects of lipoprotein lipase gene variations, a high-carbohydrate low-fat diet, and gender on serum lipid profiles in healthy Chinese Han youth

A high-carbohydrate low-fat (HC/LF) diet and lipoprotein lipase gene (LPL) Ser447Stop and Hind III polymorphisms have separately been found to be associated with triacylglycerol (TG) and high density lipoprotein cholesterol (HDL-C). This study sought to test the effects of LPL polymorphisms and an HC/LF diet on the serum lipid profile of Chinese with a lower incidence of coronary artery disease (CAD) consuming a diet with less fat and more carbohydrates. Fifty-six healthy subjects (22.89 &plusmn; 1.80 years) were given a control diet of 30.1% fat and 54.1% carbohydrates for 7 days, followed by an HC/LF diet of 13.8% fat and 70.1% carbohydrate for 6 days; there were no changes in the fatty acid composition or restrictions on total energy. Serum lipid profiles at baseline, before and after the HC/LF diet, and LPL polymorphisms were analyzed. After 6 days of the HC/LF diet, TG and the homeostasis model assessment of insulin resistance (HOMAIR) index were found to increase only in females with S447S. No decrease in HDL-C was noted. In subjects with Hind III polymorphism, increased TG was found in all females but not in males. Increased HDL-C, together with apolipoprotein (apo) AI, was found in male H- carriers but not in males with H+/H+ and females. In conclusion, LPL Ser447Stop and Hind III polymorphisms modified the effects of an HC/LF diet on the serum lipid profiles of a young Chinese population in different ways. Effective strategies for dietary interventions targeted at younger populations should take into account the interplay between genetic polymorphisms, diet, and gender.<br /

Quantification of preexisting lung ground glass opacities on CT for predicting checkpoint inhibitor pneumonitis in advanced non-small cell lung cancer patients

Abstract Background Immune checkpoint inhibitors (ICIs) can lead to life-threatening pneumonitis, and pre-existing interstitial lung abnormalities (ILAs) are a risk factor for checkpoint inhibitor pneumonitis (CIP). However, the subjective assessment of ILA and the lack of standardized methods restrict its clinical utility as a predictive factor. This study aims to identify non-small cell lung cancer (NSCLC) patients at high risk of CIP using quantitative imaging. Methods This cohort study involved 206 cases in the training set and 111 cases in the validation set. It included locally advanced or metastatic NSCLC patients who underwent ICI therapy. A deep learning algorithm labeled the interstitial lesions and computed their volume. Two predictive models were developed to predict the probability of grade ≥ 2 CIP or severe CIP (grade ≥ 3). Cox proportional hazard models were employed to analyze predictors of progression-free survival (PFS). Results In a training cohort of 206 patients, 21.4% experienced CIP. Two models were developed to predict the probability of CIP based on different predictors. Model 1 utilized age, histology, and preexisting ground glass opacity (GGO) percentage of the whole lung to predict grade ≥ 2 CIP, while Model 2 used histology and GGO percentage in the right lower lung to predict grade ≥ 3 CIP. These models were validated, and their accuracy was assessed. In another exploratory analysis, the presence of GGOs involving more than one lobe on pretreatment CT scans was identified as a risk factor for progression-free survival. Conclusions The assessment of GGO volume and distribution on pre-treatment CT scans could assist in monitoring and manage the risk of CIP in NSCLC patients receiving ICI therapy. Clinical relevance statement This study’s quantitative imaging and computational analysis can help identify NSCLC patients at high risk of CIP, allowing for better risk management and potentially improved outcomes in those receivingICI treatment

Additional file 1 of Conteltinib (CT-707) in patients with advanced ALK-positive non-small cell lung cancer: a multicenter, open-label, first-in-human phase 1 study

Additional file 1: Table S1. In vitro potency of crizotinib and conteltinib (CT-707). Table S2. Intracranial response of conteltinib (CT-707) in ALK-positive patients with brain metastasis