BackgroundLung adenocarcinoma (LUAD) is the commonest subtype of primary lung cancer. A comprehensive analysis of the association of immunity with amino acid metabolism in LUAD is critical for understanding the disease.MethodsThe present study examined LUAD and noncancerous cases from the TCGA database. Differentially expressed genes (DEGs) between LUAD and noncancerous tissues were detected by analyzing processed expression profiles. We cross-referenced the up-regulated DEGs with Immune and Amino Acid Metabolism-related genes (I&AAMGs), resulting in Immune and Amino Acid Metabolism related differentially expressed genes (IAAAMRDEGs). The STRING database was employed to analyze PPI on IAAAMRDEGs, obtaining excavated hub genes, whose biological processes, molecular functions and cellular components were examined with GO/KEGG. Potential mechanisms related to LUAD were investigated by GSEA and GSVA. A prognostic model was built by LASSO-COX analysis, taking into consideration risk scores and prognostic factors to determine biomarkers affecting LUAD occurrence and prognosis.ResultsTotally 377 genes were detected at the intersection of upregulated DEGs and I&AAMGs. Analysis of PPI on these 377 IAAAMRDEGs yielded 17 hub genes. A LASSO regression analysis was utilized to assess the prognostic values of the 17 hub genes. Validation using the combined dataset confirmed 4 genes, e.g., polo-like kinase (PLK1), Ribonucleotide Reductase Subunit M2 (RRM2), Thyroid Hormone Receptor Interactor 13 (TRIP13), and Hyaluronan-Mediated Motility Receptor (HHMR). The model’s accuracy was further assessed by ROC curve analysis and the COX model. In addition, immunohistochemical staining obtained from the HPA database, revealed enhanced PLK1 expression in LUAD samples.ConclusionLUAD pathogenesis is highly associated with immunity and amino acid metabolism. The PLK1, RRM2, TRIP13, and HMMR genes have prognostic values for LUAD. PLK1 upregulation in LUAD might be involved in tumorigenesis by modulating the cell cycle and represents a potential prognostic factor in clinic.

BACKGROUND:In the quest to manage hepatocellular carcinoma (HCC), the focus has shifted to a more holistic approach encompassing both data analytics and innovative treatments. Analyzing rich data resources, such as the cancer genome atlas (TCGA), and examining progressive therapies can potentially reshape the trajectory of HCC treatment. AIM:To elucidate the immunological genes and the underlying mechanism of the combined Kombo knife and sorafenib regimen for HCC by analyzing data from TCGA and machine learning data. METHODS:Immune attributes were evaluated via TCGA's postablation HCC RNA sequencing data. Using weighted gene coexpression network analysis and machine learning, we identified genes with high prognostic value. The therapeutic landscape and safety metrics of the integrated treatment were critically evaluated across cellular and animal models. RESULTS:Immune genes-specifically, peptidylprolyl isomerase A and solute carrier family 29 member 3-emerged as significant prognostic markers. Enhanced therapeutic outcomes, such as prolonged progression-free survival and an elevated overall response rate, characterize the combined approach, with peripheral blood mononuclear cells displaying potent effects on HCC dynamics. CONCLUSION:The combination of Kombo knife with sorafenib is an innovative HCC treatment modality anchored in immune-centric strategies.

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.

Ethnopharmacological relevance: Huachansu (HCS) is a traditional Chinese medicine obtained from the dried skin glands of Bufo gargarizans and clinical uses of HCS have been approved in China to treat malignant tumors. The traditional Chinese medicine theory states that HCS relieves patients with cancer by promoting blood circulation to remove blood stasis. However, the material basis and underlying mechanism have not yet been elucidated.Aim of the study: To investigate the therapeutic potential of HCS for the treatment of pancreatic cancer in in situ transplanted tumor nude mouse model. Furthermore, this study sought to elucidate the molecular mechanisms underlying its efficacy and assess the impact of HCS on the microenvironment of pancreatic cancer. To identify the antitumor effect of HCS in in situ transplanted tumor nudemouse model and determine the Chemopreventive mechanism of HCS on tumor microenvironment (TME).Methods: Using the orthotopic transplantation nude mouse model with fluorescently labeled pancreatic cancer cell lines SW1990 and pancreatic stellate cells (PSCs), we examined the effect of HCS on the PDAC microenvironment based on the TGF-β/Smad pathway. The expression of TGF-β, smad2, smad3, smad4, collagen Ⅰ genes and proteins in nude mouse model were detected by qRT-PCR and Western blot.Results: HCS significantly reduced tumor growth rate, increased the survival rate, and ameliorated the histopathological changes in the pancreas. It was found that HCS concentration-dependently reduced the expression of TGF-β1 and collagen Ⅰ genes and proteins, decreased the expression of Smad2 and Smad3 genes, and downregulated the phosphorylation level of Smad2/3. Additionally, the gene and protein expression of Smad4 were promoted by HCS. Further, the promoting effect gradually enhanced with the rise of HCS concentration.Conclusions: The results demonstrated HCS could regulate the activity of the TGF-β/Smad pathway in PDAC, improved the microenvironment of PDAC and delayed tumor progression. This study not only indicated that the protective mechanism of HCS on PDAC might be attributed partly to the inhibition of cytokine production and the TGF-β/Smad pathway, but also provided evidence for HCS as a potential medicine for PDAC treatment.

Purpose: Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung adenocarcinoma (LUAD) relapse by "nourishing yin and clearing heat". In this study, the mechanism of YHT in LUAD recurrence was investigated. Methods: Firstly, the bioactive compounds and targets of YHT, as well as related targets of LUAD recurrence, were collected from public databases. The protein-protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to find the pivotal compounds, hub genes, functional annotation and main pathways. Subsequently, RNA sequencing of recurrent tumor tissues from Lewis lung carcinoma mice treated with YHT was used to explore the main pathways. At the same time, pathways screened by network pharmacology and RNA sequencing analysis were considered the most important pathways. Finally, liquid chromatography mass spectrometry was used to validate the pivotal active ingredients. Molecular docking technology was performed to validate the binding association between the hub genes and the pivotal active ingredients. PCR and WB analysis were used to validate the main pathways. Results: There were 128 active compounds and 419 targets interacting with YHT and LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub gene related to the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The molecular docking verified that the pivotal compounds could good affinity with S1PR5. The PCR and WB analysis verified YHT suppressed Lewis lung cancer cells proliferation and migration by inhibiting the sphingolipid signaling pathway. Conclusion: The potential mechanism and therapeutic effect of YHT against the recurrence of LUAD may be ascribed to inhibition of the sphingolipid signaling pathway.

This study aimed to test cinobufacini therapeutic potential for pancreatic cancer, verify its potential molecular mechanism, and evaluate the cinobufacini impact on pancreatic cancer microenvironment. First, the effect of cinobufacini-treated pancreatic stellate cells (PSCs) supernatant on the value-added ability of pancreatic cancer (PCCs) was tested. The results show that cinobufacini can effectively reduce the ability of PSCs supernatant to promote the value-added PCCs. Further results show that cinobufacini can effectively reduce the concentration of TGFβ in the supernatant of PSCs. Subsequently, the impact of cinobufacini on the transcription and translation levels of key genes in the TGFβ/Smads pathway was examined. The results showed that the impact of cinobufacini on the transcription levels of Smad2, Smad3, and Smad7 was in a concentration-dependent manner, while the transcriptional activity of collagen I mRNA was decreased with the increase of cinobufacini concentration. The results of protein expression showed that cinobufacini could upregulate the expression of inhibitory protein Smad7, inhibit the phosphorylation level of p-Smad2/3, and then suppress the expression of type I collagen (collagen I). On the one hand, this study shows that cinobufacini can inhibit the promotion of PSCs on the proliferation of PCCs. On the other hand, cinobufacini can upregulate the expression of the inhibitory molecule, Smad7, through the TGFβ/Smads pathway and reduce the phosphorylation level of p-Smad2/3, thereby inhibiting the expression of collagen I and pancreatic fibrosis. cinobufacin can inhibit the proliferation of SW1900 cells by blocking the TGFβ/Smads pathway of pancreatic stellate cells. These results provide a clinical basis for the treatment of pancreatic cancer.

Background Cisplatin is an extensively used chemotherapy agent for lung cancer, but its drug resistance serves as a huge obstacle for chemotherapy failure of lung cancer patients. Hence, researchers aimed to determine role of sirtuin 3 (SIRT3) considering its action in cisplatin resistance of lung cancer. Methods The expression patterns of SIRT3, FOXO3, and CDT1 were determined using RT-qPCR and Immunoblotting in lung cancer. Immunofluorescence and Co-IP were adopted to detect co-localization and interaction of FOXO3 and CDT1. Loss- and gain-function assays were conducted to determine roles of SIRT3, FOXO3, and CDT1 in resulting pathological changes, while biological behavior of cells was determined using a combination of CCK-8, flow cytometry, colony formation, and Transwell assays. The effects of SIRT3 and CDT1 were determined in the nude mice xenografted with the tumor. The proliferation-, angiogenesis-, and apoptosis-associated factors levels were determined using Immunoblotting. Results SIRT3, FOXO3, and CDT1 expression was suppressed in the lung cancer tissues and cells. FOXO3 positively regulates the CDT1 expression pattern and SIRT3 elevation inhibits FOXO3 at the acetylated level, thus, elevating FOXO3 expression. The elevation of SIRT3, FOXO3, or CDT1 inhibited cell cisplatin resistance of lung cancer cells as well as inhibited viability, proliferation, and invasion in vitro. In vivo experiments, SIRT3 depletion elevated Ki-67 and VEGFA levels, but downregulated cleaved caspase 3 level. Conclusion Collectively, overexpressed SIRT3 elevates expression of FOXO3a/CDT1 axis, thus, contributing to enhanced sensitivity of lung cancer cells.

This study analyzes the expression and clinical significance of long non-coding RNA (lncRNA) BM466146 in breast cancer, and explores the role of BM466146 in immune regulation. The expression of BM466146 in 89 cases of breast cancer and their corresponding non-cancerous breast tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis was applied to evaluate patient survival. EDU and CCK-8 experiments on breast cancer cells were performed to verify the function of BM466146 in vitro . The target genes of BM466146 were screened by informatics analysis to predict associated miRNAs and their corresponding mRNAs, immune genes associated with lncRNAs and chemokines associated with CD8. Immunohistochemistry was used to detect the expression of CD8, Ki-67, and CXCL-13 in the 89 breast cancer tissues. It was found that the expression of lncRNA BM466146 in breast cancer tissues was significantly lower than that in normal breast tissues ( P < 0.001). In breast cancer, tissues that overexpressed BM466146 exhibited a lower Ki-67 index compared with that of low BM466146 expression ( P = 0.048). Kaplan-Meier survival analysis showed that breast cancer patients with overexpression of BM466146 had longer overall survival. EDU and CCK8 experiments showed that overexpression of BM466146 inhibited the proliferation of breast cancer cells. The hsa-miR-224-3p is associated with BM466146, and its target gene might be CXCL-13. The positive CD8 cells in the BM466146 overexpression group was higher than that in the low BM466146 expression group ( P =0.027), and the positive CD8 cells in the CXCL-13 positive group was higher ( P =0.023) than that of the negative group. Our results indicate that the lncRNA BM466146 has the function of tumor suppressor gene. Overexpression of BM466146 is associated with better prognosis. BM466146 could regulate CXCL-13 by adsorbing hsa-miR-224-3p and inducing CD8 + T cells to accumulate in the tumor area which regulate immune response. Therefore, BM466146 could be a prognostic biomarker and a molecular immune target of breast cancer.

Introduction National Comprehensive Cancer Network has recommended cryoablation to replace the resection in the treatment of medically operable non-small cell lung cancer (NSCLC). Cryoablation also has been used for the advanced NSCLC in randomised controlled trials. However, they have not been systematically reviewed. Here, we provide a protocol to evaluate the effectiveness and safety of cryoablation in the treatment of advanced NSCLC.Methods and analyses We will search PubMed, Embase, the Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database without language restrictions from inception until 1 February 2020. Trial registers (International Clinical Trials Registry platform, the US National Institutes of Health Ongoing Trials Register and the ISRCTN registry) and reference lists of retrieved articles will also be searched. Two reviewers will independently extract data on participants, interventions, comparisons, outcomes and assess the methodological quality by the Cochrane risk of bias tool. The strength of evidences will be evaluated according to the Grading of Recommendations Assessment, Development and Evaluation approach. Review Manager V.5.3 software will be used for data analyses. Meta-analyses will be performed if the data are sufficiently homogeneous. The primary outcomes will be objective response rate and overall survival. The secondary outcomes will be adverse effects, health-related quality of life, changes of immune indicators and surrogate outcomes (disease control rate, progression-free survival and survival rate).Ethics and dissemination Ethics approval is not required, as this study will not involve patients. The results of this study will be submitted to a peer-reviewed journal for publication, to inform both clinical practice and further research.PROSPERO registration number CRD42019138660.

Increasing evidences suggest that insufficient radiofrequency ablation (IRFA) can paradoxically promote tumor invasion and metastatic processes, whereas the effects of moderate hyperthermia on cancer progression are not well illustrated. Our study found that IRFA can increase the in vitro migration, invasion, and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells via induction of Snail, a master regulator of EMT events. Among measured miRNAs, IRFA can decrease the expression of miR-148a-5p in HCC cells. Whereas overexpression of miR-148a-5p can reverse IRFA-induced migration of HCC cells and upregulation of Snail, mechanistically overexpression of miR-148a-5p can directly target and decrease the expression of protein kinase ATM (ataxia telangiectasia mutated), which can increase protein stability of Snail. Collectively, our data suggest that IRFA can regulate the miR-148a-5p/ATM/Snail axis to trigger migration of HCC cells.

随着疾病流行模式的快速转变,恶性肿瘤等慢性非传染性疾病成为居民致死的主要原因.2018的统计资料显示,全球恶性肿瘤新发病例约1 808万例,中国约占23.7 ％;死亡病例约 956 万例,中国约占30 ％.我国发病率和死亡率均高于全球平均水平.

《健康中国行动 ——癌症防治实施方案(2019-2022)》提出的行动之一,是"实施危险因素控制行动,降低癌症患病风险".也就是要把预防癌症的工作列在首位. 随着人均寿命的增长,生活行为方式等环境因素的改变,恶性肿瘤已成为严重危害人类健康的重要疾病.

宋金元时期的医家普遍继承了《内经》《难经》《神农本草经》等对肿瘤的认识,并从肿瘤的临床特征将其归纳为“喦”“岩”,被当时多位医家应用.在治疗原则方面,历经了从宋代以攻逐祛邪为主,到金元时期发展、争鸣、变革,以易水学派、补土派强调养正,攻邪派强调“达”“发”“夺”“泄”“折”五法,滋阴派推崇从痰论治等,可谓继承、发展、创新,百家争鸣.

Purpose: There are two kinds of thawing temperatures commonly adopted in cancer cryosurgery. We attempted to compare their efficacy differences in this study to optimize the surgical method.Method: Forty-five C57BL/6 J mice with GFP-labeled Lewis lung cancer were randomized into three groups (n = 15 for each): control group, TO group (thawing temperature 0 degrees C), and T40 group (thawing temperature 40 degrees C). Cryoablation was performed using a combined surgical system. When the ice ball reached the border of the tumor, they were rewarmed to 0 degrees C and 40 degrees C, respectively, using a single freeze thaw cycle. After the surgery, weight of these mice, length/width and the fluorescence intensity (FI) of the tumors were recorded. All mice were sacrificed on Day 14 after the procedures and their xenografts were excised and weighed immediately. We also checked for pulmonary metastasis, and examined tumor specimens using HE staining.Results: Body weights, tumor volumes and Fl in the three groups did not differ significantly at baseline. On Day 14, 39% of the tumors in the TO group decreased in volume, whereas only 17% in the T40 group did. The average Fl in the control group increased by 60%, but declined by 72% in TO mice and 69% in T40 mice. Tumor inhibition rates were 71.64% in the TO group and 68.12% in the T40 group. Lung metastases rates and histological changes were compatible between the two intervention groups.Conclusion: Using 0 degrees C as the thawing temperature may have more potential benefits in cryoablation efficacy. (C) 2017 Elsevier Inc. All rights reserved.

The purpose of this study was to determine the efficacy and safety of dutasteride compared with finasteride, used for the treatment of benign prostatic hyperplasia (BPH). Pertinent studies were identified by searching of PubMed and Web of Science. The random effect model was used to combine the results. Both direct comparison using traditional meta-analysis method and indirect comparison using network meta-analysis method were performed. Twenty-one articles involving a total of 29,094 patients were included in this network meta-analysis. Pooled data demonstrated a significantly reduction in International Prostate Symptom Score in the dutasteride group compared with finasteride group [weighted mean difference (WMD) = −1.80, 95% confidence interval (CI), −2.90 to −0.11]. The treatment effects of dutasteride compared with finasteride were not significant in peak urinary flow (Q max) (WMD = 0.76, 95% CI, −0.67 to 2.00) and total prostate volume (WMD = −7.6, 95% CI, −21 to 6.6). Also, there is no significant association between dutasteride and finasteride of the safety for the treatment of BPH. Our results suggested that there were no statistically significant differences in the treatment of symptomatic BPH among dutasteride compared with finasteride except that dutasteride can improve BPH symptoms measured by International Prostate Symptom Score.

Objective:This intervention has been shown to be clinically efficacious and safe.The aim of this study was to determine the effect of different intervention times on the efficacy of gastroparesis external application prescription versus placebo for the treatment of gastrointestinal tumor postoperative,postsurgical gastroparesis.Methods:A multicenter,randomized,double-blind,placebo controlled phase Ⅲ clinical trial was designed to demonstrate superiority and conducted at four grade 3 A hospitals in Beijing.Patients diagnosed with gastrointestinal tumor postsurgical gastroparesis and local cold syndrome in the abdomen were enrolled and received conventional treatment（nutritional support,gastrointestinal decompression,and prokinetic medication）.Treatment and control groups respectively received gastroparesis external application prescription or placebo acupoint application over a treatment course of 14 days or until the primary efficacy endpoint（clinical efficiency） was achieved.Results:A total of 120 patients were enrolled in the treatment and control groups（n=60 per group）,and 15 patients dropped out of the study because of skin allergies（n=7） or poor efficacy（n=8）.The efficacy among patients in Class B of Group A（treatment group） was marginally better than that of Group B（control group）（64.28% vs.55.56%） although the difference between the two groups was not significant.However,the efficacy among patients in Class C of Group A was significantly better than that of Group B（79.49% vs.43.33%）.For Group A,the time for patients in the three classes to achieve the efficacy endpoint increased significantly with disease progression（3.00,6.78,and 8.29 days for Class A,B,and C,respectively）.Conclusions:Gastroparesis external application prescription can effectively treat gastrointestinal tumor postsurgical gastroparesis and may be more efficacious in progressive disease compared placebo.Patients with gastrointestinal tumor postsurgical gastroparesis should therefore undergo intervention at an earlier stage.

Modern cryoablation has been performed in solid tumor management for more than two decades. Following the surgical spirits, it seems natural to pursue radical procedures in clinical practice, which results in unnecessary adverse effects. The attempt to use non-extended procedure made some marked achievements in practice but was criticized severely, because it was supposed to induce residual tumors, which would trigger the rapid development of cancer. Oncologists favored this procedure, however, claiming that non-extended cryoablation let lung cancer patients have higher quality of lives and longer survivals, in light of clinical observations. Therefore, this study was conducted trying to solve this controversy. In this study, fifty female C57BL/6J mice were grafted green fluorescent protein (GFP)-labeled Lewis lung cancer and randomized into two groups. The bidirectional diameters and fluorescence intensity of tumors, and the body weight of mice were recorded. Two weeks after the intervention, tumor volumes increased 20.95% in the cryoablation group, significantly different from that in the control group; the fluorescence intensity decreased 49.85% in the cryoablation group but increased 125.07% in the control group. Lung metastases could be observed in only 20% of mice in the cryosurgery group, contrasted to 64% in the control group. The non-extended lung cancer cryoablation does induce marginal tumor residuals, but will not trigger rapid tumor development. Inversely, the residual tumor cells are severely struck and the metastases are suppressed after the intervention. It could be a new strategy in lung cancer management, even for patients not in early stage.

Objective To investigate the changing rules of TCM syndrome patterns, the possible factors contributing to changes of syndrome patterns, and the effects of the Chinese medicinal interventions based on syndrome differentiation before and after Argon-helium cryoablation on elderly patients with non-small cell lung cancer ( NSCLC). Methods 130 NSCLC Patients were divided into two groups. 65 patients from Combination Group ( Group I) were given the treatments of TCM combined with best supportive care (BSC) after argon-helium cryoablation. The rest 65 patients of Western Medicine Multi-modality ( group II) were given the treatments of BSC alone. TCM syndrome types were observed and analyzed on the 1st day before operation, 1 week, 1 month and 3 months after the surgery respectively. Results The patterns of syndrome could be mainly classified into 4 patterns: qi deficiency, yin deficiency, phlegm-damp and blood stasis. (1) Qi deficiency syndrome:the frequency of qi deficiency in group I was less than those in group II 1 month and 3 months after the surgery(P<0. 05). The frequency of qi deficiency in group II was increased 1 week and 3 months after the surgery with statistical difference (P<0. 05). (2) Yin deficiency syndrome: there were no statistical differences of the frequency of yin deficiency between 2 groups ( P > 0. 05). (3) Dampness-phlegm syndrome: the frequency of dampness-phlegm in group I was less than group II 1 month and 3 months after the surgery(P<0. 05). The frequency of dampness-phlegm in group II was increased 1 month and 3 months after the surgery, with statistical difference (P<0. 05). (4)Blood stasis: the frequency of blood stasis in group II was increased 1 month and 3 months after the surgery with statistical difference (P<0. 05). Conclusion TCM treatments based on syndrome differentiation can significantly improve effectiveness of treatments, especially for qi deficiency, phlegm-damp and blood stasis. Moreover, the following principles can be used to guide clinical treatments: reinforcing qi, nourishing yin, eliminating phlegm and resolving stasis.

Small cell lung cancer (SCLC) is common in oncology clinical practice, which is characterized by high malignant level and poor prognosis. Typically, patients with SCLC rarely survive more than a few months without effective treatment. The median survival for patients with limited disease SCLC is only 15-20 months, with the 5-year survival rate 10%-13%. Here we report a case, female, 58 years, with unresectable limited stage SCLC (6.5cm × 5.5cm, in the right middle lung), who survived from 5 cycles of low doses of chemotherapy, 2 cryosurgery and botanical drugs therapy, living with the primary tumor stably more than 7 years and holding great quality of life.