Objective
To investigate the value of circulating tumor cells (CTCs) in the evaluation of chemotherapeutic effect in non-small cell lung cancer (NSCLC).
Methods
A total of 23 cases of patients with NSCLC receiving chemotherapy were enrolled in this study from January 2015 to June 2017 in the First Affiliated Hospital of the Fourth Military Medical University.Venous blood (5 ml) was extracted from 23 patients prior to chemotherapy, 24h before the first, second, and third cycles of chemotherapy, CTCs were analyzed by CanPatrol™.In the meantime, the tumors were monitored by computed tomography at baseline, and 6 weeks after the first cycle of chemotherapy.According to the response evaluation criteria in solid tumors (RECIST), the patients at the time of 6 weeks after the first cycle of chemotherapy were divided into the effective group [partial response (PR)] and the ineffective group [progressive disease (PD) and stable disease (SD)].
Results
The effect of chemotherapy was determined according to RECIST at the time of 6 weeks after the first cycle of chemotherapy, among the 23 patients who went under chemotherapy, the outcomes consisted of partial response in 12 cases (52.2%), stable disease in 1 case (4.3%) and progressive disease in 10 cases (43.5%); the effect of chemotherapy was determined according to the changes of CTCs at the time of 6 weeks after the first cycle of chemotherapy too, and the outcomes consisted of complete response and partial response in 13 cases (56.5%), progressive disease in 10 cases (43.5%). As the results of the Fisher′s exact test showed, there were no significant differences between the two methods in the evaluation of curative effect (P=1.0). Spearman correlation analysis showed that the changes of CTCs number at the time of 6 weeks after the first cycle of chemotherapy were correlated with the curative effect (r=0.861, P=0.000). In the effective group, the number of CTCs of patients at the time of 3 weeks [5.5(4.3, 14.0)CTCs/5 ml] and 6 weeks [3.0(1.3, 5.8)CTCs/5 ml] after the first cycle of chemotherapy were lower than that of before chemotherapy [10.5(7.0, 26.3)CTCs/5 ml], the difference was statistically significant (Z=-2.941, -3.065, both P<0.05); conversely, in the ineffective group the number of CTCs of patients at the time of 3 weeks [7.0(3.0, 9.0)CTCs/5 ml] and 6 weeks [11.0(3.0, 13.0)CTCs/5 ml] after the first cycle of chemotherapy were higher than that of before chemotherapy [3.0(2.0, 5.0)CTCs/5 ml], the difference was statistically significant (Z=-2.687, -2.803, both P<0.05).
Conclusions
In patients with NSCLC, the therapeutic effect can be evaluated in early stage according to the changes of CTCs number in peripheral blood after chemotherapy.CTCs detection may be a useful supplement to the evaluation system of RECIST.
Key words:
Non-small cell lung cancer; Circulating tumor cells; Chemotherapy; Evaluation
The study focuses on the water saving technology for external cooling system of DC transmission converter station equipment, a water saving design applicable to external cooling system of such key equipment cooled by water as converter valve and transformer in the converter station of the conventional/flexible DC transmission project. Current external cooling method for converter valve equipment in the converter station mostly combines the closed-circuit cooling tower and spray cooling. This method, however, has the disadvantages of, for example, high water consumption and large quantity of blowdown. In view of this, this paper proposes a water saving technology by sewage recycling through spray treatment system based on two-stage reverse osmosis. In this technology, the water in the converter station can be recycled, thus achieving the purpose of water saving and blowdown reduction. For the transformer cooled by external cooling with water, this paper provides an optimized design of common configuration in which the external cooling systems of converter valve and transformer share the same spray pool and spray treatment equipment. This design will not only save water resources, but also facilitate the operation, maintenance and comprehensive management of converter station. It is thus in accord with the green development philosophy of converter station.
// Yuan Lu 1, * , Yuan Wang 1, * , Mi Zhang 3, * , Li Liu 1, 2 , Fakai Li 1 , Jian Zhang 1 , Mingxiang Ye 1 , Hu Zhao 4 , Jing Zhao 5 , Bo Yan 5 , Angang Yang 6 , Rui Zhang 5 , Xia Li 5 , Xinling Ren 1 1 Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, China 2 Department of Geriatrics, Xianyang Central Hospital, Xianyang, China 3 Department of Respiratory Medicine, PLA General Hospital, Beijing, China 4 Organ Transplant Institute, Fuzhou General Hospital (DongFang Hospital), Xiamen University, Fuzhou, China 5 State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, China 6 State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi’an, China * These authors have contributed equally to this work Correspondence to: Rui Zhang, email: ruizhang@fmmu.edu.cn Xia Li, email: lixia@fmmu.edu.cn Xinling Ren, email: majrenxl@fmmu.edu.cn Keywords: non-small cell lung cancer, EGFR, HER2, single-chain viable-fragment antibody, small interfering RNA Received: September 30, 2015 Accepted: February 29, 2016 Published: March 14, 2016 ABSTRACT Overexpression of human epidermal growth factor receptor type2 (HER2) is closely associated with aggressive progression and poor prognosis in non-small cell lung cancer (NSCLC). Here, we generated an EGFR-scFv-arginine nonamer peptide fusion protein (scFv-9R) as a cargo to deliver HER2 specific siRNA into HER2-positive NSCLC cells both in vitro and in vivo . HER2-siRNAs delivered by scFv-9R effeciently silenced HER2 expression in EGFR-positive NSCLC cells, and consequently resulted in G1 arrest and cell growth inhibition. Importantly, intravenous injection of scFv-9R/HER2-siRNA complex markedly suppressed growth of EGFR-positive NSCLC xenograft in nude mice, resulting from downregulated HER2 expression, reduced cell proliferation and enhanced cell apoptosis. Collectively, our study provides a novel therapeutic strategy for the treatment of EGFR-positive, HER2-overexpressed NSCLC.
The overexpression of epidermal growth factor receptor (EGFR) is closely associated with a poor outcome in non-small cell lung cancer (NSCLC), and EGFR is an ideal biomarker for the targeted therapy of NSCLC. Although patients with EGFR-activating mutations respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs), they eventually acquire resistance, which typically results from a secondary EGFR mutation or the activation of other signaling pathways. Novel approaches to overcome or prevent EGFR-TKI resistance are clinically important. In this study, we developed an EGFR-scFv-arginine nonamer peptide fusion protein, s-9R, as an siRNA carrier. Here, we show that s-9R effectively and specifically delivers EGFR-siRNAs, KRAS-siRNA and MET-siRNA into NSCLC cells and silences the expression of target genes. The sensitivity of NSCLC cells to gefitinib was restored after treatment with the s-9R/siRNA complex, and the apoptosis rates of the treated cells were significantly higher than those of the control groups. Furthermore, the co-administration of s-9R/siRNA and gefitinib successfully suppressed the progression of H1975 xenograft tumors and extended the life span of tumor-bearing nude mice. Collectively, the results of this study provide not only a new scFv derivative for delivering siRNA into EGFR-overexpressing, TKI-resistant NSCLC cells but also a novel method for overcoming TKI resistance.
Objective
To observe the effects of shikonin on the proliferation of lung adenocarcinoma cells H1975, and explore its possible anticancer mechanism.
Methods
The cytostatic effects of shikonin on H1975 cells were evaluated by MTT assay and the cell morphology was observed under the microscope.The effects of shikonin on apoptosis and cycle of H1975 cells were determined by flow cytometry (FCM). The expressions of epidermal growth factor receptor (EGFR) signal pathway related proteins and proteins of Bcl-2 and PARP in H1975 cells were detected by Western blot.
Results
MTT assay showed that shikonin could potently inhibit the growth of H1975 cells.FCM result showed that the apoptotic rate was significantly high and the blocking cell was in the S phase.The protein expressions of EGFR, ERK, AKT, p-EGFR, p-ERK, p-AKT, Bcl-2 in H1975 cells could be down-regulated, and expression of PARP protein could be markedly sheared by shikonin.
Conclusions
Shikonin can significantly inhibit H1975 cell proliferation and promote tumor cell apoptosis, which may be related to regulating the protein expression of Bcl-2, PARP and protein expressions in EGFR signal pathway.
Key words:
Shikonin; Non-small cell lung cancer; H1975; Anticancer mechanisms
Abstract Background The Skeletal Muscle Index (SMI) is an objective indicator for evaluating the nutritional status in malignant tumors. The baseline nutritional status may affect the efficacy and prognosis of targeted anti-tumor therapy, and growth factor tyrosine kinase inhibitors often lead to drug-related sarcopenia. Fruquintinib has been approved for metastatic colorectal cancer. In this study, we analyzed the prognostic value of baseline SMI in metastatic colorectal cancer treated with fruquintinib, and observed the incidence of SMI reduction after fruquintinib treatment to evaluate its impact on prognosis. Methods A retrospective multi-center analysis of metastatic colorectal cancer patients treated with fruquintinib in eight medical centers in China was performed. The muscle area of the third lumbar spine was evaluated, the baseline SMI and post-treatment SMI were calculated separately. The correlation with survival was analyzed. Results The median PFS of 105 patients was 4.2 months (95% CI, 3.7 months to 4.9 months), and the median OS was 10.2 months (95% CI, 9.0 months to 12.7 months). The baseline SMI before fruquintinib therapy was significantly correlated with OS (P = 0.0077). Multivariate analysis demonstrated that the baseline SMI was an independent prognostic factor for OS (P = 0.005). Twenty-eight point eight seven percent (28.87%) patients experienced sarcopenia after oral administration of fruquintinib. However, there was no significant difference in OS between the SMI reduced group and the SMI nonreduced group after treatment with fruquintinib. Conclusion The baseline SMI was an independent prognostic factor for OS and it could affect the survival of patients treated with fruquintinib in metastatic colorectal cancer. Although fruquintinib can cause sarcopenia, there is no correlation between post-treatment SMI changes and survival.
Porcine astroviruses (PAstVs) are common in pigs worldwide. There are five distinct lineages with each lineage representing a different ancestral origin. Recently, multiple reports have demonstrated the evidence of extra-intestinal infection of PAstVs, but little is known about viremia.In this study, a total of 532 fecal samples and 120 serum samples from healthy pigs were collected and tested from 2013 to 2015 in Guangxi province, China; of these 300/532 (56.4%) and 7/120 (5.8%) of fecal samples tested positive for PAstVs, respectively. Our study revealed that there was wide genetic diversity and high prevalence of the virus in the pig population. All five of the known PAstVs genotypes (1-5) prevailed in the pig population of Guangxi province and were distributed in all age groups of pigs, from suckling piglets to sows, with PAstV2 (47.7%), PAstV1 (26.2%) and PAstV5 (21.5%) seen predominantly. Phylogenetic analysis of partial ORF1b and partial capsid sequences from fecal and serum samples revealed that they were divided into the five lineages. Among these genotypes, based on partial ORF2 genes sequencing 23 strains were grouped as PAstV1, including 6 serum-derived strains, and were regarded as the causative agents of viremia in pigs.Due to the information regarding the types of PAstV in blood is limit. This is the first report for the presence of PAstV1 in blood and PAstV3 in the feces of nursery pigs of China. This study provides a reference for understanding the prevalence and genetic evolution of PAstVs in pigs in Guangxi province, China. It also provides a new perspective for understanding of the extra-intestinal infection of PAstVs in pigs.
The Skeletal Muscle Index (SMI) serves as an objective metric for assessing nutritional status in patients with malignant tumors. Research has found baseline nutritional status can influence both the efficacy and prognosis of targeted anti-tumor therapies, with growth factor tyrosine kinase inhibitors frequently inducing drug-related sarcopenia. Fruquintinib has received approval for the treatment of metastatic colorectal cancer. This study examines the prognostic significance of baseline SMI in patients with metastatic colorectal cancer undergoing treatment with fruquintinib. Additionally, the study investigates the incidence of SMI reduction following fruquintinib therapy to assess its impact on patient prognosis. A retrospective multicenter study was conducted to analyze patients with metastatic colorectal cancer who received fruquintinib treatment across eight medical centers in Eastern China. The muscle area at the third lumbar vertebra was assessed, and both baseline and post-treatment SMI values were calculated independently. The relationship between SMI and patient survival was subsequently examined. The median progression-free survival (PFS) for the cohort of 105 patients was 4.2 months (95% CI, 3.7 to 4.9 months), while the median overall survival (OS) was 10.2 months (95% CI, 9.0 to 12.7 months). Notably, the baseline SMI prior to the initiation of fruquintinib therapy exhibited a significant correlation with OS (P = 0.0077). Multivariate analysis indicated that baseline SMI serves as an independent prognostic factor for OS (P = 0.005). Furthermore, after Propensity Score Matching (PSM) analysis, there was still a significant correlation between baseline SMI and OS. Among the patients, 28.87% developed sarcopenia following oral administration of fruquintinib. However, no statistically significant difference in OS was observed between the group with reduced SMI and the group without SMI reduction after treatment with fruquintinib. The baseline SMI was identified as an independent prognostic factor for OS and may influence the survival outcomes of patients with metastatic colorectal cancer undergoing treatment with fruquintinib. Despite the potential of fruquintinib to induce sarcopenia, no significant correlation was observed between changes in SMI following treatment and patient survival.
Increasing evidence indicates that the inflammatory tumor microenvironment can lead to cancer cell metastasis. Shikonin, which is extracted from the Chinese herb Zicao (the dried root of Lithospermum erythrorhizon), possesses various pharmacological effects, but its effect on tumor metastasis in the inflammatory microenvironment remains unknown. In the present study, we aimed to investigate the potential effect of shikonin on tumor metastasis in an inflammatory microenvironment as well as the underlying molecular mechanisms. It was found that, in the inflammatory microenvironment simulated by THP‑1 cell conditioned medium (THP‑1‑CM) in vitro, shikonin significantly inhibited the epithelial‑mesenchymal transition (EMT), migration and invasion of human lung adenocarcinoma cell lines A549 and H1299. In addition, we found that interleukin‑6 (IL‑6), which is expressed in THP‑1‑CM, promoted the EMT of lung adenocarcinoma cells, and shikonin markedly inhibited IL‑6‑induced EMT and cell motility. Moreover, shikonin inhibited IL‑6‑induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), prevented phosphorylated STAT3 (p‑STAT3) translocation into the nucleus, and suppressed p‑STAT3 transactivation activity. Additionally, it was found that shikonin inhibited lung metastasis, EMT and expression of p‑STAT3 of A549 cells in vivo. Furthermore, IL‑6 levels in human lung adenocarcinoma tissues were significantly associated with tumor‑node‑metastasis stage and lymph node metastasis, and its expression was correlated with tumor‑associated macrophage (TAM) infiltration. Together, these results suggest that shikonin suppresses the migration and invasion of human lung adenocarcinoma cells in an inflammatory microenvironment involving the IL‑6/STAT3 signaling pathway.
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